@article {pmid42040960,
year = {2026},
author = {Valverde, A and Capistrano, K and Naqvi, RA and Elshourbagy, S and Etminan, S and Sandoval, G and Bambrilla, M and Nares, S and Shukla, D and Schwartz, J and Naqvi, A},
title = {Periodontitis Primes the Oral Microenvironment for PS-Dependent Non-Canonical Entry Pathways Linked to SARS-CoV-2 Susceptibility.},
journal = {Research square},
volume = {},
number = {},
pages = {},
pmid = {42040960},
issn = {2693-5015},
abstract = {SARS-CoV-2 infection extends beyond the respiratory tract, with the oral cavity emerging as a critical site of viral activity shaped by epithelial receptor expression, microbial interactions, and inflammatory status. Periodontal disease (PD), a chronic dysbiotic condition, may heighten susceptibility to SARS-CoV-2 through inflammation-driven upregulation of non-canonical viral entry pathways. In this study, we investigated genes in the phosphatidylserine (PS)-dependent pathway, including ADAM17, ATP11c, TIM1, TIM3, and TIM4, in gingival tissue, saliva, and oral keratinocytes to define how PD and SARS-CoV-2 coordinately modulate oral viral entry mechanisms. Prepandemic gingival biopsies revealed significant upregulation of all non-canonical receptors in inflamed tissue, indicating that PD alone establishes a permissive molecular environment for PS-mediated microbial entry. In a post-vaccination cohort, salivary expression of these receptors was markedly elevated in COVID-19-positive individuals with PD, accompanied by significantly increased salivary PS levels, suggesting synergistic effects of viral exposure and periodontal inflammation. In vitro co-infection of primary human oral keratinocytes with SARS-CoV-2 and periodontal pathogens (P. gingivalis, A. actinomycetemcomitans) induced robust, synergistic activation of PS-dependent entry genes, particularly TIM family receptors. Together, these findings identify PS and its associated receptors as inflammation-responsive mediators that expand SARS-CoV-2 entry routes in the oral mucosa. This work highlights a mechanistic intersection between COVID-19 and periodontal disease, with implications for viral persistence, immune dysregulation, and long-term oral health outcomes.},
}

@article {pmid42107843,
year = {2026},
author = {Floridia, M and Weimer, LE and Lo Forte, A and Palange, P and Agostoni, P and Ciardi, MR and Tosato, M and Lacedonia, D and Gnerre, P and Barisione, E and Martino, GP and Vagheggini, G and Onder, G and , },
title = {Dyspnea and fatigue in Long-COVID: definition of risk factors and of DLCO-based phenotypes in a multicenter study of 765 patients from Italy.},
journal = {Respiratory medicine},
volume = {},
number = {},
pages = {108880},
doi = {10.1016/j.rmed.2026.108880},
pmid = {42107843},
issn = {1532-3064},
abstract = {BACKGROUND: Dyspnea and fatigue represent common Long-COVID symptoms, but their presence is not always accompanied by lung function abnormalities. Aim of the study was to evaluate dyspnea and fatigue in relation to pulmonary function and exercise capacity.

METHODS: Multicenter cohort study. Multivariable analyses were used to characterize, for both symptoms, functional phenotypes with and without pulmonary impairment according to the diffusing lung capacity for carbon monoxide (DLCO). Exercise capacity was assessed through the distance walked in 6 minutes (6MWD).

RESULTS: Among 765 patients evaluated at a mean interval of six months from COVID-19, rates of dyspnea and fatigue were 41.3% and 41.6%, respectively. Roughly half of the patients with these two symptoms (51.6% and 54.7%, respectively) had normal pulmonary function at DLCO testing (≥80% of predicted). Low-DLCO (<80%) dyspnea was significantly associated with female sex, anxiety, duration of hospitalisation, use of corticosteroids and of monoclonal neutralizing antibodies, and its risk decreased at the increasing in time from acute infection. Normal-DLCO dyspnea was associated with younger age and obesity. Low-DLCO fatigue was associated with female sex, heart failure, anxiety and use of corticosteroids. Normal-DLCO fatigue was not associated with demographics, comorbidities, or COVID-19 severity. For both symptoms, the low-DLCO phenotypes had a significantly lower 6MWD.

CONCLUSIONS: The clinical phenotypes of dyspnea and fatigue with normal pulmonary function should be further explored, possibly with additional tests that assess cardiorespiratory and cardiovascular function. DLCO testing should be included in the evaluation of patients who report dyspnea and/or fatigue as possible Long-COVID symptoms.},
}

@article {pmid42108247,
year = {2026},
author = {Yamamoto, S and Kurano, M and Okamoto, K and Kubota, M and Tsutsumi, T and Aoki, J and Moriya, K},
title = {Sphingolipid and glycerophospholipid profiling in post-acute sequelae of SARS-CoV-2 infection.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-50505-2},
pmid = {42108247},
issn = {2045-2322},
abstract = {Post-acute sequelae of severe acute respiratory syndrome coronavirus 2 infection (PASC) is a heterogeneous multisystemic condition with unclear pathogenesis. Emerging evidence suggests that the disruption in metabolism, including lipid metabolism, can be involved in the pathogenesis of coronavirus disease 2019 (COVID-19). We previously measured the bioactive lipids in acute COVID-19, and we hypothesized that bioactive lipid dysregulation play a role in PASC pathogenesis. We conducted targeted LC-MS/MS analysis of sphingolipids and glycerophospholipids in serum samples from individuals with acute-phase COVID-19, including those who developed PASC, alongside healthy controls. We systematically examined lipidomic changes in serum samples, including analyses using linear mixed model, and found that no sphingolipid or glycerophospholipid species differed between the COVID-19 and PASC groups. Although these results are exploratory, the group x time interaction in the linear mixed model suggested that phosphatidylglycerol (PG) may represent a bioactive lipid distinguishing the COVID-19 and PASC groups. Given the small PASC sample size and that the signal was detected only at specific time points, these findings are hypothesis generating and should be confirmed in larger, adequately powered, and independently validated cohorts.},
}

@article {pmid42108528,
year = {2026},
author = {Mosha Miller, SA and Hicar, MD and Berry, CS and Anderson, KB and Lindo, JF and Morse, GD and Christie, CDC},
title = {Long COVID-19 in Hospitalized and Ambulatory Children in Jamaica.},
journal = {The Pediatric infectious disease journal},
volume = {},
number = {},
pages = {},
doi = {10.1097/INF.0000000000005259},
pmid = {42108528},
issn = {1532-0987},
abstract = {This retrospective observational cohort study evaluated acute illness predictors of pediatric Long coronavirus disease 2019 in Jamaica. Poisson regression modeling associated acute univariate symptoms of vomiting, abdominal pain, ageusia, anosmia, fatigue, confusion, brain fog, and multisystem inflammatory syndrome in children and multivariable composite predictors of multisystem inflammatory syndrome in children, vomiting and ageusia. The 47.3% incidence supports the need for improvements in similar resource-constrained settings.},
}

@article {pmid42108714,
year = {2026},
author = {Jang, E and Nan, Y and Chang, H and Young, LE},
title = {Disentangling the Network Structure of Online Social Support: A Multilayer Network Analysis of a Twitter Long COVID Community.},
journal = {Health communication},
volume = {},
number = {},
pages = {1-12},
doi = {10.1080/10410236.2026.2672056},
pmid = {42108714},
issn = {1532-7027},
abstract = {Online social support has been shown to be an important resource for people experiencing chronic illnesses. Although numerous studies have examined online support communities, few have conducted in-depth analyses grounded in social network theory and methodologies. To address this gap, this study investigates the types of support and the overall patterning of such exchanges (i.e., the network structure) on Twitter (now X), focusing on a community of people who seek and provide support for Long COVID. Using an exhaustive keyword-based corpus of Long COVID tweets (N = 19,196) collected from August 1-31, 2021, we identified two types of social support shared in this community-informational and emotional-through human annotation combined with supervised machine learning. Conducting descriptive and stochastic social network analysis, we examined how exchanges of each type of support were structured. We focused on the density, reciprocity, and centralization of support ties-three structural features shown to be related to specific types of support. Our results showed that informational support was more prevalent than emotional support. Additionally, these informational and emotional support networks tended to be both reciprocal and concentrated around a small number of central users who received considerable support (i.e., were centralized). Our findings suggest that online health communities hosted on platforms such as Twitter may be better suited for informational support. We also observed that central actors play an important role in facilitating these exchanges. These findings provide practical insights for effective social network interventions.},
}

@article {pmid42109469,
year = {2026},
author = {Cardenas-Jara, AR and Ongaya, A and Shiluli, C and Ramos, LB and Senador, LC and Flores, JA and Kanoi, BN and Reijneveld, JF and Ruvalcaba, A and Perez, D and Waiganjo, P and Lindestam-Arlehamn, CS and Henrich, TJ and Peluso, MJ and Leon, SR and Gitaka, J and Suliman, S},
title = {Prevalence of Long COVID in Mycobacterium tuberculosis-exposed groups.},
journal = {Journal of clinical tuberculosis and other mycobacterial diseases},
volume = {44},
number = {},
pages = {100610},
pmid = {42109469},
issn = {2405-5794},
abstract = {OBJECTIVES: Long COVID (LC), i.e. the persistence of new or worsening symptoms for 3 months after Severe Acute Respiratory Syndrome of Coronavirus 2 (SARS-CoV-2) infection, is an emerging global health burden. The prevalence of LC remains poorly characterized in low- and middle-income countries (LMICs), where other respiratory diseases, like tuberculosis (TB), are prevalent. We aimed to address this gap in Mycobacterium tuberculosis (Mtb)-exposed populations in Peru.

METHODS: We recruited people with TB (n = 36) and their asymptomatic household contacts (n = 63) in Peru. We collected clinical data using a questionnaire adapted from a United States-based study of LC. Participants were recruited within 2 years of SARS-CoV-2 diagnosis.

RESULTS: In Peru, 41% participants reported LC symptoms. The most common LC symptoms were neurological (e.g., headache) and musculoskeletal (e.g., back pain). We did not detect an association between TB disease or Mtb infection and LC at this sample size. However, the quality-of-life dimensions worsened during the post-COVID period.

CONCLUSIONS: LC prevalence in Peru aligns with global trends, underscoring significant health burdens. Those with LC reported high levels of musculoskeletal and neurological symptoms, highlighting the need for long-term follow-up and larger studies in different geographic settings to dissect the impact of TB comorbidity on LC.},
}

@article {pmid42109976,
year = {2026},
author = {Ballard, DW and Warton, EM and Skarbinski, J and Siqueiros, MH and Cholleti, SM and Vinson, DR and Mark, DG and Durant, EJ and DiLena, DD and Reed, ME},
title = {The Long Tail of Long COVID-19: Broad and Extensive Increase in Utilization Within an Integrated Healthcare System.},
journal = {Cureus},
volume = {18},
number = {4},
pages = {e106676},
pmid = {42109976},
issn = {2168-8184},
abstract = {BACKGROUND: The impact of the emergence of Long COVID on healthcare utilization in a U.S. community setting remains underexplored.

OBJECTIVE: To examine the healthcare utilization of Long COVID patients compared with pre-COVID-19 era controls before and after SARS-CoV-2 infection within a large integrated delivery system.

METHODS: This was a retrospective cohort study of adult patients with documented SARS-CoV-2 infection (1/1/2021-6/30/2022) in a multi-site Northern California health system. Long COVID diagnosis was defined by at least one encounter with an associated International Classification of Diseases, Tenth Revision code and/or referral to Long COVID specialty care. Utilization outcomes included inpatient/outpatient encounters, laboratory/imaging/functional testing, specialty care referrals/encounters, and medication use. We used propensity-weighted difference-in-differences models adjusted for study month to compare outcomes between baseline and post-SARS-CoV-2 infection (Long COVID window).  Results: Among 600,295 patients with 635,230 SARS-CoV-2 episodes, 3,545 met criteria for Long COVID care-seeking. Long COVID patients had higher baseline utilization and greater increases in post-diagnosis utilization in adjusted analyses. After propensity weighting, these differences persisted and were consistent across the study period, particularly in cardiac and pulmonary care. Total encounters per year were 29.9 post and 14.1 pre (Long COVID) versus 17.7 post and 12.5 pre (NO Long COVID). Total annual ED visits per 100 patients were 65.1 post and 38.0 pre (Long COVID) versus 38.0 post and 32.0 pre (NO Long COVID). Annual hospitalizations per 100 patients were 10.5 post and 5.3 pre (Long COVID) versus 7.4 post and 5.5 pre (NO Long COVID).

CONCLUSION: Long COVID patients had higher healthcare utilization before and after diagnosis, with sharper increases across nearly all outcomes.},
}

@article {pmid42111378,
year = {2026},
author = {Mali, I and Harrison, M and Frizzell, B and Castro, M and McHorse, A and Que, LG and Mummy, D and Niedbalski, PJ},
title = {Using hyperpolarised xenon-129 magnetic resonance imaging to investigate longitudinal effects of long COVID on pulmonary function.},
journal = {ERJ open research},
volume = {12},
number = {2},
pages = {},
pmid = {42111378},
issn = {2312-0541},
abstract = {Hyperpolarised [129]Xe MRI shows significant improvements in VDP and select gas exchange metrics at ∼20 months compared to ∼14 months following initial COVID-19 infection https://bit.ly/3LoJry4.},
}

@article {pmid42103518,
year = {2027},
author = {Philip, KEJ and Owles, H and McVey, S and Pagnuco, T and Bruce, K and Warnock, B and Chomacki, A and Brunjes, H and Mollica, J and Lound, A and Zumpe, S and Abrahams, AM and Padmanaban, V and Hardy, TH and Lewis, A and Lalvani, A and Elkin, SL and Hopkinson, NS},
title = {An online singing-based breathing and wellbeing programme (ENO Breathe) in people with long COVID breathlessness in the UK: a cohort study.},
journal = {The Lancet. Digital health},
volume = {},
number = {},
pages = {100988},
doi = {10.1016/j.landig.2026.100988},
pmid = {42103518},
issn = {2589-7500},
abstract = {BACKGROUND: Post-COVID-19 condition (also known as long COVID) breathlessness is a common, complex, and frequently debilitating problem for which few evidence-based interventions exist. A previous randomised trial found that participation in an online 6-week breathing and wellbeing programme (ENO Breathe), using singing techniques, was associated with improvements in health-related quality of life (HRQOL) and breathlessness. We aimed to assess the impact of this intervention outside a trial setting.

METHODS: In this cohort study, participants were referred from 51 UK-based National Health Service (NHS) long COVID clinics, where they had been diagnosed with breathlessness due to long COVID. The eligibility criteria of ENO Breathe were age 18 years or older, having long COVID with associated breathlessness, diagnosis and referral from a specialist collaborating NHS long COVID clinic, and access and ability to engage with the online programme. We compared baseline and post-intervention data to assess the effect of the ENO Breathe programme on HRQOL assessed using the RAND-36 Mental and Physical Health Composite (MHC and PHC) primary outcome, with an estimated minimally clinically important difference of 3; breathlessness (assessed using Dyspnoea-12 scores and visual analogue scales [VAS] for breathlessness at rest, walking, using stairs, and running); anxiety (assessed using the Generalised Anxiety Disorder-7 questionnaire [GAD-7]); and respiratory symptoms (assessed using the COPD Assessment Test [CAT]).

