@article {pmid40837716,
year = {2025},
author = {Escrivá, N and Moreno-Galarraga, L and Barado, E and Torres, MG and Fernandez-Montero, A},
title = {Association Between Acute COVID-19 Infection and Long COVID in a Non-Hospitalized Population: A Retrospective Case-Control Study.},
journal = {Health science reports},
volume = {8},
number = {8},
pages = {e71043},
pmid = {40837716},
issn = {2398-8835},
abstract = {BACKGROUND AND AIMS: Long COVID (LC) is a condition characterized by the persistence of physical or psychological symptoms after acute SARS-CoV-2 infection. While its pathophysiology remains unclear, it is essential to identify acute-phase risk factors associated with its development. This study aimed to investigate the association between symptoms during acute COVID-19 and the risk of developing LC, and to evaluate the impact of LC on functional status in a nonhospitalized population.

METHODS: A retrospective observational case-control study was conducted between May 2022 and March 2024 including 434 participants with confirmed SARS-CoV-2 infection. Participants were classified as cases (those with LC; n = 226) or controls (those without LC; n = 208). Data were collected using a structured electronic form, including self-reported sociodemographic, clinical, and lifestyle information. Severity and number of acute symptoms were recorded. Functional status was assessed using the Post-COVID functional status (PCFS) Scale. Logistic and linear regression analyses were performed to explore associations, adjusted for potential confounders.

RESULTS: Severe acute COVID-19 (defined as pneumonia or hospitalization) was associated with a significantly increased risk of LC (adjusted OR = 7.22; 95% CI: 2.79-18.70). Additionally, each additional symptom during the acute phase increased the odds of LC by 52% (adjusted OR = 1.52; 95% CI: 1.35-1.77). Dyspnea and chest pain were the symptoms most strongly associated with LC.

CONCLUSION: The severity and symptom burden of acute COVID-19 are strongly associated with the development of LC and with long-term functional impairment. These findings highlight the importance of early identification and follow-up in patients with severe initial COVID-19 symptoms.},
}

@article {pmid40836768,
year = {2025},
author = {Al-Jabr, H and Castle, DJ and Thompson, DR and Windle, K and Belcher, J and Valenzuela, MMI and Helliwell, T and Ski, CF},
title = {Long COVID Optimal Health Programme to Enhance Mental and Physical Health: A Feasibility Randomised Controlled Trial.},
journal = {Health expectations : an international journal of public participation in health care and health policy},
volume = {28},
number = {4},
pages = {e70399},
doi = {10.1111/hex.70399},
pmid = {40836768},
issn = {1369-7625},
support = {//This study was supported by Mental Health Alliance (East Suffolk, West Suffolk and North East Essex) (SIV02/0000555)./ ; },
mesh = {Humans ; Female ; Feasibility Studies ; Male ; *COVID-19/psychology/complications ; Middle Aged ; *Mental Health ; Adult ; United Kingdom ; Aged ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Surveys and Questionnaires ; },
abstract = {INTRODUCTION: Long COVID (LC) is characterised by fatigue, muscle weakness and impaired concentration among other symptoms. No standardised diagnostic or treatment pathway is yet available, though a holistic, person-centred approach to symptom management is recommended. The LC Optimal Health Programme (LC-OHP) is a psychoeducational programme designed to support the mental and physical health of people with LC. This study aimed to examine the feasibility of delivering the LC-OHP to people with LC.

METHODS: This was a feasibility randomised controlled trial of the LC-OHP conducted across the UK. Adults diagnosed with LC were recruited and randomised to control (usual care) or to intervention (LC-OHP) groups; follow-up questionnaires were completed at three- and 6-months (December 2021 to May 2023).

RESULTS: Sixty participants were recruited with a completion rate of 83% (n = 50). Most participants in the LC-OHP group completed programme sessions (n = 19, 68%), rated the programme positively (n = 23, 87%); and felt that it had potential to improve health outcomes (n = 42, 70%). Initial findings demonstrate improvements across all variables at 3- and 6-months, and more so for the LC-OHP group than the control group in the short-term.

CONCLUSION: Findings support the feasibility of delivering the LC-OHP to people with LC. Further, initial data demonstrate potential for the programme to improve most outcomes at three and 6 months. Data from this feasibility trial will be used as an evidence base to support a fully powered RCT of the LC-OHP on patients with LC.

The LC-OHP programme was adapted from the original OHP. Taking into account the various symptoms that people with LC experience, including fatigue and brain fog, public members were not directly involved in the design of the study; however, several approaches were considered to obtain ongoing support from public members while conducting the study, to suit people with LC. This included consulting with practitioners who care for people with LC and implementing their feedback, implementing prior feedback from patients with other chronic health conditions who used the OHP in previous studies, and collecting and implementing feedback from participants receiving this programme in this study. Additionally, two public members with lived LC experience were members of the data management committee that overviewed the study progress and provided continuous support. Public members and practitioners provided advice and guidance on different aspects related to the LC-OHP programme and to the process of delivering it to study participants. This included making the programme concise, visual, colourful, and more user-friendly, and adjusting and adapting the mode and timing of delivering the programme sessions (i.e., reduce the session duration, use convenient delivery methods) as preferred by study participants.

TRIAL REGISTRATION: ISRCTN trial register: registration number 38746119, https://doi.org/10.1186/ISRCTN38746119.},
}

Humans
Female
Feasibility Studies
Male
*COVID-19/psychology/complications
Middle Aged
*Mental Health
Adult
United Kingdom
Aged
SARS-CoV-2
Post-Acute COVID-19 Syndrome
Surveys and Questionnaires

@article {pmid40834724,
year = {2025},
author = {Abbas, U and Ahmed, I and Khalid, MU and Hafeez, S and Mukhtiar, S and Hussain, N and Nasrumminallah, M and Khan, MS and Babar, N and Ashraf, S and Kumar, P},
title = {Biochemical Profile of Recovered Individuals With Mild COVID-19: A Cross-Sectional View at Two Different Time Points.},
journal = {Archives of medical research},
volume = {57},
number = {1},
pages = {103286},
doi = {10.1016/j.arcmed.2025.103286},
pmid = {40834724},
issn = {1873-5487},
abstract = {AIM: This study was designed to cross-sectionally evaluate the frequency of long COVID-19, along with their hematological and biochemical parameters in survivors of mild COVID-19 after 6-15 months of acute infection.

METHODS: We recruited 75 age-matched healthy controls (HC) and 150 individuals who had recovered from mild cases of COVID-19. The recovered individuals were grouped according to the time elapsed since acute infection: 6-10 month (CoV_A) and >10-15 month of recovery (CoV_B). A brief clinical history was taken and detailed hematological and biochemical blood parameters were measured.

RESULTS: In our study, 64% of individuals had symptoms of long COVID. There were differential symptoms and presenting complaints associated with time since acute infection. The recovered group had significantly different hemoglobin concentration, red blood cell (RBC) count, white blood cell (WBC) count, lymphocyte, interleukin-6 (IL-6), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and vitamin D3 levels, compared with the healthy controls (p<0.05). Differences were also found between the 6-10 months and the >10-15 month recovery groups (p<0.05).

CONCLUSION: Differential biochemical markers related to the time elapsed since acute infection show a different metabolic and biochemical status of the host at different time points after infection. Moreover, the pathophysiological pathways involved in these dysregulated biochemical markers should also be studied in relation to the long term impact of COVID-19 infection.},
}

@article {pmid40833451,
year = {2025},
author = {Chandler, D and Abramoff, B and Bramson, C and Cappelleri, JC and Chohan, A and Harrington, M and Jamal, H and Lusk, J and Mazar, I and Paredes, R and Tatlock, S and Ustianowski, A and Weinstein, E and Mokgokong, R},
title = {Development and content validation of the Long COVID/ post-acute sequelae of COVID-19 (PASC) patient-reported outcome (PRO) instrument.},
journal = {Journal of patient-reported outcomes},
volume = {9},
number = {1},
pages = {105},
pmid = {40833451},
issn = {2509-8020},
mesh = {Humans ; *Patient Reported Outcome Measures ; *COVID-19/complications ; Post-Acute COVID-19 Syndrome ; Female ; Male ; SARS-CoV-2 ; Middle Aged ; Reproducibility of Results ; Qualitative Research ; Quality of Life ; Adult ; Aged ; Surveys and Questionnaires ; },
abstract = {BACKGROUND: Post-acute sequelae of COVID-19 (PASC) or Long COVID is a post-viral complication of SARS-CoV-2 infection, causing ongoing symptoms and impaired function over a prolonged period of time. There is limited understanding of how the signs and symptoms of Long COVID/PASC affect patients' lives and how to measure them, which is essential when developing care strategies. This study aimed to develop and evaluate the content validity for a novel patient-reported outcome (PRO) instrument in Long COVID/PASC through qualitative research, which was informed by the patient experience of Long COVID/PASC and both patient and clinician input.

METHODS: A review of literature and PRO instruments developed for Long COVID/PASC identified measurement gaps for the context of use (i.e., weekly assessment of signs/symptoms in clinical trial research). This informed the development of the preliminary Long COVID/PASC PRO instrument, which was tested via patient interviews (combined concept elicitation and cognitive debriefing) to align with regulatory standards, and discussions with clinical experts were conducted to provide clinical insights. The final instrument was modified based on this input to further promote its content validity.

RESULTS: Thirty participants were interviewed about their Long COVID/PASC experiences. Participants most frequently reported experiencing tiredness after physical activity (n = 29/30; 97%), general tiredness (n = 28/30; 93%), shortness of breath (n = 25/30; 83%), cough (n = 23/30; 77%) and muscle/body aches (n = 23/30; 77%). All participants reported that Long COVID/PASC had an impact on their health-related quality of life. Almost all (n = 27/28; 96%) sign/symptom concepts were reported in the first three sets of interviews suggesting conceptual saturation was achieved. Items, response options and the recall period of the preliminary Long COVID/PASC PRO instrument were understood as intended (≥ 90%) and relevant to most participants across both rounds (≥ 47%). Modifications were made to the instrument following patient input, resulting in the 18-item Long COVID/PASC instrument. Clinician input (n = 3) corroborated participant interview results, supporting the content validity of the Long COVID/PASC PRO instrument.

CONCLUSION: The Long COVID/PASC PRO instrument has been developed in line with regulatory standards and the qualitative evidence demonstrated strong content validity in a Long COVID/PASC population. Research to evaluate psychometric properties will provide further evidence of the instrument's measurement properties.},
}

Humans
*Patient Reported Outcome Measures
*COVID-19/complications
Post-Acute COVID-19 Syndrome
Female
Male
SARS-CoV-2
Middle Aged
Reproducibility of Results
Qualitative Research
Quality of Life
Adult
Aged
Surveys and Questionnaires

@article {pmid40833176,
year = {2025},
author = {Rafałowicz, J and Wagner, L and Rafałowicz, B},
title = {Lesions located on the tongue after SARS-CoV-2 infection: A retrospective study.},
journal = {Dental and medical problems},
volume = {62},
number = {4},
pages = {619-626},
doi = {10.17219/dmp/179008},
pmid = {40833176},
issn = {2300-9020},
mesh = {Humans ; *COVID-19/complications ; Male ; Female ; Retrospective Studies ; *Tongue Diseases/etiology/pathology/virology ; Middle Aged ; Adult ; Aged ; *Tongue/pathology ; SARS-CoV-2 ; },
abstract = {BACKGROUND: The post-coronavirus disease (post-COVID) syndrome (PCS), which occurs after severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) infection, can manifest a variety of symptoms in the oral cavity. Changes to the tongue tend to persist longer than other symptoms in this area.

OBJECTIVES: The aim of the study was to present the changes and lesions that occur on the tongue after SARS-CoV-2 infection, as well as their healing as a consequence of the therapy used or lack thereof.

MATERIAL AND METHODS: The study sample included 426 individuals who had contracted SARS-CoV-2 and presented with changes on the tongue. Periodic checkups enabled to determine their variability and duration in response to treatment or lack thereof.

RESULTS: The presence of various oral manifestations was reported, including strawberry tongue (women (F): 143; men (M): 65), depapillation (F: 86, M: 156), geographic tongue (F: 65, M: 124), vascular changes (F: 102, M: 46), aphthous changes (F: 106, M: 58), candidiasis (F: 89, M: 57), edema (F: 42, M: 52), herpetic lesions (F: 38, M: 49), ulcers (F: 38, M: 46), erosions (F: 32, M: 28), nodular lesions (F: 6, M: 19), and necrotic changes (F: 9, M: 7). Fungiform papillae were found to be enlarged in 189 women and 213 men. On average, from 3 to 5 changes were identified concurrently. In the majority of cases, the changes disappeared on their own and persisted from 4 weeks to 36 months. In 20% of cases, they recurred. Local therapy resulted in a 50% reduction in the duration of PCS.

CONCLUSIONS: Changes that manifest on the tongue require observation and basic or specialized treatment. In the absence of pain, monitoring is recommended for a period of 4 weeks, after which a spontaneous disappearance should be expected. In the event that various changes occur in the oral cavity, the patient should be referred for specialized treatment.},
}

Humans
*COVID-19/complications
Male
Female
Retrospective Studies
*Tongue Diseases/etiology/pathology/virology
Middle Aged
Adult
Aged
*Tongue/pathology
SARS-CoV-2

@article {pmid40832812,
year = {2025},
author = {Ableidinger, S and DeGennaro, L and Mota-Rolim, S and Scarpelli, S and Bolstad, CJ and Bjorvatn, B and Espie, CA and Dauvilliers, Y and Korman, M and Landtblom, AM and Plazzi, G and Matsui, K and Yordanova, J and Bjelajac, AK and Reis, C and Chung, F and Merikanto, I and Wing, YK and Partinen, M and Macêdo, T and Nadorff, MR and Holzinger, B},
title = {Lucid Dreaming: Not Just Awareness, but Agency.},
journal = {Journal of sleep research},
volume = {},
number = {},
pages = {e70181},
doi = {10.1111/jsr.70181},
pmid = {40832812},
issn = {1365-2869},
abstract = {During lucid dreaming (LD), dreamers are aware that they are dreaming and may be able to influence the oneiric content. There has been recent debate about the relative importance of the ability to influence the dream and having agency over the pure awareness of dreaming. To underline this, we examined the associations of lucid dreams without agency (LD-Ag) and lucid dreams with agency (LD + Ag) to sleep and mental health problems and long COVID during the pandemic. We collected data in 16 countries on four continents from May to December 2021 on 10,715 subjects. Logistic regression was performed to predict LD-Ag and LD + Ag, with a sample of 8133 participants. We found that 30% of the participants frequently knew they were dreaming during the pandemic. About half of those (17%) reported that they could influence their dreams. Female gender and anxiety symptoms were negatively associated with LD + Ag. Dream recall, nightmares, insomnia, dream enactment behaviour (DEB), sleep vocalisation, short and long COVID and PTSD were positively associated with LD + Ag. Old age, dream recall, nightmares and anxiety symptoms were positively associated with LD-Ag, while short sleep length, being an evening type, and short COVID were negatively associated with LD-Ag. The different associations for LD-Ag and LD + Ag suggest that they may be distinct sleep states. This is also the first study to show that both COVID-19 and long COVID are associated with LD.},
}

@article {pmid40832427,
year = {2025},
author = {Bramante, CT and Stewart, TG and Boulware, DR and McCarthy, MW and Gao, Y and Rothman, RL and Mourad, A and Thicklin, F and Cohen, JB and Garcia Del Sol, IT and Shah, NS and Mehta, M and Quintero Cardona, O and Scott, J and Ginde, AA and Castro, M and Jayaweera, D and Sulkowski, M and Gentile, N and McTigue, K and Felker, GM and Collins, S and Dunsmore, SE and Adam, SJ and Lindsell, CJ and Hernandez, AF and Naggie, S and , },
title = {Metformin on the Presence of COVID-19 Symptoms Over 6 Months: The ACTIV-6 Randomized Clinical Trial.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.08.08.25333305},
pmid = {40832427},
abstract = {BACKGROUND: The effect of metformin on preventing long-term COVID-19 symptoms among low-risk adults has not been studied. The objective of this study was to Assess metformin compared with placebo during acute SARS-CoV-2 infection on the presence of COVID-19 symptoms 180 days later.

METHODS: The ACTIV-6 platform evaluated repurposed medications for mild to moderate COVID-19. Between September 19, 2023 and May 1, 2024, 2983 outpatient adults ≥30 years with confirmed SARS-CoV-2 infection and ≥2 COVID-19 symptoms for ≤7 days were included from 90 sites. Participants were randomized to metformin (titrated to 1500 mg daily) or placebo for 14 days. Post-acute sequelae of SARS-CoV-2 or death (PASCD) was ascertained by asking whether participants had symptoms they attributed to COVID-19 on day 180. Secondary outcomes included clinician diagnosis of long COVID. For the primary outcome, the single-sided threshold for efficacy was 0.975.

RESULTS: Among 2983 participants, the median age was 47 years (interquartile range [IQR] 38-57); 63% were female; 47% Hispanic/Latino; 83% reported ≥1 prior COVID-19 infections or SARS-CoV-2 vaccines. There were no deaths. Overall, 96 (3.2%) reported COVID-19 symptoms on day 90, 101 (3.4%) on day 120, and 79 (2.6%) on day 180. The covariate-adjusted risk of PASCD on day 180 was lower in the metformin group (-0.008; 95% credible interval [CrI] -0.022 to 0.006; posterior probability of efficacy [PPE] 0.83), compared with the placebo group with an adjusted risk ratio of 0.79 (95% CrI 0.474 to 1.230). The risk of clinician diagnosis of long COVID (secondary outcome) on day 180 was lower in the metformin group (-0.007; 95% CrI -0.015 to 0.001; PPE 0.96), with a relative risk of 0.495 (95% CrI 0.155 to 0.995).

CONCLUSIONS: The posterior probability of efficacy for metformin preventing the primary endpoint did not exceed the prespecified threshold of 0.975 for declaring efficacy. Secondary outcomes were numerically better with metformin.

TRIAL REGISTRATION: ClinicalTrials.gov (NCT04885530).},
}

@article {pmid40832415,
year = {2025},
author = {Kehl-Floberg, KE and Freisberg, E and Pop-Vicas, A and Gangnon, R and Edwards, DF},
title = {Long COVID risk by pre-infection symptoms and functional status: A retrospective cohort study of data from the All of Us Research Program.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.08.07.25333259},
pmid = {40832415},
abstract = {IMPORTANCE: Over seven million U.S. adults experience "long COVID", or persistent health issues after COVID-19. Multiple guidelines recommend the inclusion of functional status in long COVID diagnostic criteria, but more evidence is needed to guide this recommendation. This study explores the adjusted odds of developing long COVID by pre-infection symptoms and functional status, and the feasibility of estimating functional status using health records data.

DESIGN: Retrospective cohort study in a multicenter national longitudinal cohort of U.S. adults with history of COVID-19, using health records and survey responses through July 2022 (All of Us CDR 7.0).

EXPOSURE(S): Pre-infection (-5 years) incidences of (a) at least one symptom common in long COVID, and (b) functional status, indicated by All of Us baseline survey responses and diagnostic/procedure/billing codes. Disease and demographic data covariates were included in the adjusted models.

RESULTS: N = 65,464 met inclusion criteria (n=40,655 had post-infection occurrences of at least one symptom (long COVID group), while n=24,809 had none). Adjusted odds ratios within 99% confidence intervals [99% CI] of developing long COVID increased with lower pre-infection self-reported mental health ("Good" compared to "Excellent" AOR=1.14 [1.04,1.25], P>0.000), and more pre-infection symptoms (compared to the median of four, people with zero had much lower odds (AOR=0.15 [0.04,0.61], P=0.008). Adjusted odds were not significantly affected by any single pre-infection symptom, self-rated physical ability, or clinical documentation of functional impairment.

CONCLUSIONS: Greater pre-illness symptom burden and lower self-rated mental health increased the odds of long COVID symptoms, after adjusting for demographics, variant, functional status, and individual symptoms. Long COVID represents a change from baseline functioning and health, even in people with pre-infection incident symptoms and functional impairments. This estimation of pre-infection functional status using harmonized electronic health records data demonstrated the feasibility of these data in developing the diagnostic utility of functional status changes in long COVID.},
}

@article {pmid40831631,
year = {2025},
author = {Zydek, I and Thümmler, L and Beckmann, N and Sehl, C and Soddemann, M and Grüneberg, R and Elsner, C and Kamler, M and Dittmer, U and Witzke, O and Kadow, S and Gulbins, E and Becker, KA and Krawczyk, A},
title = {Amitriptyline potently neutralizes distinct SARS-CoV-2 variants including D614G, Omicron BA.5, and Omicron XBB.1.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1631947},
pmid = {40831631},
issn = {1664-302X},
abstract = {INTRODUCTION: COVID-19, caused by SARS-CoV-2, remains a global health challenge despite the availability of vaccines and antiviral treatments. The emergence of immune escape variants and the persistence of long COVID symptoms continue to complicate prevention and therapy, especially in low-resource settings. Functional inhibitors of acid sphingomyelinase (FIASMAs) have shown promise as broad-spectrum antiviral agents.

METHODS: We evaluated the antiviral efficacy of amitriptyline, a widely used antidepressant and known FIASMA, against SARS-CoV-2. In vitro neutralization assays using pseudotyped virus-like particles (VLPs) and clinical isolates were performed to assess its ability to inhibit viral entry and replication.

RESULTS: Amitriptyline significantly inhibited infection by SARS-CoV-2 VLPs bearing spike proteins, including those with mutations in the receptor-binding domain. Moreover, it reduced replication of clinical SARS-CoV-2 isolates D614G, Omicron BA.5, and Omicron XBB.1 in a dose-dependent manner at subtoxic concentrations.

DISCUSSION: Our findings demonstrate that amitriptyline neutralizes SARS-CoV-2 across multiple variants. These results support the potential of amitriptyline as a repurposed antiviral drug. Further clinical studies are warranted to evaluate its efficacy and safety in treating COVID-19 in humans.},
}

@article {pmid40830954,
year = {2025},
author = {Büchner, R and Sander, C and Schindler, S and Walter, M and Scheibenbogen, C and Schomerus, G},
title = {"Have you considered that it could be burnout?"-psychologization and stigmatization of self-reported long COVID or post-COVID-19 vaccination syndrome.},
journal = {BMC medicine},
volume = {23},
number = {1},
pages = {488},
pmid = {40830954},
issn = {1741-7015},
mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; Anxiety/psychology ; *COVID-19/psychology/prevention & control ; *COVID-19 Vaccines/adverse effects ; Cross-Sectional Studies ; Depression/psychology ; Loneliness/psychology ; Self Concept ; Self Report ; *Social Stigma ; },
abstract = {BACKGROUND: People reporting long COVID (LC) or post-COVID-19 vaccination syndrome (PCVS) not only suffer from their symptoms but also from stigmatization. Despite ample account and characterization of stigma experiences so far, its mechanisms and consequences on health outcomes, and particularly the role of "psychologization" remain unclear.

METHODS: In a cross-sectional observational study, we examined a large convenience sample of adults who report having LC or PCVS. We translated and adapted the "Long Covid Stigma Scale" to measure stigmatization. We measured generally perceived and personally experienced psychologization with newly developed scales/items. Outcome measures included disclosure concerns, loss of trust in medicine, life satisfaction, depression, anxiety, self-esteem, and loneliness. We calculated overall prevalences of stigma and psychologization and their correlations with the outcomes. Using mediation analysis with SEM, we tested the hypothesis that psychologization of LC and PCVS syndromes causes harm by increasing stigmatization.

RESULTS: Altogether, N = 2053 individuals (68% reporting LC, 32% reporting PCVS) were included in the analyses. The overall prevalences of stigma experiences were high: 83% of those reporting LC and 90% of those reporting PCVS experienced stigma. Prevalences of perceived psychologization (LC: 87%, PCVS: 91%) and experienced psychologization (LC: 82%, PCVS: 87%) were similarly high. Both stigmatization and psychologization were positively correlated with disclosure concerns, loss of trust in medicine, depression, anxiety, and loneliness as well as negatively correlated with life satisfaction and self-esteem. Mediation analysis indicated that stigmatization mediated a relevant proportion of the relationship between psychologization and negative outcomes.

CONCLUSIONS: People reporting LC or PCVS are subject to stigmatization and psychologization. From a patient perspective, psychologization appears to be an important driver of stigmatization and negative outcomes.},
}

Adult
Aged
Female
Humans
Male
Middle Aged
Young Adult
Anxiety/psychology
*COVID-19/psychology/prevention & control
*COVID-19 Vaccines/adverse effects
Cross-Sectional Studies
Depression/psychology
Loneliness/psychology
Self Concept
Self Report
*Social Stigma

@article {pmid40830439,
year = {2025},
author = {Jyonouchi, H and Kornitzer, J and Geng, L},
title = {Favorable responses to upadacitinib, a JAK1 inhibitor, in long COVID patients with predominant neuropsychiatric symptoms: case reports in 2 autistic patients and one typically developing patient.},
journal = {BMC neurology},
volume = {25},
number = {1},
pages = {342},
pmid = {40830439},
issn = {1471-2377},
mesh = {Humans ; *COVID-19/complications/psychology ; Male ; *Heterocyclic Compounds, 3-Ring/therapeutic use ; *Autism Spectrum Disorder/complications/drug therapy ; Female ; *Janus Kinase 1/antagonists & inhibitors ; *COVID-19 Drug Treatment ; Janus Kinase Inhibitors/therapeutic use ; },
abstract = {The long-term impact of coronavirus disease 2019 (COVID-19) has become evident over the past 3-4 years, with the recognition of post-COVID long-term sequelae, often referred to as long COVID. Neuropsychiatric symptoms are one of the hallmarks of long COVID. In severe cases, it can even present features of encephalopathy. Since some of the neuropsychiatric symptoms associated with long COVID overlap symptoms found in neuropsychiatric disorders, it has been difficult to sort out the effects of long COVID in such subjects. This is especially true in patients diagnosed with autism spectrum disorders (ASD), given their difficult behavioral symptoms and other co-morbid conditions. COVID-19 is thought to affect the onset or progress of encephalopathy symptoms by activation of the immune system through the type 1 interferon (IFN) signaling pathway. In that case, treatment would require an immunomodulating agent that targets such pathways. However, such measures may not be applied to ASD subjects, in whom long COVID may not even be considered as the cause of their symptoms. In this study, we present the beneficial effects of upadacitinib, a JAK (janus kinase) 1 inhibitor, that blocks downstream signaling of type 1 IFNs, on 3 patients, 2 with ASD and one without ASD. In these patients, long COVID was thought to have triggered or aggravated encephalopathy-like symptoms. The beneficial effects of upadacitinib were not only noted by an improvement of their behavioral symptoms but also shown by an improvement of monocyte cytokine profiles (less activated state); peripheral blood monocytes were used as surrogates of microglial cells. These three cases presented highlight a possible use of JAK inhibitors for treating long COVID-associated neuropsychiatric symptoms in both ASD and non-ASD subjects. The presented cases highlight the inherent difficulty of diagnosing long COVID in ASD cases.},
}

Humans
*COVID-19/complications/psychology
Male
*Heterocyclic Compounds, 3-Ring/therapeutic use
*Autism Spectrum Disorder/complications/drug therapy
Female
*Janus Kinase 1/antagonists & inhibitors
*COVID-19 Drug Treatment
Janus Kinase Inhibitors/therapeutic use

@article {pmid40828804,
year = {2025},
author = {Wasilewski, MB and Leighton, J and Reis, L and Vijayakumar, A and English, M and Sanchez, K and Hitzig, SL and Nelson, MLA and Sheppard, C and Robinson, L and Steinberg, R and Nguyen, M and Bayley, M and Daneman, N and Levy, C and Goulding, S and Ho, C and Simpson, R},
title = {Coping with stressful life disruptions due to long COVID: A qualitative study.},
journal = {PloS one},
volume = {20},
number = {8},
pages = {e0329831},
doi = {10.1371/journal.pone.0329831},
pmid = {40828804},
issn = {1932-6203},
abstract = {BACKGROUND: Long COVID impacts people's physical health and cognition which immensely affects their psychosocial well-being. A larger study was conducted that explored the psychosocial impacts of Long COVID on individuals and caregivers. This paper focuses on the impact of these stressful disruptions on one's health and psychosocial well-being, and how individuals cope with them.

METHODS: Utilizing a qualitative descriptive approach, we conducted interviews with 67 participants (52 people with Long COVID (mean age: 50.4) and 15 caregivers (mean age: 50.0)). People with Long COVID and caregivers were recruited from healthcare institutions through care team referrals, patient partners, and health organizations and via social media platforms. A thematic codebook developed through inter-coder agreement processes was used to analyze the data.

FINDINGS: Three key themes were identified: (1) Disruptions in people with Long COVID and caregivers' lives are characterized by a deviation from their perceived 'normalcy', (2) Disruptions lead to substantial stress, loss and grief (independence, agency, meaning, and purpose), and (3) People with Long COVID and caregivers cope with stressful disruptions by adapting their daily activities.

CONCLUSION: Our findings make the case for supportive rehabilitation strategies that address the psychosocial repercussions of Long COVID to help mitigate feelings of loss and grief, thereby increasing individuals' overall quality of life and well-being.},
}

@article {pmid40821912,
year = {2025},
author = {Hata, R and Sugawara, H and Hayashi, R and Okamoto, Y and Nishihara, R and Yamasaki, T and Hatanaka, A and Harada, K and Hori, H},
title = {Trichotillomania in long COVID successfully treated with escitalopram: A case report.},
journal = {PCN reports : psychiatry and clinical neurosciences},
volume = {4},
number = {3},
pages = {e70190},
pmid = {40821912},
issn = {2769-2558},
}

@article {pmid40818641,
year = {2025},
author = {Barrero-Santiago, L and Bellosta-López, P and Doménech-García, V and Pérez-Pérez, L and Tellería, JJ and Almansa, R and Montero-Cuadrado, F},
title = {Determinants of quality of life in long-COVID patients with new-onset chronic pain.},
journal = {The journal of pain},
volume = {35},
number = {},
pages = {105531},
doi = {10.1016/j.jpain.2025.105531},
pmid = {40818641},
issn = {1528-8447},
abstract = {Chronic pain is highly prevalent in Long-COVID syndrome and significantly impacts quality of life (QoL). Given the complexity of long-COVID, a comprehensive approach is necessary to understand how the interactions of psychosocial, pain and functional factors may influence patients' well-being. This study aimed to explore key factors associated with QoL in long-COVID patients with new-onset chronic pain, and to multidimensionally characterize this population. A case-control design was used, recruiting 163 Long-COVID patients (49.04±8.23 years, 80% females) and 151 controls (48.86±8.28 years, 78% females). Socio-demographic, psychosocial, pain-related and functional outcomes were measured. QoL, assessed by the EQ-5D, was considered the main outcome. Anxiety was negatively associated with QoL (β=-0.012,95%CI:[-0.015, -0.008],p<0.001), while aerobic capacity showed a positive association (β=0.001,95%CI:[0.001,0.002],p<0.001). Employment status (β=0.175,95%CI:[0.091,0.260],p<0.001), pain intensity (β=-0.003,95%CI:[-0.005,-0.001],p=0.004) and symptom complexity (β=-0.32,95%CI:[-0.51,-0.13],p<0.001) were also significant associated factors. The strongest factor associated with being a case was higher levels of symptoms complexity (OR=1.09;95%CI:[1.05, 1.15];p<0.001) followed by higher levels of depression (OR=1.13; 95%CI:[1.04,1.22];p=0.002). Long-COVID patients reported poorer self-perceived QoL and had significantly lower overall QoL, as well as worse outcomes in functional, pain-related and psychosocial variables when compared to control subjects (p<0.001). Clinicians should pay attention to anxiety levels, aerobic capacity, work status and pain intensity early in the course of the disease to try to minimize the loss of QoL in this population. These findings may also assist clinicians in profiling their patients and guiding them toward an early and target ed intervention that addresses the associated factors, ultimately improving functionality and QoL of patients. PERSPECTIVE: This study identifies key clinical and psychosocial factors linked to new-onset chronic pain and reduced quality of life in long-COVID. Understanding these insights may help clinicians implement early, targeted, and interdisciplinary interventions to improve patient functionality and long-term outcomes.},
}

@article {pmid40810942,
year = {2025},
author = {Gunturkun, F and Hedlin, H and Botzheim, B and Deng, Y and Bonilla, H and Jagannathan, P and Quach, TC and Kim, S and Lin, M and O'Riordan, G and Tzeng, H and Adamowicz, L and Demanuele, C and Cai, X and Yang, PC and Singh, U and Geng, LN},
title = {Digital Biometric Measures in Long COVID: A Secondary Analysis of the STOP-PASC Randomized Clinical Trial.},
journal = {JAMA network open},
volume = {8},
number = {8},
pages = {e2526901},
pmid = {40810942},
issn = {2574-3805},
abstract = {IMPORTANCE: Digital biometrics can be used to monitor disease, but there is limited research on their applications for assessing postacute sequelae of SARS-CoV-2 (PASC) or long COVID.