FINDINGS: 1413 programme participants were included in this analysis (mean age 49 years [SD 11·9], BMI 28 kg/m[2] [7·2]). 1130 (80%) participants were female, 273 (19%) were male, and ten (1%) did not disclose their gender. 1165 (82%) participants were White, 87 (6%) were Asian, 47 (3%) were Black, 48 (3%) were of mixed or multiple ethnic backgrounds, 31 (2%) reported their ethnicity or race as other (ie, not one of the categories specified), and 35 (2%) did not disclose their ethnicity or race. Participants reported having long COVID symptoms for a median of 415 days (IQR 246-601) at the time of registration with the programme. 1188 (84%) of 1413 participants provided follow-up data on completion of the programme. Completing ENO Breathe was associated with improvements in HRQOL (median difference in RAND-36 MHC 2·98, IQR -1·53 to 8·42; and median difference in PHC 1·69, -1·32 to 5·01), breathlessness (mean difference in Dyspnoea-12 -4·29, 95% CI -4·64 to -3·94; VAS breathlessness scores walking median difference -5, IQR -18 to 6; stairs median difference -10, -25 to 3; and running median difference -3, -19 to 0), anxiety (median GAD-7 score difference -1, IQR -4 to 1), and respiratory symptom impact (mean CAT score difference -2·50, -2·81 to -2·19; all p<0·0001). The VAS breathlessness score at rest did not significantly change (median difference 0, IQR -10 to 13; p=0·24). The response to the ENO Breathe intervention did not differ by age, gender, ethnicity, or pre-existing asthma. There were no reported clinically significant adverse events.

INTERPRETATION: The ENO Breathe programme can improve HRQOL, breathlessness, anxiety, and respiratory symptoms in people with long COVID and breathlessness. ENO Breathe could be tested in other major causes of breathlessness and might help inform the development and delivery of other related interventions.

FUNDING: Imperial College London.},
}

@article {pmid42106490,
year = {2026},
author = {Azabou, E and Pillot, A and Bao, G and Mehlal, S and Arnould, A and Agar-Hug, N and Zagdoun, M and Genolini, A and Russo, A and Rangon, CM and Azouvi, P},
title = {Transcutaneous auricular vagus nerve stimulation improves dysautonomia, post-traumatic stress disorder and cognitive impairment in long covid patients: a pilot study.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-52582-9},
pmid = {42106490},
issn = {2045-2322},
abstract = {Long COVID is frequently associated with persistent autonomic dysfunction, cognitive impairment, and psychological distress, reflecting sustained neuroimmune and autonomic dysregulation. Effective disease-modifying therapies remain scarce. To evaluate the effects of transcutaneous auricular vagus nerve stimulation (taVNS) on autonomic symptoms, post-traumatic stress symptoms, and cognitive performance in patients with long COVID. In this open-label, single-arm prospective pilot study, seventeen patients with long COVID underwent weekly one-hour taVNS sessions for eight consecutive weeks. Autonomic symptoms were assessed using the Composite Autonomic Symptom Score-31 (COMPASS-31), psychological symptoms using the PTSD Checklist for DSM-5 (PCL-5), and cognitive function using a standardized attention and executive function battery (COGBAT). Outcomes were evaluated at baseline and post-intervention. Paired non-parametric analyses were performed. Following taVNS, autonomic symptoms improved significantly, with mean COMPASS-31 scores decreasing from 33.71 ± 16.81 to 13.78 ± 9.38 (p < 0.0001). Post-traumatic stress symptoms were significantly reduced (PCL-5: 25.76 ± 14.99 to 19.47 ± 14.63; p = 0.028). Cognitive performance improved, with COGBAT scores increasing from 37.71 ± 25.75 to 49.41 ± 26.79 (p = 0.011). No adverse events were reported. taVNS appears to be a safe and promising non-pharmacological intervention for improving autonomic dysfunction, cognitive impairment, and psychological symptoms in long COVID. These findings warrant confirmation in randomized, sham-controlled trials.},
}

@article {pmid42095154,
year = {2026},
author = {Rakab, MS and Mirza, I and Ali, MM and Khan, A and Darbar, D and Mahmoud, AM},
title = {Endothelial and cardiac dysfunction in long COVID With cardiovascular symptoms is associated with imbalance in the ADMA-DDAH-NOx pathway.},
journal = {Frontiers in cardiovascular medicine},
volume = {13},
number = {},
pages = {1802359},
pmid = {42095154},
issn = {2297-055X},
abstract = {BACKGROUND: Post-acute sequelae of COVID-19 (PASC) commonly feature lingering symptoms of persistent cardiovascular pathology, yet the mechanisms remain incompletely defined. The ADMA-DDAH-NOx axis is a central regulator of endothelial function: ADMA inhibits endothelial NOx synthase, while DDAH clears most circulating ADMA. Although ADMA is linked to acute COVID-19 severity, its regulation in PASC remains largely unknown.

METHODS: We performed integrated vascular and cardiac phenotyping in 49 RECOVER participants: never-infected controls (n = 10), recovered COVID-19 without persistent symptoms (PASC-, n = 20), and PASC with persistent cardiovascular-related symptoms lasting ≥12 weeks post-infection (PASC+, n = 19). We measured ADMA, DDAH, NO, inflammatory/coagulation markers, endothelial function [brachial and microvascular flow-mediated dilation (FMD)], and cardiac structure and function using comprehensive echocardiography with speckle-tracking strain.

RESULTS: PASC+ exhibited the highest inflammatory and thrombotic markers, with D-dimer being > 3-fold higher than controls, and hs-CRP nearly threefold higher. PASC+ demonstrated lower NOx and substantially higher ADMA than the other two groups, accompanied by only modest DDAH upregulation, suggesting insufficient counter-regulation. Endothelial function was significantly impaired in the PASC+ group compared to the control and PASC- groups, as evidenced by lower brachial and microvascular FMD. PASC+ individuals exhibited worse longitudinal mechanics and higher levels of hs-troponin and NT-proBNP. Ejection fraction was lower in PASC+ compared with Controls and PASC-.

CONCLUSIONS: These findings identify an imbalance in the ADMA-DDAH-NOx axis that is associated with endothelial dysfunction and cardiac involvement in cardiovascular-symptom PASC, supporting a potentially targetable pathway for risk stratification and therapeutic investigation.},
}

@article {pmid42099508,
year = {2026},
author = {Kawaguchi, M and Sakurada, Y and Tokumasu, K and Otsuka, Y and Nakano, Y and Matsuda, Y and Honda, H and Omura, D and Matsuki, N and Furukawa, M and Higashikage, A and Otsuka, F},
title = {Clinical Utility of SARS-CoV-2 Antibody Titers in the Management of Patients With Long COVID Infected With the Omicron Variant.},
journal = {British journal of biomedical science},
volume = {83},
number = {},
pages = {16255},
pmid = {42099508},
issn = {2474-0896},
mesh = {Humans ; Male ; Female ; *COVID-19/immunology/blood/virology/diagnosis ; Middle Aged ; *SARS-CoV-2/immunology ; Retrospective Studies ; *Antibodies, Viral/blood ; Adult ; Aged ; Spike Glycoprotein, Coronavirus/immunology ; COVID-19 Vaccines/administration & dosage/immunology ; Coronavirus Nucleocapsid Proteins/immunology ; },
abstract = {BACKGROUND: Long COVID (LC) presents persistent symptoms that pose a major clinical challenge. Identification of reliable biomarkers to evaluate LC pathophysiology is needed.

OBJECTIVES: To investigate whether serum S- and N-antibody titers against SARS-CoV-2 spike and nucleocapsid proteins reflect the clinical features of LC.

METHODS: This retrospective observational study included patients diagnosed with Omicron variant-related LC who attended a post-COVID-19 outpatient clinic between July 2023 and November 2024 and provided informed consent for antibody testing.

RESULTS: Among 275 patients (129 men and 146 women), 57 (21%) were unvaccinated. Median S- and N-antibody titers in vaccinated versus unvaccinated patients were 20,963 U/mL and 24.8 cut-off index (COI) versus 24 U/mL and 44.5 COI, respectively. S-antibody titers were associated with the number of vaccine doses received, whereas N-antibody titers correlated with disease severity during the acute phase of COVID-19 infection, with females having higher titers by multivariable analysis. N-antibody titers in unvaccinated patients with LC were negatively correlated with time interval from infection to clinic visit, with an estimated daily decline of 0.34% in measured N-antibody levels. Patients with LC having memory impairment had low S-antibody titers by multivariable logistic regression analysis, and low S-antibody levels were associated with reduced quality of life (QOL). Additionally, N-antibody titers positively correlated with lymphocyte counts and immunoglobulin levels.

CONCLUSION: Serum N-antibody titers reflect immune responses to COVID-19, although they are affected by gender differences and interval between infection and evaluation. Lower S-antibody titers were associated with brain fog symptoms and reduced QOL in patients with LC.},
}

Humans
Male
Female
*COVID-19/immunology/blood/virology/diagnosis
Middle Aged
*SARS-CoV-2/immunology
Retrospective Studies
*Antibodies, Viral/blood
Adult
Aged
Spike Glycoprotein, Coronavirus/immunology
COVID-19 Vaccines/administration & dosage/immunology
Coronavirus Nucleocapsid Proteins/immunology

@article {pmid42099668,
year = {2026},
author = {McAlpine, LS and Shorer, EF and Chiarella, J and Nelson, A and Veenhuis, R and Azola, A and Lee, A and Pierce, R and Farhadian, S and Rubin, LH and Spudich, SS and , and , },
title = {Vascular inflammation in neuropsychiatric long COVID.},
journal = {Brain, behavior, & immunity - health},
volume = {54},
number = {},
pages = {101247},
pmid = {42099668},
issn = {2666-3546},
abstract = {The role of vascular inflammation in neuropsychiatric Long COVID (LC) is suspected but not well understood. This study evaluated whether vascular inflammation is present in individuals with neuropsychiatric LC and how it relates to cognitive and mental health symptoms. This cross-sectional, case-control study included individuals with acute COVID-19 (AC), neuropsychiatric LC, and recovered controls. Participants were enrolled from the COVID Mind Study and the Yale IMPACT Study (hospitalized), and an independent cohort from the Johns Hopkins University (JHU) Long COVID Study. Fifty individuals with neuropsychiatric LC (new symptoms a median of 368 days post-COVID), 28 with AC, and 29 recovered controls (>3 months post-COVID) were evaluated. All underwent blood sampling and neuropsychiatric testing. The JHU cohort included 114 individuals with late LC (median 1065 days post-COVID illness associated with LC onset) and 31 recovered controls (median 852 days). Fourteen plasma biomarkers of vascular inflammation were measured. ANCOVA was used to compare groups, adjusting for comorbidities. Non-hospitalized participants completed the Global Neuropsychological Assessment, GAD-7, and PHQ-9. LC and recovered groups were demographically similar, while AC participants had higher obesity and hypertension rates. LC participants had elevated circulating biomarkers of endothelial, leukocyte, and platelet adhesion (sL-selectin, ADAMTS13, sP-selectin, sICAM-1) compared to recovered controls. Coagulation markers (D-dimer, fibrinogen) did not differ. Most biomarkers were highest in AC and lower in LC; however, fetuin, sL-selectin, and α-2 macroglobulin were higher in LC than AC. In LC, higher sP-selectin correlated with lower fluency and verbal learning. Lower α1-acid glycoprotein levels were strongly associated with poorer verbal memory, verbal learning, fluency, depression, and anxiety. In the JHU cohort, late LC and recovered controls showed no differences in biomarkers or demographics, suggesting normalization over time. Persistent dysregulation at the intersection of inflammation, platelet adhesion, and endothelial dysfunction is strongly linked to neuropsychiatric Long COVID. Elevated markers of endothelial adhesion in LC suggest distinct pathophysiology from AC. These biomarkers correlate with lower fluency and verbal learning, linking vascular dysfunction to brain function. This study underscores the critical need for longitudinal, within-person investigations to elucidate how vascular inflammation evolves over time.},
}

@article {pmid42099690,
year = {2026},
author = {Phafane, MP and Isabirye, A and Reddy, P},
title = {Predictors of Long COVID-19 Syndrome and Hospital Admissions Among COVID-19-Diagnosed Adult Patients Who Self-Isolated at Home in KwaZulu-Natal Province, South Africa.},
journal = {Nursing research and practice},
volume = {2026},
number = {},
pages = {9317685},
pmid = {42099690},
issn = {2090-1429},
abstract = {Long COVID-19 (LC) syndrome is a complex systemic illness that is currently recognised to have a high morbidity rate and hospitalisations. The study analysed factors linked to LC in adults self-isolated during COVID-19 infection in KwaZulu-Natal Province, South Africa, focusing on two densely populated districts (uMgungundlovu and eThekwini Metro Municipality). We employed a cross-sectional study among individuals aged 18 years and above who self-isolated at home. Demographic data, COVID-19 vaccination status, and post-COVID-19 health symptoms were collected using a standardised questionnaire. The National Health and Nutrition Survey's Physical Functioning Questionnaire was adapted to evaluate health and functional outcomes six months after a COVID-19 diagnosis, addressing both physical and psychosocial symptoms during that timeframe. A modified Poisson regression model was used to determine the predictors of LC and hospitalisation. Of the 280 participants, 46% (n = 130) reported having at least one health-related symptom, while 36% (n = 47) had ≥ five symptoms. Approximately half of the participants (50%, n = 139) had at least one hospital admission following infection due to persistent symptoms. Older age (aIRR 1.5; 95% CI: 1.2-3.2; p = 0.021), reinfection (aIRR 2.0; 95% CI: 1.3-3.0; p = 0.001), having positive household contacts (aIRR 2.1; 95% CI: 1.4-3.2; p < 0.001) and hospitalisation (aIRR 7.7; 95% CI: 3.8-15.6; p < 0.001) increased the risk of developing LC. Post-infection hospitalisation was significantly associated with symptoms such as anxiety (aIRR 1.4; 95% CI: 1.1-1.7; p = 0.009), depression (aIRR 1.9; 95% CI: 1.6-2.3; p < 0.001), sore throat (aIRR 1.5; 95% CI: 1.7-2.0; p = 0.002) and weight loss (aIRR 1.8; 95% CI: 1.4-2.4; p < 0.001). A considerable percentage of participants with post-SARS-CoV-2 infections presented with long-term complications and required medical intervention. Postpandemic healthcare planning and resource allocation need to be considered since increased morbidities associated with LC place a burden on the already inadequately funded healthcare system.},
}

@article {pmid42101066,
year = {2026},
author = {Boufleuer, E and Vieira, TW and Sakamoto, VTM and Anschau, F and Tavares, JP and Filho, FFD and Pai, DD},
title = {Psychological and Cognitive Sequelae of COVID-19: Systematic Review and Meta-Analysis.},
journal = {Journal of psychiatric and mental health nursing},
volume = {},
number = {},
pages = {},
doi = {10.1111/jpm.70139},
pmid = {42101066},
issn = {1365-2850},
support = {312850/2025-5//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; },
abstract = {INTRODUCTION: COVID-19 pandemic has exacerbated global mental health problems with the development of persistent symptoms.

AIM: To conduct a prevalence meta-analysis of persistent psychological and cognitive sequelae of COVID-19 based on cohort studies.

METHOD: This study followed PRISMA. Cohort studies that followed individuals for at least 12 weeks post-COVID-19 were included and pediatric studies were excluded. The databases Embase, Lilacs/BVS, PubMed, SciELO and Scopus were searched in November 2023. Meta-analyses were performed with subgroup analyses conducted. Results were presented with forest plot graphs and tables. Risk of bias and methodological quality were assessed using Eggers's Test and the Newcastle-Ottawa Scale.

RESULTS: 2,456 studies were identified and screened. Forty-seven articles were included in the systematic review, and 46 in the meta-analysis (192,158 participants). The most prevalent psychological outcome was anxiety (0.17; 95% CI 0.11-0.27, 19 studies), followed by cognitive impairments (0.15; 95% CI 0.11-0.20, 35 studies), sleep disturbances (0.14; 95% CI 0.09-0.19, 33 studies) and depression (0.11; 95% CI 0.06-0.19, 16 studies).

DISCUSSION: The mental health consequences of COVID-19 highlight the need for long-term monitoring and represent a significant public health challenge. The limitation is the heterogeneity among the studies.

These findings represent a public health issue emphasizing the need for public policies and support strategies to mitigate consequences.

CONCLUSION: Although high prevalence rates were identified, the prediction intervals were wide and heterogeneity remained high-common characteristics of studies conducted during the pandemic.

REGISTRATION: Registered in the international Prospective Register of Ongoing Systematic Reviews (PROSPERO) under number CRD42023460632, on September 5, 2023.},
}

@article {pmid42101068,
year = {2026},
author = {Lin, CH and Lai, CY and Chang, CY and Chao, TC and Song, CY and Chang, CC and Chang, WY and Huang, CY and Jhuang, JW and Chiang, SL},
title = {Factors associated with low anaerobic threshold and its impact on sleep quality and health-related quality of life in individuals with long COVID.},
journal = {PM & R : the journal of injury, function, and rehabilitation},
volume = {},
number = {},
pages = {},
doi = {10.1002/pmrj.70133},
pmid = {42101068},
issn = {1934-1563},
support = {TSGH-E-113279//Tri-Service General Hospital/ ; TSGH-E-114273//Tri-Service General Hospital/ ; TSGH-E-115276//Tri-Service General Hospital/ ; MND-MAB-D-114120//Medical Affairs Bureau, Ministry of National Defense/ ; MND-MAB-D-115223//Medical Affairs Bureau, Ministry of National Defense/ ; 114-2221-E-016-002-MY2//National Science and Technology Council/ ; },
abstract = {INTRODUCTION: Anaerobic threshold (AT), a crucial indicator of submaximal exercise capacity and cardiorespiratory function, has been reported to be impaired in individuals with long COVID. However, the predictors of reduced AT during exercise in this population and its impacts on patient-reported outcomes, including sleep quality and health-related quality of life (HRQL), remain unknown. This study aims to identify factors associated with low AT and examine its relationship with patient-reported outcomes.

OBJECTIVE: To investigate the predictors of low AT and compare patient-reported outcomes (sleep quality and HRQL) between individuals with normal and low AT among those with long COVID.

DESIGN: Cross-sectional study.

SETTING: Post-COVID integrated outpatient clinic at a medical center in northern Taiwan.

PATIENTS (OR PARTICIPANTS): Eligible patients aged 20-80 years with long COVID were recruited.

INTERVENTIONS: Not applicable.

MAIN OUTCOME MEASURE(S): AT, peak oxygen consumption (peak VO2), and patient-reported outcomes, including sleep quality and HRQL, assessed using the Taiwanese version of the World Health Organization Quality of Life-BREF and Pittsburgh Sleep Quality Index.

RESULTS: Factors associated with low AT included younger age (odds ratio [OR] = 0.904, 95% confidence interval [CI]: 0.867-0.942, p < .001) and lower peak VO2 (OR = 0.737, 95% CI: 0.659-0.842, p < .001). Participants with low AT exhibited impaired patient-reported outcomes including poorer sleep quality (p = .008), and lower HRQL scores across all domains, as compared to those with normal AT. After adjustment for significant covariates, only the psychological domain of HRQL remained statistically significant (adjusted p = .035).

CONCLUSIONS: Low AT in individuals with long COVID was associated with younger age and lower peak VO2. Its independent impact on sleep quality and HRQL appears limited, suggesting that patient-reported outcomes may be influenced by multiple interacting factors and warrant further investigation.},
}

@article {pmid42101592,
year = {2026},
author = {Knowles, LM and O'Loughlin, KM and Gentile, NL and Herring, TE},
title = {Managing Anxiety and Depression Symptoms in Long COVID.},
journal = {American family physician},
volume = {113},
number = {4},
pages = {315-317},
pmid = {42101592},
issn = {1532-0650},
}

@article {pmid42102594,
year = {2026},
author = {Shen, Y and Shahn, Z and Robertson, MM and Gebo, K and Nash, D and , },
title = {Effect of a third COVID-19 vaccine dose on the incidence of Long COVID among adults who completed a primary vaccine series: a target trial emulation in a community-based cohort.},
journal = {Vaccine},
volume = {84},
number = {},
pages = {128666},
doi = {10.1016/j.vaccine.2026.128666},
pmid = {42102594},
issn = {1873-2518},
abstract = {BACKGROUND: Evidence on whether a third COVID-19 vaccine dose lowers long COVID risk is mixed. We estimated the effect of receiving ≥1 third dose versus completing only a primary series on 6- and 12-month long COVID incidence using a target-trial emulation in a U.S. community cohort.

METHODS: We analyzed the CHASING COVID Cohort, a prospective, community-based study of U.S. adults. Eligible participants were ≥ 18 years, had completed a two-dose primary series, had no prior long COVID, and had no SARS-CoV-2 infection in the 3 months before time zero. Strategies compared were: receive a third dose at time zero vs. not receive a third dose during follow-up. Long COVID was defined as ≥1 new symptom at or beyond 3 months post-infection with concurrent activity limitation, both absent in the prior year. Follow-up was 6 and 12 months. We used a per-protocol analog: participants were artificially censored upon deviating from their assigned strategy or lost-to-follow-up, with inverse-probability weights to address selection due to censoring and time-varying confounding. We fit weighted pooled logistic models to estimate weighted incidence, differences, and ratios at each horizon.

RESULTS: Across 16 sequential trials (18,930 person-trials; 4044 unique individuals), 3321 person-trials received a third dose at time zero and 15,609 did not. At 6 months, weighted long COVID incidence was 0.9% (95% CI, 0.5%, 1.3%) with a third dose vs. 1.0% (0.8%, 1.1%) without (risk difference (RD), -0.1%; 95% CI, -0.5%, 0.4%; risk ratio (RR), 0.93; 95% CI, 0.54, 1.44). At 12 months, incidence was 4.9% (4.1%, 5.9%) with a third dose vs. 4.5% (4.1%, 4.8%) without (RD, 0.4%; 95% CI, -0.5%, 1.4%; RR, 1.09; 95% CI, 0.90, 1.33).

CONCLUSION: In this community-based target-trial emulation, receiving a third COVID-19 vaccine dose did not meaningfully reduce 6- or 12-month long COVID incidence compared with completing only a primary series.},
}

@article {pmid42103380,
year = {2026},
author = {Manuel, K and Davis, A and Little, K and Peng, F and Gwilt, I and Laver, K and Adey-Wakeling, Z and Seaforth, C and Crotty, M},
title = {Model of care to promote recovery in older people with long COVID: findings from interviews and a co-design workshop.},
journal = {BMJ open},
volume = {16},
number = {5},
pages = {e109911},
doi = {10.1136/bmjopen-2025-109911},
pmid = {42103380},
issn = {2044-6055},
mesh = {Humans ; *COVID-19/therapy/psychology ; Aged ; South Australia ; Female ; Male ; SARS-CoV-2 ; Interviews as Topic ; Aged, 80 and over ; Chronic Disease ; Qualitative Research ; Patient-Centered Care ; },
abstract = {OBJECTIVES: This study aimed to co-design a tailored model of care for older people with long COVID.

DESIGN: Using a human-centred design approach, semistructured interviews were conducted with patients and health professionals from a long COVID service to explore their experiences. Insights were further developed during a co-design workshop involving patients, health professionals and community members who identified as older people and who had experience with chronic illness. Key themes were identified and used to map an ideal patient journey and inform the final model of care.

SETTING: Long COVID outpatient service in a tertiary hospital in Adelaide, South Australia.

PARTICIPANTS: Four patients and four health professionals participated in the interviews. The workshop included four patients, five health professionals and seven community members.

RESULTS: The co-design process identified challenges experienced by people with long COVID, including lack of validation, delayed multidisciplinary care, mental health deterioration and difficulties navigating the healthcare system. These challenges were described as having particular relevance for older adults. In response, a model of care was developed focused on comprehensive assessment, coordinated multidisciplinary care, education for self-management, mental health support and opportunities for research participation.

CONCLUSIONS: A comprehensive and adaptable model of care is needed to address the complex and multifaceted nature of long COVID. This human-centred design approach ensured the model was grounded in lived experience, clinically informed and aligned with patient priorities. While not unique to older adults, the findings highlight areas that may require particular attention in this population, including care coordination, validation and support for comorbidities and social vulnerabilities. While developed in a single tertiary service, these principles may inform the design of services for similar populations in other healthcare settings.},
}

Humans
*COVID-19/therapy/psychology
Aged
South Australia
Female
Male
SARS-CoV-2
Interviews as Topic
Aged, 80 and over
Chronic Disease
Qualitative Research
Patient-Centered Care

@article {pmid42094075,
year = {2026},
author = {Chen, Z and Zhang, Z and Huang, Y and Du, Z and Chen, R and Chen, N and Liu, T and Cheng, Y and Wang, H and Xiong, H and Song, L and Ye, Y and Lu, Y and Lv, Z and Cao, T and Li, Y and Zhu, B and Zou, X and Lu, J and Fang, S and Cowling, BJ},
title = {Epidemiological Trends of COVID-19 Infection and Symptom Incidence in China Following the Adjustment of Zero-COVID Policy: A Prospective, Community-Based Cohort Study.},
journal = {Transboundary and emerging diseases},
volume = {2026},
number = {},
pages = {5590977},
pmid = {42094075},
issn = {1865-1682},
mesh = {Humans ; *COVID-19/epidemiology/prevention & control ; China/epidemiology ; Incidence ; Middle Aged ; Male ; Female ; Prospective Studies ; Adult ; Aged ; SARS-CoV-2 ; Young Adult ; Adolescent ; COVID-19 Vaccines/administration & dosage ; },
abstract = {This study tracked the postadjustment infection rates and symptom trends within community settings. Conducted from May 2023 to May 2024 across four districts in Shenzhen, involving 3246 participants, over 80% had received at least one vaccine dose. Postpolicy adjustment witnessed three significant infection surges. Among the cohort, 63.7% reported only one Coronavirus disease 2019 (COVID-19) infection, 30.3% two infections, and 1.7% three infections, with 4.3% remaining uninfected throughout the follow-up. Older adults and those with lower IgG levels had increased reinfection risk. Notably, 3.8% (95% CI: 3.1-4.6) reported long COVID, with higher susceptibility in those with underlying conditions (adjusted odds ratio [AOR] = 3.73, 95% CI: 2.20-6.34) and reduced incidence among fully vaccinated individuals (AOR = 0.57, 95% CI: 0.36-0.90). The policy change led to widespread exposure, shifting from first infections to reinfections. These insights underscore the need for ongoing research to inform future pandemic responses.},
}

Humans
*COVID-19/epidemiology/prevention & control
China/epidemiology
Incidence
Middle Aged
Male
Female
Prospective Studies
Adult
Aged
SARS-CoV-2
Young Adult
Adolescent
COVID-19 Vaccines/administration & dosage

@article {pmid42094409,
year = {2026},
author = {Montague, Z and Grover, RM and Baumgartner, A and Trofimov, A and Hadlock, J and Nourmohammad, A},
title = {T-cell repertoire response in individuals with post-acute sequelae of COVID-19.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.04.27.721205},
pmid = {42094409},
issn = {2692-8205},
abstract = {T-cells are central to SARS-CoV-2 clearance and immunological memory, yet their contribution to the persistence of post-acute sequelae of COVID-19 (PASC) remains poorly understood. The immunological features that distinguish individuals who develop PASC from those who recover fully are unresolved, in part due to the phenotypic heterogeneity of the condition and the likely multiplicity of its underlying mechanisms. Here, we profiled longitudinal bulk TCR β repertoires from 120 individuals in the INCOV cohort-71 with PASC and 49 without-sampled at two to three time points spanning the acute and post-acute phases of infection. Using robust statistical modeling of repertoire composition and clonal dynamics, we found that global statistics such as V, J gene usage and CDR3 length do not differ between groups, but that locally enriched sequence motifs and differentially dynamic clones reveal distinct T-cell signatures associated with PASC status. Clones contracting following the peak of the acute response were significantly enriched for SARS-CoV-2 specificity in both groups. Interestingly, Influenza A-specific TCRs were disproportionately enriched among contracting clones in PASC [+] repertoires, implicating viral co-infection as a potential contributor to early disease severity and, possibly, PASC pathogenesis. Rare public TCR clones were markedly enriched for SARS-CoV-2 specificity, with PASC [+] individuals harboring a modestly but significantly higher proportion than PASC [-] individuals. Together, we identified over 1,000 candidate TCR β receptors potentially discriminating PASC [+] from PASC [-] immune responses, opening a path toward the identification of disease-relevant T-cell specificities and the development of T-cell-based immunological biomarkers for long COVID.},
}

@article {pmid42088012,
year = {2026},
author = {Kim, TH and Yoon, J and Kang, BK and Kang, JW and Jin, YH and Kwon, CY and Kwon, S},
title = {Herbal medicine (Kyungok-go) for fatigue in Long COVID patients: A prospective multicenter pilot study.},
journal = {Integrative medicine research},
volume = {15},
number = {3Part A},
pages = {101336},
pmid = {42088012},
issn = {2213-4220},
abstract = {BACKGROUND: Long COVID, defined as symptoms persisting beyond 12 weeks after acute SARS-CoV-2 infection, has emerged as a significant global health concern. Fatigue is one of its most common and disabling symptoms, yet robust clinical evidence for effective treatments remains limited.

METHODS: We conducted a multicenter, prospective, single-arm pilot study to evaluate the feasibility and potential effectiveness of Kyungok-go (Qiong-Yu-Gao), a traditional Korean herbal medicine, in individuals with Long COVID-related fatigue. A total of 100 participants experiencing fatigue for at least 12 weeks following a COVID-19 diagnosis received Kyungok-go (22.5 g twice daily) for 12 weeks. The primary outcome was the change in Fatigue Severity Scale (FSS) scores. Secondary outcomes included fatigue severity assessed by a Visual Analog Scale (VAS) and the Chalder Fatigue Scale (ChFS), along with sleep quality, depressive symptoms, cognitive and physical function, and quality of life. Feasibility was assessed through recruitment rate, treatment adherence, and dropout rates.

RESULTS: Ninety-four participants completed the study. FSS scores improved significantly (mean difference (MD) -2.1; 95% CI, -2.4, -1.9), accompanied by significant reductions in fatigue severity on the VAS (MD -35.6; 95% CI, -39.7, -31.4) and ChFS total score (MD -29.1; 95% CI, -32.3, -25.9). Sleep quality (MD -4.0; 95% CI, -4.8, -3.2), depressive symptoms (MD -8.1; 95% CI, -9.6, -6.7), and overall quality of life (EQ-5D-5L, MD 0.1; 95% CI, -0.1, 0.1) also showed improvements. Cognitive (MD 0.9; 95% CI, 0.2, 1.5) and physical function (MD 0.2; 95% CI, 0.0, 0.3) showed modest or limited changes. Medication adherence exceeded 97%, and no serious treatment-related adverse reactions were observed.

CONCLUSION: Kyungok-go was well-tolerated and showed promising effects in alleviating fatigue among patients with Long COVID. These findings support its feasibility and potential as a therapeutic option, warranting further evaluation in randomized controlled trials.

TRIAL REGISTRATION: CRIS, KCT0009410 (https://cris.nih.go.kr/).},
}

@article {pmid42088257,
year = {2026},
author = {Jia, X and Wang, J and Cui, X and Li, T and Tian, Y and Lu, R and Tian, Y and Shen, X and Dang, S and Wang, W},
title = {Trends in long COVID among US adults, 2022-2024.},
journal = {Frontiers in public health},
volume = {14},
number = {},
pages = {1809635},
pmid = {42088257},
issn = {2296-2565},
mesh = {Humans ; Female ; Male ; Middle Aged ; *COVID-19/epidemiology ; United States/epidemiology ; Adult ; Cross-Sectional Studies ; Prevalence ; Socioeconomic Factors ; Aged ; SARS-CoV-2 ; Health Surveys ; Activities of Daily Living ; Young Adult ; Adolescent ; },
abstract = {IMPORTANCE: Long COVID poses a significant public health challenge. However, population-level trends and associated factors in the general US population during the post-pandemic era are not fully characterized.

OBJECTIVE: To analyze trends in long COVID prevalence among US adults from 2022 to 2024, identify associated demographic and socioeconomic factors, and assess its impact on daily activities.