OBJECTIVE: To better understand digital biometric patterns in long COVID using wearable device technology and whether there are any differences between the nirmatrelvir-ritonavir and placebo-ritonavir intervention arms.

This secondary analysis is an exploratory substudy of a placebo-controlled randomized clinical trial (Selective Trial of Paxlovid for PASC [STOP-PASC]) that was conducted from November 2022 to September 2023 at Stanford University. Trial participants were randomized, and a subset enrolled into the prespecified substudy.

INTERVENTION: Participants were randomized 2:1 to receive oral nirmatrelvir (300 mg) and ritonavir (100 mg) or placebo-ritonavir twice daily for 15 days. Substudy participants were provided with a smartwatch and asked to wear it for 24 hours a day, 7 days a week for the 15-week study.

MAIN OUTCOMES AND MEASURES: Mean changes in digital biometric measures in physical activity, heart rate, and oxygen saturation tracked by a smartwatch. Biometric measures were summarized by treatment arm for each of 5 different time frames: baseline, treatment period, and 3 subsequent time intervals. Summary measure trajectories were clustered and demographics and clinical characteristics were compared among clusters using absolute standardized differences expressed in units of SDs.

RESULTS: Of the 94 participants enrolled in the substudy, 50 (37 in nirmatrelvir-ritonavir and 13 in placebo-ritonavir) met the analysis eligibility criteria based on wear time and data completeness. These participants had a mean (SD) age of 42.7 (13.2) years and included 29 females (58.0%). Using mixed models for repeated measures, no significant differences were detected between the intervention arms in the change in biometric measures over time, consistent with the patient-reported outcomes in the STOP-PASC trial. In the overall substudy cohort, latent class mixed models and cluster analysis identified distinct longitudinal trajectories of long COVID over the 15-week study that tracked with different symptoms. Participants with lower daytime physical activity reported more severe fatigue (9 of 9 [100%] vs 21 of 23 [91.3%]; absolute standardized difference [ASD], 0.30), shortness of breath (9 of 9 [100%] vs 7 of 23 [30.4%]; ASD, 1.31), and cardiovascular symptoms (8 of 9 [88.9%] vs 12 of 23 [52.2%]; ASD, 0.70). Those with higher nighttime physical activity reported more gastrointestinal symptoms (2 of 3 [66.7%] vs 11 of 35 [31.4%]; ASD, 0.50). Additionally, participants with higher median daytime heart rates reported less fatigue (7 of 9 [77.8%] vs 39 of 40 [97.5%]; ASD, 0.63) and shortness of breath (3 of 9 [33.3%] vs 23 of 40 [57.5%]; ASD, 0.50) compared with those with lower heart rates.

CONCLUSIONS AND RELEVANCE: This secondary analysis identified distinct longitudinal trajectories of physiological and behavioral digital biometric measures captured from wearable devices that reflect the heterogeneity and track with different symptoms of long COVID. Digital biometric measures from wearable devices have promising utility for long COVID research.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05576662.},
}

@article {pmid40809128,
year = {2024},
author = {Sun, J and Aikawa, M and Ashktorab, H and Beckmann, ND and Enger, ML and Espinosa, JM and Gai, X and Horne, BD and Keim, P and Lasky-Su, J and Letts, R and Maier, CL and Mandal, M and Nichols, L and Roan, NR and Russell, MW and Rutter, J and Saade, GR and Sharma, K and Shiau, S and Thibodeau, SN and Yang, S and Miele, L and , },
title = {A multi-omics strategy to understand PASC through the RECOVER cohorts: a paradigm for a systems biology approach to the study of chronic conditions.},
journal = {Frontiers in systems biology},
volume = {4},
number = {},
pages = {1422384},
pmid = {40809128},
issn = {2674-0702},
abstract = {Post-Acute Sequelae of SARS-CoV-2 infection (PASC or "Long COVID"), includes numerous chronic conditions associated with widespread morbidity and rising healthcare costs. PASC has highly variable clinical presentations, and likely includes multiple molecular subtypes, but it remains poorly understood from a molecular and mechanistic standpoint. This hampers the development of rationally targeted therapeutic strategies. The NIH-sponsored "Researching COVID to Enhance Recovery" (RECOVER) initiative includes several retrospective/prospective observational cohort studies enrolling adult, pregnant adult and pediatric patients respectively. RECOVER formed an "OMICS" multidisciplinary task force, including clinicians, pathologists, laboratory scientists and data scientists, charged with developing recommendations to apply cutting-edge system biology technologies to achieve the goals of RECOVER. The task force met biweekly over 14 months, to evaluate published evidence, examine the possible contribution of each "omics" technique to the study of PASC and develop study design recommendations. The OMICS task force recommended an integrated, longitudinal, simultaneous systems biology study of participant biospecimens on the entire RECOVER cohorts through centralized laboratories, as opposed to multiple smaller studies using one or few analytical techniques. The resulting multi-dimensional molecular dataset should be correlated with the deep clinical phenotyping performed through RECOVER, as well as with information on demographics, comorbidities, social determinants of health, the exposome and lifestyle factors that may contribute to the clinical presentations of PASC. This approach will minimize lab-to-lab technical variability, maximize sample size for class discovery, and enable the incorporation of as many relevant variables as possible into statistical models. Many of our recommendations have already been considered by the NIH through the peer-review process, resulting in the creation of a systems biology panel that is currently designing the studies we proposed. This system biology strategy, coupled with modern data science approaches, will dramatically improve our prospects for accurate disease subtype identification, biomarker discovery and therapeutic target identification for precision treatment. The resulting dataset should be made available to the scientific community for secondary analyses. Analogous system biology approaches should be built into the study designs of large observational studies whenever possible.},
}

@article {pmid40808898,
year = {2025},
author = {Townsend, L and Domegan, L and Wang, W and Quirke, S and , and Bergin, C and Fleming, C},
title = {Factors influencing healthcare worker symptomatic respiratory infection and vaccine uptake during the post-COVID-19 pandemic period.},
journal = {Antimicrobial stewardship & healthcare epidemiology : ASHE},
volume = {5},
number = {1},
pages = {e183},
pmid = {40808898},
issn = {2732-494X},
abstract = {OBJECTIVE: Investigate the factors associated with symptomatic respiratory infection and uptake of seasonal SARS-CoV-2 and influenza vaccine amongst healthcare workers (HCWs).

DESIGN: Longitudinal prospective multi-center study.

SETTING: Two tertiary healthcare centers in Ireland.

PARTICIPANTS: N = 893 self-selected HCWs across all disciplines.

METHODS: Monthly self-reported questionnaires from September 2024 to February 2025 completed by all participants, providing infection symptoms, self-testing for COVID-19 and receipt of vaccination against SARS-CoV-2 or influenza in the preceding 30 days. Additional data collected included comorbidities, known diagnosis of Long COVID, demographic data, prior infection and vaccination status, and healthcare role. Multivariable logistic regression models assessed the factors associated with symptom development, self-testing, and vaccine uptake.

RESULTS: Symptomatic respiratory illness was reported by n = 321 (36%) of participants during the study period, with a preexisting diagnosis of Long COVID associated with developing symptoms. Testing for COVID-19 was performed by 63% (n = 202) of symptomatic individuals, with a shorter duration since prior infection the only significant predictor of self-testing. Vaccine uptake was variable, with 37% receiving influenza and 22% receiving SARS-CoV-2 vaccination for that period. Older age and shorter interval since previous vaccine were associated with increased uptake of both vaccines, while men were more likely to be vaccinated against COVID-19.

CONCLUSIONS: In the postpandemic period, self-reported symptomatic respiratory infections remain common amongst HCWs. The legacy of the pandemic influences this, with a preexisting diagnosis of Long COVID associated with increased symptom burden, while low vaccination rates and understanding the factors associated with this present a challenge to ongoing risk mitigation.},
}

@article {pmid40805931,
year = {2025},
author = {Mazzonetto, LF and Cordeiro, JFC and Correia, IM and Oliveira, AS and Moraes, C and Brilhadori, J and Gomide, EBG and Kudlacek, M and Machado, DRL and Anjos, JRCD and Santos, APD},
title = {Physical Training Protocols for Improving Dyspnea and Fatigue in Long COVID: A Systematic Review with Meta-Analysis.},
journal = {Healthcare (Basel, Switzerland)},
volume = {13},
number = {15},
pages = {},
pmid = {40805931},
issn = {2227-9032},
abstract = {Objective: This study aimed to evaluate physical training protocols for alleviating long COVID symptoms, especially dyspnea and fatigue, through a systematic review with meta-analysis. Method: Data were collected from EMBASE, LILACS, PubMed, Scopus, CINAHL, Web of Science, and grey literature (Google Scholar, medRxiv). Studies evaluating dyspnea and/or fatigue before and after physical rehabilitation, using validated questionnaires, were included. Studies lacking pre- and post-assessments or physical training were excluded. Two reviewers independently extracted data on intervention type, duration, frequency, intensity, and assessment methods for dyspnea and fatigue. Bias risk was evaluated using the Cochrane tool. Results: Combined methods, such as respiratory muscle training with strength and aerobic exercise, were common for long COVID symptoms. Aerobic exercise notably improved dyspnea and/or fatigue. Among 25 studies, four had a low risk of bias. Meta-analysis of two studies found no significant reduction in fatigue. Conclusion: Combined training methods, particularly aerobic exercise, alleviate dyspnea and fatigue in long COVID. More high-quality studies are needed to confirm these findings.},
}

@article {pmid40804645,
year = {2025},
author = {Paval, NE and Căliman-Sturdza, OA and Lobiuc, A and Dimian, M and Sirbu, IO and Covasa, M},
title = {MicroRNAs in long COVID: roles, diagnostic biomarker potential and detection.},
journal = {Human genomics},
volume = {19},
number = {1},
pages = {90},
pmid = {40804645},
issn = {1479-7364},
support = {285/30.11.2022//Ministerul Cercetării, Inovării şi Digitalizării/ ; },
abstract = {Long COVID or Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), marked by persistent symptoms lasting weeks to months after acute SARS-CoV-2 infection, affects multiple organ systems including the respiratory, cardiovascular, neurological, gastrointestinal, and renal systems. These prolonged effects stem from chronic inflammation, immune dysregulation, and direct viral injury. MicroRNAs (miRNAs)-small non-coding RNAs involved in gene regulation-play a pivotal role in this process by modulating immune responses, inflammation, and cellular stress. Altered miRNA expression patterns during and after infection contribute to the pathogenesis of Long COVID. While conventional miRNA detection techniques have been valuable, they face limitations in sensitivity, throughput, and detecting RNA modifications. This review highlights Oxford Nanopore Sequencing (ONS) as a promising alternative, offering real-time, long-read, amplification-free RNA sequencing that preserves native modifications. ONS enables direct sequencing of full-length miRNAs and their precursors, providing novel insights into miRNA processing and regulatory roles. Despite current challenges with short-read accuracy, ongoing technical advances are improving ONS performance. Its integration in miRNA profiling holds significant potential for uncovering novel regulatory interactions and advancing clinical biomarker discovery in Long COVID and other conditions.},
}

@article {pmid40802983,
year = {2025},
author = {Antar, AAR and Peluso, MJ},
title = {CROI 2025: Acute and Postacute COVID-19.},
journal = {Topics in antiviral medicine},
volume = {33},
number = {3},
pages = {555-568},
pmid = {40802983},
issn = {2161-5853},
abstract = {New research on acute and postacute COVID-19 was presented at the 2025 Conference on Retroviruses and Opportunistic Infections (CROI). Results of the SCORPIO-PEP (Stopping COVID-19 Progression With Early Protease Inhibitor Treatment-Postexposure Prophylaxis) study indicated that the protease inhibitor ensitrelvir is effective for postexposure prophylaxis. Results from the second phaseof the Ubuntu study suggested that monovalent or bivalent booster doses of mRNA vaccines are equally protective in people with or without HIV. A phase II study of an inhaled broad-spectrum antiviral small interfering RNA showed faster clearance of virus and more rapid resolution of symptoms with its use. In addition, numerous studies improved our understanding of the long-term consequences of SARS-CoV-2 infection, including immunologic, metabolic, cardiovascular, neurologic, and other clinical sequelae. The application of new and more specific case definitions in research studies of long COVID provided new insights into the epidemiology and pathogenesis of this condition, although data on therapeutics from randomized clinical trials are still lacking.},
}

@article {pmid40802429,
year = {2025},
author = {Sevdimbaş, SH and İnal, AS and Kuşcu, F and Kurtaran, B and Candevir, A and Taşova, Y and Kömür, S},
title = {Follow-up evaluation of long COVID syndrome in patients with SARS-CoV-2 infection.},
journal = {Revista da Sociedade Brasileira de Medicina Tropical},
volume = {58},
number = {},
pages = {e00462025},
pmid = {40802429},
issn = {1678-9849},
abstract = {BACKGROUND: Long COVID, which refers to persistent symptoms following acute COVID-19, is being increasingly reported. However, available data regarding its prevalence and characteristics are limited. This study was conducted to evaluate the occurrence and presentation of long COVID in patients with COVID-19 who were followed up in outpatient, ward, or intensive care settings.

METHODS: This study included patients who were diagnosed with COVID-19 at least four weeks prior to the start of the study. The patients underwent symptom assessment at baseline and 1, 3, 6, and 12 months post-infection. Functional status was evaluated using the Post-COVID-19 Functional Status (PCFS) Scale, and quality of life was assessed using the SF-36 Health Survey questionnaire.

RESULTS: A total of 134 patients (71 males [54.2%]), with a mean age of 43.7 (15.3) years, participated in this study. The distribution of patients across care settings was as follows: 51.1% outpatients, 35.9% in wards, and 13% in intensive care units (ICUs). Fatigue during exertion was the most frequently reported long COVID symptom. Patients treated in ICUs experienced a higher burden of long COVID symptoms than those treated in outpatient or ward settings. Furthermore, patients treated in ICUs and wards had a significantly poorer quality of life and functional status than the outpatients.

CONCLUSIONS: Long COVID poses a significant ongoing health concern, particularly for patients who require intensive care during acute COVID-19. Vigilant monitoring of long-term sequelae, particularly those that affect quality of life and functional status, is crucial for individuals recovering from COVID-19.},
}

@article {pmid40802282,
year = {2025},
author = {Gerzanich, V and Zhang, C and Zhang, J and Sallapalli, BT and Pei, S and Nasr, M and Tosun, C and Zhang, Y and Tang, Q and Simard, JM and Zhao, RY},
title = {COVID-19-associated neuroinflammation and astrocyte death in the brain linked to ORF3a-induced activation of Sur1-mediated ion channels.},
journal = {mBio},
volume = {},
number = {},
pages = {e0201225},
doi = {10.1128/mbio.02012-25},
pmid = {40802282},
issn = {2150-7511},
abstract = {The coronavirus disease 2019 (COVID-19) pandemic has disproportionately affected individuals with pre-existing medical conditions, such as neurocognitive disorders. Premorbid neurocognitive conditions compounded by COVID-19 can escalate into COVID-associated neurological complications, leading to severe illness or even death. As COVID-19 continues to persist and vaccines lose efficacy against emerging variants, individuals with neurocognitive disorders often experience prolonged symptoms that are further exacerbated by repeated breakthrough infections of highly diversified viral variants due to emergence of new viral mutations. Despite the significance of neurocognitive disorders as risk factors for COVID-19-related mortality and long COVID, the underlying causes remain largely unknown. In this study, we report a link between ORF3a expression and COVID-associated neuroinflammation and neurocytotoxicity in postmortem brain tissues from COVID-19 patients. These findings were further verified through neural cell-based in vitro and in vivo animal studies introducing ORF3a either alone or in the context of viral infection. As a membrane-associated protein, ORF3a induces upregulation of Sur1-regulated ion channels, resulting in intracellular Ca[2+] influx, apoptosis, and necrosis through both NF-kB-dependent and independent proinflammatory responses in astrocytes. These findings reveal a novel clinical and mechanistic link between ORF3a and Sur1-regulated ion channels, which are highly responsive to neuroinflammatory conditions causing neurodegeneration. Additionally, we have identified a Food and Drug Administration-approved drug, glibenclamide, and a natural antiviral compound glycyrrhizin that effectively mitigates the neuropathological effects of ORF3a, underscoring the therapeutic potential and clinical significance of these findings.IMPORTANCECoronavirus disease 2019 (COVID-19) disproportionately affects individuals with pre-existing neurocognitive conditions primarily due to COVID-19-associated neuroinflammation and neurotoxicity (CNN), which can progress to COVID-associated neurological disorders (CANDs), leading to severe illness and mortality. Despite CNN's significant contribution to CANDs and related morbidity and mortality, its underlying causes remain poorly understood. Our study identifies ORF3a as a key driver of CNN, establishing a direct clinical and functional link between ORF3a and CNN linking to CANDs. Mechanistically, ORF3a disrupts ion homeostasis in astrocytes by promoting Ca[2][+] influx through Sur1-regulated ion channels, contributing to CNN. Notably, the Food and Drug Administration-approved drug glibenclamide, a Sur1-specific inhibitor, and the natural compound glycyrrhizin effectively mitigate ORF3a-induced neuropathology, highlighting ORF3a as a promising therapeutic target. These findings present a potential strategy to eliminate CNN and prevent CANDs.},
}

@article {pmid40801614,
year = {2025},
author = {Sonkodi, B},
title = {Underlying Piezo2 Channelopathy-Induced Neural Switch of COVID-19 Infection.},
journal = {Cells},
volume = {14},
number = {15},
pages = {},
pmid = {40801614},
issn = {2073-4409},
abstract = {The focal "hot spot" neuropathologies in COVID-19 infection are revealing footprints of a hidden underlying collapse of a novel ultrafast ultradian Piezo2 signaling system within the nervous system. Paradoxically, the same initiating pathophysiology may underpin the systemic findings in COVID-19 infection, namely the multiorgan SARS-CoV-2 infection-induced vascular pathologies and brain-body-wide systemic pro-inflammatory signaling, depending on the concentration and exposure to infecting SARS-CoV-2 viruses. This common initiating microdamage is suggested to be the primary damage or the acquired channelopathy of the Piezo2 ion channel, leading to a principal gateway to pathophysiology. This Piezo2 channelopathy-induced neural switch could not only explain the initiation of disrupted cell-cell interactions, metabolic failure, microglial dysfunction, mitochondrial injury, glutamatergic synapse loss, inflammation and neurological states with the central involvement of the hippocampus and the medulla, but also the initiating pathophysiology without SARS-CoV-2 viral intracellular entry into neurons as well. Therefore, the impairment of the proposed Piezo2-induced quantum mechanical free-energy-stimulated ultrafast proton-coupled tunneling seems to be the principal and critical underlying COVID-19 infection-induced primary damage along the brain axes, depending on the loci of SARS-CoV-2 viral infection and intracellular entry. Moreover, this initiating Piezo2 channelopathy may also explain resultant autonomic dysregulation involving the medulla, hippocampus and heart rate regulation, not to mention sleep disturbance with altered rapid eye movement sleep and cognitive deficit in the short term, and even as a consequence of long COVID. The current opinion piece aims to promote future angles of science and research in order to further elucidate the not entirely known initiating pathophysiology of SARS-CoV-2 infection.},
}

@article {pmid40801304,
year = {2025},
author = {Ellen, A},
title = {From Stagnation to Strategy: Challenges in Advancing Long COVID Research.},
journal = {Journal of evaluation in clinical practice},
volume = {31},
number = {5},
pages = {e70180},
pmid = {40801304},
issn = {1365-2753},
abstract = {BACKGROUND: Long COVID is a debilitating multisystemic condition and is a major public health burden, yet the pathophysiology remains poorly understood and there are no effective treatments. Despite the urgent need for better management strategies, research into long COVID is losing momentum.

OBJECTIVES: To help tackle this loss of momentum, this article analyses the major challenges impeding progress and proposes innovative strategies to navigate them and to reinvigorate this research field.

METHOD: The analysis of the long COVID research domain drew on a broad range of scientific literature to identify major barriers to research and potential pathways forward.

RESULTS: The research highlighted critical obstacles, including the lack of reliable biomarkers which has necessitated a reliance on symptom reporting that is inherently heterogenous, temporally complex and often confounded by symptoms arising from pre-existing comorbidities. The absence of pre-infection baseline data further complicates the distinction between long COVID-specific pathophysiology and the effects of pre-existing co-morbidities. Additionally, the long COVID patient population has heterogenous multiorgan pathology, and this diversity makes it difficult to identify and interpret clinical findings.

CONCLUSION: Addressing these methodological and conceptual challenges is essential to accelerate the understanding of long COVID pathophysiology and guide the development of effective interventions.},
}

@article {pmid40800841,
year = {2025},
author = {Reas, ET and Alderson-Myers, A and Solders, SK and Shen, Q and Rivera, CS and Wang, X and Stiver, J and Banks, SJ and Graves, JS},
title = {Long COVID-related blood-brain barrier breakdown and microstructure in older adults are modified by sex and Alzheimer's disease genetic risk.},
journal = {Imaging neuroscience (Cambridge, Mass.)},
volume = {3},
number = {},
pages = {},
pmid = {40800841},
issn = {2837-6056},
abstract = {Long COVID is characterized by lingering symptoms following SARS-CoV-2 infection, which may include neurological and cognitive complaints. Hypothesized mechanisms, including blood-brain barrier (BBB) dysfunction and neuroinflammation, are shared with Alzheimer's disease (AD) and related dementias. To address concern that long COVID may accelerate cognitive decline and neurodegeneration, this study examined neuroimaging-based markers of BBB breakdown and brain microstructure among older adults with long COVID, and modification by AD risk factors. Individuals with persistent cognitive complaints following SARS-CoV-2 infection (neurological long COVID, NLCV) and cognitively normal controls (50-90 years, 61% women) underwent neuropsychological evaluation, genotyping, dynamic contrast-enhanced MRI to measure BBB permeability, and multi-compartment diffusion MRI to measure brain microstructure. Cognitive and brain measures were compared between NLCV and controls using analysis of covariance, and associations among measures were assessed using linear regression. Interaction models probed modification by sex and AD genetic risk, quantified with a polygenic hazard score. Compared to controls, NLCV exhibited cognitive impairment, BBB breakdown, and subcortical microstructural abnormalities. NLCV-related BBB leakage was widespread across the brain and more pronounced among men, whereas white matter and subcortical microstructural differences were stronger among women. AD polygenic hazard score modified associations of BBB permeability with memory and microstructure, such that higher caudate BBB permeability correlated with worse immediate recall, and higher white matter permeability correlated with higher free water only for those with elevated genetic risk. BBB dysfunction and microstructural compromise may contribute to cognitive symptoms of long COVID in older adults. Sex-specific patterns, and more deleterious associations between brain and memory abnormalities among individuals with elevated AD genetic risk, highlight the need for precision medicine diagnostic and therapeutic approaches for long COVID.},
}

@article {pmid40799952,
year = {2025},
author = {Di Micco, P and Siniscalchi, C and Imbalzano, E and Russo, V and Camporese, G and Lodigiani, C and Meschi, T and Perrella, A},
title = {COVID-19: A Disease Driven by Protease/Antiprotease Imbalance? A Specific Review Five Years into the Pandemic.},
journal = {Infection and drug resistance},
volume = {18},
number = {},
pages = {3967-3975},
pmid = {40799952},
issn = {1178-6973},
abstract = {COVID-19, caused by SARS-CoV-2, has profoundly impacted global health since late 2019. Beyond respiratory complications, the disease involves systemic manifestations driven by immune dysregulation, inflammation, and coagulopathy. Among the many mechanisms implicated in severe disease, a growing body of evidence suggests a central role for the imbalance between proteases and antiproteases. This review examines how dysregulated protease activity contributes to viral entry, cytokine activation, vascular injury, and thrombosis. We focus on the integration of proteolytic systems such as the renin-angiotensin system, coagulation cascade, and neutrophil extracellular traps with established pathways like endothelial dysfunction and immune hyperactivation. Furthermore, we highlight therapeutic strategies aimed at restoring proteolytic balance and discuss the potential relevance of this paradigm in the management of long COVID.},
}

@article {pmid40796217,
year = {2025},
author = {},
title = {Correction to: Correlation of interferons and autoimmune aspects in long COVID-19 patients.},
journal = {International immunology},
volume = {},
number = {},
pages = {},
doi = {10.1093/intimm/dxaf044},
pmid = {40796217},
issn = {1460-2377},
support = {COVID-19- K027083//Kawano Masanori Memorial Public Interest Incorporated Foundation/ ; },
}

@article {pmid40794410,
year = {2025},
author = {Gottlieb, M and Chen, J and Yu, H and Santangelo, M and Spatz, ES and Gentile, NL and Geyer, RE and Malicki, C and Gatling, K and O'Laughlin, KN and Stephens, KA and Elmore, JG and Wisk, LE and L'Hommedieu, M and Rodriguez, R and Montoy, JCC and Wang, RC and Rising, KL and Kean, E and Dyal, JW and Hill, MJ and Venkatesh, AK and Weinstein, RA and , },
title = {Work Impairment and Financial Outcomes Among Adults With vs Without Long COVID.},
journal = {JAMA network open},
volume = {8},
number = {8},
pages = {e2526310},
pmid = {40794410},
issn = {2574-3805},
mesh = {Humans ; Female ; Male ; *COVID-19/economics/epidemiology/psychology/complications ; Adult ; Middle Aged ; Prospective Studies ; Longitudinal Studies ; SARS-CoV-2 ; Quality of Life ; Efficiency ; Surveys and Questionnaires ; *Financial Stress ; },
abstract = {IMPORTANCE: While much of the focus on long COVID (LC; defined as developing new, persistent symptoms lasting 3 months or longer after SARS-CoV-2 infection) has been on health status and quality of life, the impact on individual work productivity and financial distress are less well established.

OBJECTIVES: To assess differences in work and financial outcomes among individuals with current, resolved, and no LC up to 3 years after initial infection.

This prospective, multisite, longitudinal cohort study enrolled adult participants (age ≥18 years) with at least 1 reported SARS-CoV-2 infection from December 7, 2020, to August 29, 2022. Follow-up electronic surveys were collected through April 2, 2024. Data were analyzed from January 20 to February 4, 2025.

EXPOSURE: Self-reported resolved or current LC and vaccination status.

MAIN OUTCOMES AND MEASURES: Financial toxicity was measured using Comprehensive Score for Financial Toxicity-Functional Assessment of Chronic Illness Therapy (FACIT-COST), and work impact was measured using the Work Productivity & Activity Impairment questionnaire (version 2.0).

RESULTS: Of 3663 participants (mean [SD] age, 40.2 [14.2] years; 2429 [66.3%] female), 994 (27.1%) reported current LC, 2604 (71.1%) never had LC, and 65 (1.8%) had resolved LC. Participants with current LC reported more overall work impairment due to health (mean [SD], 17.7% [25.3%] of total hours worked per week) compared with those who never had LC (mean [SD], 3.2% [11.8%] of total hours) and resolved LC (mean [SD], 5.6% [12.2%] of total hours), with significantly increased odds of any work impairment compared with those who never had LC (adjusted odds ratio [aOR], 7.24; 95% CI, 5.68-9.21). The current LC group had increased odds of missing work due to their health (aOR, 2.62; 95% CI, 1.93-3.57) and of experiencing work impairment (aOR, 11.82; 95% CI, 8.90-15.70) compared with the group who never had LC. Individuals with current LC had increased odds of having moderate to high FACIT-COST scores compared with those who never had LC (aOR, 5.20; 95% CI, 3.92-6.89) and compared with those with resolved LC (aOR, 3.16; 95% CI, 1.19-8.41). Participants who were vaccinated had lower overall work impairment (aOR, 0.71; 95% CI, 0.55-0.92), impairment while working (aOR, 0.66; 95% CI, 0.50-0.87), impairment of nonwork activities (aOR, 0.74; 95% CI, 0.57-0.96), and financial toxicity (least-squares mean difference, 1.07; 95% CI, 0.19-1.95) compared with those who were not vaccinated.

CONCLUSIONS AND RELEVANCE: In this prospective cohort study of adults with SARS-CoV-2 infection, participants with current self-reported LC reported worse work impairment, missed work, and financial distress compared with those who never had LC, while vaccination was associated with improved work outcomes and less financial distress even among individuals with LC. These data underscore the need for postpandemic assistance programs, as well as vaccination to decrease societal harms.},
}

Humans
Female
Male
*COVID-19/economics/epidemiology/psychology/complications
Adult
Middle Aged
Prospective Studies
Longitudinal Studies
SARS-CoV-2
Quality of Life
Efficiency
Surveys and Questionnaires
*Financial Stress

@article {pmid40794409,
year = {2025},
author = {Wisk, LE and L'Hommedieu, M and Diaz Roldan, K and Ebna Mannan, I and Spatz, ES and Weinstein, RA and Venkatesh, AK and Gottlieb, M and Huebinger, R and Rising, KL and Montoy, JCC and Stephens, KA and Rodriguez, RM and Hill, MJ and O'Laughlin, KN and Gentile, NL and Idris, AH and Li, SX and Santangelo, M and Kean, ER and McDonald, SA and Gatling, K and Elmore, JG and , },
title = {Variability in Long COVID Definitions and Validation of Published Prevalence Rates.},
journal = {JAMA network open},
volume = {8},
number = {8},
pages = {e2526506},
pmid = {40794409},
issn = {2574-3805},
mesh = {Humans ; Prevalence ; *COVID-19/epidemiology/diagnosis ; Female ; Middle Aged ; Male ; Adult ; Prospective Studies ; SARS-CoV-2 ; United States/epidemiology ; Aged ; Post-Acute COVID-19 Syndrome ; Young Adult ; Adolescent ; Registries ; Sensitivity and Specificity ; },
abstract = {IMPORTANCE: Long COVID definitions vary widely, and no consensus exists on how to accurately measure its prevalence, complicating both clinical care and research.

OBJECTIVE: To assess long COVID prevalence using various definitions from published literature.

This prospective, multicenter cohort study used data from the longitudinal Innovative Support for Patients With SARS-CoV-2 Infections Registry (INSPIRE). Participants aged 18 years or older with symptoms suggestive of COVID-19 illness at the time of their index SARS-CoV-2 test enrolled at 8 sites across the US from December 11, 2020, through August 29, 2022, with follow-up surveys collected through February 28, 2023.

EXPOSURE: Positive or negative SARS-CoV-2 test result at the time of acute symptoms.

MAIN OUTCOMES AND MEASURES: Long COVID prevalence among INSPIRE participants with a positive vs negative index SARS-CoV-2 test, based on long COVID definitions in published literature. Secondary outcomes were sensitivity and specificity of published definitions compared with self-reported long COVID.