We analyzed data from three cycles (2022-2024) of the National Health Interview Survey, a repeated cross-sectional, nationally representative survey. COVID-19 infection, long COVID, and daily activity limitation were determined through participant self-report. Daily activity limitation was assessed in 2023-2024. Multivariable Poisson regression identified factors associated with: (1) long COVID history and (2) significant activity limitation among those with current symptoms. All analyses incorporated survey weights to produce nationally representative estimates. Data analysis was conducted in October 2025.

RESULTS: The study included 88,731 adults (median age 47 years; 51.4% female and 48.6% male; 61.7% non-Hispanic White, 17.6% Hispanic, 11.8% non-Hispanic Black, and 8.9% non-Hispanic other). In the overall population, the prevalence of ever long COVID increased from 7.0% (95% CI, 6.6-7.3%) in 2022 to 8.4% (95% CI, 8.0-8.8%) in 2023, plateauing at 8.3% (95% CI, 7.9-8.7%) in 2024, while for current long COVID the prevalence remained stable (3.4% [95% CI, 3.1-3.6%] in 2022, 3.6% [95% CI, 3.3-3.9%] in 2023, and 3.3 [95% CI, 3.1-3.6%] in 2024). Among adults with prior COVID-19 infection, prevalence of both ever and current long COVID declined significantly, from 17.7 to 13.7% and from 8.6 to 5.5%, respectively. Long COVID was more common among women, adults in middle age (35-64 years), Hispanic or non-Hispanic White individuals, those who were widowed/separated/divorced, people with lower educational attainment, and individuals with incomes below the federal poverty threshold. Among those with current long COVID, 19.8% reported significant activity limitation, and this limitation was more common among older adults and individuals with lower incomes.

CONCLUSIONS AND RELEVANCE: From 2022 to 2024, long COVID continued to impose a substantial public health burden, with clear demographic and socioeconomic disparities. These findings underscore the necessity for continued surveillance and targeted support for high-risk groups.},
}

Humans
Female
Male
Middle Aged
*COVID-19/epidemiology
United States/epidemiology
Adult
Cross-Sectional Studies
Prevalence
Socioeconomic Factors
Aged
SARS-CoV-2
Health Surveys
Activities of Daily Living
Young Adult
Adolescent

@article {pmid42088258,
year = {2026},
author = {Huang, H and Chen, S and Fang, Z and Ma, Y and Xu, Y and Dong, G},
title = {The "two-hit" storm: a hyper-inflammatory endotype in pediatric long COVID and its role in the severity of secondary bacterial pneumonia-a mechanistic review and clinical implications.},
journal = {Frontiers in public health},
volume = {14},
number = {},
pages = {1782871},
pmid = {42088258},
issn = {2296-2565},
mesh = {Humans ; *COVID-19/immunology/complications ; Child ; SARS-CoV-2 ; *Pneumonia, Bacterial/immunology ; *Inflammation/immunology ; Severity of Illness Index ; Pneumonia, Mycoplasma/immunology ; },
abstract = {Following the COVID-19 pandemic, the clinical patterns of pediatric respiratory infections have undergone significant changes, with increasing attention on the immunological imprint left by Post-Acute Sequelae of SARS-CoV-2 infection (PASC), commonly known as Long COVID. A perplexing clinical phenomenon has been observed: some children with a history of Long COVID exhibit a disproportionately severe inflammatory response and extensive lung injury when encountering common community-acquired pneumonia, such as that caused by Mycoplasma pneumoniae or Streptococcus pneumoniae, inconsistent with their pathogen load. This review aims to dissect this phenomenon and proposes the "Immune Priming and Two-Hit" model as its core pathophysiological framework. This model posits that the Long COVID state constitutes the "first hit," establishing a "primed" or "hyper-reactive" immune baseline through viral persistence, trained immunity-induced monocyte reprogramming, and sustained endothelial dysfunction. Upon the "second hit" of a bacterial infection, this primed immune system triggers a dysregulated, synergistically amplified inflammatory cascade. The mechanisms involve the exponential release of cytokines such as Interleukin-6 (IL-6), IL-1β, and Tumor Necrosis Factor-α (TNF-α), inflammation-mediated immunothrombosis, and excessive activation of Neutrophil Extracellular Trap formation (NETosis), ultimately leading to severe outcomes like Acute Respiratory Distress Syndrome (ARDS) and necrotizing pneumonia. Consequently, identifying and defining this "Hyper-inflammatory endotype" is of critical clinical importance. We define it as an "endotype" to emphasize the distinct, host-determined pathophysiological mechanisms underlying it, rather than merely a collection of clinical manifestations. By monitoring biomarkers such as ferritin, D-dimer, lactate dehydrogenase (LDH), and lymphocyte counts, clinicians may be able to perform early risk stratification of these children. This approach not only facilitates a shift in therapeutic strategy from purely antimicrobial therapy to "host-directed therapy"-emphasizing the necessity of early, adequate corticosteroid use and consideration of anticoagulation-but also provides a new theoretical basis and intervention window for preventing long-term sequelae such as pulmonary fibrosis.},
}

Humans
*COVID-19/immunology/complications
Child
SARS-CoV-2
*Pneumonia, Bacterial/immunology
*Inflammation/immunology
Severity of Illness Index
Pneumonia, Mycoplasma/immunology

@article {pmid42090436,
year = {2026},
author = {Chu, L and Hollar, TL and Klimas, N and Bertolli, J and Tamariz, AL and Lajevardi, A and Pavlov, I and Palacio, A},
title = {Facilitators of and barriers to participation in Long COVID research: A qualitative analysis.},
journal = {PloS one},
volume = {21},
number = {5},
pages = {e0346007},
doi = {10.1371/journal.pone.0346007},
pmid = {42090436},
issn = {1932-6203},
mesh = {Humans ; *COVID-19/epidemiology/psychology/virology ; Female ; Male ; Middle Aged ; Adult ; SARS-CoV-2/isolation & purification ; Qualitative Research ; Motivation ; *Patient Selection ; Aged ; },
abstract = {BACKGROUND: Meeting recruitment targets in an expeditious manner is essential to the successful completion of any research project. However, despite the high prevalence and debilitating nature of Long COVID (LC), recruitment of participants into some LC studies has been challenging.

OBJECTIVE: We aimed to a) identify factors influencing participation in LC research among individuals who were infected by SARS-CoV-2 but had declined participation in a LC study and b) to compare these factors to those previously recognized.

METHODS: Using a semi-structured guide, we interviewed thirteen people about their thoughts, experiences, and attitudes concerning participation in LC research. We imported interview transcripts into Nvivo 14 and analyzed them using thematic analysis. For coding, we used Charmaz's coding scheme of open and focused coding within an application of the constant comparative method. Basic descriptive statistics were also deployed to supplement our qualitative analysis.

RESULTS: Fifteen factors describe the facilitators and barriers mentioned by participants. The top three facilitators were Personal and social motivation, Incentives, and Familiarity and credibility of institutions involved with COVID-19; the top three barriers were Invasiveness, Social and political context, and Lack of time. Skepticism and infringement on participants' daily lives served as major obstacles to participation while trust, personal factors, and administrative factors encouraged participation. The facilitators and barriers identified are similar to those recognized previously except that in the politically charged atmosphere surrounding the COVID-19 pandemic, trust was especially vital.

CONCLUSIONS: Many factors affect people's decisions to participate in LC research but only some are modifiable by researchers. Building trust, offering incentives participants value, and removing logistical barriers may improve recruitment rates.},
}

Humans
*COVID-19/epidemiology/psychology/virology
Female
Male
Middle Aged
Adult
SARS-CoV-2/isolation & purification
Qualitative Research
Motivation
*Patient Selection
Aged

@article {pmid42086409,
year = {2026},
author = {Elahi, S},
title = {Erythroid-hormonal axis in long COVID.},
journal = {Trends in molecular medicine},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.molmed.2026.04.006},
pmid = {42086409},
issn = {1471-499X},
abstract = {Long COVID may reflect a failure of coordinated physiological recovery rather than persistent infection. Emerging evidence identifies inflammation-driven disruption of erythropoiesis and hormonal balance as central mechanisms linking immune dysregulation, metabolic stress, and persistent symptoms. This framework positions erythroid-endocrine pathways as key determinants of recovery and promising therapeutic targets.},
}

@article {pmid42086796,
year = {2026},
author = {Pietranis, KA and Kuryliszyn-Moskal, A and Moskal-Jasińska, D and Wojciuk, M and Ciołkiewicz, M and Kaniewska, K},
title = {Effectiveness of comprehensive rehabilitation for functional recovery and symptom reduction in long COVID: results from a six‑month randomised controlled trial.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-51787-2},
pmid = {42086796},
issn = {2045-2322},
support = {SUB/1/DN/22/001/3309//Uniwersytet Medyczny w Bialymstoku/ ; },
abstract = {This study provides a comprehensive evaluation of the long-term clinical outcomes of an original rehabilitation programme for patients with long-COVID, highlighting the sustained therapeutic benefits over a six-month period. Seventy‑five patients with long‑COVID symptoms completed a six‑week programme comprising three weekly outpatient sessions. Participants were randomly assigned to two groups following an identical comprehensive protocol, incorporating aerobic training, respiratory exercises, strength and general fitness training, stretching, and respiratory resistance training with a respiratory muscle trainer, with the control group receiving placebo IMT. The study evaluated the programme's effectiveness by assessing respiratory function (spirometry, muscle strength, chest expansion, and DTF), voice and speech quality, and symptom persistence. The six-month follow-up analysis demonstrated statistically significant retention of improvements in functional and qualitative parameters compared with post-rehabilitation values, with further gains relative to baseline. Our findings indicate that the multi‑component rehabilitation programme is broadly beneficial, with the greatest functional gains in patients with lower baseline capacity, while offering equitable, low‑cost support across age and sex groups and enabling targeted allocation of intensive monitoring to those with the highest potential for clinically meaningful improvement. The study is the first comprehensive analysis of the relationship between long‑COVID and voice and speech‑related disabilities, while also validating the clinical efficacy of the intervention.Clinical trials registration: NCT05449379; 08/07/2022.},
}

@article {pmid42086912,
year = {2026},
author = {Guardo, C and Xinmeng, Z and Gangireddy, S and Chao, Y and Kerchberger, VE and Dickson, AL and Pfaff, ER and Master, H and Yi, X and Basford, M and Chute, CG and Tran, NK and Mancuso, S and Syed, TA and Zhongming, Z and QiPing, F and Haendel, M and Lunt, C and Harris, PA and Lang, L and Ginsburg, GS and Denny, JC and Roden, DM and Wei-Qi, W},
title = {Multi-scale data improves performance of machine learning model for long COVID identification.},
journal = {Communications medicine},
volume = {},
number = {},
pages = {},
doi = {10.1038/s43856-026-01621-7},
pmid = {42086912},
issn = {2730-664X},
support = {U01HG011181//U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI)/ ; R01HL171809//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01AG084550//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; R01 GM139891/GM/NIGMS NIH HHS/United States ; },
abstract = {BACKGROUND: Long COVID affects a substantial proportion of the over 778 million individuals infected with SARS-CoV-2, yet predictive models remain limited in scope. While existing efforts, such as the National COVID Cohort Collaborative (N3C), have leveraged electronic health record (EHR) data for risk prediction and identification, accumulating evidence points to additional contributions from social, behavioral, and genetic factors.

METHODS: Using a diverse cohort of SARS-CoV-2-infected individuals (n > 17,200) from the NIH All of Us Research Program, we investigated whether integrating EHR data with survey-based and genomic information improves model performance.

RESULTS: Our multi-scale approach outperforms EHR-only model's area under the receiver operating curve 0.736 (95% CI: 0.730, 0.741), achieving an area of 0.748 (0.741,0.755). Among the top predictors, active-duty service status, and self-reported fatigue are the most informative survey features.

CONCLUSIONS: These findings highlight the importance of incorporating multi-scale data to improve risk stratification and inform personalized interventions for long COVID. However the relative increase in accuracy is modest, and the cost of collecting genetic and survey data should be considered before implementation.},
}

@article {pmid42087199,
year = {2026},
author = {Yoon, GY and Chung, YC and Choi, JH and Ha, Y and Seo, SY and Ku, KB and Kim, DY and Hwang, WY and Jeong, GU and Ahn, DG and Kim, KD and Rhee, JK and Shin, WH and Kwon, YC},
title = {SARS-CoV-2 infection is associated with hypothalamic orexin suppression and persistent cortical NeuN attenuation.},
journal = {Journal of neuroinflammation},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12974-026-03842-y},
pmid = {42087199},
issn = {1742-2094},
support = {RS-2025-25441317//Ministry of Education, South Korea/ ; RS-2021-NR061451//Ministry of Science and ICT, South Korea/ ; KK-2505-01//Korea Institute of Toxicology, South Korea/ ; KK2633-20//Korea Research Institute of Chemical Technology, South Korea/ ; RS-2023-00208568//Ministry of Education, Science and Technology/ ; },
abstract = {Long COVID frequently presents with persistent neurological symptoms, including cognitive impairment, fatigue, and sleep disturbances; however, its underlying mechanisms remain unclear. Here, we show that SARS-CoV-2 infection induces lasting cortical neuronal injury and hypothalamic orexin (hypocretin) dysfunction in vivo. In K18-hACE2 and wild-type BALB/c mice, viral RNA persisted in the brain and coincided with focal loss of Neuronal Nuclei (NeuN)-positive cortical neurons beyond acute infection. SARS-CoV-2, but not the influenza A virus, triggered rapid and sustained suppression of hypothalamic orexin expression, defining a virus-specific neuropathological signature. Considering the downregulation of orexin and focal cortical NeuN attenuation, we found that exogenous orexin-A/B supplementation increased NeuN abundance in vitro and in vivo under the tested conditions. Overall, these findings identify the orexin system as a candidate neural vulnerability to SARS-CoV-2 and suggest that orexinergic dysfunction may contribute to the neurological manifestations of Long COVID.},
}

@article {pmid42074658,
year = {2026},
author = {Le Breton, C and Klopfenstein, T and Zayet, S},
title = {Current Difficulties for General Practitioners in the Diagnosis and Management of Long COVID Patients: A Cross-Sectional Study Assessing an Online Questionnaire.},
journal = {Journal of clinical medicine},
volume = {15},
number = {8},
pages = {},
doi = {10.3390/jcm15082855},
pmid = {42074658},
issn = {2077-0383},
abstract = {Background: Long COVID presents a novel and emerging public health challenge. As the first point of contact, general practitioners (GPs) play a key role in diagnosing and coordinating the care of patients presenting with post-acute sequelae of COVID-19 (PASC), despite a lack of experience. This study aimed to identify the main difficulties encountered by GPs in Franche-Comté, France, in managing adult outpatients with long COVID. Methods: We conducted a cross-sectional survey using an anonymous online questionnaire, which contained 21 questions and was distributed to GPs in Franche-Comté, France. The survey assessed definition, diagnostic and therapeutic challenges in managing long COVID. Results: Among the 410 questionnaires distributed, 90 general practitioners (GPs) responded (response rate: 21.9%). The mean age of participants was 34 ± 10 years, and 64.4% were women (n = 58). Regarding knowledge of long COVID, three participants (3.3%) did not recognize it as a distinct clinical entity, while more than half (58.9%, n = 53) reported insufficient knowledge. The main challenges identified were therapeutic management (76.7%, n = 69) and diagnosis (75.6%, n = 68). Only 4.5% of respondents (n = 4) reported no difficulty in defining post-acute sequelae of SARS-CoV-2 infection (PASC). The most frequently reported diagnostic difficulty was distinguishing long COVID from differential diagnoses (93.3%, n = 83/89), particularly fibromyalgia (94.3%, n = 83/88). Only 37.1% of participants (n = 33/89) reported actively following up patients with PASC. During initial management, the main challenge was the difficulty in objectively assessing patients' complaints using available diagnostic tools (80.7%, n = 67/83). Additionally, a large majority of GPs reported difficulties in addressing patients' questions (86.7%, n = 72/83) and managing associated anxiety disorders (75.9%, n = 63/83). Conclusions: These findings highlight the immediate need to enhance GP training in Franche-Comté, France, in dealing with long COVID. Improvements such as harmonizing long COVID definitions, testing diagnoses, and strengthening interdisciplinary coordination are essential to provide coherent and patient-centered care for this disease.},
}

@article {pmid42074690,
year = {2026},
author = {Lucaciu, FC and Wellmann, N and Mihai, AM and Sima, A and Rosca, O and Suba, MI and Tarau, A and Bosoanca, A and Marc, M},
title = {Post-COVID Respiratory Sequelae in COPD: Mucus Plugging, Infectious Complications, and Risk-Stratified Follow-Up.},
journal = {Journal of clinical medicine},
volume = {15},
number = {8},
pages = {},
doi = {10.3390/jcm15082890},
pmid = {42074690},
issn = {2077-0383},
abstract = {Context/Objectives: In patients with COPD (chronic obstructive pulmonary disease), SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection represents an overlap of viral injury on a lung already affected by pathological mucus, altered mucociliary clearance, chronic inflammation, and impaired antiviral immunity. Methods: A focused narrative review (2020-2025) was conducted using clinical, experimental, and consensus evidence. The evidence was synthesized qualitatively, with priority given to cohort studies, meta-analyses, and mechanism-focused studies with clinical relevance. Results: Mucus obstruction ("mucus plugs") is frequent in COPD (41-67%) and is associated with unfavorable outcomes. COPD also increases the risk of post-COVID respiratory sequelae. Bacterial coinfection at presentation is uncommon (3-5%), whereas secondary bacterial infections are more frequent (14-18%), especially in severe disease requiring intensive care, where VA-LRTI/VAP (ventilator-associated lower respiratory tract infection/ventilator-associated pneumonia) become predominant. Sepsis, whether viral or mixed, reflects disease severity and may contribute to functional decline and susceptibility to reinfections; however, the concept of a post-acute "sepsis legacy" in COPD after COVID-19 should currently be regarded as a clinically plausible but still emerging hypothesis rather than an established COPD-specific outcome. During recovery, acute exacerbation risk rises to 5.6% versus 3.9%, peaking in the first 30 days after severe disease (aHR ≈ 8.14). Persistent dyspnea and reduced DLCO (diffusing capacity for carbon monoxide) suggest ARDS-related injury, tissue remodeling, and microvascular dysfunction. Conclusions: In COPD, post-COVID respiratory sequelae result from the interaction of mucus, immunity, and infectious/sepsis-related complications. The first post-discharge month is a critical period requiring careful risk stratification and targeted follow-up.},
}

@article {pmid42074919,
year = {2026},
author = {Avram, CA and Craciun, ML and Pah, AM and Iurciuc, S and Crisan, S and Vacarescu, C and Cotet, I and Virzob, CRB and Surducan, DA and Avram, C},
title = {Pulmonary Embolism in Hospitalized COVID-19 Patients: Incidence, Clinical Predictors, and Short-Term Outcomes.},
journal = {Journal of clinical medicine},
volume = {15},
number = {8},
pages = {},
doi = {10.3390/jcm15083117},
pmid = {42074919},
issn = {2077-0383},
support = {Victor Babeș University of Medicine and Pharmacy Timișoara//Victor Babeș University of Medicine and Pharmacy Timișoara/ ; },
abstract = {Background/Objectives: Pulmonary embolism (PE) represents a major thrombotic complication in hospitalized patients with coronavirus disease 2019 (COVID-19), yet data on its incidence, clinical predictors, and short-term outcomes in actual cohorts remain heterogeneous. Methods: We conducted a retrospective observational cohort study including 395 consecutive adults hospitalized with RT-PCR-confirmed COVID-19 at a tertiary infectious diseases center between March 2020 and December 2024. Clinical, laboratory, imaging, and treatment data were extracted from electronic records, and PE was defined by computed tomography pulmonary angiography. Univariable and multivariable logistic regression analyses were used to identify independent predictors of PE in the subset of patients who underwent CTPA (n = 120), in whom PE status was definitively ascertained (47 with PE and 73 without PE). Results: Pulmonary embolism was diagnosed in 47 patients (11.9%). Patients with PE more frequently had prior venous thromboembolism (19.1% vs. 8.3%) and prolonged immobilization (61.7% vs. 23.0%), and were more often admitted to the intensive care unit (12.8% vs. 4.3%) than those without PE. Peak D-dimer levels were almost ten-fold higher in the PE group (median 5322 vs. 529.5 µg/L). In multivariable logistic regression, peak D-dimer was independently associated with PE (per log-unit increase, adjusted OR 3.9, 95% CI 2.1-7.1), and prolonged immobilization conferred a substantially higher risk of PE (adjusted OR 5.1, 95% CI 2.4-10.9). Patients with PE experienced more complex hospital courses and more frequent need for advanced therapies, although in-hospital mortality did not differ significantly between groups. Conclusions: In hospitalized COVID-19 patients, PE is frequent and closely linked to marked D-dimer elevation and acquired in-hospital risk factors, particularly prolonged immobilization. This evidence supports the use of dynamic D-dimer assessment and careful evaluation of immobilization status to improve risk stratification, guide decisions on diagnostic imaging and anticoagulation intensity, and identify patients who may benefit from closer post-discharge cardiovascular follow-up (this hypothesis requires confirmation in future prospective studies).},
}

@article {pmid42075130,
year = {2026},
author = {Bačić, A and Gmizić, T and Branković, M and Rajilić-Stojanović, M},
title = {Multi-Strain Probiotic Intervention Modestly Modulates Microbial Composition and Inflammatory Profile in Individuals with Long COVID.},
journal = {Microorganisms},
volume = {14},
number = {4},
pages = {},
doi = {10.3390/microorganisms14040734},
pmid = {42075130},
issn = {2076-2607},
support = {No. 451-03-34/2026-03/ 200135//Ministry of Education, Science and Technological Development of the Republic of Serbia/ ; },
abstract = {Probiotics are widely used to support host health by modulating microbial communities and immune-metabolic homeostasis. Such interventions may be particularly relevant in long COVID syndrome, a condition characterized by persistent symptoms, low-grade inflammation, and microbiota alterations following SARS-CoV-2 infection. This study investigated the effects of a multi-strain probiotic on gut microbiota composition and predicted functional potential and biochemical parameters in individuals with long COVID and convalescent participants. Healthy individuals were included as reference controls. In an interventional study, 34 participants received a 12-week probiotic formulation containing Saccharomyces boulardii, Lacticaseibacillus rhamnosus GG, and two Lactiplantibacillus plantarum strains, while 40 served as non-supplemented controls. Fecal microbiota, assessed using 16S rRNA sequencing, and biochemical markers were measured at baseline and post-intervention. Probiotic supplementation induced selective compositional changes without significantly altering overall microbial diversity. Effects were more pronounced in long COVID participants and included enrichment of bacteria associated with metabolic and immune regulation, including Adlercreutzia, Coprococcus, and Eubacterium. Functional prediction analysis identified a probiotic-responsive signature in long-COVID-affected individuals, characterized by enrichment of pathways related to energy metabolism and redox balance. These microbial changes were accompanied by a consistent trend toward reduced inflammatory and hepatic markers. Overall, probiotic intervention demonstrated microbiota-status-dependent potential in long COVID recovery.},
}

@article {pmid42076806,
year = {2026},
author = {Foran, AM and Jetten, J and Muldoon, OT},
title = {Health benefit or burden? Unpacking the dual effects of religious group membership on long COVID prevalence and severity.},
journal = {Journal of health psychology},
volume = {},
number = {},
pages = {13591053261445238},
doi = {10.1177/13591053261445238},
pmid = {42076806},
issn = {1461-7277},
abstract = {While religious group membership is often linked to positive health outcomes, it can also influence engagement with health advice in ways that present challenges. The role of religious group membership in long COVID prevalence and severity therefore warrants closer examination. This study used cross-sectional data from Round 11 of the European Social Survey (N = 25,124) across 24 countries. Multilevel multinomial logistic mediation models tested whether the association between religious group membership and long COVID was mediated by two divergent pathways: religious attendance (enactment) and religiosity (significance of beliefs). Results showed that membership was indirectly associated with a lower likelihood of reporting long COVID symptoms via more frequent attendance at religious services. By contrast, greater religiosity was associated with a higher likelihood of reporting persistent symptoms. These findings suggest that the health advantages of religious group membership may lie in opportunities for social connexion.},
}

@article {pmid42076812,
year = {2026},
author = {Belton, S and Goss, H and Whyte, E and McCaffrey, N and Gibney, S and Sheridan, K},
title = {'I Want Everyone to Have It, and Everyone to Be on It': A Feasibility Study of the Transforming Long Covid Intervention.},
journal = {Health expectations : an international journal of public participation in health care and health policy},
volume = {29},
number = {3},
pages = {e70681},
doi = {10.1111/hex.70681},
pmid = {42076812},
issn = {1369-7625},
mesh = {Humans ; Feasibility Studies ; *COVID-19/complications/therapy/psychology ; Male ; Female ; Middle Aged ; Adult ; Aged ; *Self-Management/methods ; Focus Groups ; SARS-CoV-2 ; },
abstract = {BACKGROUND: An understanding of the nature of long Covid (LC) is evolving, with recent evidence highlighting the role of increased sympathetic activation and decreased parasympathetic response. Building upon this emerging science, the 'Transforming Long COVID' (TLC) programme was developed to support participants in their recovery by (i) introducing education on the neuroscience underpinning persistent symptoms (with a particular focus on the autonomic nervous system) and (ii) the development of self-management strategies to support recovery. The aim of this study was to examine the feasibility of the TLC programme with a cohort of people significantly affected by LC.

METHODS: Seventeen participants took part in the 8-week TLC programme which comprised of seven content sessions and one discussion (Q&A) session. Participants completed survey scales (investigating anxiety, pain-related interference, pain catastrophising, sleep disturbance and fatigue) at baseline, immediately post-programme (at 8 weeks), and retention (at 13 weeks). Participants also took part in focus group interviews to investigate their experiences of the programme.

RESULTS: Fourteen participants (82%) attended at least six of the seven TLC content sessions. Decreases in mean values over time were observed across all measures, indicating a positive (non-significant) change. Participants reported an increase in understanding of LC, new hope for recovery, belief that they now had a realistic pathway for recovery, validation of their experiences and symptoms, meaningful improvements in function, and enhanced ability to respond to and attenuate physical symptoms. No adverse events were reported. Participants highlighted a number of programme strengths, along with some potential areas for improvement.

CONCLUSION: The TLC programme was shown to be feasible based on engagement, adherence, acceptable completion of surveys, and no adverse events. Study findings point to the potential for this programme to be refined, trialled and evaluated with a larger sample.

Four people (living with LC, ME/CFS, chronic migraine and chronic Lyme, fibromyalgia, and centralised pain syndrome), who have experience of applying a recovery approach aligned with the TLC programme, acted in a PPI (Public and Patient Involvement in research) capacity on this study. In addition, the lead author has personal experience with the illness, and developing the recovery approach, which helped inform programme structure and development [1]. These individuals provided advice and guidance on the potential structure for the group programme, course duration, tool selection, and language and wording of the programme and materials. Further detail is provided in the Supplementary Materials.},
}

Humans
Feasibility Studies
*COVID-19/complications/therapy/psychology
Male
Female
Middle Aged
Adult
Aged
*Self-Management/methods
Focus Groups
SARS-CoV-2

@article {pmid42077647,
year = {2026},
author = {Lindberg, P and Wiqvist, S and Juszczyk, M and Lee, S and Kisiel, MA and Wachtler, C and Ståhlberg, M and Wheelock, ÅM and Fedorowski, A and Carlsson, AC},
title = {Long COVID and risk of incident cardiovascular disease: a prospective cohort study using the Multimorbidity Integrated Registry Across Care Levels in Stockholm (MIRACLE-S) cohort.},
journal = {EClinicalMedicine},
volume = {94},
number = {},
pages = {103846},
pmid = {42077647},
issn = {2589-5370},
abstract = {BACKGROUND: Long COVID has emerged as a global health challenge, with increasing evidence of cardiovascular sequelae. Most previous studies have focused on hospitalised cohorts, whereas cardiovascular risk in community-managed long COVID cases remains less explored. We aimed to investigate the incidence of major cardiovascular events in individuals with long COVID compared to those without long COVID in a large population-based setting.

METHODS: Multimorbidity Integrated Registry Across Care Levels in Stockholm (MIRACLE-S) is a population-based cohort that covers all providers of healthcare for around 2.5 million residents in Stockholm County. Individuals aged 18-65 years with a physician-assigned long COVID diagnosis (ICD-10: U09.9) between October 2020 and January 2025 were identified. Exclusion criteria were hospitalisation for acute COVID-19 or pre-existing cardiovascular disease. Cox proportional hazards models estimated the effect of long COVID on a composite cardiovascular outcome (myocardial infarction, heart failure, cardiac arrhythmias, stroke, peripheral arterial disease), adjusting for demographic, lifestyle, and mental health factors.

FINDINGS: Among 1,217,693 individuals, 8999 (0.7%) had long COVID diagnosis (66% women). Cumulative incidence of any cardiovascular event was higher in long COVID group (women 18.2%, men 20.6%) compared with control group (women 8.4%, men 11.1%). In a fully adjusted model, long COVID was associated with the composite cardiovascular outcome (women HR 2.06, 95% CI 1.92-2.22; men HR 1.33, 1.20-1.48), cardiac arrhythmia (women HR 3.11, 2.85-3.39; men HR 1.61, 1.41-1.85), and coronary artery disease (women HR 1.25, 1.04-1.52; men HR 1.26, 1.05-1.51). Heart failure incidence was elevated in women only (HR 1.25, 1.00-1.55), as also was peripheral artery disease (HR 1.25, 1.05-1.50). Long COVID was not associated with stroke in either sex.

INTERPRETATION: Long COVID is associated with increased risk of incident cardiovascular disease, particularly cardiac arrhythmias, heart failure, and coronary artery disease. These findings underscore the need for systematic follow-up and integration of long COVID into cardiovascular risk assessment.

FUNDING: Region Stockholm and Heart Lung Foundation.},
}

@article {pmid42079856,
year = {2026},
author = {Yang, C and Mao, W and Senbaklavaci, Ö},
title = {Editorial: Managing COVID-19 in heart and lung transplantation: clinical challenges and emerging solutions.},
journal = {Frontiers in surgery},
volume = {13},
number = {},
pages = {1843253},
pmid = {42079856},
issn = {2296-875X},
}

@article {pmid42080492,
year = {2026},
author = {Brady Sawant, H and Ross, D and Flannery, T and Tarrant, R and Haugh, J and Grimaldi, J and Mackreth, P and Sivan, M},
title = {Evaluating a Digital Patient Reported Outcome Measure for Long COVID in a Community Rehabilitation Service.},
journal = {Journal of primary care & community health},
volume = {17},
number = {},
pages = {21501319261437896},
doi = {10.1177/21501319261437896},
pmid = {42080492},
issn = {2150-1327},
mesh = {Humans ; *Patient Reported Outcome Measures ; *COVID-19/rehabilitation ; Male ; Female ; Middle Aged ; Adult ; Aged ; SARS-CoV-2 ; Surveys and Questionnaires ; Qualitative Research ; Mobile Applications ; Community Health Services ; },
abstract = {BACKGROUND: Long COVID presents with a wide range of persistent symptoms which can significantly affect daily functioning and increases pressure on already stretched National Health Service. A Digital Patient-Reported Outcome Measure application incorporating 4 outcome measure scales (COVID-19-Yorkshire Rehabilitation Scale, EuroQol 5 Dimension Scale, Modified Fatigue Impact Scale, and Medical Research Council Dyspnoea Scale) was introduced into a Long COVID community rehabilitation pathway in 2021. However, there was little known about its acceptability, uptake, or user experience.

METHODS: A qualitative service evaluation was conducted. Quantitative data was collected, over 2 months, from 100 people using the service, including registration, usage patterns, and demographics. Semi structured questionnaires collected qualitative data from 20 participants. Template analysis was used to explore experiences, enablers, and barriers.