RESULTS: A total of 4575 INSPIRE participants were included (mean [SD] age, 40.40 [14.58] years). Most were female (3013 of 4448 [67.7%]) and aged 18 to 49 years (3338 of 4541 [73.5%]). Applying 5 published definitions for long COVID yielded a prevalence that ranged from 30.84% (95% CI, 29.33%-32.40%) to 42.01% (95% CI, 40.37%-43.66%) at 3 months and 14.23% (95% CI, 13.01%-15.55%) to 21.94% (95% CI, 20.47%-23.47%) at 6 months postinfection; in the 5 comparator studies, reported prevalence of long COVID at 1 to 5 months postinfection ranged from 2.6% (≥84 days) to 47.4% (3-5 months) and at 6 or more months postinfection ranged from 10.0% (95% CI, 8.8%-11.0%) to 61.9% (6-11 months). Using participants' self-reported long COVID as a criterion standard, existing published definitions had low-to-moderate sensitivity (up to 66.32% [95% CI, 62.59%-69.90%] at 3 months and 45.53% [95% CI, 41.51%-49.60%] at 6 months) and high specificity (up to 81.29% [95% CI, 79.32%-83.15%] at 3 months and 94.26% [95% CI, 92.98%-95.37%]) at 6 months.

CONCLUSIONS AND RELEVANCE: In this cohort study, variability in long COVID prevalence across published definitions highlights the need for a standardized, validated definition to improve clinical recognition and research comparability, ultimately guiding more accurate diagnosis and treatment strategies.},
}

Humans
Prevalence
*COVID-19/epidemiology/diagnosis
Female
Middle Aged
Male
Adult
Prospective Studies
SARS-CoV-2
United States/epidemiology
Aged
Post-Acute COVID-19 Syndrome
Young Adult
Adolescent
Registries
Sensitivity and Specificity

@article {pmid40791479,
year = {2025},
author = {Morad, H and Vanhala, T and Kisiel, MA and Andreason, A and Li, M and Andersson, G and Laurell, G and Finger, TE and Hellekant, G},
title = {Taste dysfunction in Long COVID.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.07.17.661973},
pmid = {40791479},
issn = {2692-8205},
abstract = {Persistent taste dysfunction may occur both as acute and long-term symptoms of SARS-CoV-2 infection (Long COVID), yet the underlying mechanisms are unknown at the histological, cellular, and molecular levels. This study investigates the underlying pathology in 28 non hospitalized subjects who reported persistent taste disturbances for over 12 months after testing positive for SARS-CoV-2. To assess taste function, subjects completed the Waterless Empirical Taste Test (WETT), which quantifies the subject's ability to taste each of the five human taste qualities: sweet, umami, bitter, sour, and salty. Biopsies of fungiform papillae were collected from 20 participants and analyzed histologically for overall taste bud structure and innervation and by quantitative PCR (qPCR) for expression of markers for different taste receptor cells (TRCs). Although all subjects reported subjective taste dysfunction, only five scored below the 20th percentile on overall taste sensitivity. However, 12 subjects exhibited total loss of one or more taste qualities and another 13 subjects tested below the 95% confidence interval for at least one taste modality. Notably, loss of sweet, umami, or bitter tastes - qualities mediated by a PLCβ2-transduction cascade - was significantly more common than loss of sour and salty, and this loss correlated with reduced expression of PLCβ2 mRNA. Histological analysis revealed generally preserved taste bud structure and innervation in all cases, with occasional disorganization resulting in isolated PLCβ2-immunoreactive cells. Our findings suggest long term taste dysfunction after COVID-19 disproportionately impacts PLCβ2-dependent taste 38 qualities and is not due to widespread structural damage of the taste periphery.},
}

@article {pmid40791384,
year = {2025},
author = {Dang, H and Edwards, CE and Kato, T and Reidel, B and Meganck, RM and Esther, CR and Ehre, C and Fulcher, ML and Bailey, AB and Cooley, MR and Mikami, Y and Asakura, T and Hawkins, PE and Saito, M and Myers, JL and Konopka, K and Gerayeli, FV and Park, HY and Sin, DD and Livraghi-Butrico, A and Okuda, K and Pickles, RJ and Klein, S and Randell, SH and O'Neal, WK and Baric, RS and Boucher, RC},
title = {Airway Epithelial SARS-CoV-2 Infectious and Repair Responses: Relationships to Age, Sex, and Post-COVID Pulmonary Syndromes.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.07.17.663733},
pmid = {40791384},
issn = {2692-8205},
abstract = {The long-term pulmonary sequelae of SARS-CoV-2 respiratory infections reflect infection severity, innate and adaptive immunity, and respiratory epithelial repair. This study investigated the acute and reparative responses as a function of age and sex in primary human bronchial epithelial (HBE) cultures utilizing a 14-day SARS-CoV-2 infection protocol. SARS-CoV-2 infection peaked at 3 days post-infection (dpi) with an ∼ 2 log titer suppression at 14 dpi. SARS-CoV-2 infection induced interferon, interferon-induced gene, and cell damage responses. No age- or sex-dependent effects on SARS-CoV-2 infection were detected. Airway epithelia repaired to an abnormal mucus metaplastic/inflammatory state that reflected potentially beneficial and adverse consequences at 14 dpi. Repair processes were infection severity-dependent, not sex-dependent, and were more robust in young donor cultures. Analyses of long-COVID subjects with persistent pulmonary fibrosis or persistent bronchitic airway diseases exhibited expression of HBE 14 dpi failed repair gene signatures, including ISG gene signatures. Human airway epithelial repair post-SARS-CoV-2 is prolonged and incomplete in vitro over 14 days, and persistently abnormal repair may contribute to phenotypes of people with long-COVID pulmonary syndrome.},
}

@article {pmid40783127,
year = {2025},
author = {McInnes, K and Fanucchi, S},
title = {A clot to uncover: SARS-CoV-2 nucleocapsid can outcompete the FOXP3 forkhead domain for DNA binding in vitro.},
journal = {Biochimie},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.biochi.2025.08.006},
pmid = {40783127},
issn = {1638-6183},
abstract = {During COVID-19, systemic coagulopathy can lead to strokes and embolisms and may also contribute to long COVID. This coagulopathy is the result of overactivated platelets in circulation that lead to inappropriate clot formation. FOXP3 is a transcription factor involved in platelet development. Loss of FOXP3 function leads to abnormal platelets resembling those seen during COVID-19. Thus, FOXP3 may be dysregulated in COVID-19. The SARS-CoV-2 nucleocapsid (NC) is a multifunctional protein typically associated with viral genome packaging and virion assembly. However, it is also capable of binding DNA and may alter host gene expression. Here, potential interactions between the DNA-binding forkhead domain (FHD) of FOXP3 and the SARS-CoV-2 NC were investigated. Identification of a novel interaction between FOXP3 and SARS-CoV-2 NC may provide new clues to the pathophysiology of COVID-19. To address this aim, both proteins were overexpressed in T7 E. coli, purified via immobilised metal affinity chromatography, and monitored for interactions in the absence and presence of DNA using pull-down assays, electrophoretic mobility shift assays, and fluorescence anisotropy. A direct interaction was identified between the two proteins in the absence of DNA in vitro. Additionally, both proteins were found to bind DNA simultaneously under limiting conditions, but competed for binding under saturating conditions, where excess NC led to dissociation of FHD from the FHD-NC-DNA complex. This result implicates NC in FOXP3 dysfunction, potentially contributing to the coagulopathy and other symptoms observed during COVID-19. This work may inform future therapeutic strategies for severe COVID-19.},
}

@article {pmid40778129,
year = {2025},
author = {Bruiners, N and Ukey, R and Konvinse, KC and Harris, M and Kalaycioglu, M and Yang, JH and Yang, E and Ganapathi, U and Honnen, W and Andrews, T and Richlin, B and Suarez, C and Gaur, S and Ricciardi, E and Hasan, UN and Cuddy, W and Singh, AR and Bukulmez, H and Kaelber, DC and Kimura, Y and Pinter, A and Napoli, S and Moroso-Fela, S and Kleinman, LC and Horton, DB and Utz, PJ and Gennaro, ML},
title = {Antibody repertoire associated with clinically diverse presentations of pediatric SARS-CoV-2 infection.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {40778129},
support = {OT2 HL161847/HL/NHLBI NIH HHS/United States ; R33 HD105619/HD/NICHD NIH HHS/United States ; UL1 TR003017/TR/NCATS NIH HHS/United States ; R38 HL143615/HL/NHLBI NIH HHS/United States ; R33 HD105593/HD/NICHD NIH HHS/United States ; R01 AI158911/AI/NIAID NIH HHS/United States ; R01 AI182319/AI/NIAID NIH HHS/United States ; R01 AI175771/AI/NIAID NIH HHS/United States ; },
abstract = {Pediatric SARS-CoV-2 infection results in clinical presentations ranging from asymptomatic/mild infection to severe pulmonary COVID-19, to Multisystem Inflammatory Syndrome in Children (MIS-C), characterized by hyperinflammation and multi-organ involvement. While various aspects of antibody responses to pediatric SARS-CoV-2 infection manifestations have been reported, parallel studies of antibody responses to viral and self-antigens are understudied. We tested whether clinical presentations of increasing severity corresponded to different antiviral antibody and autoantibody signatures. Using custom arrays, we found that, relative to uninfected subjects, all SARS-CoV-2 infection manifestations were associated with increased autoantibody production, suggesting pediatric SARS-CoV-2 infection as a risk factor for autoimmune complications. Subtle differences were seen in autoantibody patterns among infection groups, with some autoantibodies more associated with mild manifestations and others with severe ones. When we compared MIS-C and severe COVID-19 subjects, we found differences in IgG (mostly IgG1) abundance but not in Fc-mediated effector functions. Thus, MIS-C may be associated with abnormal antibody function, suggesting that this syndrome, and perhaps other post-acute sequelae of SARS-CoV-2 infection, may be associated with antibody dysfunction. Our study shows that the antibody repertoire varies with clinical presentation of SARS-CoV-2 in children and its analysis may help understand long COVID pathogenesis.},
}

@article {pmid40772993,
year = {2025},
author = {Siqueira, IFB and Figueiredo, LA and Fernandes, CEM and Cintra, LP and de Oliveira, GF and Rios, MA and Maciel, R and Ferretjans, R and Guimarães, NS and Magno, LAV},
title = {Metabolic brain changes in post-acute COVID-19: systematic review and meta-analysis of [18F]-FDG-PET findings.},
journal = {Brain structure & function},
volume = {230},
number = {7},
pages = {128},
pmid = {40772993},
issn = {1863-2661},
mesh = {Humans ; *COVID-19/metabolism/diagnostic imaging/complications ; Positron-Emission Tomography/methods ; Fluorodeoxyglucose F18 ; *Brain/metabolism/diagnostic imaging ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Radiopharmaceuticals ; Glucose/metabolism ; },
abstract = {Individuals with long COVID exhibit neurological and psychiatric symptoms that often persist well beyond the initial SARS-CoV-2 infection. Studies using [18F]-FDG positron emission tomography (FDG-PET) have revealed diverse abnormalities in brain glucose metabolism during the post-acute phase of COVID-19. We conducted a systematic review and meta-analysis to assess the spatial distribution and heterogeneity of brain metabolic changes in patients in the post-acute phase of COVID-19 relative to controls. We searched the MEDLINE, EMBASE, and CENTRAL databases in June 2025 for studies reporting FDG-PET data in patients with post-acute COVID-19 who have persistent neurological symptoms. Of the 14 eligible studies (584 scans), 13 reported glucose hypometabolism across frontoparietal regions, with the frontal cortex being the most consistently affected. This finding was confirmed by meta-analysis, which revealed a large and significant effect in the frontal cortex (Hedges' g = 1.34; 95% CI: 0.79-1.88; p < 0.001), despite high heterogeneity (I[2] = 93.6%). The systematic review indicates that brain metabolism generally improves over time, with widely varying recovery timelines, and consistently correlates hypometabolism with neurological symptom burden. These findings underscore the clinical relevance of frontoparietal hypometabolism in post-acute COVID-19 and its association with neurocognitive deficits, highlighting the need for longitudinal, quantitative PET studies to elucidate temporal dynamics and inform therapeutic development.},
}

Humans
*COVID-19/metabolism/diagnostic imaging/complications
Positron-Emission Tomography/methods
Fluorodeoxyglucose F18
*Brain/metabolism/diagnostic imaging
Post-Acute COVID-19 Syndrome
SARS-CoV-2
Radiopharmaceuticals
Glucose/metabolism

@article {pmid40720834,
year = {2025},
author = {Feldman, CH and Santacroce, L and Bassett, IV and Thaweethai, T and Alicic, R and Atchley-Challenner, R and Chung, A and Goldberg, MP and Horowitz, CR and Jacobson, KB and Kelly, JD and Knight, S and Lutrick, K and Mudumbi, P and Parthasarathy, S and Prendergast, H and Quintana, Y and Sharareh, N and Shellito, J and Sherif, ZA and Taylor, BD and Taylor, E and Tsevat, J and Wiley, Z and Williams, NJ and Yee, L and Aponte-Soto, L and Baissary, J and Berry, J and Charney, AW and Costantine, MM and Duven, AM and Erdmann, N and Ernst, KC and Feuerriegel, EM and Flaherman, VJ and Go, M and Hawkins, K and Jacoby, V and John, J and Kelly, S and Kindred, E and Laiyemo, A and Levitan, EB and Levy, BD and Logue, JK and Marathe, JG and Martin, JN and McComsey, GA and Metz, TD and Minor, T and Montgomery, AP and Mullington, JM and Ofotokun, I and Okumura, MJ and Peluso, MJ and Pogreba-Brown, K and Raissy, H and Rosas, JM and Singh, U and VanWagoner, T and Clark, CR and Karlson, EW},
title = {Social Determinants of Health and Risk for Long COVID in the U.S. RECOVER-Adult Cohort.},
journal = {Annals of internal medicine},
volume = {},
number = {},
pages = {},
pmid = {40720834},
issn = {1539-3704},
support = {OT2 HL156812/HL/NHLBI NIH HHS/United States ; OT2 HL161841/HL/NHLBI NIH HHS/United States ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; },
abstract = {BACKGROUND: Social determinants of health (SDoH) contribute to disparities in SARS-CoV-2 infection, but their associations with long COVID are unknown.

OBJECTIVE: To determine associations between SDoH at the time of SARS-CoV-2 infection and risk for long COVID.

DESIGN: Prospective observational cohort study.

SETTING: 33 states plus Washington, DC, and Puerto Rico.

PARTICIPANTS: Adults (aged ≥18 years) enrolled in RECOVER-Adult (Researching COVID to Enhance Recovery) between October 2021 and November 2023 who were within 30 days of SARS-CoV-2 infection; completed baseline SDoH, comorbidity, and pregnancy questionnaires; and were followed prospectively.

MEASUREMENTS: Social risk factors from SDoH baseline questionnaires, ZIP code poverty and household crowding measures, and a weighted score of 11 or higher on the Long COVID Research Index 6 months after infection.

RESULTS: Among 3787 participants, 418 (11%) developed long COVID. After adjustment for demographic characteristics, pregnancy, disability, comorbidities, SARS-CoV-2 severity, and vaccinations, financial hardship (adjusted marginal risk ratio [ARR], 2.36 [95% CI, 1.97 to 2.91]), food insecurity (ARR, 2.36 [CI, 1.83 to 2.98]), less than a college education (ARR, 1.60 [CI, 1.30 to 1.97]), experiences of medical discrimination (ARR, 2.37 [CI, 1.94 to 2.83]), skipped medical care due to cost (ARR, 2.87 [CI, 2.22 to 3.70]), and lack of social support (ARR, 1.79 [CI, 1.50 to 2.17]) were associated with increased risk for long COVID. Living in ZIP codes with the highest (vs. lowest) household crowding was also associated with greater risk (ARR, 1.36 [CI, 1.05 to 1.71]).

LIMITATION: Selection bias may influence observed associations and generalizability.

CONCLUSION: Participants with social risk factors at the time of SARS-CoV-2 infection had greater risk for subsequent long COVID than those without. Future studies should determine whether social risk factor interventions mitigate long-term effects of SARS-CoV-2 infection.

PRIMARY FUNDING SOURCE: National Institutes of Health.},
}

@article {pmid40700379,
year = {2025},
author = {Gottlieb, M and Spatz, ES and Yu, H and Ebna Mannan, I and Santangelo, M and Malicki, C and Gentile, NL and Geyer, RE and Charlton, A and Dyal, JW and Elmore, JG and Gatling, K and Hill, MJ and Montoy, JCC and O'Laughlin, KN and Rising, KL and Saydah, S and Stephens, KA and Wang, RC and Wisk, LE and Venkatesh, AK and Weinstein, RA and , },
title = {Effects of long COVID on healthcare utilization.},
journal = {PloS one},
volume = {20},
number = {7},
pages = {e0327218},
pmid = {40700379},
issn = {1932-6203},
mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *COVID-19/epidemiology ; Emergency Service, Hospital/statistics & numerical data ; Hospitalization/statistics & numerical data ; Longitudinal Studies ; *Patient Acceptance of Health Care/statistics & numerical data ; Prospective Studies ; SARS-CoV-2/isolation & purification ; Telemedicine ; United States/epidemiology ; Secondary Data Analysis ; },
abstract = {BACKGROUND: While most research on Long COVID (LC) has focused on symptoms and quality of life, there remains a critical need to better understand the effect of LC on resource utilization. This study sought to determine the type and amount of healthcare utilization among participants with versus without LC.

METHODS: This was a secondary analysis of a prospective, longitudinal, multicenter U.S. study of adult participants with symptomatic COVID-19, confirmed with testing, who completed 3-month post-infection surveys and had electronic health record data for at least 180 days pre- and post-index testing. We excluded participants with any COVID-19 infections within the 6 months following enrollment. Consistent with prior work, LC was defined as ≥3 post-infectious symptoms at 3 months, while those with <3 symptoms were categorized as not having LC. Our primary outcome was to compare the change in visit types between pre- and post-index testing (hospitalization, emergency department visit, office visit, procedure, telehealth, and other). As secondary outcomes, we assessed differences in visit complexity using the summative length of each encounter for each category as a measure of total healthcare usage.

RESULTS: A total of 847 participants met inclusion criteria (179 LC, 668 non-LC). When compared with the pre-index period, there was an overall increase in visit numbers of all six visit categories during the post-index period for all groups, most pronounced in office and telehealth visits. When compared with the non-LC group, the LC group was less likely to have ED visits (OR: 0.1; 95% CI 0.0-0.5). However, among those with LC who had at least one hospitalization, they were more likely to have additional hospitalizations (OR: 2.6; 95% CI 1.5-4.6). Visit length for office visits and hospitalization in the LC group was increased when compared with the non-LC group, though this diminished after adjustment for patient baseline characteristics.

CONCLUSIONS: All participants who were infected with SARS-CoV-2 had a marked increase in healthcare utilization during the subsequent 180 days. The LC group had significantly higher rates of additional hospitalization compared with those without LC, which may help to inform healthcare resource planning.},
}

Adult
Aged
Female
Humans
Male
Middle Aged
*COVID-19/epidemiology
Emergency Service, Hospital/statistics & numerical data
Hospitalization/statistics & numerical data
Longitudinal Studies
*Patient Acceptance of Health Care/statistics & numerical data
Prospective Studies
SARS-CoV-2/isolation & purification
Telemedicine
United States/epidemiology
Secondary Data Analysis

@article {pmid40694553,
year = {2025},
author = {Ma, KPK and Stober, T and Gottlieb, M and Geyer, RE and Rising, K and Saydah, S and Santangelo, M and Gatling, K and Grau, D and Wang, RC and Montoy, JC and Idris, A and MacDonald, S and Hill, MJ and Huebinger, R and Prado, MG and Gentile, NL and Spatz, E and Maliki, C and Dorney, J and Elmore, JG and L'Hommedieu, M and Weinstein, RA and Venkatesh, AK and Stephens, KA and , },
title = {Participant engagement in a national longitudinal study of COVID-19: Insights from the INSPIRE study.},
journal = {PloS one},
volume = {20},
number = {7},
pages = {e0325948},
pmid = {40694553},
issn = {1932-6203},
mesh = {Humans ; *COVID-19/epidemiology/psychology/virology ; Longitudinal Studies ; Male ; Female ; Middle Aged ; Adult ; Motivation ; United States/epidemiology ; Surveys and Questionnaires ; SARS-CoV-2/isolation & purification ; Aged ; *Patient Participation/psychology ; Registries ; },
abstract = {OBJECTIVE: To examine participants' motivations and their experiences throughout a decentralized, longitudinal COVID-19 study in the U.S.

METHODS: We recruited 355 participants from the Innovative Support for Patients with SARS-CoV-2 Infections Registry (INSPIRE) between November 2022 - March 2023 to answer five qualitative survey questions anonymously. We used an inductive content analysis approach to analyze the data.

RESULTS: We identified five key themes from the analysis, which reflected participants' a) motivations to join the study, b) study benefits, c) perceptions of survey questions, d) experiences with the research process, and e) preferences for disseminating research findings. Participants were motivated to learn with researchers about COVID-19. They expressed divided opinions about the relevance of INSPIRE research questions. They reported difficulties navigating the virtual research platform and the need for making survey participation less cognitively demanding. They sought more regular feedback on study findings.

CONCLUSIONS: Our findings offered insights into incorporating decentralized participatory methods in longitudinal research, strengthening reciprocal research communications, making virtual research platforms user-friendly, and employing strategies to reduce participants' cognitive burden in research.

POLICY IMPLICATIONS: Longitudinal studies should focus on optimizing these aspects of participant engagement to produce rigorous findings that inform policy and practice on lasting effects of COVID-19 including Long COVID.},
}

Humans
*COVID-19/epidemiology/psychology/virology
Longitudinal Studies
Male
Female
Middle Aged
Adult
Motivation
United States/epidemiology
Surveys and Questionnaires
SARS-CoV-2/isolation & purification
Aged
*Patient Participation/psychology
Registries

@article {pmid40685660,
year = {2025},
author = {Davis, S and Mon-Yee, M and Sutton, A and Leaviss, J and Forsyth, JE and Burton, C},
title = {Cost effectiveness of non-pharmacological interventions for fatigue in patients with long-term conditions: a systematic literature review.},
journal = {Expert review of pharmacoeconomics & outcomes research},
volume = {},
number = {},
pages = {1-8},
doi = {10.1080/14737167.2025.2537194},
pmid = {40685660},
issn = {1744-8379},
abstract = {INTRODUCTION: We aimed to assess the cost-effectiveness of non-pharmacological interventions for fatigue in patients with chronic conditions in the UK.

METHODS: This systematic review of cost-effectiveness studies aligns with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) 2020 statement. Data sources: Electronic databases and citation searches. Inclusion criteria: Studies including adults with one or more long-term health condition, either physical or mental. Exclusion criteria: Studies associated with cancer, long-COVID, post-viral fatigue, medically unexplained conditions, developmental disorders and injuries. Assessment: A single reviewer completed a two-stage sifting process.

RESULTS: Four studies met the inclusion criteria. They included patients with either multiple sclerosis or inflammatory rheumatic conditions, and assessed either cognitive behavioral therapy (CBT) or a personalized exercise program (PEP). CBT was either dominated by usual care or had an incremental cost-effectiveness ratio (ICER) over £30,000. PEP dominated CBT, with the ICER for PEP versus usual care ranging from £13,159 to £35,424.

CONCLUSIONS: The economic literature on this topic is much more limited than the clinical effectiveness literature, both in terms of interventions and populations covered. Future research should focus on a de novo economic evaluation to identify interventions with a high potential to be cost-effective across multiple conditions.

REGISTRATION: PROSPERO (CRD42023440141).},
}

@article {pmid40645616,
year = {2025},
author = {Rohner, S and Schnepper, R and Meinlschmidt, G and Schaefert, R and Mayr, M and Bopp, K and Meienberg, A},
title = {Basel Long COVID Cohort Study (BALCoS): protocol of a prospective cohort study.},
journal = {BMJ open},
volume = {15},
number = {7},
pages = {e093981},
pmid = {40645616},
issn = {2044-6055},
mesh = {Female ; Humans ; Male ; *COVID-19/complications/psychology/epidemiology ; Post-Acute COVID-19 Syndrome ; Prospective Studies ; Psychometrics ; Research Design ; Switzerland/epidemiology ; Observational Studies as Topic ; },
abstract = {INTRODUCTION: The recent pandemic caused by SARS-CoV-2 had a profound global impact. While many individuals recovered from COVID-19, some developed long-lasting symptoms that significantly disrupted daily life. The WHO defines this condition as post-COVID-19 condition (PCC). Common symptoms include fatigue, dyspnoea, sleep disturbances and cognitive difficulties. Increasing evidence suggests that PCC is a multifactorial condition, shaped not only by biomedical but also psychological and social factors. This article presents the protocol of the Basel Long COVID Cohort Study (BALCoS), which aims to improve understanding of PCC by capturing clinical, functional and psychosocial aspects through repeated assessments over the course of 1 year.

METHODS AND ANALYSIS: BALCoS is a prospective, single-site cohort study. Inclusion criteria include either a probable or confirmed history of SARS-CoV-2 infection with persistent symptoms consistent with the WHO definition of PCC, sufficient German language skills and age ≥18 years. At baseline, we collected detailed information on previous SARS-CoV-2 infections, symptom history, reinfections, COVID-19 vaccination status and pre-existing medical conditions. The study includes standardised psychometric assessments, physical performance tests, ecological momentary assessments (EMAs), neurocognitive testing and blood sample collection. Assessments are scheduled at baseline and at 3-month, 6-month and 12-month follow-up. All participants complete psychometric assessments at each time point. Blood samples are only collected at baseline. Neurocognitive testing and physical performance measures are collected at baseline and 12-month follow-up for in-person participants only. Participants who are unable to attend in person complete a remote version of the study, excluding these in-clinic assessments. EMAs are initiated the day after each time point and consist of eight questions over 10 consecutive days. The study is exploratory in nature, with a target sample size of 120 participants. BALCoS is part of the Horizon Europe Long COVID project, a multinational interdisciplinary research consortium integrating mechanistic, clinical and interventional studies.

ETHICS AND DISSEMINATION: The study was approved by the Ethics Commission of Northwest and Central Switzerland (BASEC-ID: 2023-00359) and is registered at ClinicalTrials.gov (ID: NCT05781893). All participants provide written informed consent. Study findings will be disseminated through peer-reviewed publications.

TRIAL REGISTERATION NUMBER: NCT05781893.},
}

Female
Humans
Male
*COVID-19/complications/psychology/epidemiology
Post-Acute COVID-19 Syndrome
Prospective Studies
Psychometrics
Research Design
Switzerland/epidemiology
Observational Studies as Topic

@article {pmid40645608,
year = {2025},
author = {Cabello Fernandez, C and Didone, V and Slama, H and Dupuis, G and Fery, P and Delrue, G and Lesoinne, A and Collette, F and Willems, S},
title = {Profiles of Individuals With Long COVID Reporting Persistent Cognitive Complaints.},
journal = {Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists},
volume = {},
number = {},
pages = {},
doi = {10.1093/arclin/acaf064},
pmid = {40645608},
issn = {1873-5843},
support = {LCOV21-1303//Belgian Health Care Knowledge Centre/ ; },
abstract = {OBJECTIVE: A subset of COVID-19 patients continues to experience cognitive difficulties 24 months post-infection. The factors driving these symptoms are complex, and the underlying pathophysiology is unclear. This study aimed to characterize individuals with Long COVID reporting cognitive issues.

METHOD: One hundred twenty-three patients underwent a comprehensive neuropsychological evaluation resulting from the baseline of an RCT study (COVCOG), along with questionnaires assessing cognitive complaints, fatigue, sleep difficulties, quality of life, psychological distress, and impact on daily activities. Latent Profile Analyses on cognitive scores were conducted to investigate the presence of different patient profiles. Robust analyses of variance and Pearson's chi-square examined the profiles' effects on demographic variables and questionnaire scores.

RESULTS: Patients had had predominantly mild to moderate infections (87.8%) and were assessed an average of 20.9 (±8.6) months post-infection. Neuropsychological assessment showed cognitive impairment in at least one domain in 72% of the patients, mainly in attention and executive functions. Over 80% reported sleep problems and fatigue, 97% concentration problems, and some 80% memory and word-finding problems. The self-report questionnaires also revealed significant complaints. Three profiles emerged (all ps < .001). Profiles 1 and 2 both experienced widespread cognitive issues; Profile 1 patients expressed more complaints about cognitive functioning and daily fatigue (all ps < .045). Patients in Profile 3 were more frequently men (all ps < .049) with a specific impairment of verbal long-term memory and fewer complaints.

CONCLUSIONS: The study identifies three different profiles of individuals with Long COVID, highlighting the need for comprehensive evaluations including neuropsychological, psychological, somatic, and functional aspects to implement effective, tailored interventions. Clinicaltrials.gov: NCT05167266.},
}

@article {pmid40595626,
year = {2025},
author = {Carreras-Vidal, L and Pacheco-Jaime, L and Ariza, M and Cano, N and Garolera, M and Garcia-Vicente, C and Roura, I and Capdevila-Lacasa, C and Oltra, J and Pardo, J and Martín-Barceló, C and Campabadal, A and Sala-Llonch, R and Bargallo, N and Barrué, C and Bejar, J and Cortés, CU and Junqué, C and , and Segura, B},
title = {Functional brain abnormalities in post COVID-19 condition and their relationship with cognition.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {22259},
pmid = {40595626},
issn = {2045-2322},
support = {LCF/BQ/DR22/11950012//'la Caixa' Foundation/ ; PRE2018-086675//Ministerio de Ciencia e Innovación/ ; PRE2021-099674//Ministerio de Economía y Competitividad/ ; },
mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *Brain/physiopathology/diagnostic imaging ; *Cognition/physiology ; *Cognitive Dysfunction/physiopathology/etiology/diagnostic imaging ; *COVID-19/complications/physiopathology/diagnostic imaging ; Magnetic Resonance Imaging ; Neuropsychological Tests ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; },
abstract = {After COVID-19 infection, some patients develop a post-COVID condition (PCC) that is popularly referred to as long COVID. Among its symptoms is persistent cognitive dysfunction that is potentially linked to altered brain functional connectivity (FC). While research has explored functional reorganization in patients with PCC, the intra- and inter- network connectivity and its relationship with cognitive status and clinical outcomes remain unclear. In this study, we recruited 121 individuals with PCC (67 with, and 54 without, cognitive impairment), 20 months after infection, along with 37 non-infected healthy controls from the NAUTILUS Project (ClinicalTrials.gov IDs: NCT05307549 and NCT05307575). Participants underwent resting-state functional magnetic resonance imaging and comprehensive neuropsychological assessment. Resting-state networks were characterized using independent component analyses, dual regression and network modelling for individual FC characterization. Group differences in intra- and inter-network FC, and their associations with clinical and neuropsychological data, were studied. Significance was set at a corrected p-value of < 0.05. Patients with PCC showed increased intra-network FC in 10 cognitively relevant networks, including the default mode, salience, executive control, auditory and basal ganglia networks, correlating positively with general cognition (Montreal Cognitive Assessment scores), time since infection, fatigue and subjective memory failures. Increased inter-network FC between default mode and sensorimotor networks was also observed. Increases in FC may reflect an inefficient compensatory mechanism in patients with PCC, associated with fatigue, subjective memory complaints and persistence of PCC.},
}

Adult
Aged
Female
Humans
Male
Middle Aged
*Brain/physiopathology/diagnostic imaging
*Cognition/physiology
*Cognitive Dysfunction/physiopathology/etiology/diagnostic imaging
*COVID-19/complications/physiopathology/diagnostic imaging
Magnetic Resonance Imaging
Neuropsychological Tests
Post-Acute COVID-19 Syndrome
SARS-CoV-2

@article {pmid40549427,
year = {2025},
author = {Luo, X and Li, Y and Xu, J and Zheng, Z and Ying, F and Huang, G},
title = {AI in Medical Questionnaires: Scoping Review.},
journal = {Journal of medical Internet research},
volume = {27},
number = {},
pages = {e72398},
pmid = {40549427},
issn = {1438-8871},
mesh = {Humans ; *Artificial Intelligence ; Surveys and Questionnaires ; COVID-19/epidemiology ; *Mental Disorders/diagnosis ; SARS-CoV-2 ; },
abstract = {UNLABELLED: This systematic review aimed to explore the current applications, potential benefits, and issues of artificial intelligence (AI) in medical questionnaires, focusing on its role in 3 main functions: assessment, development, and prediction. The global mental health burden remains severe. The World Health Organization reports that >1 billion people worldwide experience mental disorders, with the prevalence of depression and anxiety among children and adolescents at 2.6% and 6.5%, respectively. However, commonly used clinical questionnaires such as the Hamilton Depression Rating Scale and the Beck Depression Inventory suffer from several problems, including the high degree of overlap of symptoms of depression with those of other psychiatric disorders and a lack of professional supervision during administration of the questionnaires, which often lead to inaccurate diagnoses. In the wake of the COVID-19 pandemic, the health care system is facing the dual challenges of a surge in patient numbers and the complexity of mental health issues. AI technology has now been shown to have great promise in improving diagnostic accuracy, assisting clinical decision-making, and simplifying questionnaire development and data analysis. To systematically assess the value of AI in medical questionnaires, this study searched 5 databases (PubMed, Embase, Cochrane Library, Web of Science, and China National Knowledge Infrastructure) for the period from database inception to September 2024. Of 49,091 publications, a total of 14 (0.03%) studies met the inclusion criteria. AI technologies showed significant advantages in assessment, such as distinguishing myalgic encephalomyelitis or chronic fatigue syndrome from long COVID-19 with 92.18% accuracy. In questionnaire development, natural language processing using generative models such as ChatGPT was used to construct culturally competent scales. In terms of disease prediction, one study had an area under the curve of 0.790 for cataract surgery risk prediction. Overall, 24 AI technologies were identified, covering traditional algorithms such as random forest, support vector machine, and k-nearest neighbor, as well as deep learning models such as convolutional neural networks, Bidirectional Encoder Representations From Transformers, and ChatGPT. Despite the positive findings, only 21% (3/14) of the studies had entered the clinical validation phase, whereas the remaining 79% (11/14) were still in the exploratory phase of research. Most of the studies (10/14, 71%) were rated as being of moderate methodological quality, with major limitations including lack of a control group, incomplete follow-up data, and inadequate validation systems. In summary, the integrated application of AI in medical questionnaires has significant potential to improve diagnostic efficiency, accelerate scale development, and promote early intervention. Future research should pay more attention to model interpretability, system compatibility, validation standardization, and ethical governance to effectively address key challenges such as data privacy, clinical integration, and transparency.