RESULTS: Of 100 participants, 38 were active app users, 46 were non active users, and 16 did not register. Engagement varied, depending on education employment status and digital literacy. Four themes emerged from qualitative data collected from 20 service users: Technology, Personal Experience, Symptom Tracking, and Support Requirements. Digital symptom monitoring was valued, but challenges were identified with navigation, clarity of the questions, guidance of use, and awareness of key functions such as symptom tracking graphs.

CONCLUSION(S): Opportunities were identified for development of the use of Digital Patient-Reported Outcome Measures. User feedback highlighted the need for improved usability, clearer information, and increased guidance to optimise engagement. These insights inform recommendations for the development and implementation of future Digital Patient Reported Outcome Measures.},
}

Humans
*Patient Reported Outcome Measures
*COVID-19/rehabilitation
Male
Female
Middle Aged
Adult
Aged
SARS-CoV-2
Surveys and Questionnaires
Qualitative Research
Mobile Applications
Community Health Services

@article {pmid42082458,
year = {2026},
author = {Vilser, D and Han, I and Vogel, K and Jakobs, P and Lorenz, M and Huppke, P and Newman, L and Paszkier, M and Kuhle, J and Mohr, J and Aign, C and Reinhold, A and Reinhold, D and Weinzierl, S and Ullmann, E and Proquitté, H and Brunner-Weinzierl, MC},
title = {Immune-metabolic trajectories delineate subgroups in paediatric long COVID.},
journal = {Nature communications},
volume = {17},
number = {1},
pages = {},
pmid = {42082458},
issn = {2041-1723},
support = {Br1860/18//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 01EP2101//Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research)/ ; },
mesh = {Humans ; *COVID-19/immunology/metabolism/virology ; Child ; Male ; Adolescent ; Female ; SARS-CoV-2/immunology ; Child, Preschool ; Metabolomics ; Cytokines/immunology/metabolism ; Infant ; Autoantibodies/immunology/blood ; Cohort Studies ; },
abstract = {Most children and adolescents recover rapidly from SARS-CoV-2 infection, yet a subset develops paediatric long COVID (LC). How immune ontogeny shapes LC biology and heterogeneity remains unclear. We deeply phenotype a two-visit cohort with severe LC (n = 74) and controls (n = 27) spanning up to 3.2 years post index infection. Symptom burden remains high and neurofilament light chain (NfL) percentiles inversely associate with functional status (Bell score; r = -0.3536, P = 0.0060). Cardiopulmonary assessment and serology are unremarkable. Conventional autoantibodies are not enriched, whereas anti-DFS70 supports subgrouping. Immune features are temporally structured; SARS-CoV-2-associated mediators decline within 1 year, while innate-weighted, Th2-skewed cytokines persist. Metabolomics (43 metabolites) recapitulate the identified subgroups and align with EBV serostatus, disease phase (<1 year versus years 1-3.2), and anti-DFS70 positivity. In EBV-naïve LC, higher haemoglobin concentration (MCHC) tracks worse function, whereas higher IL-12p40, thiamine and basophils track milder impairment (all P ≤ 0.0170). These data delineate immune-metabolic and haematological axes of paediatric LC heterogeneity and support biomarker-guided stratification.},
}

Humans
*COVID-19/immunology/metabolism/virology
Child
Male
Adolescent
Female
SARS-CoV-2/immunology
Child, Preschool
Metabolomics
Cytokines/immunology/metabolism
Infant
Autoantibodies/immunology/blood
Cohort Studies

@article {pmid42082813,
year = {2026},
author = {Donath, Q and Haegele, M and Schindler, D and Welzhofer, T and Christa, C and Grabbe, A and Leone, A and Ilhan, C and Weidmann, C and Eberhartinger, M and Bechtold, S and Bursch, N and Wolf, H and Hieber, H and Peo, LC and Bucka, LA and Stojanov, S and Warlitz, C and Alberer, M and Gerrer, K and Hausruckinger, A and Mittelstrass, K and Wendtner, CM and Hoechstetter, MA and Grübl, A and Toepfner, N and Pricoco, R and Scheibenbogen, C and Mihatsch, LL and Behrends, U},
title = {Risk factors for severe post-COVID condition in children, adolescents, and young adults.},
journal = {European journal of pediatrics},
volume = {185},
number = {5},
pages = {},
pmid = {42082813},
issn = {1432-1076},
support = {2490-PCS-2023-V13, 2490-PC-2021-V6-D44360/2021//Bavarian State Ministry of Health and Care/ ; },
mesh = {Humans ; Adolescent ; Child ; Female ; Male ; *COVID-19/complications/epidemiology/diagnosis ; Risk Factors ; Young Adult ; Severity of Illness Index ; Germany/epidemiology ; Adult ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Registries ; *Fatigue Syndrome, Chronic/diagnosis/epidemiology/etiology ; },
abstract = {Post-COVID condition (PCC) in children and young people (CYP, PCCcyp) remains a significant health burden. Early identification of patients at risk for severe disease, including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), is crucial for timely and adequate care. This monocentric, observational registry study, performed at a tertiary pediatric hospital in Germany, included CYP aged 7-25 years with PCCcyp at diagnosis. Standardized clinical assessment tools and patient-reported outcome measures were applied, including the novel Munich Long COVID Symptom Questionnaire (MLCSQ). Severe PCC was defined by chronic symptom clusters, Fatigue Severity Scale (FSS), Total Composite Autonomic Symptom Score-31 (COMPASS-31), SF-36 composite scores, Bell Score, and confirmed ME/CFS diagnosis. Among 120 participants, severe PCCcyp was associated with a higher number of acute symptoms (ORadj 1.22, P < 0.001), acute orthostatic intolerance (ORadj 9.87, P = 0.002), acute trouble concentrating (ORadj 11.8, P = 0.005), and female sex (OR 3.31, P = 0.031). Categorizing acute symptoms at a threshold of ≥ 12 yielded optimal model performance (AUC 0.857; sensitivity 65.6%; specificity 90.2%). ME/CFS was diagnosed in 24% of participants, all within the severe PCCcyp cluster, and was characterized by greater acute symptom complexity, more fatigue, more autonomic symptoms, and poorer function. Conclusions: The number and pattern of acute symptoms during SARS-CoV-2 infection may serve as early, specific predictors of severe PCCcyp. Patients with ≥ 12 acute symptoms should be closely monitored to enable early diagnosis of severe PCCcyp and ME/CFS. A distinct cluster of severely affected patients, frequently with ME/CFS, was identified.Trial registration: ClinicalTrials.gov: NCT05638724; Ethics approval (511/21, 2025-465-S-SB).},
}

Humans
Adolescent
Child
Female
Male
*COVID-19/complications/epidemiology/diagnosis
Risk Factors
Young Adult
Severity of Illness Index
Germany/epidemiology
Adult
SARS-CoV-2
Post-Acute COVID-19 Syndrome
Registries
*Fatigue Syndrome, Chronic/diagnosis/epidemiology/etiology

@article {pmid42068900,
year = {2026},
author = {Liira, H and Varonen, M and Vangelova-Korpinen, V and Venäläinen, MS and Arokoski, J and Kvarnström, K and Vuokko, A and Malmivaara, A},
title = {Somatic symptom burden and distress in post COVID-19 and persistent physical symptoms: Evidence from combined SSD-12 and PHQ-15 factor analysis.},
journal = {Journal of psychosomatic research},
volume = {208},
number = {},
pages = {112686},
doi = {10.1016/j.jpsychores.2026.112686},
pmid = {42068900},
issn = {1879-1360},
abstract = {BACKGROUND AND AIM: Post COVID-19 condition (PCC) and persistent physical symptoms (PPS) may involve overlapping symptom presentations. We examined whether symptom-related dimensions differ or overlap between PCC and functional somatic disorders by comparing Somatic Symptom Disorder-B Criteria Scale (SSD-12; cognitive-affective distress) and the Patient Health Questionnaire-15 (PHQ-15; somatic symptom burden), and by performing a joint factor analysis of their items.

METHODS: Two cohorts at Helsinki University Hospital were analysed: the Sympa cohort (2020-2024), comprising patients with PPS, and the Long Covid (LC) cohort (2021-2023), including patients with PCC and age- and sex-matched controls.

RESULTS: The study included 557 patients with PPS, 433 with PCC, and 197 controls; two-thirds of patients in both cohorts were female. Patients showed markedly higher somatic symptom burden than controls, with 52.2% of patients with PPS and 48.0% of those with PCC exceeding the combined SSD-12 and PHQ-15 threshold indicating concurrent high somatic symptom burden and symptom-related distress. Joint factor analysis revealed a four-factor structure: one dominant cognitive-affective distress factor; a narrower persistence-worry factor; and two symptom clusters reflecting pain/gastrointestinal and autonomic-neurological symptoms. Participants above the threshold had poorer quality of life, lower resilience, and more comorbidities and symptoms across cohorts (all p < 0.001).

CONCLUSIONS: Approximately half of rehabilitation clinic patients with PPS or PCC exhibited high somatic symptom burden and symptom-related distress. Despite differing clinical entry points, the two cohorts showed broadly similar symptom-related dimensions. High symptom-related distress identifies a subgroup with greater impairment who may benefit from targeted rehabilitation approaches.},
}

@article {pmid42071077,
year = {2026},
author = {Nielsen, NM and Spiliopoulos, L and Sørensen, AIV and O'Regan, E and Bager, P and Ethelberg, S and Koch, A and Videbech, P and Hviid, A},
title = {Acute SARS-CoV-2 infection and self-reported post-acute cognitive dysfunctions from the Danish EFTER-COVID survey.},
journal = {Communications medicine},
volume = {6},
number = {1},
pages = {},
pmid = {42071077},
issn = {2730-664X},
abstract = {BACKGROUND: The extent and burden of post-acute cognitive dysfunctions following SARS-CoV-2 infection is uncertain.

METHODS: 25,485 SARS-CoV-2 test-positive and 25,032 test-negative individuals were repeatedly asked to score symptoms of subjective cognitive deficits 2 to 18 months after test using the "Cognitive complaints in bipolar disorder rating assessment" (COBRA) tool. Poisson mixed-effects models were used to estimate Score Ratios (SRs) by comparing scores between test-positive and test-negative individuals.

RESULTS: At each follow-up point, test-positive individuals have low but slightly higher mean COBRA scores compared with test-negatives. For the combined 2-18 months period, COBRA scores among test-positive individuals are 11% higher than corresponding scores among test-negatives (SR2-18mth = 1.11 (95% CI; 1.09-1.13)). Of effect modifiers explored, being hospitalized with a positive SARS-CoV-2 test particularly elevates COBRA scores (SR2-18mth = 1.38 (95% CI; 1.24-1.54)).

CONCLUSION: In the general population of SARS-CoV-2 infected individuals, self-reported post-acute scores of cognitive dysfunctions are low and only slightly higher than corresponding scores among test-negatives. Higher COBRA scores among hospitalized SARS-CoV-2 test positives corroborate with long-term cognitive impairment being most pronounced among those with severe SARS-CoV-2 infection.},
}

@article {pmid42063202,
year = {2026},
author = {Neilens, H and Allgar, V and Sands, KA and Chynoweth, J and Lord, A and Aspinall, PJ and Hambly, H and Barnett, A and Skipper, L and Bewick, T and Maidment, I and Razak, HA and Ashton, R and Strain, D and Knapp, K and Faghy, MA},
title = {An open-label, clinical feasibility study of the efficacy of Remdesivir for Long-COVID.},
journal = {Pilot and feasibility studies},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40814-026-01823-9},
pmid = {42063202},
issn = {2055-5784},
abstract = {BACKGROUND: Long COVID (LC) affects around two million people in the UK and over 65 million people globally. Antiviral medications have shown positive effects in reducing the risk of progression to severe disease in high-risk patients during an acute SARS-CoV-2 infection and have improved outcomes in those living with LC. Research testing the feasibility and efficacy of antiviral medications is ongoing, and clinical trials should determine the use of Remdesivir and its impact on LC symptoms, patient-reported outcomes, quality of life and functional status.

METHODS: Seventy-two patients ≥ 18 years of age who have a confirmed LC diagnosis will be recruited across two sites to trial RemdesivirTM treatment delivered via intravenous infusion over 5 days. This feasibility study will provide high-quality data to estimate screening rates, recruitment through different pathways, retention and treatment adherence. The study will also determine the definitive trial's most clinically relevant primary outcome. After a detailed screening process, patient-reported and clinical outcome measures (including EQ-5D-5L, Symptom Burden Questionnaire™ for LC (SBQ™), cardiopulmonary exercise tests (CPET), lung function, biomarkers and inflammatory profiles) will be collected to determine symptoms and impact of their condition, which will be repeated post-treatment. A subset of 20 participants will undergo whole-body parametric Fluorodeoxyglucose (FDG) PET/CT to measure multi-organ metabolic activity. Due to the established physical, cognitive and clinical impairment impacts of LC, patient involvement has been extensively embedded within the design and implementation of all study processes to increase patient safety and delivery.

DISCUSSION: This study will provide data on the feasibility of a trial of 5-day intravenous treatment with Remdesivir for patients with LC. The treatment is already effective in the treatment of patients with acute severe cases of SARS-CoV-2. Remdesivir has an established safety profile and carries no higher risk to patients than standard medical care. The findings will inform the design of a future definitive study.

TRIAL REGISTRATION: ISRCTN Number: 72940450. Date registered: 07/06/2024. URL: https://www.isrctn.com/ISRCTN72940450.

CLINICALTRIALS: gov Number: NCT05911906.},
}

@article {pmid42063762,
year = {2026},
author = {Spanoghe, M and Molmans, THJ and Antonacci, T and Burel, E and Herschke, F and Schneider, N and Oustric, P and Thielemans, P and Nicolas, JB and Dauby, N and Nicaise, C and Van Weyenbergh, J and Jamoulle, M},
title = {Commentary: Internal medicine at the crossroads of long COVID diagnosis and management.},
journal = {Frontiers in medicine},
volume = {13},
number = {},
pages = {1798119},
pmid = {42063762},
issn = {2296-858X},
}

@article {pmid42065099,
year = {2026},
author = {Tuller, D},
title = {Comments regarding "Effects of therapeutic interventions on long COVID: a meta-analysis of randomized controlled trials".},
journal = {EClinicalMedicine},
volume = {95},
number = {},
pages = {103882},
pmid = {42065099},
issn = {2589-5370},
}

@article {pmid42065101,
year = {2026},
author = {Tan, C and Meng, J and Dai, X and Gao, S},
title = {Authors' reply: Comments regarding "Effects of therapeutic interventions on long COVID: a meta-analysis of randomized controlled trials".},
journal = {EClinicalMedicine},
volume = {95},
number = {},
pages = {103883},
pmid = {42065101},
issn = {2589-5370},
}

@article {pmid42066215,
year = {2026},
author = {Maeda, T and Yohannes, AM},
title = {Expanding Pulmonary Rehabilitation Beyond Chronic Obstructive Pulmonary Disease and Long COVID: ITS ROLE IN COMPARATIVE EVIDENCE.},
journal = {Journal of cardiopulmonary rehabilitation and prevention},
volume = {46},
number = {3},
pages = {155-157},
pmid = {42066215},
issn = {1932-751X},
}

@article {pmid41410968,
year = {2025},
author = {Stafseth, M},
title = {[Long COVID].},
journal = {Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke},
volume = {145},
number = {15},
pages = {},
doi = {10.4045/tidsskr.25.0629},
pmid = {41410968},
issn = {0807-7096},
}

@article {pmid41872922,
year = {2026},
author = {Cohen, JG and Estopier-Castillo, V and Olivier, C and Destors, M and Ferretti, GR and Pépin, JL and Tamisier, R and Bayat, S},
title = {Imaging biomarkers of post-COVID dyspnea: insights from machine learning CT patterns and parametric response mapping.},
journal = {Respiratory research},
volume = {27},
number = {1},
pages = {},
pmid = {41872922},
issn = {1465-993X},
abstract = {BACKGROUND: Dyspnea is one of the most common symptoms in the post-acute phase of COVID-19 pneumonia. Conventional pulmonary function tests and computed tomography (CT) scores often fail to show correlation with symptom severity, highlighting the need for more sensitive imaging biomarkers. Machine-learning–based quantitative CT analysis and parametric response mapping (PRM) can capture subtle structural and functional abnormalities that may be associated with persistent dyspnea.