BACKGROUND: The World Health Organization reports that >1 billion people worldwide experience mental disorders, with the prevalence of depression and anxiety among children and adolescents at 2.6% and 6.5%, respectively. However, commonly used clinical questionnaires such as the Hamilton Depression Rating Scale and the Beck Depression Inventory suffer from several problems, including the high degree of overlap of symptoms of depression with those of other psychiatric disorders and a lack of professional supervision during administration of the questionnaires, which often lead to inaccurate diagnoses. In the wake of the COVID-19 pandemic, the health care system is facing the dual challenges of a surge in patient numbers and the complexity of mental health issues. Artificial Intelligence (AI) technology has now been shown to have great promise in improving diagnostic accuracy, assisting clinical decision-making, and simplifying questionnaire development and data analysis.

OBJECTIVE: This review aimed to explore the current applications, potential benefits, and issues of AI in medical questionnaires, focusing on its role in 3 main functions: assessment, development, and prediction. The global mental health burden remains severe.

METHODS: The review included peer-reviewed studies that applied AI technologies to medical, psychological, or physiological questionnaires and reported measurable outcomes; non–peer-reviewed, non-English/Chinese, ethically noncompliant, or AI-unrelated studies were excluded. Five databases (PubMed, Embase, Cochrane Library, Web of Science, and CNKI) were searched from inception through September 2024. Three independent reviewers conducted data extraction, quality appraisal using the Joanna Briggs Institute tools, and narrative synthesis of AI applications across questionnaire assessment, development, and prediction tasks.

RESULTS: Of 49,091 publications, a total of 14 (0.03%) studies met the inclusion criteria. AI technologies showed advantages in assessment, such as distinguishing myalgic encephalomyelitis or chronic fatigue syndrome from long COVID-19 with 92.18% accuracy. In questionnaire development, natural language processing using generative models such as ChatGPT was used to construct culturally competent scales. In terms of disease prediction, one study had an area under the curve of 0.790 for cataract surgery risk prediction. Overall, 24 AI technologies were identified, covering traditional algorithms such as random forest, support vector machine, and k-nearest neighbor, as well as deep learning models such as convolutional neural networks, Bidirectional Encoder Representations From Transformers, and ChatGPT. Despite the positive findings, only 21% (3/14) of the studies had entered the clinical validation phase, whereas the remaining 79% (11/14) were still in the exploratory phase of research. Most of the studies (10/14, 71%) were rated as being of moderate methodological quality, with major limitations including lack of a control group, incomplete follow-up data, and inadequate validation systems.

CONCLUSIONS: In summary, the integrated application of AI in medical questionnaires has significant potential to improve diagnostic efficiency, accelerate scale development, and promote early intervention. Future research should pay more attention to model interpretability, system compatibility, validation standardization, and ethical governance to effectively address key challenges such as data privacy, clinical integration, and transparency.},
}

Humans
*Artificial Intelligence
Surveys and Questionnaires
COVID-19/epidemiology
*Mental Disorders/diagnosis
SARS-CoV-2

@article {pmid40460818,
year = {2025},
author = {Drobinska, N and Nehme, M and Assal, F and Laffitte, E and Guessous, I and Lascano, AM},
title = {Small Fiber Neuropathy in Long COVID: A Cohort Study with Multimodal Assessment and Follow-Up.},
journal = {European neurology},
volume = {88},
number = {2},
pages = {52-63},
doi = {10.1159/000546015},
pmid = {40460818},
issn = {1421-9913},
abstract = {INTRODUCTION: Given the increasing number of patients suffering from pain associated with dysautonomic symptoms following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we aimed to estimate the occurrence of small fiber neuropathy (SFN) in a cohort of long coronavirus disease 19 (COVID-19) patients reporting postinfectious neuropathic pain.

METHODS: The study cohort included 18 patients suffering from neuropathic pain (neuropathic pain score DN4 ≥4) appearing after or during SARS-CoV-2 infection and lasting ≥90 days; presenting normal nerve conduction studies excluding large fiber damage. Patients underwent multimodal SFN evaluation by skin biopsy, quantitative sensory testing (QST), laser evoked potential (LEP) recording and electrochemical skin conductance (ESC; Sudoscan).

RESULTS: Out of 18 patients, 17 were analyzed. Participants' ages averaged 44 ± 9 years, with 94% females. Fourteen (82%) had abnormal skin biopsy results. Notably, 12/17 (70%) patients presented with autonomic complaints, all of whom had abnormal skin biopsy results. At 6-month follow-up, 10/17 patients reported a subjective improvement in pain and/or dysautonomia with or without symptomatic pharmacological or non-pharmacological treatment. In our cohort, QST showed the highest sensibility (79%) and specificity (67%), followed by LEP (sensibility 71%, specificity 67%). ESC showed poor reliability in the screening of SFN with a sensibility of 7% and specificity of 50%.

CONCLUSION: The results of our study suggest that SFN may develop during or shortly after SARS-CoV-2 infection, provoking disabling sensory and dysautonomic symptoms that tend to persist for more than 6 months. Furthermore, our findings imply that noninvasive exams are a useful complement to biopsy in the diagnostic process of SFN.},
}

@article {pmid40386957,
year = {2025},
author = {},
title = {Corrigendum to "Clinical Phenotyping of Long COVID Patients Evaluated in a Specialized Neuro-COVID Clinic".},
journal = {Annals of clinical and translational neurology},
volume = {12},
number = {8},
pages = {1727},
doi = {10.1002/acn3.70069},
pmid = {40386957},
issn = {2328-9503},
}

@article {pmid40310209,
year = {2025},
author = {Uswatte, G and Taub, E and Ball, K and Mitchell, BS and Blake, JA and McKay, S and Biney, F and Iosipchuk, O and Hempfling, P and Harris, E and Dickerson, A and Lokken, K and Knight, AJ and Mark, VW and Agnihotri, S and Cutter, G},
title = {Long COVID brain fog treatment: An early-phase randomized controlled trial of constraint-induced cognitive therapy signals go.},
journal = {Rehabilitation psychology},
volume = {},
number = {},
pages = {},
pmid = {40310209},
issn = {1939-1544},
support = {R01 AG070049/AG/NIA NIH HHS/United States ; //National Institutes of Health; National Institute on Aging/ ; //National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR)/ ; },
abstract = {PURPOSE: Long COVID brain fog is often disabling. Yet, no empirically supported treatments exist. This study's objectives were to evaluate the feasibility and efficacy, provisionally, of a new rehabilitation approach, Constraint-Induced Cognitive Therapy (CICT), for post-COVID-19 cognitive sequelae.

DESIGN: Sixteen community residents ≥3 months post-COVID-19 infection with mild cognitive impairment and dysfunction in instrumental activities of daily living (IADL) were enrolled. Participants were randomized to Immediate-CICT or treatment as usual (TAU) with crossover to CICT. CICT combined behavior change techniques modified from Constraint-Induced Movement Therapy with Speed of Processing Training, a computerized cognitive training program. CICT was deemed feasible if (a) ≥ 80% of participants were adherent, (b) the same found treatment highly satisfying and at most moderately difficult, and (c) < 2 study-related, serious adverse events occurred. The primary outcome was IADL performance in daily life (Canadian Occupational Performance Measure). Employment status and brain fog (Mental Clutter Scale) were also assessed.

RESULTS: Fourteen completed Immediate-CICT (n = 7) or TAU (n = 7); two withdrew from TAU before their second testing session. Completers were, M (SD): 10 (7) months post-COVID; 51 (13) years old; 10 females, four males; one African American, and 13 European American. All the feasibility benchmarks were met. Immediate-CICT, relative to TAU, produced very large improvements in IADL performance (M = 3.7 points, p < .001, d = 2.6) and brain fog (M = -4 points, p < .001, d = -2.9). Four of five nonretired Immediate-CICT participants returned to work posttreatment; no TAU participants did, p = .048.

CONCLUSION: Those who received CICT adhered to the protocol and were highly satisfied with their outcomes. The findings warrant a large-scale randomized controlled trial with an active-comparison group. (PsycInfo Database Record (c) 2025 APA, all rights reserved).},
}

@article {pmid40300093,
year = {2025},
author = {Rane Levendovszky, S and Patel, P and Zhu, C and Rutman, AM and Basha, MM},
title = {Neuroimaging biomarkers of post-acute sequelae of Coronavirus Disease 2019.},
journal = {The British journal of radiology},
volume = {98},
number = {1172},
pages = {1165-1175},
doi = {10.1093/bjr/tqaf090},
pmid = {40300093},
issn = {1748-880X},
support = {R01 HL162743/HL/NHLBI NIH HHS/United States ; //Chronic Post COVID-19 Infection Neuroimaging and Cerebrovascular Imaging/ ; //Bayer Healthcare LLC/ ; //Long terms effects of COVID-19/ ; },
mesh = {Humans ; *COVID-19/complications/diagnostic imaging ; *Neuroimaging/methods ; *Brain/diagnostic imaging/pathology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Biomarkers ; Magnetic Resonance Imaging/methods ; Diffusion Tensor Imaging ; },
abstract = {COVID-19, caused by SARS-CoV-2, has led to the condition known as Long COVID or post-acute sequelae of COVID-19 (PASC), where individuals experience persistent debilitating symptoms long after the initial infection. We provide here a comprehensive review of findings in the central nervous system associated with PASC. Neuroimaging has been instrumental in identifying brain changes associated with PASC. Structural MRI studies consistently reveal grey matter volume reductions in the frontal and temporal lobes and white matter hyperintensities, particularly in the periventricular regions. Studies especially found these changes to correlate strongly with cognitive deficits. Diffusion tensor imaging has shown increased tissue damage and oedema in the brain's white matter tracts, particularly in the sagittal stratum and thalamic radiation. Resting-state functional MRI studies indicate altered brain connectivity in PASC patients, especially in those with post-traumatic stress symptoms. Reduced connectivity within and between critical networks, such as the default mode network and the executive control network, has been observed. These changes correlate with cognitive impairments, such as attention and memory deficits. Dynamic functional connectivity analyses further reveal that PASC patients spend less time in states with rich inter-regional connectivity, and transitions between connectivity states were linked to post-traumatic stress disorder symptoms. Positron emission tomography scans have shown hypometabolism in the frontal and temporal lobes, particularly in regions associated with memory and executive functions. Hypometabolism in the hippocampus and thalamus is linked to symptoms like anosmia and fatigue. Despite the heterogeneity in clinical presentations and diagnostic criteria, these neuroimaging findings underscore the significant impact of COVID-19 on brain structure and function. Continued research using advanced imaging techniques is essential for a deeper understanding of PASC's neurological effects. This will aid in developing targeted interventions and improving outcomes for those affected by Long COVID and inform studies investigating downstream effects of viral infections on the brain.},
}

Humans
*COVID-19/complications/diagnostic imaging
*Neuroimaging/methods
*Brain/diagnostic imaging/pathology
Post-Acute COVID-19 Syndrome
SARS-CoV-2
Biomarkers
Magnetic Resonance Imaging/methods
Diffusion Tensor Imaging

@article {pmid40249096,
year = {2025},
author = {Uhlig-Reche, H and Rolin, S and Karnik, R and Lyons, M and Verduzco-Gutierrez, M},
title = {Compassion fatigue, work engagement, and psychological distress in health care workers treating patients with long COVID.},
journal = {PM & R : the journal of injury, function, and rehabilitation},
volume = {},
number = {},
pages = {},
pmid = {40249096},
issn = {1934-1563},
support = {U18 HS029947/HS/AHRQ HHS/United States ; },
abstract = {BACKGROUND: Health care workers (HCWs) caring for patients with chronic disease are more likely to experience compassion fatigue. The impacts on HCWs caring for patients with a new complex chronic disease, long COVID, are unknown.

OBJECTIVE: To measure compassion fatigue, work engagement, and psychological distress in HCWs caring for patients with long COVID and investigate associations with personal history of long COVID and demographic and occupational characteristics.

DESIGN: Cross-sectional survey study assessing demographic and occupational characteristics, Compassion Fatigue-Short Scale (CF-SS), Utrecht Work Engagement Scale-3 (UWES-3), and Screening Tool for Psychological Distress (STOP-D) in HCWs caring for patients with long COVID.

SETTING: Online survey from March-June 2023.

PARTICIPANTS: 116 HCWs caring for patients with long COVID.

INTERVENTIONS: Not applicable.

MAIN OUTCOME MEASURES: CF-SS, UWES-3, and STOP-D scores and associations with personal history of long COVID, demographic and occupational factors.

RESULTS: HCWs with a personal history of long COVID had worse scores in all outcome measures compared to those without long COVID. Effects were moderate (UWES-3: η[2] = -0.09, p = .01; STOP-D: η[2] = 0.06, p = .02; CF-SS: η[2] = 0.07, p = .02). Outcome measures were comparable between physical medicine and rehabilitation physicians and other HCWs (p > .05). CF-SS showed a small positive correlation (rs = 0.19, n = 112, p = .04) with the percentage of the provider's patient population with long COVID. Mean outcome measures differed between career-level groups with medium to large effects (UWES-3: η[2] = 0.13, STOP-D: η[2] = 0.06, CF-SS: η[2] = 0.06). Work engagement was worse in early career compared to late career (p  <.01). Psychological distress was worse in middle career compared to late career (p = .02). Compassion fatigue was worse in early career compared to late career (p = .02).

CONCLUSIONS: Among HCWs caring for patients with long COVID, mean scores for all primary outcomes were worse in HCWs with a personal history of long COVID compared to those without. Early career HCWs caring for this population are less engaged and experience greater compassion fatigue whereas those in middle career experience greater psychological distress.},
}

@article {pmid40184184,
year = {2025},
author = {Adams, K and Garg, S and Tartof, SY and Irving, SA and DeSilva, MB and Klein, NP and Natarajan, K and Dascomb, K and Grannis, SJ and Ong, TC and Salas, SB and Sy, LS and Lewin, B and Qian, L and Naleway, AL and Koppolu, PD and McEvoy, CE and Akinsete, O and Essien, I and Fireman, B and Zerbo, O and Jacobson, KB and Timbol, J and Neelam, V and Reeves, EL and Dickerson, M and Ray, C and Link-Gelles, R and Mak, J and Ball, SW and O'Reilly, M and Olsen, SJ and Tenforde, MW},
title = {Patterns in prescribing and dispensing of influenza antivirals among adults with influenza presenting to urgent care and emergency department settings, VISION Network, 2023-2024.},
journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America},
volume = {},
number = {},
pages = {},
pmid = {40184184},
issn = {1537-6591},
support = {CC999999/ImCDC/Intramural CDC HHS/United States ; R01 AI168373/AI/NIAID NIH HHS/United States ; },
abstract = {BACKGROUND: We describe prescribing and dispensing patterns of influenza antivirals among patients with laboratory-confirmed influenza within U.S. urgent care and emergency department settings.

METHODS: A retrospective cross-sectional study was conducted for encounters from four large, integrated health systems participating in the VISION network of adult patients presenting with acute respiratory illness to urgent cares or emergency departments and with positive influenza virus test results during the 2023-2024 influenza season. The analysis was restricted to adult patients at higher risk of influenza complications based on presence of underlying medical conditions, older age, pregnancy, and severe obesity. We calculated proportions and odds of prescribed and dispensed antivirals by demographic and clinical characteristics.

RESULTS: A total of 10,700 patient encounters were eligible for analysis. Among encounters with a positive standard molecular influenza test result (N=5,231), 58% (range across sites: 47-64%) were prescribed antivirals, with 67% of prescribing occurring on the encounter date. Among those prescribed antivirals (N=3,050), 80% (range across sites: 75-91%) had them dispensed, with 65% of dispensing occurring on the prescription date. Encounters among persons aged ≥65 years had lower odds of same-day prescribing (0.57 [95% CI: 0.42-0.78]) and lower odds of same-day dispensing (0.58 [95% CI: 0.36-0.94]) compared to those 18-49 years.

CONCLUSIONS: Gaps in antiviral treatment within urgent care and emergency department settings remain for patients at higher risk of influenza complications, notably among older adults. Strategies to improve earlier initiation of antiviral treatment may help reduce the risk of influenza-associated complications.},
}

@article {pmid40084807,
year = {2025},
author = {Tang, CC and Wu, WW and Ho, SJ and Liu, WD and Pan, MY and Chang, SC and Wang, WS and Yeh, YC and Chen, CH and Chang, JC},
title = {Clinically Significant Functional Impairments and Symptoms in COVID-19 Survivors: Empirical Research Quantitative.},
journal = {Journal of clinical nursing},
volume = {},
number = {},
pages = {},
doi = {10.1111/jocn.17715},
pmid = {40084807},
issn = {1365-2702},
support = {//Collaborative Research Projects of National Taiwan University College of Medicine/ ; //National Taiwan University Hospital/ ; 109F005-110-P//Min-Sheng General Hospital/ ; },
abstract = {BACKGROUND: COVID-19 survivors may experience complex, distressing and persistent symptoms, referred to as long COVID, lasting months or years after diagnosis. More evidence is needed for effective long COVID screening and management.

AIM: To explore the clinical profile of long COVID and factors associated with its development.

DESIGN: A multicentre correlational study using a cross-sectional design.

METHODS: Adults diagnosed with COVID-19 6-9 months earlier were recruited via social media and referrals from three facilities. Participants provided demographic data and assessed their symptoms and functional status using validated questionnaires. Data were analysed using descriptive statistics and binomial logistic regression.

RESULTS: Among 102 participants, 13%-30% reported significant impairments in cognitive, emotional and physical functioning. Over 10% experienced symptoms such as diarrhoea, sleep problems, dyspnoea, nausea, fatigue and pain. These impairments and symptoms were associated with acute symptom severity, chronic disease, overweight status, regular exercise and living without partners.

CONCLUSION: This study adds to the literature by examining long-term functional status and symptoms in omicron survivors using comprehensive, validated tools. The findings highlight the prevalence and clinical significance of long COVID symptoms, aiding in the identification of functional impairments requiring medical and nursing interventions.

Nurses should recognise these symptoms and educate survivors about potential challenges. Policies addressing long-term issues, including research, health services and education, are essential.

REPORTING METHOD: This study follows the STROBE guideline (Table S1).

Patients self-reported symptoms for this study.

TRIAL REGISTRATION: ClinicalTrials.gov (NCT05303103).},
}

@article {pmid39994126,
year = {2025},
author = {Datta, A},
title = {Assessing the effects of long-COVID on mental health in the United States: a population based study.},
journal = {Discover mental health},
volume = {5},
number = {1},
pages = {23},
pmid = {39994126},
issn = {2731-4383},
abstract = {BACKGROUND: While most individuals recover fully from COVID-19, a significant proportion of survivors experience prolonged symptoms lasting three months or more, a condition commonly referred to as long-COVID. Long-COVID conditions have been associated with reduced quality of life. By utilizing a nationally representative sample of nearly a million Americans, this study provides insights into the prevalence and impact of long-COVID on anxiety and depression in the U.S.

METHODS: We utilize the Household Pulse Survey data, which provides the first population-based sample on the prevalence of long-COVID, beginning with its June 2022 wave. This survey also includes questions on respondents' mental health status-specifically anxiety and depression. We employ a quasi-experimental difference-in-differences framework to conduct research using control groups, to predict anxiety and depression among individuals who suffered from long-COVID.

RESULTS: Approximately 51.8% of those surveyed tested positive for COVID-19 and of these 27.3% reported suffering from long-COVID. Individuals with long-COVID were twice as likely to experience anxiety and depression relative to those with mild/asymptomatic COVID-19. Our analysis at the sub-group level revealed that younger adults and females were disproportionately affected, reporting higher rates of anxiety and depression in both the COVID-19 and long-COVID groups. Additionally, individuals with lower income and educational attainment were more likely to experience mental health challenges. Relative to the reference group (Asians), Whites, Blacks, and Hispanics exhibited significantly higher odds of anxiety and depression in both groups. Notably, long-COVID was linked to a higher incidence of depression among males, which is consistent with previous research.

CONCLUSION: This study fills a significant gap in the literature regarding the mental health effects of long-COVID. The findings from this study provide strong evidence of the link between long-COVID and anxiety and depression, utilizing a large nationally representative sample, and employing rigorous analysis with control groups.},
}

@article {pmid39990545,
year = {2025},
author = {Song, Y and Mehl, F and Muehling, LM and Canderan, G and Enfield, K and Sun, J and Yin, MT and Ratcliffe, SJ and Wilson, JM and Kadl, A and Woodfolk, JA and Zeichner, SL},
title = {ACE-2-like Enzymatic Activity in COVID-19 Convalescents with Persistent Pulmonary Symptoms Associated with Immunoglobulin.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.02.12.25322167},
pmid = {39990545},
support = {R01 AI176515/AI/NIAID NIH HHS/United States ; R21 AI138077/AI/NIAID NIH HHS/United States ; R21 AI160334/AI/NIAID NIH HHS/United States ; R56 AI178669/AI/NIAID NIH HHS/United States ; },
abstract = {Many difficult to understand clinical features characterize COVID-19 and Post-Acute Sequelae of COVID-19 (PASC or Long COVID, LC). These can include blood pressure instability, hyperinflammation, coagulopathies, and neuropsychiatric complaints. The pathogenesis of these features remains unclear. The SARS-CoV-2 Spike protein Receptor Binding Domain (RBD) binds Angiotensin Converting Enzyme 2 (ACE2) on the surface of host cells to initiate infection. We hypothesized that some people convalescing from COVID-19 may produce anti-RBD antibodies that resemble ACE2 sufficiently to have ACE2-like catalytic activity, that is they are ACE2-like proteolytic abzymes that may help mediate the pathogenesis of COVID-19 and LC. In previous work, we showed that some people with acute COVID-19 had immunoglobulin-associated ACE2-like proteolytic activity, suggesting that some people with COVID-19 indeed produced ACE2-like abzymes. However, it remained unknown whether ACE2-like abzymes were seen only in acute COVID-19 or whether ACE2-like abzymes could also be identified in people convalescing from COVID-19. Here we show that some people convalescing from COVID-19 attending a clinic for people with persistent pulmonary symptoms also have ACE2-like abzymes and that the presence of ACE2-like catalytic activity correlates with alterations in blood pressure in an exercise test.},
}

@article {pmid39921694,
year = {2025},
author = {Hattori, F and Nishiyama, J and Hasuo, H},
title = {Correlation of interferons and autoimmune aspects in long COVID-19 patients.},
journal = {International immunology},
volume = {37},
number = {6},
pages = {355-363},
pmid = {39921694},
issn = {1460-2377},
support = {COVID-19- K027083//Kawano Masanori Memorial Public Interest Incorporated Foundation/ ; },
mesh = {Humans ; *COVID-19/immunology/blood ; *Interferons/blood/immunology ; *SARS-CoV-2/immunology ; Female ; Male ; Middle Aged ; Adult ; *Autoimmunity ; Antibodies, Antinuclear/blood/immunology ; Aged ; Post-Acute COVID-19 Syndrome ; Lupus Erythematosus, Systemic/immunology ; Autoantibodies/blood/immunology ; },
abstract = {Long COVID, or post-acute sequelae of COVID-19 (PASC), represents a major global health challenge, with its underlying mechanisms remaining poorly understood despite substantial research and clinical trials. This study investigates the role of the interferon (IFN) axis in the pathogenesis of PASC, drawing parallels to systemic lupus erythematosus (SLE). The potential pathogenic role of IFNs was detected by meta-analyses of mRNA sequencing data comparing PASC patients to healthy controls. We analyzed serum samples from 39 PASC patients and found significant correlations among multiple IFN sub types, including IFN alpha-2, beta, gamma, lambda-1, and lambda-2/3. The biological activity of IFNs in the serum was positively correlated with levels of both total and type III IFNs. Notably, we detected the widespread presence of anti-double-stranded DNA (anti-dsDNA) and anti-Smith (anti-Sm) antibodies in these patients, with anti-dsDNA levels showing a strong correlation with IFN activity. On the basis of these findings, we propose a hypothetical autoimmune pathogenesis for PASC highlighting the crucial role of IFN signaling.},
}

Humans
*COVID-19/immunology/blood
*Interferons/blood/immunology
*SARS-CoV-2/immunology
Female
Male
Middle Aged
Adult
*Autoimmunity
Antibodies, Antinuclear/blood/immunology
Aged
Post-Acute COVID-19 Syndrome
Lupus Erythematosus, Systemic/immunology
Autoantibodies/blood/immunology

@article {pmid39920063,
year = {2025},
author = {Zeraatkar, D and Ling, M and Kirsh, S and Jassal, T and Pitre, T and Chakraborty, S and Turner, T and Turkstra, L and McIntyre, RS and Izcovich, A and Mbuagbaw, L and Agoritsas, T and Flottorp, SA and Garner, P and Couban, RJ and Busse, JW},
title = {Interventions for the management of post-COVID-19 condition (long COVID): protocol for a living systematic review and network meta-analysis.},
journal = {BMJ open},
volume = {15},
number = {2},
pages = {e086407},
pmid = {39920063},
issn = {2044-6055},
mesh = {Humans ; *COVID-19/complications/therapy ; Systematic Reviews as Topic ; Network Meta-Analysis as Topic ; SARS-CoV-2 ; Fatigue/therapy/etiology ; Research Design ; Post-Acute COVID-19 Syndrome ; Myalgia/therapy/etiology ; Cognitive Dysfunction/therapy/etiology ; },
abstract = {BACKGROUND: Up to 15% of survivors of COVID-19 infection experience long-term health effects, including fatigue, myalgia and impaired cognitive function, termed post-COVID-19 condition or long COVID. Several trials that study the benefits and harms of various interventions to manage long COVID have been published and hundreds more are planned or are ongoing. Trustworthy systematic reviews that clarify the benefits and harms of interventions are critical to promote evidence-based practice.

OBJECTIVE: To create and maintain a living systematic review and network meta-analysis addressing the benefits and harms of pharmacologic and non-pharmacologic interventions for the treatment and management of long COVID.

METHODS: Eligible trials will randomise adults with long COVID to pharmacologic or non-pharmacologic interventions, placebo, sham or usual care. We will identify eligible studies by searching MEDLINE, EMBASE, CINAHL, PsycINFO, AMED and CENTRAL from inception, without language restrictions.Reviewers will work independently and in duplicate to screen search records, collect data from eligible trials, including trial and patient characteristics and outcomes of interest and assess risk of bias. Our outcomes of interest will include patient-reported fatigue, pain, postexertional malaise, changes in education or employment status, cognitive function, mental health, dyspnoea, quality of life, physical function, recovery and serious adverse events.For each outcome, when possible, we will perform a frequentist random-effects network meta-analysis. When there are compelling reasons to suspect that certain interventions are only applicable or effective for a subtype of long COVID, we will perform separate network meta-analyses. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach will guide our assessment of the certainty of evidence.We will update our living review biannually, on the publication of a seminal trial, or when new evidence emerges that may change clinical practice.

CONCLUSION: This living systematic review and network meta-analysis will provide comprehensive, trustworthy and up-to-date summaries of the evidence addressing the benefits and harms of interventions for the treatment and management of long COVID. We will make our findings available publicly and work with guideline-producing organisations to inform their recommendations.

ETHICS AND DISSEMINATION: The study describes the protocol for a systematic review that uses data from published trial reports. Therefore, the study is exempt from ethics review. We intend to deposit all data in a public repository and publish each iteration of the living review online.},
}

Humans
*COVID-19/complications/therapy
Systematic Reviews as Topic
Network Meta-Analysis as Topic
SARS-CoV-2
Fatigue/therapy/etiology
Research Design
Post-Acute COVID-19 Syndrome
Myalgia/therapy/etiology
Cognitive Dysfunction/therapy/etiology

@article {pmid39910549,
year = {2025},
author = {Yang, XJ and Zhang, LB and Wang, LL and Deng, H and Li, YL and Zhao, RJ and Xu, JY and Yang, YC and Zhou, SJ},
title = {Status and risk factors for depression, anxiety, and insomnia symptoms among adolescents in the post-pandemic era.},
journal = {BMC public health},
volume = {25},
number = {1},
pages = {471},
pmid = {39910549},
issn = {1471-2458},
mesh = {Humans ; Adolescent ; Female ; *Sleep Initiation and Maintenance Disorders/epidemiology ; Male ; Risk Factors ; *Anxiety/epidemiology ; *Depression/epidemiology ; China/epidemiology ; *COVID-19/epidemiology/psychology ; Surveys and Questionnaires ; Prevalence ; Pandemics ; },
abstract = {BACKGROUND: Owing to their vulnerability to public health crises, adolescents' mental health status, and related risk factors in the post-pandemic era in China require examination. This study aimed to lay a foundation for subsequent interventions and mental disorder prevention among adolescents.

METHODS: An anonymous online survey was conducted January 8-18, 2023. The survey comprised two parts. The first part collected personal information. The second part included the nine-item Patient Health Questionnaire, seven-item Generalized Anxiety Disorder Scale, and Pittsburgh Sleep Quality Index.

RESULTS: Of 50,666 adolescent participants, 46.8% displayed depressive symptoms, 31.5% showed anxiety symptoms, and 47.9% experienced difficulties initiating sleep within 30 min, while 4.9% manifested depressive, anxiety, and insomnia symptoms simultaneously. Chi-square tests revealed significant variations in the prevalence of these conditions according to age, sex, coronavirus disease-2019 (COVID-19) infection status, family infection status, and increased screen time (P < 0.001). Logistic regression analysis indicated heightened rates of depression, anxiety, and insomnia symptoms among rural adolescents, females, those aged 16-18 years, individuals with a history of COVID-19, those with a long COVID-19 illness, and those with increased screen time (all P < 0.001).