METHODS: We analyzed inspiratory and paired inspiratory–expiratory CT scans of early (3–6 months) post-COVID-19 pneumonia patients. Inspiratory CT images were segmented using a random forest algorithm to quantify lung parenchymal patterns. Paired inspiratory/expiratory scans were co-registered to derive ventilation metrics and PRM-defined functional small airway disease (fSAD), emphysema, emptying emphysema, and normal lung. Associations between imaging metrics and patient-reported dyspnea assessed by a visual analogue scale (VAS) were evaluated using univariable and multivariable linear regression, with adjustment for age, sex, BMI, and smoking history.

RESULTS: One hundred twenty-three patients had usable inspiratory CT scans, and 116 patients had paired inspiratory/expiratory scans of sufficient quality for analysis. In the adjusted multivariable models, greater PRM-defined functional small airway disease (fSAD) was positively associated with dyspnea (standardized β = 1.21, p = 0.002). Moreover, a lower standard deviation of dense ground-glass attenuation in the left lung (standardized β = −0.82, p = 0.033) and greater total volume of dense ground-glass opacities (standardized β = 0.71, p = 0.033) were independently associated with dyspnea.

CONCLUSIONS: In early post-COVID-19 pneumonia, machine-learning–based CT pattern recognition and PRM revealed that functional small airway disease, and the total volume and heterogeneity of lung dense ground-glass opacities are significantly associated with persistent dyspnea. These findings highlight the potential of quantitative CT to identify pulmonary imaging biomarkers relevant to long COVID symptom burden.

TRIAL REGISTRATION: ClinicalTrials.gov (NCT04406324).},
}

@article {pmid42056917,
year = {2026},
author = {Bergqvist, E and Valerio-Shewmaker, M and Swartz, M and Patel, J and Padilla, L and Amavisca, XF and Gandhi, H and Messiah, SE},
title = {Association of race, ethnicity, and pediatric long COVID and MIS-C: a systematic review and meta-analysis.},
journal = {BMC infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12879-026-12848-z},
pmid = {42056917},
issn = {1471-2334},
}

@article {pmid42057113,
year = {2026},
author = {Heemskerk, SCM and Brus, IM and de Groot, A and Rijssenbeek-Nouwens, L and Tieleman, P and Ter Wolbeek, M and Burdorf, A and Biere-Rafi, S and Haagsma, JA},
title = {Opportunities and barriers in care for patients with post COVID-19 condition: a Delphi study among healthcare workers.},
journal = {BMC health services research},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12913-026-14489-z},
pmid = {42057113},
issn = {1472-6963},
}

@article {pmid42059350,
year = {2026},
author = {Loblundo, C and Chun, WB and Nguyen, SA and Meenan, K and O'Rourke, AK},
title = {Laryngeal Dysfunction Following COVID-19: A TriNetX Retrospective Cohort Study.},
journal = {The Laryngoscope},
volume = {},
number = {},
pages = {},
doi = {10.1002/lary.70590},
pmid = {42059350},
issn = {1531-4995},
abstract = {OBJECTIVE(S): Long COVID affects multiple organ systems, yet the incidence and risk factors for post-COVID-19 laryngeal dysfunction remain underexplored. This study evaluated the incidence of laryngeal dysfunction following COVID-19.

METHODS: A retrospective cohort study was performed using the TriNetX Global Collaborative EHR Network (> 180 million records). Adults without prior laryngeal dysfunction or major comorbidities were stratified by COVID-19 exposure and compared with uninfected controls. Outcomes included chronic cough, dysphagia, voice disorders, vocal fold paralysis, and laryngeal spasm, assessed up to 5 years post-infection. After propensity score matching, odds ratios (OR) and risk differences (RD) with 95% confidence intervals (CI) were calculated.

RESULTS: COVID-19 was associated with significantly increased odds of chronic cough (peak OR 7.12; RD 0.33%, p < 0.0001), dysphagia (peak OR 2.71; RD 0.36%, p < 0.0001), voice disorders (peak OR 3.25; RD 0.12%, p < 0.0001), vocal fold paralysis (peak OR 2.17; RD 0.01%, p < 0.0001), and laryngeal spasm (peak OR 2.79; RD 0.003%, p < 0.0001). Incidence peaked at 1-2 years for most outcomes and at 2-3 years for laryngeal spasm. Hospitalization and mechanical ventilation were associated with increased rates of dysphagia (HR 2.63; HR 5.26), voice disorders (HR 1.15; HR 4.45), and vocal cord paralysis (HR 2.09; HR 9.35), but reduced rates of chronic cough (HR 0.68; HR 0.45). Vaccinated patients showed higher rates of chronic cough (HR 1.36) and voice disorders (HR 1.22).

CONCLUSION: COVID-19 is associated with increased incidence of new-onset laryngeal dysfunction, most commonly peaking 1-2 years after infection and influenced by hospitalization, mechanical ventilation, and vaccination status.},
}

@article {pmid42059960,
year = {2026},
author = {Tuomaala, J and Saraste, M and Smith, E and Kuusi, M and Westerberg, E and Honkonen, E and Kargar, R and Laaksonen, S and Lehto, J and Luoma, A and Matilainen, M and Misin, O and Atosuo, J and Kanerva, M and Liira, H and Laakso, S and Posharina, T and Saunavaara, V and Wahlroos, S and Rajander, J and Airas, L},
title = {Association between post-COVID-19 neuropsychiatric symptoms and persistent glial activation in the limbic system: a TSPO PET study.},
journal = {Journal of neurology},
volume = {273},
number = {5},
pages = {},
pmid = {42059960},
issn = {1432-1459},
support = {330902//Academy of Finland/ ; 374291//Academy of Finland/ ; 337530//Academy of Finland/ ; 357910//Academy of Finland/ ; 358823//Academy of Finland/ ; 101057553//HORIZON EUROPE Health/ ; },
mesh = {Humans ; *COVID-19/complications/diagnostic imaging/psychology/metabolism ; Male ; Female ; Adult ; Positron-Emission Tomography ; Middle Aged ; *Receptors, GABA/metabolism ; *Neuroglia/metabolism ; *Limbic System/diagnostic imaging/metabolism ; Multiple Sclerosis/diagnostic imaging/metabolism/psychology ; Magnetic Resonance Imaging ; *Mental Disorders/diagnostic imaging/etiology ; },
abstract = {BACKGROUND: A subset of individuals experience prolonged neurological and psychiatric symptoms following SARS-CoV-2 infection, a condition referred to as long COVID (LC). Limited evidence implicates ongoing neuroinflammatory processes as a driver of LC. This study investigates neuroinflammation in LC using translocator protein positron emission tomography (TSPO PET).

METHODS: 14 LC, 11 healthy control (HC) and 13 multiple sclerosis (MS) participants were included in the study. They underwent [[11]C]PK11195 TSPO PET and 3T magnetic resonance imaging (MRI) to evaluate glial activation, white matter (WM) pathology and brain volumetrics. Serum neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) were measured as markers of neuronal and glial damage. LC participants completed neurological examinations and mental health assessments.

RESULTS: TSPO availability, measured as distribution volume ratio (DVR), was not elevated in LC compared to HCs but was significantly lower in LC compared to MS (WM DVR 1.03 vs. 1.06; p = 0.007). Individuals imaged within 16 months of SARS-CoV-2 infection showed higher WM DVR compared to those with a longer disease duration (1.05 vs. 1.02; p = 0.04). Moreover, lower quality of life was associated with higher DVRs in the hippocampus, amygdala and thalamus (ρ = - 0.83- - 0.70), and depression and anxiety correlated positively with DVRs in the hippocampus and amygdala (ρ = 0.75-0.97).

CONCLUSIONS: LC TSPO availability did not differ from HCs in any studied brain area. However, lower WM TSPO availability in individuals with longer LC duration suggests COVID-19-associated neuroinflammation may subside with time, while the association between limbic TSPO availability and LC severity may imply a role for limbic activity in LC symptomology.},
}

Humans
*COVID-19/complications/diagnostic imaging/psychology/metabolism
Male
Female
Adult
Positron-Emission Tomography
Middle Aged
*Receptors, GABA/metabolism
*Neuroglia/metabolism
*Limbic System/diagnostic imaging/metabolism
Multiple Sclerosis/diagnostic imaging/metabolism/psychology
Magnetic Resonance Imaging
*Mental Disorders/diagnostic imaging/etiology

@article {pmid42061273,
year = {2026},
author = {Jürgensen, M and Frisk, B and Kvale, G and Espehaug, B},
title = {Improvements in long COVID symptoms, functional level and the impact of illness perceptions after concentrated micro-choice-based rehabilitation: A1-year prospective uncontrolled study.},
journal = {Journal of psychosomatic research},
volume = {208},
number = {},
pages = {112687},
doi = {10.1016/j.jpsychores.2026.112687},
pmid = {42061273},
issn = {1879-1360},
abstract = {BACKGROUND: Patients with long COVID face persisting physical and psychiatric symptoms. Illness perceptions are associated with increased symptom burden and poorer recovery. However, little is known about how changes in illness perceptions in rehabilitation impact symptoms and functional levels. This study assessed longitudinal changes in symptoms of anxiety and depression, insomnia, fatigue, dyspnea, illness perception, and functional levels in patients with long COVID following a micro-choice-based intervention.

METHODS: This prospective uncontrolled study with 12-month follow-up included 78 patients with long COVID aged 19-67 years, mean age 40.3 ± 12.0 years. The intervention consisted of three equally important phases: pre-treatment preparation, a 3-day concentrated micro-choice-based intervention and integration of changes into daily life.

RESULTS: At 3- and 12-month follow-ups significant improvements were observed in symptoms of anxiety (p < 0.001), depression (p < 0.001), fatigue (p < 0.001), illness perceptions (p < 0.001) and functional levels (p < 0.001). Caseness of anxiety and depression were reduced from 26.9% at baseline to 10.0% 12-month follow-up and from 51.3% to 20.0%, respectively. Changes in functional level strongly correlated with changes in illness perception. Patients with a history of psychiatric illness did not experience the same short-term improvements in illness perception compared to those without such a history, but theses differences were not present at 12-month follow-up.

CONCLUSION: Patients with long COVID participating in a concentrated micro-choice-based rehabilitation showed consistent improvements in both psychiatric symptoms and functional levels, including those with a history of psychiatric illness. Changes in illness perception was associated with sustained reduction in symptom burden and increased functional levels.

CLINICAL TRIALS REGISTRATION: NCT05234281, with an approval date of 10 February 2022. The study were approved by the Western Norway Regional Committees for Medical and Health Research Ethics (REK 2020/101648).},
}

@article {pmid42051331,
year = {2026},
author = {Wilches-Luna, EC and Perez-Hortúa, V and Asencio-Santofimio, H and Aguilar-Zambrano, J and Arzayus-Patiño, L},
title = {Distribution of pulmonary ventilation in women with post-COVID-19 before and after the use of a respiratory incentive device (UBICU): a pilot study.},
journal = {Frontiers in digital health},
volume = {8},
number = {},
pages = {1789878},
pmid = {42051331},
issn = {2673-253X},
abstract = {INTRODUCTION: In the aftermath of the COVID-19 pandemic, restrictive pulmonary complications have emerged as a common long-term sequela. To address these impairments, a novel flow-based respiratory incentive device, UBICU, was developed to promote lung expansion through gamification and visual feedback. The aim of this study was to describe the pulmonary ventilation distribution using Electrical Impedance Tomography (EIT) in women with long COVID and restrictive pulmonary impairment, before and after using the UBICU device.

METHODS: This exploratory (pre-post) pilot study included eight women with post-COVID-19 restrictive impairment, as determined by spirometry in accordance with ATS/ERS guidelines. Pulmonary ventilation distribution was assessed before and after the intervention using electrical impedance tomography. Participants were provided with the UBICU device and instructed to perform three sets of 10 repetitions daily for seven consecutive days. The study was approved by the Institutional Ethics Committee, adhered to the principles of the Declaration of Helsinki, and written informed consent was obtained from all participants.

RESULTS: An asymmetric regional ventilation pattern was observed before and after the intervention. Statistically significant improvements were found in ROI 1 (p = 0.007), ROI 3 (p = 0.007), and ROI 4 (p = 0.007) after using the UBICU device.

CONCLUSION: Use of the UBICU device was associated with improvements in pulmonary ventilation distribution, suggesting its potential as an adjunctive therapeutic tool in the management of women with long COVID and restrictive pulmonary impairment.},
}

@article {pmid42051540,
year = {2026},
author = {Jin, H and An, Y and Huang, J and Luo, T and Wu, X},
title = {Pathophysiological mechanisms of post-exertional malaise: an integrative analysis based on the metabolism-immune-neuro interaction model.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1774310},
pmid = {42051540},
issn = {1664-3224},
mesh = {Humans ; *COVID-19/immunology/complications/metabolism/physiopathology ; *SARS-CoV-2 ; *Fatigue Syndrome, Chronic/immunology/physiopathology/metabolism ; Exercise/physiology ; Mitochondria/metabolism ; Neuroimmunomodulation ; Post-Acute COVID-19 Syndrome ; Reactive Oxygen Species/metabolism ; },
abstract = {Post-exertional malaise (PEM) is a common core symptom in various chronic debilitating conditions, such as Post COVID-19 Condition (PCC, also known as Long COVID) and Chronic Fatigue Syndrome (CFS). It is characterized by the delayed and persistent exacerbation of symptoms following even mild physical or cognitive activities. This review presents a systematic review of the pathophysiological mechanisms involved in PEM, proposing a dynamic framework of multi-system interactions that may lead to homeostatic imbalance. The etiology of PEM is multifactorial, potentially involving factors such as the persistent presence of pathogens, exposure to environmental toxins, and genetic predisposition. Collectively, these factors may establish a vulnerable baseline that heightens the body's physiological response to stressors, such as exercise, potentially triggering a pathological reaction. First, mitochondrial dysfunction and metabolic abnormalities may act as potential initiating factors in PEM, manifesting as impaired ATP synthesis, overproduction of reactive oxygen species (ROS), and the accumulation of metabolic byproducts. It is crucial to emphasize that exercise itself induces a 'toxic excitatory effect,' whereby healthy individuals enhance mitochondrial function and antioxidant defenses through physical activity. However, in individuals predisposed to PEM, due to underlying pathological conditions (e.g., sequelae of viral infections), this adaptive process is disrupted, preventing effective restoration of mitochondrial homeostasis and may initiate a potential vicious cycle of dysfunction. Second, ROS and mitochondrial DNA (mtDNA), as damage-associated molecular patterns (DAMPs), along with pathogen-associated molecular patterns (PAMPs), may activate the NLRP3 inflammasome and induce the release of pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α, potentially transforming localized metabolic stress into a systemic inflammatory response. Subsequently, peripheral inflammation may be transmitted to the central nervous system through disruption of the blood-brain barrier and vagal nerve pathways, activating glial cells and initiating neuroinflammation. This process may ultimately affect the brain's interoceptive network, particularly the insular cortex, resulting in altered perception and processing of signals related to fatigue and pain. Furthermore, mitochondrial dysfunction in neurons may contribute to central energy depletion, which may impair synaptic plasticity and induce cognitive deficits and brain fatigue. Ultimately, this review proposes that PEM may arise from a complex interplay among mitochondrial dysfunction, immune activation, and neuroinflammation, which together form a self-perpetuating loop of "energy exhaustion - inflammation amplification," potentially contributing to the chronic and multi-system nature of PEM symptoms. The integrated "metabolism-immune-neuro" interaction model presented in this article may provide a potential comprehensive framework for understanding PEM and highlights the need for a multi-target, collaborative intervention approach that may help disrupt the pathological cycle.},
}

Humans
*COVID-19/immunology/complications/metabolism/physiopathology
*SARS-CoV-2
*Fatigue Syndrome, Chronic/immunology/physiopathology/metabolism
Exercise/physiology
Mitochondria/metabolism
Neuroimmunomodulation
Post-Acute COVID-19 Syndrome
Reactive Oxygen Species/metabolism

@article {pmid42052332,
year = {2025},
author = {Lee, EJ and Tsang, C and Pérez, MLG and Abouzari, M and Djalilian, HR},
title = {Calcitonin Gene-Related Peptide-Induced Central Sensitization: A Hypothesis for Long COVID Symptoms.},
journal = {Medical hypotheses},
volume = {195},
number = {},
pages = {},
pmid = {42052332},
issn = {1532-2777},
abstract = {Central sensitization (CS) denotes aberrant processing of sensory stimuli within the central nervous system, wherein innocuous inputs activate pain pathways, leading to pain hypersensitivity. Features observed in CS conditions are often present in patients with long COVID, suggesting a potentially shared pathophysiological mechanism. We hypothesize that elevated levels of calcitonin gene-related peptide (CGRP), a neuropeptide known to play an integral role in the development of CS, may contribute to the persistent symptoms observed in long COVID. This article explores the role of CGRP within the context of CS and proposes its potential relationship to long COVID.},
}

@article {pmid42052381,
year = {2026},
author = {Lin, J and Chen, S and Zhang, L and Qiu, M and Zuo, W and Wang, L and He, Q and Li, Y and Jin, H and Tan, S and Huang, M and Zhu, C and Jin, Q and Wang, M and Wan, Y and Hu, B},
title = {Two-year trajectory of cognitive decline and neurological sequelae in COVID-19 survivors with acute neurological symptoms.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1724803},
pmid = {42052381},
issn = {1663-4365},
abstract = {INTRODUCTION: The COVID-19 pandemic caused by SARS-CoV-2 has profound implications for global public health. It significantly affects the nervous system and cognitive function. The emergence of long COVID has raised concerns regarding long-term cognitive impairment, particularly among patients who experienced neurological symptoms during the acute phase of infection.