CONCLUSION: The mental health status of adolescents in the post-pandemic era should be taken seriously, particularly that of females, high school students, and adolescents with increased use of electronic screens. Among such efforts, school administrators should strengthen their connection with psychologists, as early identification and intervention in adolescents are important for preventing school crises.},
}

Humans
Adolescent
Female
*Sleep Initiation and Maintenance Disorders/epidemiology
Male
Risk Factors
*Anxiety/epidemiology
*Depression/epidemiology
China/epidemiology
*COVID-19/epidemiology/psychology
Surveys and Questionnaires
Prevalence
Pandemics

@article {pmid39868023,
year = {2024},
author = {Schäfer, LN and Rief, W},
title = {The influence of expectations on shame, rumination and cognitive flexibility: an experimental investigation on affect-regulatory characteristics of deceptive placebos.},
journal = {Frontiers in psychology},
volume = {15},
number = {},
pages = {1502460},
pmid = {39868023},
issn = {1664-1078},
abstract = {BACKGROUND: Several studies identified affect-regulatory qualities of deceptive placebos within negative and positive affect. However, which specific characteristics of an affect-regulatory framing impacts the placebo effect has not yet been subject to empirical investigations. In particular, it is unclear whether placebo- induced expectations of direct emotion inhibition or emotion regulation after emotion induction elicit stronger effects in affect regulation.

PURPOSE: The aim of the study was to identify whether specifically framed expectations on the occurrence (antecedent-focused) vs. regulation capability (response-modulating) of affect, induced with an active placebo nasal-spray, have effects on affect-regulatory processes. Because personality traits have been suspected to influence placebo responses and affect regulation, an additional goal of the study was to examine modulating influences of shame proneness, level of depression, experiential avoidance, and emotional control.

METHODS: Healthy volunteers (n = 121) were randomized to either a deceptive placebo condition (antecedent-focused vs. response-modulating instruction) or a no-treatment control group before shame was experimentally induced via autobiographical recall. Groups were compared on outcomes of state shame, rumination, and cognitive flexibility.

RESULTS: Both antecedent-focused and response-modulating placebo framings influenced changes in state shame (b = 3.08, 95% CI = [0.80-5.92], p = 0.044), rumination (b = 4.80, 95% CI = [1.50-8.09], p ≤ 0.001) and cognitive flexibility outcomes (b = -3.63, 95% CI = [-6.75 - -0.51], p = 0.011) after shame-induction interventions. Only the antecedent-focused placebo response was modulated by personality traits. Experiential avoidance modulated shame experience (F(2,115) = 3.470, p = 0.031) whereas emotional control influenced the reports of state rumination (F(2,115) = 4.588, p = 0.012). No modulatory influences of levels of depression and shame proneness could be observed (ps > 0.05).

CONCLUSION: The results suggest that shame, rumination and cognitive flexibility can be positively influenced by placebo treatment in healthy subjects. Personality traits of emotional control and experiential avoidance influenced the placebo response of the antecedent-focused treatment rationale on outcomes individually.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT05372744.},
}

@article {pmid39849114,
year = {2025},
author = {Buonsenso, D and Cotugno, N and Amodio, D and Pascucci, GR and Di Sante, G and Pighi, C and Morrocchi, E and Pucci, A and Olivieri, G and Colantoni, N and Romani, L and Rotili, A and Neri, A and Morello, R and Sali, M and Tremoulet, A and Raffaelli, F and Zampino, G and Rossi, P and Valentini, P and Palma, P},
title = {Distinct pro-inflammatory/pro-angiogenetic signatures distinguish children with Long COVID from controls.},
journal = {Pediatric research},
volume = {},
number = {},
pages = {},
pmid = {39849114},
issn = {1530-0447},
abstract = {BACKGROUND: Recent proteomic studies have documented that Long COVID in adults is characterized by a pro-inflammatory signature with thromboinflammation. However, if similar events happen also in children with Long COVID has never been investigated.

METHODS: We performed an extensive protein analysis of blood plasma from pediatric patients younger than 19 years of age Long COVID and a control group of children with acute COVID-19, MIS-C, and healthy controls resulted similar for sex distribution and age. Children were classified as Long COVID if symptoms persisted for at least 8 weeks since the initial infection, negatively impacted daily life and could not be explained otherwise.

RESULTS: 112 children were included in the study, including 34 children fulfilling clinical criteria of Long COVID, 32 acute SARS-CoV-2 infection, 27 MIS-C and 19 healthy controls. Compared with controls, pediatric Long COVID was characterized by higher expression of the proinflammatory and pro-angiogenetic set of chemokines CXCL11, CXCL1, CXCL5, CXCL6, CXCL8, TNFSF11, OSM, STAMBP1a. A Machine Learning model based on proteomic profile was able to identify LC with an accuracy of 0.93, specificity of 0.86 and sensitivity of 0.97.

CONCLUSIONS: Pediatric Long COVID patients have a well distinct blood protein signature marked by increased ongoing general and endothelial inflammation, similarly as happens in adults.

IMPACT: Pediatric Long COVID has a distinct blood protein signature marked by increased ongoing general and endothelial inflammation. This is the first study studying and documenting proinflammatory profile in blood samples of children with long COVID. Long COVID was characterized by higher expression of the proinflammatory and pro-angiogenetic set of chemokines CXCL11, CXCL1, CXCL5, CXCL6, CXCL8, TNFSF11, OSM, STAMBP1a. A proteomic profile was able to identify Long COVID with an accuracy of 0.93, specificity of 0.86 and sensitivity of 0.97. These findings may inform development of future diagnostic tests.},
}

@article {pmid39843379,
year = {2025},
author = {Wu, S and Luo, Z and Liu, H and Zhu, J and Zhu, Y and Hou, D and Wei, T and Liu, T and Zheng, C and Zhu, Z and Huang, W and Bai, W and Yu, X and Yuan, H and Bao, W and Zhang, M and Niu, X},
title = {Multicentre, multitime, multidimension, prospective follow-up cohort study on patients during the first wave of COVID-19 in China: a study protocol.},
journal = {BMJ open},
volume = {15},
number = {1},
pages = {e083023},
pmid = {39843379},
issn = {2044-6055},
mesh = {Adult ; Female ; Humans ; Male ; China/epidemiology ; *COVID-19/epidemiology/complications ; Follow-Up Studies ; Magnetic Resonance Imaging ; Multicenter Studies as Topic ; Neuroimaging ; Post-Acute COVID-19 Syndrome ; Prospective Studies ; SARS-CoV-2 ; },
abstract = {INTRODUCTION: During the first wave of the COVID-19 outbreak in China, the surge of COVID-19 cases was rapid and drastic. Emerging evidence suggests that beyond the acute phase, patients with COVID-19 may experience a wide range of postacute or long COVID sequelae. However, the mechanism and burden of COVID-19, especially long COVID, have not yet been comprehensively clarified. To fill this knowledge gap, this large prospective follow-up study aims to investigate the short-term and long-term effects of COVID-19, explore the underlying biological mechanism and identify predictive neuroimaging and haematological biomarkers associated with these effects.

METHODS AND ANALYSIS: This multicentre study will recruit patients infected during the first wave of COVID-19 in China and healthy controls (HCs) with no history of COVID-19 infection from nine participating hospitals. Confirmed patients with mild or moderate COVID-19 will complete the following programmes during the acute infection phase and at 3, 12 and 24 months after infection: (a) blood test at the local laboratory, (b) multimodal brain and spine MRI scan and (c) the neuropsychological scales and questionnaires. Similarly, the uninfected HCs will complete the same programmes as the infected group mentioned above at the time of inclusion. At the first time point, 501 participants (418 patients and 83 HCs) from nine recruiting hospitals have been observed. Ultimately, all of these results will be analysed to explore the short-term and long-term effects of COVID-19.

ETHICS AND DISSEMINATION: Ethics approval was granted by Ethics Committee of the First Affiliated Hospital of Xi'an Jiaotong University (XJTU1AF2023LSK-013). Findings will be presented at national and international conferences, as well as published in peer-reviewed scientific journals.

TRIAL REGISTRATION NUMBER: NCT05745805.},
}

Adult
Female
Humans
Male
China/epidemiology
*COVID-19/epidemiology/complications
Follow-Up Studies
Magnetic Resonance Imaging
Multicenter Studies as Topic
Neuroimaging
Post-Acute COVID-19 Syndrome
Prospective Studies
SARS-CoV-2

@article {pmid39820838,
year = {2025},
author = {Boscolo-Rizzo, P and Zandonella Callegher, R and Cancellieri, E and Pellegrini, L and Tirelli, G and Albert, U},
title = {Association between psychophysically measured olfactory dysfunction and mental health status in long COVID patients.},
journal = {Rhinology},
volume = {63},
number = {2},
pages = {221-229},
doi = {10.4193/Rhin24.295},
pmid = {39820838},
issn = {0300-0729},
mesh = {Humans ; *COVID-19/complications/psychology ; Male ; Female ; Cross-Sectional Studies ; Middle Aged ; Quality of Life ; *Olfaction Disorders/psychology/etiology ; Adult ; *Mental Health ; Anxiety/psychology/etiology ; Depression/psychology ; SARS-CoV-2 ; Aged ; },
abstract = {BACKGROUND: Long COVID frequently presents with persistent olfactory dysfunction (OD), affecting both physical and psychological well-being. This study aims to evaluate the mental health consequences of OD in long COVID patients.

METHODOLOGY: A cross-sectional study involved 86 adult patients. Participants presented OD for at least three months post-COVID- 19 and were evaluated using the extended battery of Sniffin' Sticks test (SST). Psychological assessments included the Impact of Event Scale-Revised (IES-R), Beck Hopelessness Scale (BHS), Depression, Anxiety, and Stress Scale-21 (DASS-21), and Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q).

RESULTS: Significant differences in mental health factors were observed between patients with and without OD: in comparison to normosmic patients, hyposmic patients showed higher IES-R Total, Avoidance, and Hyperarousal scores, along with increased DASS-21 Anxiety scores and BHS total scores.

CONCLUSIONS: OD in long COVID patients were significantly associated with increased post-traumatic stress symptoms, anxiety symptoms and hopelessness, and with lower quality of life. Limited sample size, inability to determine causation and exploratory nature of the study may limit the generalizability of results. Comprehensive management addressing both physical and mental health should be assessed in long COVID patients.},
}

Humans
*COVID-19/complications/psychology
Male
Female
Cross-Sectional Studies
Middle Aged
Quality of Life
*Olfaction Disorders/psychology/etiology
Adult
*Mental Health
Anxiety/psychology/etiology
Depression/psychology
SARS-CoV-2
Aged

@article {pmid39763550,
year = {2024},
author = {Worden, L and Wannier, R and Archer, H and Blumberg, S and Kwan, A and Sears, D and Porco, TC},
title = {COVID-19 Reproduction Numbers and Long COVID Prevalences in California State Prisons.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {39763550},
support = {K12 EY031372/EY/NEI NIH HHS/United States ; R01 GM130900/GM/NIGMS NIH HHS/United States ; T32 HL007185/HL/NHLBI NIH HHS/United States ; U01 CK000590/CK/NCEZID CDC HHS/United States ; },
abstract = {Prisons have been hotspots for COVID-19 and likely an important driver of racial disparity in disease burden. From the first COVID-19 case detected through March 25, 2022, 66,684 of 196,652 residents of California's state prison system were infected, most of them in two large winter waves of outbreaks that reached all 35 of the state prisons. We used individual-level data on disease timing and nightly room assignments in these prisons to reconstruct locations and pathways of transmission statistically, and from that estimated reproduction numbers, locations of unobserved infection events, and the subsequent magnitude and distribution of long COVID prevalence. Where earlier work has recommended smaller cells over large dormitory housing to reduce transmission, recommended use of cells with solid doors over those with bars only, and cautioned against reliance on solid doors (e.g., in cold months when HVAC systems can circulate aerosols), we found evidence of substantial transmission in both dorms and cells regardless of the door and season. Effective reproduction numbers were found to range largely between 0 and 5, in both cells and dorms of all door types. Our estimates of excess case rates suggest that as a result of disparities in incarceration, prison outbreaks contributed to disproportionate disease burden on Black and Indigenous people in California. We estimated that 9,100-11,000 people have developed long COVID as a result of infection in these prison outbreaks, 1,700-2,000 of them with disabling consequences, and that this burden is disproportionately on Black and Indigenous people in comparison to the state as a whole. We urge high-quality medical care for prison residents affected by long COVID, and decarceration to reduce the risk of future outbreaks of both COVID-19 and other diseases.},
}

@article {pmid39673203,
year = {2025},
author = {Grant, A and Adams, NN and MacIver, E and Skåtun, D and Scott, N and Kennedy, C and Douglas, F and Hernandez-Santiago, V and Torrance, N},
title = {Long COVID in healthcare workers: longitudinal mixed-methods study.},
journal = {Occupational medicine (Oxford, England)},
volume = {75},
number = {3},
pages = {171-178},
pmid = {39673203},
issn = {1471-8405},
support = {//Chief Scientist Office of the Scottish Government Health Directorates/ ; },
mesh = {Humans ; *COVID-19/epidemiology/psychology ; Longitudinal Studies ; *Health Personnel/psychology/statistics & numerical data ; Male ; Female ; Adult ; Middle Aged ; Quality of Life ; Surveys and Questionnaires ; SARS-CoV-2 ; Sick Leave/statistics & numerical data ; Qualitative Research ; },
abstract = {BACKGROUND: Healthcare workers (HCWs) report higher rates of long coronavirus disease (COVID) (LC) than other occupational groups. It is still unclear whether LC is a lifelong condition. Workforce shortfalls are apparent due to sick leave, reduced hours and lower productivity.

AIMS: To investigate the lived experience of LC on a range of HCWs, including impact on health-related quality-of-life (HRQL), use of health services, working and personal lives and household finances.

METHODS: Longitudinal mixed methods with online surveys and qualitative interviews 6-months apart. HCWs including healthcare professionals, ancillary and administration staff who self-report LC were recruited through social media and National Health Service channels. Interviewees were purposively sampled from survey responses.

RESULTS: The first survey was completed by 471 HCWs (S1) and 302 (64%) the follow-up (S2). A total of 50 HCWs were interviewed initially and 44 at second interview. All participants experienced various relapsing, remitting, changing and prolonged LC symptoms (mean 7.1 [SD 4.8] at S2) and a third reported day-to-day activities 'limited a lot'. Most participants were working in a reduced capacity: reduced hours, different role or location. Healthcare was limited, and often unsatisfactory. Participants feared reinfection, their future, ability to work and financial security (59% (n = 174) at S2). They experienced stigma, distress, grief for their former self and some felt unsupported, however, as awareness of LC grew some experienced improved understanding and support.

CONCLUSIONS: Most participants continued working, managing complex and dynamic symptoms effecting their everyday life and ability to work. Most did not report significant improvements over time and feared for their future and financial security.},
}

Humans
*COVID-19/epidemiology/psychology
Longitudinal Studies
*Health Personnel/psychology/statistics & numerical data
Male
Female
Adult
Middle Aged
Quality of Life
Surveys and Questionnaires
SARS-CoV-2
Sick Leave/statistics & numerical data
Qualitative Research

@article {pmid39641021,
year = {2024},
author = {Birtolo, LI and Di Pietro, G and Ciuffreda, A and Improta, R and Monosilio, S and Prosperi, S and Cimino, S and Galea, N and Severino, P and Galardo, G and Colaiacomo, MC and Pasculli, P and Petroianni, A and Palange, P and Mastroianni, CM and de Vito, L and Catalano, C and Pugliese, F and Ciardi, MR and Celli, P and Badagliacca, R and Fedele, F and Vizza, CD and Maestrini, V and Mancone, M and , },
title = {The impact of vaccination status on post-acute sequelae in hospitalized COVID-19 survivors using a multi-disciplinary approach: An observational single center study.},
journal = {Heliyon},
volume = {10},
number = {22},
pages = {e40409},
pmid = {39641021},
issn = {2405-8440},
abstract = {BACKGROUND: COVID-19 vaccines reduced mortality, hospitalizations and ICUs admissions. Conversely, the impact of vaccination on Long COVID-19 syndrome is still unclear. This study compared the prevalence of post-acute sequelae at short and long-term follow-up among hospitalized unvaccinated and vaccinated COVID-19 survivors through a multidisciplinary approach.

METHODS: After 2 months from discharge, unvaccinated and vaccinated COVID-19 survivors underwent a follow-up visit at a dedicated "post-COVID-19 Outpatient Clinic". The follow-up visit included a cardiovascular evaluation, blood tests, chest computed tomography, 6-min walking test (6MWT), spirometry. A one-year telephone follow-up was performed to assess re-hospitalizations, death and long-lasting symptoms. An additional 1:1 case-control matching analysis adjusted for baseline characteristics was performed.

RESULTS: Between June 2020 and June 2022, a total of 458 unvaccinated and vaccinated patients (229 per group) underwent the follow-up visit. Vaccinated patients had lower rates of ICU admissions (1.7 % vs 9.6 %, p= <0.001) and severe respiratory complications requiring intubation (1.3 % vs 7 %, p = 0.002) or non-invasive ventilation such as high-flow nasal oxygen therapy (1.7 % vs 7.9 %, p = 0.02), CPAP (1.3 % vs 20.1 %, p= < 0.001), and low-flow oxygen therapy (3.5 % vs 63.3 %, p= <0.001) compared to unvaccinated ones. At 2-month follow-up, vaccinated patients had fewer persistent ground-glass opacities (2.6 % vs 52.8 %, p= <0.001) or consolidations (0.9 % vs 8.3 %, p= <0.001). Additionally, unvaccinated patients experienced more frequent myocarditis (4.8 % vs 0.9 %, p = 0.013) and pulmonary embolism (1.8 % vs 0 %, p = 0.042) and exhibited more significant respiratory impairment as evidenced by desaturation during the 6MWT(10.2 % vs 3.5 %, p = 0.005) and altered spirometry (14 % vs 8.7 %, p = 0.043) compared to vaccinated ones. At one-year, unvaccinated patients reported more symptoms such as dyspnea (20.5 % vs 10 %, p = 0.002), psychological symptoms (10 % vs 3.5 %, p = 0.005) and chronic rhinosinusitis/cough (6,6 % vs 2,6 %, p = 0.04) as compared to vaccinated ones. The 1:1 case-control matching analysis also confirmed these results.

CONCLUSIONS: COVID-19 vaccines improve short-term outcomes and may reduce Long COVID-19 prevalence.},
}

@article {pmid39536121,
year = {2024},
author = {Peluso, MJ and Hanson, MR and Deeks, SG},
title = {Infection-associated chronic conditions: Why Long Covid is our best chance to untangle Osler's web.},
journal = {Science translational medicine},
volume = {16},
number = {773},
pages = {eado2101},
doi = {10.1126/scitranslmed.ado2101},
pmid = {39536121},
issn = {1946-6242},
support = {U54 AI178855/AI/NIAID NIH HHS/United States ; K23 AI157875/AI/NIAID NIH HHS/United States ; R01 AI141003/AI/NIAID NIH HHS/United States ; R01 AI158013/AI/NIAID NIH HHS/United States ; R01 NS136197/NS/NINDS NIH HHS/United States ; U54 AI178855/AI/NIAID NIH HHS/United States ; },
mesh = {Humans ; Chronic Disease ; *COVID-19/complications/virology/epidemiology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2/isolation & purification ; },
abstract = {The recognition of Long Covid has renewed efforts to understand other infection-associated chronic conditions (IACCs). Here, we describe how studies of Long Covid and other IACCs might inform one another. We argue for the importance of a coordinated research agenda addressing these debilitating illnesses.},
}

Humans
Chronic Disease
*COVID-19/complications/virology/epidemiology
Post-Acute COVID-19 Syndrome
SARS-CoV-2/isolation & purification

@article {pmid39271927,
year = {2024},
author = {Radin, JM and Vogel, JM and Delgado, F and Coughlin, E and Gadaleta, M and Pandit, JA and Steinhubl, SR},
title = {Long-term changes in wearable sensor data in people with and without Long Covid.},
journal = {NPJ digital medicine},
volume = {7},
number = {1},
pages = {246},
pmid = {39271927},
issn = {2398-6352},
support = {UL1TR002550//U.S. Department of Health & Human Services | NIH | National Center for Advancing Translational Sciences (NCATS)/ ; },
abstract = {To better understand the impact of Long COVID on an individual, we explored changes in daily wearable data (step count, resting heart rate (RHR), and sleep quantity) for up to one year in individuals relative to their pre-infection baseline among 279 people with and 274 without long COVID. Participants with Long COVID, defined as symptoms lasting for 30 days or longer, following a SARS-CoV-2 infection had significantly different RHR and activity trajectories than those who did not report Long COVID and were also more likely to be women, younger, unvaccinated, and report more acute-phase (first 2 weeks) symptoms than those without Long COVID. Demographic, vaccine, and acute-phase sensor data differences could be used for early identification of individuals most likely to develop Long COVID complications and track objective evidence of the therapeutic efficacy of any interventions.Trial Registration: https://classic.clinicaltrials.gov/ct2/show/NCT04336020 .},
}

@article {pmid39254484,
year = {2024},
author = {Pineros-Garcia, LN and Gonzalez-Sanchez, NI and Calvo-Henrique, C and Rojas-Lechuga, MJ and Hopkins, C and Mullol, J and Alobid, I},
title = {SNOT-22 in general population, a Spanish cohort study with an updated meta-analysis.},
journal = {Rhinology},
volume = {62},
number = {6},
pages = {700-709},
doi = {10.4193/Rhin24.233},
pmid = {39254484},
issn = {0300-0729},
mesh = {Humans ; *COVID-19/complications ; *Olfaction Disorders/physiopathology ; Female ; Prospective Studies ; Male ; Middle Aged ; *SARS-CoV-2 ; Spain ; Adult ; Aged ; Smell/physiology ; Cohort Studies ; },
abstract = {BACKGROUND: Olfactory loss (OL) has emerged as one of the most prevalent and debilitating symptoms of SARS-CoV-2 infection and long-COVID-19. The present prospective observational study aimed to evaluate the efficacy of olfactory training (OT) on orthonasal and retronasal olfactory function in a cohort of individuals with persistent post-COVID-19 OL.

METHODOLOGY: Participants with post-COVID-19 olfactory impairment underwent 4 months of OT, self-assessing their smell perception and undergoing comprehensive psychophysical evaluation of orthonasal and retronasal olfaction at baseline and after training. Orthonasal olfactory function was assessed using the extended Sniffin' Sticks test battery. Retronasal olfactory function was tested with powdered aromas.

RESULTS: Among 114 participants with post-COVID-19 olfactory loss, adherence to OT was 60%. In adherents, the average increase in composite TDI score was 6.0 points compared to 2.6 points in non-adherents. Fifty-seven percent of adherent participants achieved a clinically significant improvement in TDI score (≥ 5.5 points), compared to 22% of non-adherents. In retronasal olfactory identification, 56% of adherents achieved a clinically significant improvement (≥4 points), compared to 16% of non-adherents.

CONCLUSION: Adherence to a 4-month OT regimen can yield clinically meaningful improvements in both orthonasal and retronasal olfactory function among individuals with persistent post-COVID-19 olfactory dysfunction.},
}

Humans
*COVID-19/complications
*Olfaction Disorders/physiopathology
Female
Prospective Studies
Male
Middle Aged
*SARS-CoV-2
Spain
Adult
Aged
Smell/physiology
Cohort Studies

@article {pmid39158581,
year = {2024},
author = {Boscolo-Rizzo, P and Hummel, T and Menini, A and Maniaci, A and Uderzo, F and Bigolin, L and Tirelli, G},
title = {Adherence to olfactory training improves orthonasal and retronasal olfaction in post-COVID-19 olfactory loss.},
journal = {Rhinology},
volume = {62},
number = {6},
pages = {681-688},
doi = {10.4193/Rhin24.233},
pmid = {39158581},
issn = {0300-0729},
mesh = {Humans ; *COVID-19/complications/physiopathology ; Male ; Female ; *Olfaction Disorders/rehabilitation/physiopathology/etiology/virology ; Prospective Studies ; Middle Aged ; Smell/physiology ; SARS-CoV-2 ; Aged ; Adult ; Patient Compliance ; Olfactory Training ; },
abstract = {BACKGROUND: Olfactory loss (OL) has emerged as one of the most prevalent and debilitating symptoms of SARS-CoV-2 infection and long-COVID-19. The present prospective observational study aimed to evaluate the efficacy of olfactory training (OT) on orthonasal and retronasal olfactory function in a cohort of individuals with persistent post-COVID-19 OL.

METHODOLOGY: Participants with post-COVID-19 olfactory impairment underwent 4 months of OT, self-assessing their smell perception and undergoing comprehensive psychophysical evaluation of orthonasal and retronasal olfaction at baseline and after training. Orthonasal olfactory function was assessed using the extended Sniffin' Sticks test battery. Retronasal olfactory function was tested with powdered aromas.

RESULTS: Among 114 participants with post-COVID-19 olfactory loss, adherence to OT was 60%. In adherents, the average increase in composite TDI score was 6.0 points compared to 2.6 points in non-adherents. Fifty-seven percent of adherent participants achieved a clinically significant improvement in TDI score (≥ 5.5 points), compared to 22% of non-adherents. In retronasal olfactoryidentification, 56% of adherents achieved a clinically significant improvement (≥ 4 points), compared to 16% of non-adherents.

CONCLUSION: Adherence to a 4-month OT regimen can yield clinically meaningful improvements in both orthonasal and retronasal olfactory function among individuals with persistent post-COVID-19 olfactory dysfunction.},
}

Humans
*COVID-19/complications/physiopathology
Male
Female
*Olfaction Disorders/rehabilitation/physiopathology/etiology/virology
Prospective Studies
Middle Aged
Smell/physiology
SARS-CoV-2
Aged
Adult
Patient Compliance
Olfactory Training

@article {pmid39150750,
year = {2024},
author = {El-Toukhy, S and Hegeman, P and Zuckerman, G and Das, AR and Moses, N and Troendle, J and Powell-Wiley, TM},
title = {Study of Postacute Sequelae of COVID-19 Using Digital Wearables: Protocol for a Prospective Longitudinal Observational Study.},
journal = {JMIR research protocols},
volume = {13},
number = {},
pages = {e57382},
pmid = {39150750},
issn = {1929-0748},
support = {ZIA MD000011/ImNIH/Intramural NIH HHS/United States ; },
mesh = {Humans ; *COVID-19/diagnosis/epidemiology ; Prospective Studies ; Longitudinal Studies ; Adult ; Male ; Middle Aged ; Female ; *Wearable Electronic Devices ; Aged ; Young Adult ; Post-Acute COVID-19 Syndrome ; Adolescent ; },
abstract = {BACKGROUND: Postacute sequelae of COVID-19 (PASC) remain understudied in nonhospitalized patients. Digital wearables allow for a continuous collection of physiological parameters such as respiratory rate and oxygen saturation that have been predictive of disease trajectories in hospitalized patients.

OBJECTIVE: This protocol outlines the design and procedures of a prospective, longitudinal, observational study of PASC that aims to identify wearables-collected physiological parameters that are associated with PASC in patients with a positive diagnosis.

METHODS: This is a single-arm, prospective, observational study of a cohort of 550 patients, aged 18 to 65 years, male or female, who own a smartphone or a tablet that meets predetermined Bluetooth version and operating system requirements, speak English, and provide documentation of a positive COVID-19 test issued by a health care professional within 5 days before enrollment. The primary end point is long COVID-19, defined as ≥1 symptom at 3 weeks beyond the first symptom onset or positive diagnosis, whichever comes first. The secondary end point is chronic COVID-19, defined as ≥1 symptom at 12 weeks beyond the first symptom onset or positive diagnosis. Participants must be willing and able to consent to participate in the study and adhere to study procedures for 6 months.

RESULTS: The first patient was enrolled in October 2021. The estimated year for publishing the study results is 2025.

CONCLUSIONS: This is a fully decentralized study investigating PASC using wearable devices to collect physiological parameters and patient-reported outcomes. The study will shed light on the duration and symptom manifestation of PASC in nonhospitalized patient subgroups and is an exemplar of the use of wearables as population-level monitoring health tools for communicable diseases.

TRIAL REGISTRATION: ClinicalTrials.gov NCT04927442; https://clinicaltrials.gov/study/NCT04927442.

DERR1-10.2196/57382.},
}

Humans
*COVID-19/diagnosis/epidemiology
Prospective Studies
Longitudinal Studies
Adult
Male
Middle Aged
Female
*Wearable Electronic Devices
Aged
Young Adult
Post-Acute COVID-19 Syndrome
Adolescent

@article {pmid39083202,
year = {2024},
author = {Huang, Y and Wang, W and Liu, Y and Wang, Z and Cao, B},
title = {COVID-19 vaccine updates for people under different conditions.},
journal = {Science China. Life sciences},
volume = {67},
number = {11},
pages = {2323-2343},
pmid = {39083202},
issn = {1869-1889},
mesh = {Humans ; *COVID-19 Vaccines/immunology/administration & dosage ; *COVID-19/prevention & control/immunology/epidemiology ; *SARS-CoV-2/immunology ; Vaccine Efficacy ; Immunocompromised Host/immunology ; },
abstract = {SARS-CoV-2 has caused global waves of infection since December 2019 and continues to persist today. The emergence of SARS-CoV-2 variants with strong immune evasion capabilities has compromised the effectiveness of existing vaccines against breakthrough infections. Therefore, it is important to determine the best utilization strategies for different demographic groups given the variety of vaccine options available. In this review, we will discuss the protective efficacy of vaccines during different stages of the epidemic and emphasize the importance of timely updates to target prevalent variants, which can significantly improve immune protection. While it is recognized that vaccine effectiveness may be lower in certain populations such as the elderly, individuals with chronic comorbidities (e.g., diabetes with poor blood glucose control, those on maintenance dialysis), or those who are immunocompromised compared to the general population, administering multiple doses can result in a strong protective immune response that outweighs potential risks. However, caution should be exercised when considering vaccines that might trigger an intense immune response in populations prone to inflammatory flare or other complications. In conclusion, individuals with special conditions require enhanced and more effective immunization strategies to prevent infection or reinfection, as well as to avoid the potential development of long COVID.},
}

Humans
*COVID-19 Vaccines/immunology/administration & dosage
*COVID-19/prevention & control/immunology/epidemiology
*SARS-CoV-2/immunology
Vaccine Efficacy
Immunocompromised Host/immunology

@article {pmid39029889,
year = {2024},
author = {Beugelink, JW and Hóf, H and Janssen, BJC},
title = {CRTAC1 has a Compact β-propeller-TTR Core Stabilized by Potassium Ions.},
journal = {Journal of molecular biology},
volume = {436},
number = {18},
pages = {168712},
doi = {10.1016/j.jmb.2024.168712},
pmid = {39029889},
issn = {1089-8638},
mesh = {Humans ; Calcium/metabolism/chemistry ; *Calcium-Binding Proteins/chemistry/metabolism/genetics ; Crystallography, X-Ray ; Ions/metabolism/chemistry ; Models, Molecular ; *Potassium/metabolism/chemistry ; Protein Conformation ; },
abstract = {Cartilage acidic protein-1 (CRTAC1) is a secreted glycoprotein with roles in development, function and repair of the nervous system. It is linked to ischemic stroke, osteoarthritis and (long) COVID outcomes, and has suppressive activity in carcinoma and bladder cancer. Structural characterization of CRTAC1 has been complicated by its tendency to form disulfide-linked aggregates. Here, we show that CRTAC1 is stabilized by potassium ions. Using x-ray crystallography, we determined the structure of CRTAC1 to 1.6 Å. This reveals that the protein consists of a three-domain fold, including a previously-unreported compact β-propeller-TTR combination, in which an extended loop of the TTR plugs the β-propeller core. Electron density is observed for ten bound ions: six calcium, three potassium and one sodium. Low potassium ion concentrations lead to changes in tryptophan environment and exposure of two buried free cysteines located on a β-blade and in the β-propeller-plugging TTR loop. Mutating the two free cysteines to serines prevents covalent intermolecular interactions, but not aggregation, in absence of potassium ions. The potassium ion binding sites are located between the blades of the β-propeller, explaining their importance for the stability of the CRTAC1 fold. Despite varying in sequence, the three potassium ion binding sites are structurally similar and conserved features of the CRTAC protein family. These insights into the stability and structure of CRTAC1 provide a basis for further work into the function of CRTAC1 in health and disease.},
}

Humans
Calcium/metabolism/chemistry
*Calcium-Binding Proteins/chemistry/metabolism/genetics
Crystallography, X-Ray
Ions/metabolism/chemistry
Models, Molecular
*Potassium/metabolism/chemistry
Protein Conformation

@article {pmid38973985,
year = {2024},
author = {Dalmau, R and Alanazi, AM and Arora, M and Banerjee, A and Bianco, E and Gaalema, DE and Goma, FM and Hasegawa, K and Komiyama, M and Pérez Ríos, M and Willett, J and Wang, Y},
title = {A Complex Interplay: Navigating the Crossroads of Tobacco Use, Cardiovascular Disease, and the COVID-19 Pandemic: A WHF Policy Brief.},
journal = {Global heart},
volume = {19},
number = {1},
pages = {55},
pmid = {38973985},
issn = {2211-8179},
mesh = {Humans ; *COVID-19/epidemiology/prevention & control ; *Cardiovascular Diseases/epidemiology/prevention & control ; *Tobacco Use/epidemiology ; *SARS-CoV-2 ; Pandemics ; Risk Factors ; Health Policy ; },
abstract = {The Coronavirus Disease 2019, commonly referred to as COVID-19, is responsible for one of the deadliest pandemics in human history. The direct, indirect and lasting repercussions of the COVID-19 pandemic on individuals and public health, as well as health systems can still be observed, even today. In the midst of the initial chaos, the role of tobacco as a prognostic factor for unfavourable COVID-19 outcomes was largely neglected. As of 2023, numerous studies have confirmed that use of tobacco, a leading risk factor for cardiovascular and other diseases, is strongly associated with increased risks of severe COVID-19 complications (e.g., hospitalisation, ICU admission, need for mechanical ventilation, long COVID, etc.) and deaths from COVID-19. In addition, evidence suggests that COVID-19 directly affects multiple organs beyond the respiratory system, disproportionately impacting individuals with comorbidities. Notably, people living with cardiovascular disease are more prone to experiencing worse outcomes, as COVID-19 often inherently manifests as thrombotic cardiovascular complications. As such, the triad of tobacco, COVID-19 and cardiovascular disease constitutes a dangerous cocktail. The lockdowns and social distancing measures imposed by governments have also had adverse effects on our lifestyles (e.g., shifts in diets, physical activity, tobacco consumption patterns, etc.) and mental well-being, all of which affect cardiovascular health. In particular, vulnerable populations are especially susceptible to tobacco use, cardiovascular disease and the psychological fallout from the pandemic. Therefore, national pandemic responses need to consider health equity as well as the social determinants of health. The pandemic has also had catastrophic impacts on many health systems, bringing some to the brink of collapse. As a result, many health services, such as services for cardiovascular disease or tobacco cessation, were severely disrupted due to fears of transmission and redirection of resources for COVID-19 care. Unfortunately, the return to pre-pandemic levels of cardiovascular disease care activity has stagnated. Nevertheless, digital solutions, such as telemedicine and apps, have flourished, and may help reduce the gaps. Advancing tobacco control was especially challenging due to interference from the tobacco industry. The industry exploited lingering uncertainties to propagate misleading information on tobacco and COVID-19 in order to promote its products. Regrettably, the links between tobacco use and risk of SARS-CoV-2 infection remain inconclusive. However, a robust body of evidence has, since then, demonstrated that tobacco use is associated with more severe COVID-19 illness and complications. Additionally, the tobacco industry also repeatedly attempted to forge partnerships with governments under the guise of corporate social responsibility. The implementation of the WHO Framework Convention on Tobacco Control could address many of the aforementioned challenges and alleviate the burden of tobacco, COVID-19, and cardiovascular disease. In particular, the implementation of Article 5.3 could protect public health policies from the vested interests of the industry. The world can learn from the COVID-19 pandemic to better prepare for future health emergencies of international concern. In light of the impact of tobacco on the COVID-19 pandemic, it is imperative that tobacco control remains a central component in pandemic preparedness and response plans.},
}

Humans
*COVID-19/epidemiology/prevention & control
*Cardiovascular Diseases/epidemiology/prevention & control
*Tobacco Use/epidemiology
*SARS-CoV-2
Pandemics
Risk Factors
Health Policy

@article {pmid38927395,
year = {2024},
author = {Fernández-de-Las-Peñas, C},
title = {Special Issue "Latest Research in Post-COVID (Long COVID): Pathological and Treatment Studies of Sequelae and Complications".},
journal = {Biomedicines},
volume = {12},
number = {6},
pages = {},
pmid = {38927395},
issn = {2227-9059},
abstract = {The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pathogen provoked the most unprecedented sanitary outbreak of the current century by causing coronavirus disease 2019 (COVID-19), which has led to approximately 775 million confirmed cases and more than 7 million deaths globally [...].},
}

@article {pmid38843555,
year = {2024},
author = {Jeffreys, M and McKenzie, F and Irurzun Lopez, M and Russell, L and Ellison-Loschmann, L},
title = {Long COVID impacts people's ability to work: cross-sectional study in Aotearoa New Zealand.},
journal = {The New Zealand medical journal},
volume = {137},
number = {1596},
pages = {102-104},
doi = {10.26635/6965.6530},
pmid = {38843555},
issn = {1175-8716},
support = {//New Zealand Ministry of Health/ ; },
mesh = {Humans ; *COVID-19/epidemiology ; New Zealand/epidemiology ; Cross-Sectional Studies ; Male ; Female ; Adult ; Middle Aged ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Employment/statistics & numerical data ; },
}

Humans
*COVID-19/epidemiology
New Zealand/epidemiology
Cross-Sectional Studies
Male
Female
Adult
Middle Aged
SARS-CoV-2
Post-Acute COVID-19 Syndrome
Employment/statistics & numerical data

@article {pmid38816726,
year = {2024},
author = {Haslam, A and Prasad, V},
title = {Long COVID clinics and services offered by top US hospitals: an empirical analysis of clinical options as of May 2023.},
journal = {BMC health services research},
volume = {24},
number = {1},
pages = {684},
pmid = {38816726},
issn = {1472-6963},
mesh = {Humans ; *COVID-19/therapy/epidemiology ; United States ; Cross-Sectional Studies ; *SARS-CoV-2 ; Hospitals/statistics & numerical data ; Post-Acute COVID-19 Syndrome ; Referral and Consultation/statistics & numerical data ; },
abstract = {BACKGROUND: The economic and health burden of COVID-19 has transformed the healthcare system in the US. Hospitals have adapted to the heterogeneity in long COVID symptoms, and the sheer number of people affected by this condition, by building long COVID centers and programs.

OBJECTIVE: We sought to describe characteristics, services, and clinical trials of long COVID centers at top US hospitals.

DESIGN: Cross-sectional analysis.

PARTICIPANTS: Long COVID treatment programs or centers at top US hospitals.

EXPOSURES: Frequency of long COVID centers, eligibility for being treated, the services they provide, specialist to whom the patients may be referred, and the long COVID clinical trials in which these hospitals participate.

FINDINGS: Most top hospitals in the US (n = 43/50; 86%) offer long COVID services. 65% (28/43) did not describe the services provided. 12 (28%) required a referral from a primary care physician. The most common services were meeting with a team member (n = 20; 47%), ordering lab and/or radiology services (n = 8; 18.6%), and administering a physical exam (n = 7; 16%). 7 (16%) centers/programs treated only adults; 5 (12%) treated both adults and children, and 31 (72%) did not specify. The most common specialists described were psychology (n = 25; 58%), neurology (n = 25; 58%), and pulmonary (n = 24; 56%). Sixty-three trials (of 134 long COVID clinical trials) had at least one top hospital listed as a study site. The median number of clinical trials that each hospital sponsored or was a study site was 2 (interquartile range: 1, 3).

CONCLUSIONS AND RELEVANCE: We find that services offered at long COVID clinics at top hospitals in the US often include meeting with a team member and referrals to a wide range of specialists. The diversity in long COVID services offered parallels the diversity in long COVID symptoms, suggesting a need for better consensus in developing and delivering treatment.},
}

Humans
*COVID-19/therapy/epidemiology
United States
Cross-Sectional Studies
*SARS-CoV-2
Hospitals/statistics & numerical data
Post-Acute COVID-19 Syndrome
Referral and Consultation/statistics & numerical data

@article {pmid38802273,
year = {2024},
author = {Adam, R and Lotankar, Y and Sas, C and Powell, D and Martinez, V and Green, S and Cooper, J and Bradbury, K and Sive, J and Hill, DL},
title = {Understanding patterns of fatigue in health and disease: protocol for an ecological momentary assessment study using digital technologies.},
journal = {BMJ open},
volume = {14},
number = {5},
pages = {e081416},
pmid = {38802273},
issn = {2044-6055},
mesh = {Humans ; *Fatigue/etiology ; *COVID-19 ; *Ecological Momentary Assessment ; Heart Failure/physiopathology ; Digital Technology ; Multiple Myeloma/complications ; SARS-CoV-2 ; Self Report ; Research Design ; Wearable Electronic Devices ; },
abstract = {INTRODUCTION: Fatigue is prevalent across a wide range of medical conditions and can be debilitating and distressing. It is likely that fatigue is experienced differently according to the underlying aetiology, but this is poorly understood. Digital health technologies present a promising approach to give new insights into fatigue.The aim of this study is to use digital health technologies, real-time self-reports and qualitative interview data to investigate how fatigue is experienced over time in participants with myeloma, long COVID, heart failure and in controls without problematic fatigue. Objectives are to understand which sensed parameters add value to the characterisation of fatigue and to determine whether study processes are feasible, acceptable and scalable.

METHODS AND ANALYSIS: An ecological momentary assessment study will be carried out over 2 or 4 weeks (participant defined). Individuals with fatigue relating to myeloma (n=10), heart failure (n=10), long COVID (n=10) and controls without problematic fatigue or a study condition (n=10) will be recruited. ECG patches will measure heart rate variability, respiratory rate, body temperature, activity and posture. A wearable bracelet accompanied by environment beacons will measure physical activity, sleep and room location within the home. Self-reports of mental and physical fatigue will be collected via smartphone app four times daily and on-demand. Validated fatigue and affect questionnaires will be completed at baseline and at 2 weeks. End-of-study interviews will investigate experiences of fatigue and study participation. A feedback session will be offered to participants to discuss their data.Data will be analysed using multilevel modelling and machine learning. Interviews and feedback sessions will be analysed using content or thematic analyses.

ETHICS AND DISSEMINATION: This study was approved by the East of England-Cambridge East Research Ethics Committee (22/EE/0261). The results will be disseminated in peer-reviewed journals and at international conferences.

TRIAL REGISTRATION NUMBER: NCT05622669.},
}

Humans
*Fatigue/etiology
*COVID-19
*Ecological Momentary Assessment
Heart Failure/physiopathology
Digital Technology
Multiple Myeloma/complications
SARS-CoV-2
Self Report
Research Design
Wearable Electronic Devices

@article {pmid38748355,
year = {2024},
author = {Wang, J and Li, Y and Mu, Y and Huang, K and Li, D and Lan, C and Cui, Y and Wang, J},
title = {Missing microbes in infants and children in the COVID-19 pandemic: a study of 1,126 participants in Beijing, China.},
journal = {Science China. Life sciences},
volume = {67},
number = {8},
pages = {1739-1750},
pmid = {38748355},
issn = {1869-1889},
mesh = {Humans ; *COVID-19/epidemiology/microbiology/virology ; Infant ; *Gastrointestinal Microbiome ; Child, Preschool ; Female ; Male ; *RNA, Ribosomal, 16S/genetics ; Child ; *Feces/microbiology/virology ; SARS-CoV-2/isolation & purification/genetics ; Beijing/epidemiology ; Pandemics ; Bacterial Load ; Cohort Studies ; Bacteria/classification/genetics/isolation & purification ; },
abstract = {The COVID-19 pandemic has caused many fatalities worldwide and continues to affect the health of the recovered patients in the form of long-COVID. In this study, we compared the gut microbiome of uninfected infants and children before the pandemic began (BEFORE cohort, n=906) to that of after the pandemic (AFTER cohort, n=220) to examine the potential impact of social distancing and life habit changes on infant/children gut microbiome. Based on 16S rRNA sequencing, we found a significant change in microbiome composition after the pandemic, with Bacteroides enterotype increasing to 35.45% from 30.46% before the pandemic. qPCR quantification indicated that the bacterial loads of seven keystone taxa decreased by 91.69%-19.58%. Quantitative microbiome profiling, used to enhance the resolution in detecting microbiome differences, revealed a greater explained variance of pandemic on microbiome compared to gender, as well as a significant decrease in bacterial loads in 15 of the 20 major genera. The random forest age-predictor indicated the gut microbiomes were less mature in the after-pandemic cohort than in the before-pandemic cohort in the children group (3-12 years old) and had features of a significantly younger age (average of 1.86 years). Lastly, body weight and height were significantly lower in the after-pandemic cohort than in the before-pandemic cohort in infants (<1 year of age), which was associated with a decrease in bacterial loads in the fecal microbiome.},
}

Humans
*COVID-19/epidemiology/microbiology/virology
Infant
*Gastrointestinal Microbiome
Child, Preschool
Female
Male
*RNA, Ribosomal, 16S/genetics
Child
*Feces/microbiology/virology
SARS-CoV-2/isolation & purification/genetics
Beijing/epidemiology
Pandemics
Bacterial Load
Cohort Studies
Bacteria/classification/genetics/isolation & purification

@article {pmid38713673,
year = {2024},
author = {Gross, RS and Thaweethai, T and Rosenzweig, EB and Chan, J and Chibnik, LB and Cicek, MS and Elliott, AJ and Flaherman, VJ and Foulkes, AS and Gage Witvliet, M and Gallagher, R and Gennaro, ML and Jernigan, TL and Karlson, EW and Katz, SD and Kinser, PA and Kleinman, LC and Lamendola-Essel, MF and Milner, JD and Mohandas, S and Mudumbi, PC and Newburger, JW and Rhee, KE and Salisbury, AL and Snowden, JN and Stein, CR and Stockwell, MS and Tantisira, KG and Thomason, ME and Truong, DT and Warburton, D and Wood, JC and Ahmed, S and Akerlundh, A and Alshawabkeh, AN and Anderson, BR and Aschner, JL and Atz, AM and Aupperle, RL and Baker, FC and Balaraman, V and Banerjee, D and Barch, DM and Baskin-Sommers, A and Bhuiyan, S and Bind, MC and Bogie, AL and Bradford, T and Buchbinder, NC and Bueler, E and Bükülmez, H and Casey, BJ and Chang, L and Chrisant, M and Clark, DB and Clifton, RG and Clouser, KN and Cottrell, L and Cowan, K and D'Sa, V and Dapretto, M and Dasgupta, S and Dehority, W and Dionne, A and Dummer, KB and Elias, MD and Esquenazi-Karonika, S and Evans, DN and Faustino, EVS and Fiks, AG and Forsha, D and Foxe, JJ and Friedman, NP and Fry, G and Gaur, S and Gee, DG and Gray, KM and Handler, S and Harahsheh, AS and Hasbani, K and Heath, AC and Hebson, C and Heitzeg, MM and Hester, CM and Hill, S and Hobart-Porter, L and Hong, TKF and Horowitz, CR and Hsia, DS and Huentelman, M and Hummel, KD and Irby, K and Jacobus, J and Jacoby, VL and Jone, PN and Kaelber, DC and Kasmarcak, TJ and Kluko, MJ and Kosut, JS and Laird, AR and Landeo-Gutierrez, J and Lang, SM and Larson, CL and Lim, PPC and Lisdahl, KM and McCrindle, BW and McCulloh, RJ and McHugh, K and Mendelsohn, AL and Metz, TD and Miller, J and Mitchell, EC and Morgan, LM and Müller-Oehring, EM and Nahin, ER and Neale, MC and Ness-Cochinwala, M and Nolan, SM and Oliveira, CR and Osakwe, O and Oster, ME and Payne, RM and Portman, MA and Raissy, H and Randall, IG and Rao, S and Reeder, HT and Rosas, JM and Russell, MW and Sabati, AA and Sanil, Y and Sato, AI and Schechter, MS and Selvarangan, R and Sexson Tejtel, SK and Shakti, D and Sharma, K and Squeglia, LM and Srivastava, S and Stevenson, MD and Szmuszkovicz, J and Talavera-Barber, MM and Teufel, RJ and Thacker, D and Trachtenberg, F and Udosen, MM and Warner, MR and Watson, SE and Werzberger, A and Weyer, JC and Wood, MJ and Yin, HS and Zempsky, WT and Zimmerman, E and Dreyer, BP and , },
title = {Researching COVID to enhance recovery (RECOVER) pediatric study protocol: Rationale, objectives and design.},
journal = {PloS one},
volume = {19},
number = {5},
pages = {e0285635},
pmid = {38713673},
issn = {1932-6203},
support = {K23 AI159518/AI/NIAID NIH HHS/United States ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; U24 DA041147/DA/NIDA NIH HHS/United States ; },
mesh = {Humans ; *COVID-19/epidemiology/virology ; Adolescent ; Child ; Child, Preschool ; Female ; Young Adult ; Adult ; Male ; Infant ; SARS-CoV-2/isolation & purification ; Infant, Newborn ; Prospective Studies ; Research Design ; Cohort Studies ; Post-Acute COVID-19 Syndrome ; },
abstract = {IMPORTANCE: The prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or "Long COVID") in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults.

OBSERVATIONS: We describe the protocol for the Pediatric Observational Cohort Study of the NIH's REsearching COVID to Enhance Recovery (RECOVER) Initiative. RECOVER-Pediatrics is an observational meta-cohort study of caregiver-child pairs (birth through 17 years) and young adults (18 through 25 years), recruited from more than 100 sites across the US. This report focuses on two of four cohorts that comprise RECOVER-Pediatrics: 1) a de novo RECOVER prospective cohort of children and young adults with and without previous or current infection; and 2) an extant cohort derived from the Adolescent Brain Cognitive Development (ABCD) study (n = 10,000). The de novo cohort incorporates three tiers of data collection: 1) remote baseline assessments (Tier 1, n = 6000); 2) longitudinal follow-up for up to 4 years (Tier 2, n = 6000); and 3) a subset of participants, primarily the most severely affected by PASC, who will undergo deep phenotyping to explore PASC pathophysiology (Tier 3, n = 600). Youth enrolled in the ABCD study participate in Tier 1. The pediatric protocol was developed as a collaborative partnership of investigators, patients, researchers, clinicians, community partners, and federal partners, intentionally promoting inclusivity and diversity. The protocol is adaptive to facilitate responses to emerging science.

CONCLUSIONS AND RELEVANCE: RECOVER-Pediatrics seeks to characterize the clinical course, underlying mechanisms, and long-term effects of PASC from birth through 25 years old. RECOVER-Pediatrics is designed to elucidate the epidemiology, four-year clinical course, and sociodemographic correlates of pediatric PASC. The data and biosamples will allow examination of mechanistic hypotheses and biomarkers, thus providing insights into potential therapeutic interventions.

Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT05172011.},
}

Humans
*COVID-19/epidemiology/virology
Adolescent
Child
Child, Preschool
Female
Young Adult
Adult
Male
Infant
SARS-CoV-2/isolation & purification
Infant, Newborn
Prospective Studies
Research Design
Cohort Studies
Post-Acute COVID-19 Syndrome

@article {pmid38574226,
year = {2024},
author = {Ebell, MH},
title = {Cognitive Behavior Therapy Effective in Patients With Fatigue Associated With Long COVID.},
journal = {American family physician},
volume = {109},
number = {3},
pages = {Online},
pmid = {38574226},
issn = {1532-0650},
mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19/therapy ; Fatigue/etiology/therapy ; Treatment Outcome ; *Cognitive Behavioral Therapy ; *Fatigue Syndrome, Chronic/psychology/therapy ; },
}

Humans
Post-Acute COVID-19 Syndrome
*COVID-19/therapy
Fatigue/etiology/therapy
Treatment Outcome
*Cognitive Behavioral Therapy
*Fatigue Syndrome, Chronic/psychology/therapy

@article {pmid38525993,
year = {2024},
author = {Naunheim, MR and DeVore, EK and Huston, MN and Song, PC and Franco, RA and Bhattacharyya, N},
title = {Increasing Prevalence of Voice Disorders in the USA: Updates in the COVID Era.},
journal = {The Laryngoscope},
volume = {134},
number = {8},
pages = {3713-3718},
doi = {10.1002/lary.31409},
pmid = {38525993},
issn = {1531-4995},
mesh = {Humans ; *COVID-19/epidemiology ; *Voice Disorders/epidemiology ; Male ; United States/epidemiology ; Female ; Prevalence ; Adult ; Middle Aged ; Aged ; Young Adult ; SARS-CoV-2 ; Adolescent ; Health Surveys ; },
abstract = {OBJECTIVE: To estimate the current prevalence of voice disorders among adults in the United States; to determine the association of individual factors with voice disorders.

METHODS: The 2022 National Health Interview Survey (NHIS) was analyzed to identify adults reporting voice problems in the past 12 months. Demographics were assessed, as well as the duration, severity, and resolution of the voice problem. The relationship between voice problems, gender, lost workdays, and long COVID was investigated. A comparison to the 2012 NHIS was made to determine changes in voice disorder prevalence.

RESULTS: 29.9 million Americans (95%CI[28.3-31.5]) annually report a voice problem, representing 12.2% of the population (95%CI[11.7-12.8%]). Overall, 26.8% and 13.2% reported the severity of their voice problem as moderate or severe, respectively. Only 5.1% (95%CI[4.3-6.0%]) of respondents sought treatment. Most voice problems were resolved within 1 week (53.0%,95%CI[50.9-55.1%]). Females were more likely than males to report a voice problem (14.4% vs. 10.0%,95%CI[13.7-15.1] and [9.3-10.7], respectively). The 17.6 million Americans with long COVID symptoms were more likely to have voice complaints than those without (21.1% vs. 11.6%,95%CI[18.9-23.5%] and [11.1-12.1%], respectively). Lost workdays were not significantly higher for those with voice disorders compared to those without (17.1 vs. 12.9 days,95%CI[12.0-22.1] and [11.0-14.8], respectively).

CONCLUSIONS: Voice problems affect approximately 1 in 8 adults in the U.S. annually, demonstrating an alarming increased prevalence since 2012 using the same survey methodology. Relatively few individuals seek care for their voice problem, despite significant self-reported impact. Further study is required regarding the impact of COVID and changes in voice use patterns on voice disorders.

LEVEL OF EVIDENCE: 3 Laryngoscope, 134:3713-3718, 2024.},
}

Humans
*COVID-19/epidemiology
*Voice Disorders/epidemiology
Male
United States/epidemiology
Female
Prevalence
Adult
Middle Aged
Aged
Young Adult
SARS-CoV-2
Adolescent
Health Surveys

@article {pmid38177128,
year = {2024},
author = {Appelman, B and Charlton, BT and Goulding, RP and Kerkhoff, TJ and Breedveld, EA and Noort, W and Offringa, C and Bloemers, FW and van Weeghel, M and Schomakers, BV and Coelho, P and Posthuma, JJ and Aronica, E and Joost Wiersinga, W and van Vugt, M and Wüst, RCI},
title = {Muscle abnormalities worsen after post-exertional malaise in long COVID.},
journal = {Nature communications},
volume = {15},
number = {1},
pages = {17},
pmid = {38177128},
issn = {2041-1723},
mesh = {Humans ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Case-Control Studies ; *COVID-19/complications ; Fatigue/etiology ; *Musculoskeletal Abnormalities ; Muscle, Skeletal ; Pain ; Plaque, Amyloid ; },
abstract = {A subgroup of patients infected with SARS-CoV-2 remain symptomatic over three months after infection. A distinctive symptom of patients with long COVID is post-exertional malaise, which is associated with a worsening of fatigue- and pain-related symptoms after acute mental or physical exercise, but its underlying pathophysiology is unclear. With this longitudinal case-control study (NCT05225688), we provide new insights into the pathophysiology of post-exertional malaise in patients with long COVID. We show that skeletal muscle structure is associated with a lower exercise capacity in patients, and local and systemic metabolic disturbances, severe exercise-induced myopathy and tissue infiltration of amyloid-containing deposits in skeletal muscles of patients with long COVID worsen after induction of post-exertional malaise. This study highlights novel pathways that help to understand the pathophysiology of post-exertional malaise in patients suffering from long COVID and other post-infectious diseases.},
}

Humans
Post-Acute COVID-19 Syndrome
SARS-CoV-2
Case-Control Studies
*COVID-19/complications
Fatigue/etiology
*Musculoskeletal Abnormalities
Muscle, Skeletal
Pain
Plaque, Amyloid

@article {pmid38128008,
year = {2023},
author = {Metz, TD and Clifton, RG and Gallagher, R and Gross, RS and Horwitz, LI and Jacoby, VL and Martin-Herz, SP and Peralta-Carcelen, M and Reeder, HT and Beamon, CJ and Chan, J and Chang, AA and Costantine, MM and Fitzgerald, ML and Foulkes, AS and Gibson, KS and Güthe, N and Habli, M and Hackney, DN and Hoffman, MK and Hoffman, MC and Hughes, BL and Katz, SD and Laleau, V and Mallett, G and Mendez-Figueroa, H and Monzon, V and Palatnik, A and Palomares, KTS and Parry, S and Pettker, CM and Plunkett, BA and Poppas, A and Reddy, UM and Rouse, DJ and Saade, GR and Sandoval, GJ and Schlater, SM and Sciurba, FC and Simhan, HN and Skupski, DW and Sowles, A and Thaweethai, T and Thomas, GL and Thorp, JM and Tita, AT and Weiner, SJ and Weigand, S and Yee, LM and Flaherman, VJ and , },
title = {Researching COVID to enhance recovery (RECOVER) pregnancy study: Rationale, objectives and design.},
journal = {PloS one},
volume = {18},
number = {12},
pages = {e0285351},
pmid = {38128008},
issn = {1932-6203},
support = {OT2 HL156812/HL/NHLBI NIH HHS/United States ; OT2 HL161841/HL/NHLBI NIH HHS/United States ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; },
mesh = {Adult ; Female ; Humans ; Pregnancy ; *COVID-19/epidemiology ; Pandemics/prevention & control ; Post-Acute COVID-19 Syndrome ; Prospective Studies ; Retrospective Studies ; SARS-CoV-2 ; },
abstract = {IMPORTANCE: Pregnancy induces unique physiologic changes to the immune response and hormonal changes leading to plausible differences in the risk of developing post-acute sequelae of SARS-CoV-2 (PASC), or Long COVID. Exposure to SARS-CoV-2 during pregnancy may also have long-term ramifications for exposed offspring, and it is critical to evaluate the health outcomes of exposed children. The National Institutes of Health (NIH) Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC aims to evaluate the long-term sequelae of SARS-CoV-2 infection in various populations. RECOVER-Pregnancy was designed specifically to address long-term outcomes in maternal-child dyads.

METHODS: RECOVER-Pregnancy cohort is a combined prospective and retrospective cohort that proposes to enroll 2,300 individuals with a pregnancy during the COVID-19 pandemic and their offspring exposed and unexposed in utero, including single and multiple gestations. Enrollment will occur both in person at 27 sites through the Eunice Kennedy Shriver National Institutes of Health Maternal-Fetal Medicine Units Network and remotely through national recruitment by the study team at the University of California San Francisco (UCSF). Adults with and without SARS-CoV-2 infection during pregnancy are eligible for enrollment in the pregnancy cohort and will follow the protocol for RECOVER-Adult including validated screening tools, laboratory analyses and symptom questionnaires followed by more in-depth phenotyping of PASC on a subset of the overall cohort. Offspring exposed and unexposed in utero to SARS-CoV-2 maternal infection will undergo screening tests for neurodevelopment and other health outcomes at 12, 18, 24, 36 and 48 months of age. Blood specimens will be collected at 24 months of age for SARS-CoV-2 antibody testing, storage and anticipated later analyses proposed by RECOVER and other investigators.

DISCUSSION: RECOVER-Pregnancy will address whether having SARS-CoV-2 during pregnancy modifies the risk factors, prevalence, and phenotype of PASC. The pregnancy cohort will also establish whether there are increased risks of adverse long-term outcomes among children exposed in utero.

Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT05172011.},
}

Adult
Female
Humans
Pregnancy
*COVID-19/epidemiology
Pandemics/prevention & control
Post-Acute COVID-19 Syndrome
Prospective Studies
Retrospective Studies
SARS-CoV-2

@article {pmid38105936,
year = {2023},
author = {El-Toukhy, S and Hegeman, P and Zuckerman, G and Anirban, RD and Moses, N and Troendle, JF and Powell-Wiley, TM},
title = {A prospective natural history study of post acute sequalae of COVID-19 using digital wearables: Study protocol.},
journal = {Research square},
volume = {},
number = {},
pages = {},
pmid = {38105936},
issn = {2693-5015},
support = {ZIA MD000011/ImNIH/Intramural NIH HHS/United States ; },
abstract = {BACKGROUND: Post-acute sequelae of COVID-19 (PASC) is characterized by having 1 + persistent, recurrent, or emergent symptoms post the infection's acute phase. The duration and symptom manifestation of PASC remain understudied in nonhospitalized patients. Literature on PASC is primarily based on data from hospitalized patients where clinical indicators such as respiratory rate, heart rate, and oxygen saturation have been predictive of disease trajectories. Digital wearables allow for a continuous collection of such physiological parameters. This protocol outlines the design, aim, and procedures of a natural history study of PASC using digital wearables.

METHODS: This is a single-arm, prospective, natural history study of a cohort of 550 patients, ages 18 to 65 years old, males or females who own a smartphone and/or a tablet that meets pre-determined Bluetooth version and operating system requirements, speak English, and provide documentation of a positive COVID-19 test issued by a healthcare professional or organization within 5 days before enrollment. The study aims to identify wearables collected physiological parameters that are associated with PASC in patients with a positive diagnosis. The primary endpoint is long COVID-19, defined as ≥ 1 symptom at 3 weeks beyond first symptom onset or positive diagnosis, whichever comes first. The secondary endpoint is chronic COVID-19, defined as ≥ 1 symptom at 12 weeks beyond first symptom onset or positive diagnosis. We hypothesize that physiological parameters collected via wearables are associated with self-reported PASC. Participants must be willing and able to consent to participate in the study and adhere to study procedures for six months.

DISCUSSION: This is a fully decentralized study investigating PASC using wearable devices to collect physiological parameters and patient-reported outcomes. Given evidence on key demographics and risk profiles associated with PASC, the study will shed light on the duration and symptom manifestation of PASC in nonhospitalized patient subgroups and is an exemplar of use of wearables as population-level monitoring health tools for communicable diseases.

TRIAL REGISTRATION: ClinicalTrials.gov NCT04927442.},
}

@article {pmid38070892,
year = {2023},
author = {Loria, V and Aparicio, A and Hildesheim, A and Cortés, B and Barrientos, G and Retana, D and Sun, K and Ocampo, R and Prevots, DR and Zúñiga, M and Waterboer, T and Wong-McClure, R and Morera, M and Butt, J and Binder, M and Abdelnour, A and Calderón, A and Gail, MH and Pfeiffer, RM and Solís, CB and Fantin, R and Vanegas, JC and Mercado, R and Ávila, C and Porras, C and Herrero, R},
title = {Cohort profile: evaluation of immune response and household transmission of SARS-CoV-2 in Costa Rica: the RESPIRA study.},
journal = {BMJ open},
volume = {13},
number = {12},
pages = {e071284},
pmid = {38070892},
issn = {2044-6055},
support = {HHSN261201000121C/CP/NCI NIH HHS/United States ; 75N91020C00001/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; *SARS-CoV-2 ; *COVID-19/epidemiology/prevention & control ; Post-Acute COVID-19 Syndrome ; Costa Rica/epidemiology ; Prospective Studies ; Retrospective Studies ; Antibodies ; Double-Blind Method ; Immunity ; },
abstract = {PURPOSE: The RESPIRA cohort aims to describe the nature, magnitude, time course and efficacy of the immune response to SARS-CoV-2 infection and vaccination, population prevalence, and household transmission of COVID-19.

PARTICIPANTS: From November 2020, we selected age-stratified random samples of COVID-19 cases from Costa Rica confirmed by PCR. For each case, two population-based controls, matched on age, sex and census tract were recruited, supplemented with hospitalised cases and household contacts. Participants were interviewed and blood and saliva collected for antibodies and PCR tests. Participants will be followed for 2 years to assess antibody response and infection incidence.

FINDINGS TO DATE: Recruitment included 3860 individuals: 1150 COVID-19 cases, 1999 population controls and 719 household contacts from 304 index cases. The age and regional distribution of cases was as planned, including four age strata, 30% rural and 70% urban. The control cohort had similar sex, age and regional distribution as the cases according to the study design. Among the 1999 controls recruited, 6.8% reported at enrolment having had COVID-19 and an additional 12.5% had antibodies against SARS-CoV-2. Compliance with visits and specimens has been close to 70% during the first 18 months of follow-up. During the study, national vaccination was implemented and nearly 90% of our cohort participants were vaccinated during follow-up.

FUTURE PLANS: RESPIRA will enable multiple analyses, including population prevalence of infection, clinical, behavioural, immunological and genetic risk factors for SARS-CoV-2 acquisition and severity, and determinants of household transmission. We are conducting retrospective and prospective assessment of antibody levels, their determinants and their protective efficacy after infection and vaccination, the impact of long-COVID and a series of ancillary studies. Follow-up continues with bimonthly saliva collection for PCR testing and biannual blood collection for immune response analyses. Follow-up will be completed in early 2024.

TRIAL REGISTRATION NUMBER: NCT04537338.},
}

Humans
*SARS-CoV-2
*COVID-19/epidemiology/prevention & control
Post-Acute COVID-19 Syndrome
Costa Rica/epidemiology
Prospective Studies
Retrospective Studies
Antibodies
Double-Blind Method
Immunity

@article {pmid37885796,
year = {2023},
author = {Pagen, DME and van Bilsen, CJA and Brinkhues, S and Van Herck, M and Konings, K and den Heijer, CDJ and Ter Waarbeek, HLG and Spruit, MA and Hoebe, CJPA and Dukers-Muijrers, NHTM},
title = {Prevalence of Long-term Symptoms Varies When Using Different Post-COVID-19 Definitions in Positively and Negatively Tested Adults: The PRIME Post-COVID Study.},
journal = {Open forum infectious diseases},
volume = {10},
number = {10},
pages = {ofad471},
pmid = {37885796},
issn = {2328-8957},
abstract = {BACKGROUND: Long-term symptoms after a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (ie, post-coronavirus disease 2019 [COVID-19] condition or long COVID) constitute a substantial public health problem. Yet, the prevalence remains currently unclear as different case definitions are used, and negatively tested controls are lacking. We aimed to estimate post-COVID-19 condition prevalence using 6 definitions.

METHODS: The Prevalence, Risk factors, and Impact Evaluation (PRIME) post-COVID-19 condition study is a population-based sample of COVID-19-tested adults. In 2021, 61 655 adults were invited to complete an online questionnaire, including 44 symptoms plus a severity score (0-10) per symptom. Prevalence was calculated in both positively and negatively tested adults, stratified by time since their COVID-19 test (3-5, 6-11, or ≥12 months ago).

RESULTS: In positive individuals (n = 7405, 75.6%), the prevalence of long-term symptoms was between 26.9% and 64.1% using the 6 definitions, while in negative individuals (n = 2392, 24.4%), the prevalence varied between 11.4% and 32.5%. The prevalence of long-term symptoms potentially attributable to COVID-19 ranged from 17.9% to 26.3%.

CONCLUSIONS: There is a (substantial) variation in prevalence estimates when using different post-COVID-19 condition definitions, as is current practice; there is limited overlap between definitions, indicating that the essential post-COVID-19 condition criteria are still unclear. Including negatives is important to determine long-term symptoms attributable to COVID-19.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05128695.},
}

@article {pmid37851732,
year = {2023},
author = {Rover, MM and Trott, G and Scolari, FL and Silva, MMDD and Souza, D and Santos, RDRMD and Dagnino, APA and Mesquita Neto, J and Estivalete, GP and Kozesinski-Nakatani, AC and Marcolino, MS and Barreto, BB and Schvartzman, PR and Antonio, ACP and Robinson, CC and Falavigna, M and Biolo, A and Polanczyk, CA and Rosa, RG},
title = {Health-Related Quality of Life and Long-Term Outcomes after Mildly Symptomatic COVID-19: The Post-COVID Brazil Study 2 Protocol.},
journal = {Arquivos brasileiros de cardiologia},
volume = {120},
number = {9},
pages = {e20220835},
pmid = {37851732},
issn = {1678-4170},
mesh = {Humans ; Activities of Daily Living ; Brazil/epidemiology ; *COVID-19 ; COVID-19 Testing ; Multicenter Studies as Topic ; Post-Acute COVID-19 Syndrome ; Prospective Studies ; *Quality of Life/psychology ; SARS-CoV-2 ; Surveys and Questionnaires ; },
abstract = {BACKGROUND: The long-term effects of mild COVID-19 on physical, cognitive, and mental health are not yet well understood.

OBJECTIVE: The purpose of this paper is to describe the protocol for the ongoing "Post-COVID Brazil" study 2, which aims to evaluate the factors associated with health-related quality of life and long-term cardiovascular and non-cardiovascular outcomes one year after a mild episode of symptomatic COVID-19.

METHODS: The "Post-COVID Brazil" study 2 is a prospective multicenter study that plans to enroll 1047 patients (NCT05197647). Centralized, structured telephone interviews are conducted at 1, 3, 6, 9, and 12 months after COVID-19 diagnosis. The primary outcome is the health-related quality-of-life utility score, assessed using the EuroQol-5D-3L (EQ-5D-3L) questionnaire at 12 months. Secondary endpoints include the EQ-5D-3L at 3, 6, and 9 months, as well as all-cause mortality, major cardiovascular events, hospitalization, return to work or education, persistent symptoms, new disabilities in instrumental activities of daily living, cognitive impairment, anxiety, depression, and post-traumatic stress symptoms at 3, 6, 9, and 12 months after SARS-CoV-2 infection. A p-value < 0.05 will be considered statistically significant for all analyses.

RESULTS: The primary endpoint will be presented as the overall frequency of the EQ-5D-3L domains 12 months after SARS-CoV-2 infection. Main analysis will explore the association of independent variables with the study outcomes.

CONCLUSION: The "Post-COVID Brazil" study 2 aims to clarify the impact of long COVID on the quality of life and cardiovascular and non-cardiovascular outcomes of Brazilian patients who have had mild COVID-19.},
}

Humans
Activities of Daily Living
Brazil/epidemiology
*COVID-19
COVID-19 Testing
Multicenter Studies as Topic
Post-Acute COVID-19 Syndrome
Prospective Studies
*Quality of Life/psychology
SARS-CoV-2
Surveys and Questionnaires

@article {pmid37848295,
year = {2023},
author = {Virrantaus, H and Liira, H and Posharina, T and Sulg, A and Mäntylä, T and Kanerva, M and Laakso, S and Sainio, M and Malmivaara, A and Vuokko, A and Varonen, M and Venäläinen, M and Arokoski, J},
title = {Prognosis of patients with long COVID symptoms: a protocol for a longitudinal cohort study at a primary care referred outpatient clinic in Helsinki, Finland.},
journal = {BMJ open},
volume = {13},
number = {10},
pages = {e072935},
pmid = {37848295},
issn = {2044-6055},
mesh = {Adult ; Humans ; *COVID-19/epidemiology ; Cohort Studies ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Longitudinal Studies ; Prospective Studies ; Finland/epidemiology ; Quality of Life ; Hand Strength ; Prognosis ; Ambulatory Care Facilities ; Primary Health Care ; Treatment Outcome ; },
abstract = {INTRODUCTION: After COVID-19, many continue to experience persistent debilitating symptoms, that is, long COVID. Its most prevalent symptoms are chest pain, difficulties with breathing, painful muscles, ageusia or anosmia, tingling extremities and general tiredness. This paper describes the protocol of the Long COVID Cohort Study to assess the prognosis and prognostic determinants of patients with long COVID by implementing patient-reported outcome measures (PROMs), patient-reported experience measures (PREMs) and clinical examinations during a 1-year follow-up.

METHODS AND ANALYSIS: This is a prospective, single-site cohort study consisting of administering questionnaires and clinical examinations to adult patients referred to the Clinic for Long-Term Effects of COVID-19 at Helsinki University Hospital (Hospital district of Helsinki and Uusimaa). The referrals are from all healthcare units within HUS and other hospital districts during years 2021-2023. All admitted patients have had laboratory-confirmed COVID-19. The targeted study sample size is 500 participants. The questionnaires are administered at 0, 3, 6 and 12 months. The main outcome variables are the changes in self-reported functional abilities and quality of life. In addition, we will evaluate functional abilities at baseline using neurocognitive evaluation, a 6MWT and a measurement of hand grip strength. The Long COVID Cohort Study will form a quality register for the clinic and characterise the first systematic collection of PROMs, PREMs, questionnaire and clinical examinations related to long COVID in Finland. The Study belongs to a study consortium Long COVID-HORIZON-HLTH-2021-DISEASE-04 that aims to reveal the biomechanisms of long COVID.

ETHICS AND DISSEMINATION: This study has been approved by the Helsinki University Hospital research ethics committee board, ID HUS/1493/2021 on 6 March 2021. All study participants sign written informed consent for participation. The study findings will be reported for publication in peer-reviewed journals.

TRIAL REGISTRATION NUMBER: NCT05699512; Pre-results.},
}

Adult
Humans
*COVID-19/epidemiology
Cohort Studies
Post-Acute COVID-19 Syndrome
SARS-CoV-2
Longitudinal Studies
Prospective Studies
Finland/epidemiology
Quality of Life
Hand Strength
Prognosis
Ambulatory Care Facilities
Primary Health Care
Treatment Outcome

@article {pmid37832998,
year = {2023},
author = {Voss, JG and Pinto, MD and Burton, CW},
title = {How do the Social Determinants of Health Impact the Post-Acute Sequelae of COVID-19: A Critical Review.},
journal = {The Nursing clinics of North America},
volume = {58},
number = {4},
pages = {541-568},
doi = {10.1016/j.cnur.2023.07.004},
pmid = {37832998},
issn = {1558-1357},
mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Retrospective Studies ; Social Determinants of Health ; Disease Progression ; },
abstract = {The review critically analyzes the social determinants of health (SDOH) variables in the current literature of patients with post-acute sequelae (PASC) of COVID-19 in the United States. Race, gender, and age were discussed as well as health outcomes, severity of illness, and phenotypes of long-COVID. Most research was retrospectively with samples that had access to health insurance, which did not capture populations with poor or no access to health care. More research is needed that directly addresses the impact on SDOH on PASC. The current literature is sparse and provides little actionable information.},
}

Humans
*COVID-19
Post-Acute COVID-19 Syndrome
Retrospective Studies
Social Determinants of Health
Disease Progression

@article {pmid37803311,
year = {2023},
author = {Hoerger, M and Kim, S and Mossman, B and Alonzi, S and Xu, K and Coward, JC and Whalen, K and Nauman, E and Miller, J and De La Cerda, T and Peyser, T and Dunn, A and Zapolin, D and Rivera, D and Murugesan, N and Baker, CN},
title = {Cultivating community-based participatory research (CBPR) to respond to the COVID-19 pandemic: an illustrative example of partnership and topic prioritization in the food services industry.},
journal = {BMC public health},
volume = {23},
number = {1},
pages = {1939},
pmid = {37803311},
issn = {1471-2458},
mesh = {Humans ; *COVID-19/epidemiology/prevention & control ; Pandemics/prevention & control ; Community-Based Participatory Research ; Post-Acute COVID-19 Syndrome ; Community Health Services ; *Substance-Related Disorders ; },
abstract = {BACKGROUND: As an illustrative example of COVID-19 pandemic community-based participatory research (CBPR), we describe a community-academic partnership to prioritize future research most important to people experiencing high occupational exposure to COVID-19 - food service workers. Food service workers face key challenges surrounding (1) health and safety precautions, (2) stress and mental health, and (3) the long-term pandemic impact.

METHOD: Using CBPR methodologies, academic scientists partnered with community stakeholders to develop the research aims, methods, and measures, and interpret and disseminate results. We conducted a survey, three focus groups, and a rapid qualitative assessment to understand the three areas of concern and prioritize future research.

RESULTS: The survey showed that food service employers mainly supported basic droplet protections (soap, hand sanitizer, gloves), rather than comprehensive airborne protections (high-quality masks, air quality monitoring, air cleaning). Food service workers faced challenging decisions surrounding isolation, quarantine, testing, masking, vaccines, and in-home transmission, described anxiety, depression, and substance use as top mental health concerns, and described long-term physical and financial concerns. Focus groups provided qualitative examples of concerns experienced by food service workers and narrowed topic prioritization. The rapid qualitative assessment identified key needs and opportunities, with help reducing in-home COVID-19 transmission identified as a top priority. COVID-19 mitigation scientists offered recommendations for reducing in-home transmission.

CONCLUSIONS: The COVID-19 pandemic has forced food service workers to experience complex decisions about health and safety, stress and mental health concerns, and longer-term concerns. Challenging health decisions included attempting to avoid an airborne infectious illness when employers were mainly only concerned with droplet precautions and trying to decide protocols for testing and isolation without clear guidance, free tests, or paid sick leave. Key mental health concerns were anxiety, depression, and substance use. Longer-term challenges included Long COVID, lack of mental healthcare access, and financial instability. Food service workers suggest the need for more research aimed at reducing in-home COVID-19 transmission and supporting long-term mental health, physical health, and financial concerns. This research provides an illustrative example of how to cultivate community-based partnerships to respond to immediate and critical issues affecting populations most burdened by public health crises.},
}

Humans
*COVID-19/epidemiology/prevention & control
Pandemics/prevention & control
Community-Based Participatory Research
Post-Acute COVID-19 Syndrome
Community Health Services
*Substance-Related Disorders

@article {pmid37797257,
year = {2023},
author = {Baker, MG and Kvalsvig, A and Plank, MJ and Geoghegan, JL and Wall, T and Tukuitonga, C and Summers, J and Bennett, J and Kerr, J and Turner, N and Roberts, S and Ward, K and Betty, B and Huang, QS and French, N and Wilson, N},
title = {Continued mitigation needed to minimise the high health burden from COVID-19 in Aotearoa New Zealand.},
journal = {The New Zealand medical journal},
volume = {136},
number = {1583},
pages = {67-91},
doi = {10.26635/6965.6247},
pmid = {37797257},
issn = {1175-8716},
mesh = {Humans ; *COVID-19/epidemiology/prevention & control ; New Zealand/epidemiology ; Post-Acute COVID-19 Syndrome ; Pandemics/prevention & control ; Maori People ; },
abstract = {In this article we review the COVID-19 pandemic experience in Aotearoa New Zealand and consider the optimal ongoing response strategy. We note that this pandemic virus looks likely to result in future waves of infection that diminish in size over time, depending on such factors as viral evolution and population immunity. However, the burden of disease remains high with thousands of infections, hundreds of hospitalisations and tens of deaths each week, and an unknown burden of long-term illness (long COVID). Alongside this there is a considerable burden from other important respiratory illnesses, including influenza and RSV, that needs more attention. Given this impact and the associated health inequities, particularly for Māori and Pacific Peoples, we consider that an ongoing respiratory disease mitigation strategy is appropriate for New Zealand. As such, the previously described "vaccines plus" approach (involving vaccination and public health and social measures), should now be integrated with the surveillance and control of other important respiratory infections. Now is also a time for New Zealand to build on the lessons from the COVID-19 pandemic to enhance preparedness nationally and internationally. New Zealand's experience suggests elimination (or ideally exclusion) should be the default first choice for future pandemics of sufficient severity.},
}

Humans
*COVID-19/epidemiology/prevention & control
New Zealand/epidemiology
Post-Acute COVID-19 Syndrome
Pandemics/prevention & control
Maori People

@article {pmid37773184,
year = {2023},
author = {Gyöngyösi, M and Lukovic, D and Mester-Tonczar, J and Zlabinger, K and Einzinger, P and Spannbauer, A and Schweiger, V and Schefberger, K and Samaha, E and Bergler-Klein, J and Riesenhuber, M and Nitsche, C and Hengstenberg, C and Mucher, P and Haslacher, H and Breuer, M and Strassl, R and Puchhammer-Stöckl, E and Loewe, C and Beitzke, D and Hasimbegovic, E and Zelniker, TA},
title = {Effect of monovalent COVID-19 vaccines on viral interference between SARS-CoV-2 and several DNA viruses in patients with long-COVID syndrome.},
journal = {NPJ vaccines},
volume = {8},
number = {1},
pages = {145},
pmid = {37773184},
issn = {2059-0105},
support = {KLI 876/FWF_/Austrian Science Fund FWF/Austria ; },
abstract = {Epstein-Barr virus (EBV) reactivation may be involved in long-COVID symptoms, but reactivation of other viruses as a factor has received less attention. Here we evaluated the reactivation of parvovirus-B19 and several members of the Herpesviridae family (DNA viruses) in patients with long-COVID syndrome. We hypothesized that monovalent COVID-19 vaccines inhibit viral interference between SARS-CoV-2 and several DNA viruses in patients with long-COVID syndrome, thereby reducing clinical symptoms. Clinical and laboratory data for 252 consecutive patients with PCR-verified past SARS-CoV-2 infection and long-COVID syndrome (155 vaccinated and 97 non-vaccinated) were recorded during April 2021-May 2022 (median 243 days post-COVID-19 infection). DNA virus-related IgG and IgM titers were compared between vaccinated and non-vaccinated long-COVID patients and with age- and sex-matched non-infected, unvaccinated (pan-negative for spike-antibody) controls. Vaccination with monovalent COVID-19 vaccines was associated with significantly less frequent fatigue and multiorgan symptoms (p < 0.001), significantly less cumulative DNA virus-related IgM positivity, significantly lower levels of plasma IgG subfractions 2 and 4, and significantly lower quantitative cytomegalovirus IgG and IgM and EBV IgM titers. These results indicate that anti-SARS-CoV-2 vaccination may interrupt viral cross-talk in patients with long-COVID syndrome (ClinicalTrials.gov Identifier: NCT05398952).},
}

@article {pmid37464515,
year = {2023},
author = {Nasir, M and Cook, N and Parras, D and Mukherjee, S and Miller, G and Ferres, JL and Chung-Bridges, K},
title = {Using Data Science and a Health Equity Lens to Identify Long-COVID Sequelae Among Medically Underserved Populations.},
journal = {Journal of health care for the poor and underserved},
volume = {34},
number = {2},
pages = {521-534},
doi = {10.1353/hpu.2023.0047},
pmid = {37464515},
issn = {1548-6869},
mesh = {Humans ; Post-Acute COVID-19 Syndrome ; Data Science ; Medically Underserved Area ; *Health Equity ; *COVID-19/epidemiology ; Disease Progression ; },
abstract = {Understanding how post-acute COVID-19 syndrome (PACS or long COVID) manifests among underserved populations, who experienced a disproportionate burden of acute COVID-19, can help providers and policymakers better address this ongoing crisis. To identify clinical sequelae of long COVID among underserved populations treated in the primary care safety net, we conducted a causal impact analysis with electronic health records (EHR) to compare symptoms among community health center patients who tested positive (n=4,091) and negative (n=7,118) for acute COVID-19. We found 18 sequelae with statistical significance and causal dependence among patients who had a visit after 60 days or more following acute COVID-19. These sequelae encompass most organ systems and include breathing abnormalities, malaise and fatigue, and headache. This study adds to current knowledge about how long COVID manifests in a large, underserved population.},
}

Humans
Post-Acute COVID-19 Syndrome
Data Science
Medically Underserved Area
*Health Equity
*COVID-19/epidemiology
Disease Progression

@article {pmid37352211,
year = {2023},
author = {Horwitz, LI and Thaweethai, T and Brosnahan, SB and Cicek, MS and Fitzgerald, ML and Goldman, JD and Hess, R and Hodder, SL and Jacoby, VL and Jordan, MR and Krishnan, JA and Laiyemo, AO and Metz, TD and Nichols, L and Patzer, RE and Sekar, A and Singer, NG and Stiles, LE and Taylor, BS and Ahmed, S and Algren, HA and Anglin, K and Aponte-Soto, L and Ashktorab, H and Bassett, IV and Bedi, B and Bhadelia, N and Bime, C and Bind, MC and Black, LJ and Blomkalns, AL and Brim, H and Castro, M and Chan, J and Charney, AW and Chen, BK and Chen, LQ and Chen, P and Chestek, D and Chibnik, LB and Chow, DC and Chu, HY and Clifton, RG and Collins, S and Costantine, MM and Cribbs, SK and Deeks, SG and Dickinson, JD and Donohue, SE and Durstenfeld, MS and Emery, IF and Erlandson, KM and Facelli, JC and Farah-Abraham, R and Finn, AV and Fischer, MS and Flaherman, VJ and Fleurimont, J and Fonseca, V and Gallagher, EJ and Gander, JC and Gennaro, ML and Gibson, KS and Go, M and Goodman, SN and Granger, JP and Greenway, FL and Hafner, JW and Han, JE and Harkins, MS and Hauser, KSP and Heath, JR and Hernandez, CR and Ho, O and Hoffman, MK and Hoover, SE and Horowitz, CR and Hsu, H and Hsue, PY and Hughes, BL and Jagannathan, P and James, JA and John, J and Jolley, S and Judd, SE and Juskowich, JJ and Kanjilal, DG and Karlson, EW and Katz, SD and Kelly, JD and Kelly, SW and Kim, AY and Kirwan, JP and Knox, KS and Kumar, A and Lamendola-Essel, MF and Lanca, M and Lee-Lannotti, JK and Lefebvre, RC and Levy, BD and Lin, JY and Logarbo, BP and Logue, JK and Longo, MT and Luciano, CA and Lutrick, K and Malakooti, SK and Mallett, G and Maranga, G and Marathe, JG and Marconi, VC and Marshall, GD and Martin, CF and Martin, JN and May, HT and McComsey, GA and McDonald, D and Mendez-Figueroa, H and Miele, L and Mittleman, MA and Mohandas, S and Mouchati, C and Mullington, JM and Nadkarni, GN and Nahin, ER and Neuman, RB and Newman, LT and Nguyen, A and Nikolich, JZ and Ofotokun, I and Ogbogu, PU and Palatnik, A and Palomares, KTS and Parimon, T and Parry, S and Parthasarathy, S and Patterson, TF and Pearman, A and Peluso, MJ and Pemu, P and Pettker, CM and Plunkett, BA and Pogreba-Brown, K and Poppas, A and Porterfield, JZ and Quigley, JG and Quinn, DK and Raissy, H and Rebello, CJ and Reddy, UM and Reece, R and Reeder, HT and Rischard, FP and Rosas, JM and Rosen, CJ and Rouphael, NG and Rouse, DJ and Ruff, AM and Saint Jean, C and Sandoval, GJ and Santana, JL and Schlater, SM and Sciurba, FC and Selvaggi, C and Seshadri, S and Sesso, HD and Shah, DP and Shemesh, E and Sherif, ZA and Shinnick, DJ and Simhan, HN and Singh, U and Sowles, A and Subbian, V and Sun, J and Suthar, MS and Teunis, LJ and Thorp, JM and Ticotsky, A and Tita, ATN and Tragus, R and Tuttle, KR and Urdaneta, AE and Utz, PJ and VanWagoner, TM and Vasey, A and Vernon, SD and Vidal, C and Walker, T and Ward, HD and Warren, DE and Weeks, RM and Weiner, SJ and Weyer, JC and Wheeler, JL and Whiteheart, SW and Wiley, Z and Williams, NJ and Wisnivesky, JP and Wood, JC and Yee, LM and Young, NM and Zisis, SN and Foulkes, AS},
title = {Researching COVID to Enhance Recovery (RECOVER) adult study protocol: Rationale, objectives, and design.},
journal = {PloS one},
volume = {18},
number = {6},
pages = {e0286297},
pmid = {37352211},
issn = {1932-6203},
support = {P30 AG072946/AG/NIA NIH HHS/United States ; UG1 HD027869/HD/NICHD NIH HHS/United States ; R00 AG065419/AG/NIA NIH HHS/United States ; K23 AI157875/AI/NIAID NIH HHS/United States ; UG1 HD087230/HD/NICHD NIH HHS/United States ; U54 GM115516/GM/NIGMS NIH HHS/United States ; K12 HL143961/HL/NHLBI NIH HHS/United States ; S10 OD030463/OD/NIH HHS/United States ; OT2 HL161841/HL/NHLBI NIH HHS/United States ; OT2 HL156812/HL/NHLBI NIH HHS/United States ; UL1 TR002538/TR/NCATS NIH HHS/United States ; UG1 HD027915/HD/NICHD NIH HHS/United States ; UG1 HD087192/HD/NICHD NIH HHS/United States ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; L30 AI126521/AI/NIAID NIH HHS/United States ; K23 AI146268/AI/NIAID NIH HHS/United States ; UG1 HD034208/HD/NICHD NIH HHS/United States ; P20 GM109089/GM/NIGMS NIH HHS/United States ; UG1 HD040544/HD/NICHD NIH HHS/United States ; S10 OD026880/OD/NIH HHS/United States ; U54 MD007601/MD/NIMHD NIH HHS/United States ; U54 GM115428/GM/NIGMS NIH HHS/United States ; L30 AI147159/AI/NIAID NIH HHS/United States ; },
mesh = {Humans ; *COVID-19/epidemiology ; Observational Studies as Topic ; Post-Acute COVID-19 Syndrome ; Prospective Studies ; Retrospective Studies ; SARS-CoV-2 ; Adolescent ; Adult ; Multicenter Studies as Topic ; },
abstract = {IMPORTANCE: SARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or other health effects after the acute phase of infection; termed post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are ill-defined. The objectives of the Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC in Adults (RECOVER-Adult) are to: (1) characterize PASC prevalence; (2) characterize the symptoms, organ dysfunction, natural history, and distinct phenotypes of PASC; (3) identify demographic, social and clinical risk factors for PASC onset and recovery; and (4) define the biological mechanisms underlying PASC pathogenesis.

METHODS: RECOVER-Adult is a combined prospective/retrospective cohort currently planned to enroll 14,880 adults aged ≥18 years. Eligible participants either must meet WHO criteria for suspected, probable, or confirmed infection; or must have evidence of no prior infection. Recruitment occurs at 86 sites in 33 U.S. states, Washington, DC and Puerto Rico, via facility- and community-based outreach. Participants complete quarterly questionnaires about symptoms, social determinants, vaccination status, and interim SARS-CoV-2 infections. In addition, participants contribute biospecimens and undergo physical and laboratory examinations at approximately 0, 90 and 180 days from infection or negative test date, and yearly thereafter. Some participants undergo additional testing based on specific criteria or random sampling. Patient representatives provide input on all study processes. The primary study outcome is onset of PASC, measured by signs and symptoms. A paradigm for identifying PASC cases will be defined and updated using supervised and unsupervised learning approaches with cross-validation. Logistic regression and proportional hazards regression will be conducted to investigate associations between risk factors, onset, and resolution of PASC symptoms.

DISCUSSION: RECOVER-Adult is the first national, prospective, longitudinal cohort of PASC among US adults. Results of this study are intended to inform public health, spur clinical trials, and expand treatment options.

REGISTRATION: NCT05172024.},
}

Humans
*COVID-19/epidemiology
Observational Studies as Topic
Post-Acute COVID-19 Syndrome
Prospective Studies
Retrospective Studies
SARS-CoV-2
Adolescent
Adult
Multicenter Studies as Topic

@article {pmid37302406,
year = {2023},
author = {Bramante, CT and Buse, JB and Liebovitz, DM and Nicklas, JM and Puskarich, MA and Cohen, K and Belani, HK and Anderson, BJ and Huling, JD and Tignanelli, CJ and Thompson, JL and Pullen, M and Wirtz, EL and Siegel, LK and Proper, JL and Odde, DJ and Klatt, NR and Sherwood, NE and Lindberg, SM and Karger, AB and Beckman, KB and Erickson, SM and Fenno, SL and Hartman, KM and Rose, MR and Mehta, T and Patel, B and Griffiths, G and Bhat, NS and Murray, TA and Boulware, DR and , },
title = {Outpatient treatment of COVID-19 and incidence of post-COVID-19 condition over 10 months (COVID-OUT): a multicentre, randomised, quadruple-blind, parallel-group, phase 3 trial.},
journal = {The Lancet. Infectious diseases},
volume = {23},
number = {10},
pages = {1119-1129},
pmid = {37302406},
issn = {1474-4457},
support = {K23 HL166783/HL/NHLBI NIH HHS/United States ; K23 DK124654/DK/NIDDK NIH HHS/United States ; UL1 TR002494/TR/NCATS NIH HHS/United States ; UM1 TR004406/TR/NCATS NIH HHS/United States ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; UL1 TR002489/TR/NCATS NIH HHS/United States ; U54 CA210190/CA/NCI NIH HHS/United States ; T32 HL129956/HL/NHLBI NIH HHS/United States ; R21 LM012744/LM/NLM NIH HHS/United States ; OT2 HL156812/HL/NHLBI NIH HHS/United States ; R01 LM012982/LM/NLM NIH HHS/United States ; K23 HL133604/HL/NHLBI NIH HHS/United States ; KL2 TR002492/TR/NCATS NIH HHS/United States ; P01 CA254849/CA/NCI NIH HHS/United States ; },
mesh = {Adult ; Pregnancy ; Humans ; Male ; Female ; Middle Aged ; *COVID-19 ; Incidence ; Ivermectin/therapeutic use ; Post-Acute COVID-19 Syndrome ; COVID-19 Drug Treatment ; Fluvoxamine ; Outpatients ; SARS-CoV-2 ; *Metformin/therapeutic use ; Double-Blind Method ; Treatment Outcome ; },
abstract = {BACKGROUND: Post-COVID-19 condition (also known as long COVID) is an emerging chronic illness potentially affecting millions of people. We aimed to evaluate whether outpatient COVID-19 treatment with metformin, ivermectin, or fluvoxamine soon after SARS-CoV-2 infection could reduce the risk of long COVID.

METHODS: We conducted a decentralised, randomised, quadruple-blind, parallel-group, phase 3 trial (COVID-OUT) at six sites in the USA. We included adults aged 30-85 years with overweight or obesity who had COVID-19 symptoms for fewer than 7 days and a documented SARS-CoV-2 positive PCR or antigen test within 3 days before enrolment. Participants were randomly assigned via 2 × 3 parallel factorial randomisation (1:1:1:1:1:1) to receive metformin plus ivermectin, metformin plus fluvoxamine, metformin plus placebo, ivermectin plus placebo, fluvoxamine plus placebo, or placebo plus placebo. Participants, investigators, care providers, and outcomes assessors were masked to study group assignment. The primary outcome was severe COVID-19 by day 14, and those data have been published previously. Because the trial was delivered remotely nationwide, the a priori primary sample was a modified intention-to-treat sample, meaning that participants who did not receive any dose of study treatment were excluded. Long COVID diagnosis by a medical provider was a prespecified, long-term secondary outcome. This trial is complete and is registered with ClinicalTrials.gov, NCT04510194.

FINDINGS: Between Dec 30, 2020, and Jan 28, 2022, 6602 people were assessed for eligibility and 1431 were enrolled and randomly assigned. Of 1323 participants who received a dose of study treatment and were included in the modified intention-to-treat population, 1126 consented for long-term follow-up and completed at least one survey after the assessment for long COVID at day 180 (564 received metformin and 562 received matched placebo; a subset of participants in the metformin vs placebo trial were also randomly assigned to receive ivermectin or fluvoxamine). 1074 (95%) of 1126 participants completed at least 9 months of follow-up. 632 (56·1%) of 1126 participants were female and 494 (43·9%) were male; 44 (7·0%) of 632 women were pregnant. The median age was 45 years (IQR 37-54) and median BMI was 29·8 kg/m[2] (IQR 27·0-34·2). Overall, 93 (8·3%) of 1126 participants reported receipt of a long COVID diagnosis by day 300. The cumulative incidence of long COVID by day 300 was 6·3% (95% CI 4·2-8·2) in participants who received metformin and 10·4% (7·8-12·9) in those who received identical metformin placebo (hazard ratio [HR] 0·59, 95% CI 0·39-0·89; p=0·012). The metformin beneficial effect was consistent across prespecified subgroups. When metformin was started within 3 days of symptom onset, the HR was 0·37 (95% CI 0·15-0·95). There was no effect on cumulative incidence of long COVID with ivermectin (HR 0·99, 95% CI 0·59-1·64) or fluvoxamine (1·36, 0·78-2·34) compared with placebo.

INTERPRETATION: Outpatient treatment with metformin reduced long COVID incidence by about 41%, with an absolute reduction of 4·1%, compared with placebo. Metformin has clinical benefits when used as outpatient treatment for COVID-19 and is globally available, low-cost, and safe.

FUNDING: Parsemus Foundation; Rainwater Charitable Foundation; Fast Grants; UnitedHealth Group Foundation; National Institute of Diabetes, Digestive and Kidney Diseases; National Institutes of Health; and National Center for Advancing Translational Sciences.},
}

Adult
Pregnancy
Humans
Male
Female
Middle Aged
*COVID-19
Incidence
Ivermectin/therapeutic use
Post-Acute COVID-19 Syndrome
COVID-19 Drug Treatment
Fluvoxamine
Outpatients
SARS-CoV-2
*Metformin/therapeutic use
Double-Blind Method
Treatment Outcome

@article {pmid37214806,
year = {2023},
author = {Gross, R and Thaweethai, T and Rosenzweig, EB and Chan, J and Chibnik, LB and Cicek, MS and Elliott, AJ and Flaherman, VJ and Foulkes, AS and Witvliet, MG and Gallagher, R and Gennaro, ML and Jernigan, TL and Karlson, EW and Katz, SD and Kinser, PA and Kleinman, LC and Lamendola-Essel, MF and Milner, JD and Mohandas, S and Mudumbi, PC and Newburger, JW and Rhee, KE and Salisbury, AL and Snowden, JN and Stein, CR and Stockwell, MS and Tantisira, KG and Thomason, ME and Truong, DT and Warburton, D and Wood, JC and Ahmed, S and Akerlundh, A and Alshawabkeh, AN and Anderson, BR and Aschner, JL and Atz, AM and Aupperle, RL and Baker, FC and Balaraman, V and Banerjee, D and Barch, DM and Baskin-Sommers, A and Bhuiyan, S and Bind, MC and Bogie, AL and Buchbinder, NC and Bueler, E and Bükülmez, H and Casey, BJ and Chang, L and Clark, DB and Clifton, RG and Clouser, KN and Cottrell, L and Cowan, K and D'Sa, V and Dapretto, M and Dasgupta, S and Dehority, W and Dummer, KB and Elias, MD and Esquenazi-Karonika, S and Evans, DN and Faustino, EVS and Fiks, AG and Forsha, D and Foxe, JJ and Friedman, NP and Fry, G and Gaur, S and Gee, DG and Gray, KM and Harahsheh, AS and Heath, AC and Heitzeg, MM and Hester, CM and Hill, S and Hobart-Porter, L and Hong, TKF and Horowitz, CR and Hsia, DS and Huentelman, M and Hummel, KD and Iacono, WG and Irby, K and Jacobus, J and Jacoby, VL and Jone, PN and Kaelber, DC and Kasmarcak, TJ and Kluko, MJ and Kosut, JS and Laird, AR and Landeo-Gutierrez, J and Lang, SM and Larson, CL and Lim, PPC and Lisdahl, KM and McCrindle, BW and McCulloh, RJ and Mendelsohn, AL and Metz, TD and Morgan, LM and Müller-Oehring, EM and Nahin, ER and Neale, MC and Ness-Cochinwala, M and Nolan, SM and Oliveira, CR and Oster, ME and Payne, RM and Raissy, H and Randall, IG and Rao, S and Reeder, HT and Rosas, JM and Russell, MW and Sabati, AA and Sanil, Y and Sato, AI and Schechter, MS and Selvarangan, R and Shakti, D and Sharma, K and Squeglia, LM and Stevenson, MD and Szmuszkovicz, J and Talavera-Barber, MM and Teufel, RJ and Thacker, D and Udosen, MM and Warner, MR and Watson, SE and Werzberger, A and Weyer, JC and Wood, MJ and Yin, HS and Zempsky, WT and Zimmerman, E and Dreyer, BP},
title = {Researching COVID to enhance recovery (RECOVER) pediatric study protocol: Rationale, objectives and design.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {37214806},
support = {K23 AI159518/AI/NIAID NIH HHS/United States ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; U01 DA041117/DA/NIDA NIH HHS/United States ; UM1 TR004528/TR/NCATS NIH HHS/United States ; },
abstract = {IMPORTANCE: The prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or "Long COVID") in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults.

OBSERVATIONS: We describe the protocol for the Pediatric Observational Cohort Study of the NIH's RE searching COV ID to E nhance R ecovery (RECOVER) Initiative. RECOVER-Pediatrics is an observational meta-cohort study of caregiver-child pairs (birth through 17 years) and young adults (18 through 25 years), recruited from more than 100 sites across the US. This report focuses on two of five cohorts that comprise RECOVER-Pediatrics: 1) a de novo RECOVER prospective cohort of children and young adults with and without previous or current infection; and 2) an extant cohort derived from the Adolescent Brain Cognitive Development (ABCD) study (n =10,000). The de novo cohort incorporates three tiers of data collection: 1) remote baseline assessments (Tier 1, n=6000); 2) longitudinal follow-up for up to 4 years (Tier 2, n=6000); and 3) a subset of participants, primarily the most severely affected by PASC, who will undergo deep phenotyping to explore PASC pathophysiology (Tier 3, n=600). Youth enrolled in the ABCD study participate in Tier 1. The pediatric protocol was developed as a collaborative partnership of investigators, patients, researchers, clinicians, community partners, and federal partners, intentionally promoting inclusivity and diversity. The protocol is adaptive to facilitate responses to emerging science.

CONCLUSIONS AND RELEVANCE: RECOVER-Pediatrics seeks to characterize the clinical course, underlying mechanisms, and long-term effects of PASC from birth through 25 years old. RECOVER-Pediatrics is designed to elucidate the epidemiology, four-year clinical course, and sociodemographic correlates of pediatric PASC. The data and biosamples will allow examination of mechanistic hypotheses and biomarkers, thus providing insights into potential therapeutic interventions.

CLINICAL TRIALSGOV IDENTIFIER: Clinical Trial Registration: http://www.clinicaltrials.gov . Unique identifier: NCT05172011.},
}

@article {pmid37162923,
year = {2023},
author = {Metz, TD and Clifton, RG and Gallagher, R and Gross, RS and Horwitz, LI and Jacoby, VL and Martin-Herz, SP and Peralta-Carcelen, M and Reeder, HT and Beamon, CJ and Bind, MA and Chan, J and Chang, AA and Chibnik, LB and Costantine, MM and Fitzgerald, ML and Foulkes, AS and Gibson, KS and Güthe, N and Habli, M and Hackney, DN and Hoffman, MK and Hoffman, MC and Hughes, BL and Katz, SD and Laleau, V and Mallett, G and Mendez-Figueroa, H and Monzon, V and Palatnik, A and Palomares, KTS and Parry, S and Peralta-Carcelen, M and Pettker, CM and Plunkett, BA and Poppas, A and Reddy, UM and Rouse, DJ and Saade, GR and Sandoval, GJ and Schlater, SM and Sciurba, FC and Simhan, HN and Skupski, DW and Sowles, A and Thaweethai, T and Thomas, GL and Thorp, JM and Tita, AT and Weiner, SJ and Weigand, S and Yee, LM and Flaherman, VJ},
title = {Researching COVID to enhance recovery (RECOVER) pregnancy study: Rationale, objectives and design.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {37162923},
support = {U10 HD040500/HD/NICHD NIH HHS/United States ; UG1 HD027869/HD/NICHD NIH HHS/United States ; UG1 HD087230/HD/NICHD NIH HHS/United States ; UM1 TR004409/TR/NCATS NIH HHS/United States ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; UL1 TR002319/TR/NCATS NIH HHS/United States ; OT2 HL161841/HL/NHLBI NIH HHS/United States ; UG1 HD040500/HD/NICHD NIH HHS/United States ; OT2 HL156812/HL/NHLBI NIH HHS/United States ; UL1 TR002538/TR/NCATS NIH HHS/United States ; UG1 HD027915/HD/NICHD NIH HHS/United States ; UG1 HD087192/HD/NICHD NIH HHS/United States ; UG1 HD040544/HD/NICHD NIH HHS/United States ; UG1 HD034208/HD/NICHD NIH HHS/United States ; },
abstract = {IMPORTANCE: Pregnancy induces unique physiologic changes to the immune response and hormonal changes leading to plausible differences in the risk of developing post-acute sequelae of SARS-CoV-2 (PASC), or Long COVID. Exposure to SARS-CoV-2 during pregnancy may also have long-term ramifications for exposed offspring, and it is critical to evaluate the health outcomes of exposed children. The National Institutes of Health (NIH) Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC aims to evaluate the long-term sequelae of SARS-CoV-2 infection in various populations. RECOVER- Pregnancy was designed specifically to address long-term outcomes in maternal-child dyads.

METHODS: RECOVER-Pregnancy cohort is a combined prospective and retrospective cohort that proposes to enroll 2,300 individuals with a pregnancy during the COVID-19 pandemic and their offspring exposed and unexposed in utero, including single and multiple gestations. Enrollment will occur both in person at 27 sites through the Eunice Kennedy Shriver National Institutes of Health Maternal-Fetal Medicine Units Network and remotely through national recruitment by the study team at the University of California San Francisco (UCSF). Adults with and without SARS-CoV-2 infection during pregnancy are eligible for enrollment in the pregnancy cohort and will follow the protocol for RECOVER-Adult including validated screening tools, laboratory analyses and symptom questionnaires followed by more in-depth phenotyping of PASC on a subset of the overall cohort. Offspring exposed and unexposed in utero to SARS-CoV-2 maternal infection will undergo screening tests for neurodevelopment and other health outcomes at 12, 18, 24, 36 and 48 months of age. Blood specimens will be collected at 24 months of age for SARS-CoV-2 antibody testing, storage and anticipated later analyses proposed by RECOVER and other investigators.

DISCUSSION: RECOVER-Pregnancy will address whether having SARS-CoV-2 during pregnancy modifies the risk factors, prevalence, and phenotype of PASC. The pregnancy cohort will also establish whether there are increased risks of adverse long-term outcomes among children exposed in utero.

REGISTRATION: NCT05172024.},
}

@article {pmid37029117,
year = {2023},
author = {Zang, C and Zhang, Y and Xu, J and Bian, J and Morozyuk, D and Schenck, EJ and Khullar, D and Nordvig, AS and Shenkman, EA and Rothman, RL and Block, JP and Lyman, K and Weiner, MG and Carton, TW and Wang, F and Kaushal, R},
title = {Data-driven analysis to understand long COVID using electronic health records from the RECOVER initiative.},
journal = {Nature communications},
volume = {14},
number = {1},
pages = {1948},
pmid = {37029117},
issn = {2041-1723},
support = {K23 HL151876/HL/NHLBI NIH HHS/United States ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; },
mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Electronic Health Records ; SARS-CoV-2 ; Propensity Score ; },
abstract = {Recent studies have investigated post-acute sequelae of SARS-CoV-2 infection (PASC, or long COVID) using real-world patient data such as electronic health records (EHR). Prior studies have typically been conducted on patient cohorts with specific patient populations which makes their generalizability unclear. This study aims to characterize PASC using the EHR data warehouses from two large Patient-Centered Clinical Research Networks (PCORnet), INSIGHT and OneFlorida+, which include 11 million patients in New York City (NYC) area and 16.8 million patients in Florida respectively. With a high-throughput screening pipeline based on propensity score and inverse probability of treatment weighting, we identified a broad list of diagnoses and medications which exhibited significantly higher incidence risk for patients 30-180 days after the laboratory-confirmed SARS-CoV-2 infection compared to non-infected patients. We identified more PASC diagnoses in NYC than in Florida regarding our screening criteria, and conditions including dementia, hair loss, pressure ulcers, pulmonary fibrosis, dyspnea, pulmonary embolism, chest pain, abnormal heartbeat, malaise, and fatigue, were replicated across both cohorts. Our analyses highlight potentially heterogeneous risks of PASC in different populations.},
}

Humans
*Post-Acute COVID-19 Syndrome
*COVID-19/epidemiology
Electronic Health Records
SARS-CoV-2
Propensity Score

@article {pmid37019821,
year = {2023},
author = {Sykes, RA and Neves, KB and Alves-Lopes, R and Caputo, I and Fallon, K and Jamieson, NB and Kamdar, A and Legrini, A and Leslie, H and McIntosh, A and McConnachie, A and Morrow, A and McFarlane, RW and Mangion, K and McAbney, J and Montezano, AC and Touyz, RM and Wood, C and Berry, C},
title = {Vascular mechanisms of post-COVID-19 conditions: Rho-kinase is a novel target for therapy.},
journal = {European heart journal. Cardiovascular pharmacotherapy},
volume = {9},
number = {4},
pages = {371-386},
pmid = {37019821},
issn = {2055-6845},
support = {MR/S018905/1/MRC_/Medical Research Council/United Kingdom ; RE/18/6/34217/BHF_/British Heart Foundation/United Kingdom ; PG/19/28/34310/BHF_/British Heart Foundation/United Kingdom ; COV/LTE/20/10/CSO_/Chief Scientist Office/United Kingdom ; CH/12/4/29762/BHF_/British Heart Foundation/United Kingdom ; COV/GLA/20/05/CSO_/Chief Scientist Office/United Kingdom ; PG/17/25/32884/BHF_/British Heart Foundation/United Kingdom ; RE/13/5/30177/BHF_/British Heart Foundation/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; },
mesh = {Humans ; Female ; Middle Aged ; Male ; rho-Associated Kinases/metabolism ; 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid/pharmacology ; *Cardiovascular Diseases/diagnosis/drug therapy ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; },
abstract = {BACKGROUND: In post-coronavirus disease-19 (post-COVID-19) conditions (long COVID), systemic vascular dysfunction is implicated, but the mechanisms are uncertain, and the treatment is imprecise.

METHODS AND RESULTS: Patients convalescing after hospitalization for COVID-19 and risk factor matched controls underwent multisystem phenotyping using blood biomarkers, cardiorenal and pulmonary imaging, and gluteal subcutaneous biopsy (NCT04403607). Small resistance arteries were isolated and examined using wire myography, histopathology, immunohistochemistry, and spatial transcriptomics. Endothelium-independent (sodium nitroprusside) and -dependent (acetylcholine) vasorelaxation and vasoconstriction to the thromboxane A2 receptor agonist, U46619, and endothelin-1 (ET-1) in the presence or absence of a RhoA/Rho-kinase inhibitor (fasudil), were investigated. Thirty-seven patients, including 27 (mean age 57 years, 48% women, 41% cardiovascular disease) 3 months post-COVID-19 and 10 controls (mean age 57 years, 20% women, 30% cardiovascular disease), were included. Compared with control responses, U46619-induced constriction was increased (P = 0.002) and endothelium-independent vasorelaxation was reduced in arteries from COVID-19 patients (P < 0.001). This difference was abolished by fasudil. Histopathology revealed greater collagen abundance in COVID-19 arteries {Masson's trichrome (MT) 69.7% [95% confidence interval (CI): 67.8-71.7]; picrosirius red 68.6% [95% CI: 64.4-72.8]}
vs. controls [MT 64.9% (95% CI: 59.4-70.3) (P = 0.028); picrosirius red 60.1% (95% CI: 55.4-64.8), (P = 0.029)]. Greater phosphorylated myosin light chain antibody-positive staining in vascular smooth muscle cells was observed in COVID-19 arteries (40.1%; 95% CI: 30.9-49.3) vs. controls (10.0%; 95% CI: 4.4-15.6) (P < 0.001). In proof-of-concept studies, gene pathways associated with extracellular matrix alteration, proteoglycan synthesis, and viral mRNA replication appeared to be upregulated.

CONCLUSION: Patients with post-COVID-19 conditions have enhanced vascular fibrosis and myosin light change phosphorylation. Rho-kinase activation represents a novel therapeutic target for clinical trials.},
}

Humans
Female
Middle Aged
Male
rho-Associated Kinases/metabolism
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid/pharmacology
*Cardiovascular Diseases/diagnosis/drug therapy
Post-Acute COVID-19 Syndrome
*COVID-19

@article {pmid36757300,
year = {2023},
author = {Yilmaz Gokmen, G and Durmaz, D and Demir, C and Yilmaz, FN},
title = {Determining Post-COVID-19 Symptoms and Rehabilitation Needs in Hospitalized and Nonhospitalized COVID-19 Survivors with Tele-Assessment Methods.},
journal = {Telemedicine journal and e-health : the official journal of the American Telemedicine Association},
volume = {29},
number = {9},
pages = {1312-1323},
doi = {10.1089/tmj.2022.0349},
pmid = {36757300},
issn = {1556-3669},
mesh = {Humans ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; Myalgia ; Survivors/psychology ; Fatigue ; },
abstract = {Objectives: This study aimed to evaluate the post-COVID-19 symptoms, the severity of symptoms, and functional capacities seen in hospitalized and nonhospitalized COVID-19 survivors according to time periods (total 6, 1-3, and 3-6 months) by tele-assessment methods and to predict the need for periodic rehabilitation of COVID-19 survivors. Methods: Three hundred ninety-four COVID-19 survivors (50.18 ± 15.14 years) who were between 1 and 6 months after PCR(+) were included in the study, and their ongoing symptoms and the severity of these symptoms (0-10 points) were assessed with COVID-19 Yorkshire Rehabilitation Screening (C19-YRS) Tool, and the 30-s Chair Stand Test (CST) was applied by tele-assessment methods. Results: In hospitalized and nonhospitalized survivors of COVID-19, 87% experienced at least one symptom within the first 6 months. The most prevalent symptoms were anxiety (47.7%), fatigue (46.7%), and muscle pain (45.7%). The most common symptom in the nonhospitalized group was fatigue (52.6%), whereas anxiety was 46.8% in the hospitalized group. The 30-s CST score of the nonhospitalized group was significantly higher than the hospitalized group (p < 0.001). Conclusions: In the first 6 months post-COVID-19, musculoskeletal problems, anxiety, fatigue, and muscle pain were observed to be the most prevalent symptoms, regardless of time, in hospitalized and nonhospitalized survivors. There was a serious decrease in their functional capacity. Priority should be given to psychiatric, cardiopulmonary, and musculoskeletal rehabilitation in post-COVID-19. Inclusion of hospitalized/nonhospitalized COVID-19 survivors in a comprehensive rehabilitation program tailored to their needs by following a comprehensive tele-assessment by a multidisciplinary team will reduce the "long COVID-19 syndrome." ClinicalTrials.gov Registration Number: NCT04900441.},
}

Humans
*COVID-19/epidemiology
Post-Acute COVID-19 Syndrome
Myalgia
Survivors/psychology
Fatigue

@article {pmid36731604,
year = {2023},
author = {Crosier, R and Kafil, TS and Paterson, DI},
title = {Imaging for Cardiovascular Complications of COVID-19: Cardiac Manifestations in Context.},
journal = {The Canadian journal of cardiology},
volume = {39},
number = {6},
pages = {779-792},
pmid = {36731604},
issn = {1916-7075},
support = {//CIHR/Canada ; },
mesh = {Humans ; *COVID-19/complications ; *COVID-19 Vaccines/adverse effects ; Heart ; *Myocarditis/diagnostic imaging/etiology ; Post-Acute COVID-19 Syndrome ; RNA, Messenger ; },
abstract = {After the first confirmed case in 2019, COVID-19 rapidly spread worldwide and overwhelmed the medical community. In the intervening time, we have learned about COVID-19's clinical manifestations and have developed effective therapies and preventative vaccines. Severe COVID-19 infection is associated with many cardiovascular disorders in the acute phase, and patients recovered from illness can also manifest long-term sequelae, including long COVID syndrome. Furthermore, severe acute respiratory syndrome-related coronavirus-2 messenger RNA (mRNA) vaccination can trigger rare cases of myopericarditis. We have gained significant knowledge of the acute and long-term cardiovascular complications of COVID-19- and mRNA vaccine-associated myocarditis through clinical and investigative studies using cardiac imaging. In this review, we describe how cardiovascular imaging can be used to understand the cardiovascular complications and cardiac injury associated with acute COVID-19 infection, review the imaging findings in patients recovered from illness, and discuss the role and limitations of cardiac imaging in COVID-19 mRNA vaccine-associated myocarditis.},
}

Humans
*COVID-19/complications
*COVID-19 Vaccines/adverse effects
Heart
*Myocarditis/diagnostic imaging/etiology
Post-Acute COVID-19 Syndrome
RNA, Messenger

@article {pmid36552013,
year = {2022},
author = {Gryglewska-Wawrzak, K and Sakowicz, A and Banach, M and Maciejewski, M and Bielecka-Dabrowa, A},
title = {Factors of Persistent Limited Exercise Tolerance in Patients after COVID-19 with Normal Left Ventricular Ejection Fraction.},
journal = {Biomedicines},
volume = {10},
number = {12},
pages = {},
pmid = {36552013},
issn = {2227-9059},
support = {PMMHRI-BCO.75/2020//Polish Mother's Memorial Hospital Research Institute/ ; },
abstract = {Exercise intolerance de novo is one of the most common reported symptoms in patients recovering from the Coronavirus Disease 2019 (COVID-19). The present study determines etiological and pathophysiological factors influencing the mechanism of impaired exercise tolerance in patients during Long-COVID. Consequently, the factors affecting the percentage predicted oxygen uptake at peak exercise (%VO2pred) in patients after COVID-19 with a normal left ventricular ejection fraction (LVEF) were assessment. A total of 120 patients recovering from COVID-19 at three to six months after confirmed diagnosis were included. The clinical examinations, laboratory test results, echocardiography, non-invasive body mass analysis, and spiroergometry were evaluated. The subjects were divided into the following groups: study patients’ group with worsen oxygen uptake (%VO2pred < 80%; n = 47) and control group presenting%VO2pred ≥ 80% (n = 73). ClinicalTrials.gov Identifier: NCT04828629. The male gender and the percent of total body water content (TBW%) were significantly higher in the study group compared to the control group (53 vs. 29%, p = 0.007 and 52.67 (±6.41) vs. 49.89 (±4.59), p = 0.02; respectively). Patients with %VO2pred < 80% presented significantly lower global peak systolic strain (GLPS), tricuspid annular plane systolic excursion (TAPSE), and late diastolic filling (A) velocity (19.34 (±1.72)% vs. 20.10 (±1.35)%, p = 0.03; 21.86 (±4.53) vs. 24.08 (±3.20) mm, p = 0.002 and median 59.5 (IQR: 50.0−71.0) vs. 70.5 (IQR: 62.0−80.0) cm/s, p = 0.004; respectively) compared to the controls. The results of the multiple logistic regression model show that (A) velocity (OR 0.40, 95%CI: 0.17−0.95; p = 0.03) and male gender (OR 2.52, 95%CI: 1.07−5.91; p = 0.03) were independently associated with %VO2pred. Conclusions: Men have over twice the risk of persistent limited exercise tolerance in Long-COVID than women. The decreased (A) velocity, TAPSE, GLPS, and hydration status are connected with limited exercise tolerance after COVID-19 in patients with normal LVEF.},
}

@article {pmid36454631,
year = {2023},
author = {Peluso, MJ and Deveau, TM and Munter, SE and Ryder, D and Buck, A and Beck-Engeser, G and Chan, F and Lu, S and Goldberg, SA and Hoh, R and Tai, V and Torres, L and Iyer, NS and Deswal, M and Ngo, LH and Buitrago, M and Rodriguez, A and Chen, JY and Yee, BC and Chenna, A and Winslow, JW and Petropoulos, CJ and Deitchman, AN and Hellmuth, J and Spinelli, MA and Durstenfeld, MS and Hsue, PY and Kelly, JD and Martin, JN and Deeks, SG and Hunt, PW and Henrich, TJ},
title = {Chronic viral coinfections differentially affect the likelihood of developing long COVID.},
journal = {The Journal of clinical investigation},
volume = {133},
number = {3},
pages = {},
pmid = {36454631},
issn = {1558-8238},
support = {R01 AI158013/AI/NIAID NIH HHS/United States ; K24 AI145806/AI/NIAID NIH HHS/United States ; T32 AI060530/AI/NIAID NIH HHS/United States ; R21 AI167648/AI/NIAID NIH HHS/United States ; K23 AG075262/AG/NIA NIH HHS/United States ; P30 AI027763/AI/NIAID NIH HHS/United States ; R01 AI141003/AI/NIAID NIH HHS/United States ; L30 AI147159/AI/NIAID NIH HHS/United States ; R01 HL152957/HL/NHLBI NIH HHS/United States ; K23 AI157875/AI/NIAID NIH HHS/United States ; },
mesh = {Adult ; Humans ; *COVID-19/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *HIV Infections/complications/epidemiology ; *Coinfection/epidemiology ; Fatigue/epidemiology/etiology ; *Cytomegalovirus Infections ; Immunoglobulin G ; Antibodies, Viral ; },
abstract = {BACKGROUNDThe presence and reactivation of chronic viral infections, such as EBV, CMV, and HIV, have been proposed as potential contributors to long COVID (LC), but studies in well-characterized postacute cohorts of individuals with COVID-19 over a longer time course consistent with current case definitions of LC are limited.METHODSIn a cohort of 280 adults with prior SARS-CoV-2 infection, we assessed the presence and types of LC symptoms and prior medical history (including COVID-19 history and HIV status) and performed serological testing for EBV and CMV using a commercial laboratory. We used covariate-adjusted binary logistic regression models to identify independent associations between variables and LC symptoms.RESULTSWe observed that LC symptoms, such as fatigue and neurocognitive dysfunction, at a median of 4 months following initial diagnosis were independently associated with serological evidence suggesting recent EBV reactivation (early antigen-diffuse IgG positivity) or high nuclear antigen (EBNA) IgG levels but not with ongoing EBV viremia. Serological evidence suggesting recent EBV reactivation (early antigen-diffuse IgG positivity) was most strongly associated with fatigue (OR = 2.12). Underlying HIV infection was also independently associated with neurocognitive LC (OR = 2.5). Interestingly, participants who had serologic evidence of prior CMV infection were less likely to develop neurocognitive LC (OR = 0.52).CONCLUSIONOverall, these findings suggest differential effects of chronic viral coinfections on the likelihood of developing LC and association with distinct syndromic patterns. Further assessment during the acute phase of COVID-19 is warranted.TRIAL REGISTRATIONLong-term Impact of Infection with Novel Coronavirus; ClinicalTrials.gov NCT04362150.FUNDINGThis work was supported by NIH/National Institute of Allergy and Infectious Diseases grants (3R01AI141003-03S1, R01AI158013, and K24AI145806); the Zuckerberg San Francisco General Hospital Department of Medicine and Division of HIV, Infectious Diseases, and Global Medicine; and the UCSF-Bay Area Center for AIDS Research (P30-AI027763).},
}

Adult
Humans
*COVID-19/epidemiology
SARS-CoV-2
Post-Acute COVID-19 Syndrome
*HIV Infections/complications/epidemiology
*Coinfection/epidemiology
Fatigue/epidemiology/etiology
*Cytomegalovirus Infections
Immunoglobulin G
Antibodies, Viral

@article {pmid36446465,
year = {2022},
author = {Ghossein-Doha, C and Wintjens, MSJN and Janssen, EBNJ and Klein, D and Heemskerk, SCM and Asselbergs, FW and Birnie, E and Bonsel, GJ and van Bussel, BCT and Cals, JWL and Ten Cate, H and Haagsma, J and Hemmen, B and van der Horst, ICC and Kietselaer, BLJH and Klok, FA and de Kruif, MD and Linschoten, M and van Santen, S and Vernooy, K and Willems, LH and Westerborg, R and Warle, M and van Kuijk, SMJ},
title = {Prevalence, pathophysiology, prediction and health-related quality of life of long COVID: study protocol of the longitudinal multiple cohort CORona Follow Up (CORFU) study.},
journal = {BMJ open},
volume = {12},
number = {11},
pages = {e065142},
pmid = {36446465},
issn = {2044-6055},
mesh = {Humans ; Cohort Studies ; *COVID-19/epidemiology ; Follow-Up Studies ; Prevalence ; Quality of Life ; Post-Acute COVID-19 Syndrome ; },
abstract = {INTRODUCTION: The variety, time patterns and long-term prognosis of persistent COVID-19 symptoms (long COVID-19) in patients who suffered from mild to severe acute COVID-19 are incompletely understood. Cohort studies will be combined to describe the prevalence of long COVID-19 symptoms, and to explore the pathophysiological mechanisms and impact on health-related quality of life. A prediction model for long COVID-19 will be developed and internally validated to guide care in future patients.

METHODS AND ANALYSIS: Data from seven COVID-19 cohorts will be aggregated in the longitudinal multiple cohort CORona Follow Up (CORFU) study. CORFU includes Dutch patients who suffered from COVID-19 at home, were hospitalised without or with intensive care unit treatment, needed inpatient or outpatient rehabilitation and controls who did not suffer from COVID-19. Individual cohort study designs were aligned and follow-up has been synchronised. Cohort participants will be followed up for a maximum of 24 months after acute infection. Next to the clinical characteristics measured in individual cohorts, the CORFU questionnaire on long COVID-19 outcomes and determinants will be administered digitally at 3, 6, 12, 18 and 24 months after the infection. The primary outcome is the prevalence of long COVID-19 symptoms up to 2 years after acute infection. Secondary outcomes are health-related quality of life (eg, EQ-5D), physical functioning, and the prevalence of thromboembolic complications, respiratory complications, cardiovascular diseases and endothelial dysfunction. A prediction model and a patient platform prototype will be developed.

ETHICS AND DISSEMINATION: Approval was obtained from the medical research ethics committee of Maastricht University Medical Center+ and Maastricht University (METC 2021-2990) and local committees of the participating cohorts. The project is supported by ZonMW and EuroQol Research Foundation. Results will be published in open access peer-reviewed scientific journals and presented at (inter)national conferences.

TRIAL REGISTRATION NUMBER: NCT05240742.},
}

Humans
Cohort Studies
*COVID-19/epidemiology
Follow-Up Studies
Prevalence
Quality of Life
Post-Acute COVID-19 Syndrome