AIM: This study investigated the impact of neurological symptoms during acute SARS-CoV-2 infection on subsequent cognitive change and neurological sequelae over a 2-year period.

METHODS: We enrolled 3,419 hospitalized patients with confirmed infection in Wuhan, China (Dec 2022-Mar 2023), and 2,087 completed follow-ups. Propensity score matching identified 901 patients with acute neurological symptoms and 901 controls. Cognitive decline was measured with the Informant Questionnaire on Cognitive Decline in the Elderly, and cognitive status with the Telephone Interview of Cognitive Status-40. Multivariable regression was used to examine risk factors and cognitive changes, and residual neurological symptoms and new-onset symptoms were also analyzed.

RESULTS: Acute neurological symptoms, particularly central nervous system manifestations such as delirium and brain fog, were strongly associated with both cognitive decline (aOR, 2.16; 95% CI, 1.53-3.07) and cognitive impairment (aOR, 2.75; 95% CI, 1.73-4.49). Delirium, brain fog, stroke, numbness, and facial paralysis were associated risk factors (all p < 0.05). After 2 years' follow-up, most acute neurological symptoms had subsided, yet fatigue (8.66%) and brain fog (5.99%) persisted. Comorbidities did not significantly increase the risk of persistent symptoms. For the new-onset symptoms, the proportion of insomnia, tinnitus, blurred vision, movement disorder, palpitation, muscle weakness, and respiratory symptoms were much higher in the neurological symptom group (p < 0.05), with a highest proportion in insomnia (9.99% vs. 5.22%, p < 0.001), compared with the non-neurological symptom group.

CONCLUSION: Acute neurological symptoms, especially central nervous system manifestations, were strongly associated with long-term cognitive decline and new-onset symptoms (mainly insomnia) in COVID-19 survivors. This study uniquely reveals the persistence of high levels in brain fog and fatigue at 2-year's follow up, despite overall subsidence of most acute manifestations, underscoring the need for early intervention and sustained monitoring in this high-risk population.},
}

@article {pmid42052408,
year = {2026},
author = {Wang, R and Dai, R and Dai, H and French, E and Zheng, C},
title = {Controlling FDR in selecting group-level simultaneous signals from multiple data sources with application to the National COVID Collaborative Cohort data.},
journal = {Journal of applied statistics},
volume = {},
number = {},
pages = {},
pmid = {42052408},
issn = {0266-4763},
abstract = {One challenge in exploratory association studies using observational data is that the associations between the predictors and the outcome are potentially weak and rare, and the candidate predictors have complex correlation structures. False discovery rate (FDR) controlling procedures can provide important statistical guarantees for replicability in predictor identification in exploratory research. In the recently established National COVID Collaborative Cohort (N3C), electronic health record (EHR) data on the same set of grouped candidate predictors are independently collected in multiple different data contributing sites, offering opportunities to identify true associations by combining information from different sources. One challenge is to handle the heterogeneous data types for the same clinical endpoint from the multiple sites. This paper addresses this challenge by presenting a general knockoff-based variable selection algorithm to identify associations from unions of group-level conditional independence tests (simultaneous signals) with exact FDR control guarantees under finite sample settings. This algorithm can work with general regression settings, allowing heterogeneity of both the predictors and the outcomes across multiple data sources. We demonstrate the performance of this method with extensive numerical studies and an application to the N3C data.},
}

@article {pmid42053865,
year = {2026},
author = {Mignolet, M and Deroux, C and Florkin, T and Bielarz, V and De Swert, K and Halloin, N and Sprimont, L and Ladang, A and George, F and Gilloteaux, J and Abeloos, L and Garin, P and Van Weyenbergh, J and Jamoulle, M and Diederich, C and Gillet, NA and Bulpa, P and Nicaise, C},
title = {Pathogenic IgG from long COVID patients with neurological sequelae triggers sensitive but not cognitive impairments upon transfer into mice.},
journal = {Acta neuropathologica},
volume = {151},
number = {1},
pages = {},
pmid = {42053865},
issn = {1432-0533},
mesh = {Animals ; *COVID-19/immunology/complications/psychology ; *Immunoglobulin G/immunology ; Mice ; Humans ; Male ; Female ; Mice, Inbred C57BL ; *Cognitive Dysfunction/immunology/etiology ; Middle Aged ; *Autoantibodies/immunology ; SARS-CoV-2 ; Hyperalgesia/immunology ; Disease Models, Animal ; Adult ; Aged ; },
abstract = {Approximately 30% of long COVID patients still experience neurological symptoms (brain fog, pain, chronic fatigue) more than 4 months after the onset of COVID-19. This condition, known as 'neurological long COVID', remains poorly understood and might be explained by a persisting autoimmune response against nervous-derived self-antigens. The aim of this study is to determine whether IgG autoantibodies from long COVID patients with neurological sequelae can bind to central or peripheral nervous system epitopes and trigger neuropsychiatric symptoms upon passive transfer into mice, thereby mirroring patient-reported manifestations. Long COVID patients meeting the 2021 consensus WHO definition were included following a standardized neuropsychological assessment, while excluding patients with a medical history of autoimmune and neurological disorders. Age- and sex-matched asymptomatic individuals were used as healthy controls. Total IgGs were isolated using protein G purification and injected intraperitoneally into C57Bl6/J mice for four consecutive days. During the two weeks post-injections, behavioral tests assessed mechanical allodynia, thermal hyperalgesia, spatial working memory, depression, and anxiety. Mice injected with IgG from long COVID patients showed no difference with the control group in terms of anxiety or depression behaviors, short- or long-term spatial memories. However, they displayed a transient decrease of paw withdrawal threshold and thermal hypersensitivity during the first week. This effect was abolished when IgG-depleted serum or papain-digested IgGs were transferred. IgG from long COVID patients accumulated in the lumbar dorsal root ganglia of injected mice and colocalized with proprioceptive and nociceptive sensory neurons, without inducing local neuroinflammation or astrogliosis. When applied onto human post-mortem DRG tissue, patient-derived IgG also exhibited immunoaffinity for sensory neuron somata. These data demonstrate that IgGs from long COVID patients bind to peripheral sensory neurons and induce pain-related symptoms in mice. Our findings also support the hypothesis that autoantibodies mediate pain-related pathophysiology in the spectrum of long COVID symptoms.},
}

Animals
*COVID-19/immunology/complications/psychology
*Immunoglobulin G/immunology
Mice
Humans
Male
Female
Mice, Inbred C57BL
*Cognitive Dysfunction/immunology/etiology
Middle Aged
*Autoantibodies/immunology
SARS-CoV-2
Hyperalgesia/immunology
Disease Models, Animal
Adult
Aged

@article {pmid42055117,
year = {2026},
author = {Kahlon, RK and Laurin, JKH and Nath, E and Raj, SR},
title = {Successful Ivabradine Use Throughout Pregnancy for Postural Orthostatic Tachycardia Syndrome: A Case Report with Reassuring Maternal-Fetal Outcomes.},
journal = {The Canadian journal of cardiology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cjca.2026.04.019},
pmid = {42055117},
issn = {1916-7075},
abstract = {We report on a 35-year-old gravida 2 para 1 female with long-COVID postural orthostatic tachycardia syndrome (POTS) who continued all pharmacologic therapies from preconception through delivery, including ivabradine, a medication contraindicated in pregnancy due to preclinical embryotoxicity and teratogenicity. Serial fetal assessments including growth studies, fetal Dopplers, and non-stress tests remained normal throughout gestation without evidence of fetal bradycardia, arrhythmia, or structural abnormalities. Delivery at 38 weeks 5 days' gestation resulted in a healthy female neonate. This case illustrates successful use of off-label ivabradine in pregnancy with reassuring maternal-fetal outcomes under close obstetric-cardiology supervision.},
}

@article {pmid42055743,
year = {2026},
author = {Grach, SL and Seltzer, J and Mueller, MR and Aakre, CA and Natividad, LT and Lawson, DK and Ganesh, R and Hurt, RT},
title = {Underuse of Pharmacologic Therapies for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Before Specialist Evaluation.},
journal = {Annals of family medicine},
volume = {},
number = {},
pages = {},
doi = {10.1370/afm.250266},
pmid = {42055743},
issn = {1544-1717},
abstract = {PURPOSE: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multisystem neurologic disease characterized by profound fatigue and decreased functional capacity, postexertional malaise, and unrefreshing sleep, along with cognitive impairment and/or orthostatic intolerance. Its prevalence has risen exponentially with the COVID-19 pandemic. Pharmacologic therapies have been used successfully by ME/CFS specialists but may be underused by the general medical field.

METHODS: To assess this potential practice gap, we retrospectively analyzed the records of 571 patients with an ME/CFS diagnosis referred to our ME/CFS specialty clinic in Minnesota during 2018-2022. We ascertained medications that had already been tried at the time of consultation and also ascertained supplement use.

RESULTS: With the exception of medications primarily used for pain and anxiety, use of pharmacotherapy for ME/CFS symptom management as proposed by specialists was limited. Overall, 68.3% of patients had had at least 1 medication potentially prescribed for ME/CFS; the most common were serotonin-norepinephrine reuptake inhibitors, gabapentin, and tricyclic antidepressants. A slightly larger share of patients, 72.2%, reported having taken at least 1 dietary supplement; the most common were vitamin D, vitamin B12 and B complex, and fish oil.

CONCLUSION: Our findings suggest that potentially helpful medications for ME/CFS are being underprescribed in the general medical field and that patients may resort to supplements to manage symptoms. Better education of clinicians about available treatment options and treatment guides may improve management of this debilitating disease.},
}

@article {pmid42056279,
year = {2026},
author = {Faghy, MA and Wüst, RCI and Altmann, DM and Ashton, RE and McMullen, SB and Duncan, R and Ewing, AG and Hausmann, E and Gupta, S and Hornig, M and Joffe, D and Kane, B and Khan, MA and Natt, M and Owen, R and Putrino, D and Skipper, L and Taylor, C and Thomas, C and Tuller, D and Beckman, D and Kruger, A and Pretorius, E},
title = {Current status and future perspectives on the mechanistic and pathophysiological understanding of long COVID.},
journal = {Communications medicine},
volume = {6},
number = {1},
pages = {},
pmid = {42056279},
issn = {2730-664X},
abstract = {BACKGROUND: Viral and infectious illnesses can exert profound and enduring effects on population health and well-being. In the aftermath of SARS-CoV-2 infection, post-acute sequelae, collectively referred to as Long COVID, have emerged as a major global health challenge, affecting more than 400 million people and contributing to estimated annual economic costs exceeding $1 trillion.

SCOPE OF THE REVIEW: Long COVID encompasses a wide and heterogeneous spectrum of debilitating symptoms, including cognitive dysfunction, sleep disturbances, severe fatigue, and post-exertional malaise. Despite its substantial burden, fundamental uncertainties remain regarding its underlying pathophysiology, the development of robust diagnostic criteria, and the identification of effective therapeutic options.

KEY INSIGHTS: This review synthesises current evidence on the biological mechanisms thought to contribute to Long COVID, spanning immune dysregulation, viral persistence, autonomic dysfunction, microvascular pathology, and other emerging hypotheses. We examine advances and limitations in contemporary diagnostic approaches and critically appraise existing treatment strategies, highlighting inconsistencies and gaps that hinder clinical consensus.

IMPLICATIONS: By integrating interdisciplinary insights, this review underscores the urgent need for mechanistic clarity, validated diagnostic frameworks, and rigorously evaluated treatment pathways. Addressing these gaps will be essential to developing effective, evidence-based management strategies and mitigating the long-term impact of Long COVID on global health.},
}

@article {pmid42046713,
year = {2026},
author = {Wu, KK and Deng, JS and Jiang, PL and Huang, CL and Tung, TH and Zhu, JS},
title = {Prevalence and influencing factors of long COVID brain fog among college students: a cross-sectional study in Taizhou, China.},
journal = {PeerJ},
volume = {14},
number = {},
pages = {e21026},
pmid = {42046713},
issn = {2167-8359},
mesh = {Humans ; Cross-Sectional Studies ; China/epidemiology ; *COVID-19/epidemiology/complications ; Male ; Female ; *Students/statistics & numerical data/psychology ; Prevalence ; Young Adult ; Universities ; SARS-CoV-2 ; Adult ; Surveys and Questionnaires ; Adolescent ; Risk Factors ; },
abstract = {BACKGROUND: Long COVID following SARS-CoV-2 infection is a public health concern. Brain fog, a symptom of long COVID, has an impact on patients' daily lives and health. However, studies on the effects of COVID on college students are limited.

METHODS: This cross-sectional study included students from two tertiary institutions in Taizhou, China. Data were collected using WeChat-based electronic questionnaires on the Wen-Juan-Xing survey platform from July 20, 2023 to August 7, 2023. Chi-square analyses and binary logistic regression were used to evaluate the factors contributing to brain fog.

RESULTS: A total of 1,071 students participated in the survey. Of these 1,071 students, 13.7% (147/1,071) reported experiencing long COVID, of whom 27.2% (40/147) reported symptoms of brain fog. Significant associations with brain fog were observed for the following factors: age (> 20 vs. ≤ 20 years, odds ratio (OR) = 4.360, 95% confidence interval (CI) [1.620-11.740]), clinical classification of COVID-19 (OR = 2.940, 95% CI [1.230-7.010]), and a decreased sense of smell and taste (OR = 5.110, 95% CI [1.240-21.110]).

CONCLUSIONS: This study highlights the significant prevalence of long COVID brain fog among college students and identifies key associated factors, underscoring the need for specific, focused interventions and support for affected individuals.},
}

Humans
Cross-Sectional Studies
China/epidemiology
*COVID-19/epidemiology/complications
Male
Female
*Students/statistics & numerical data/psychology
Prevalence
Young Adult
Universities
SARS-CoV-2
Adult
Surveys and Questionnaires
Adolescent
Risk Factors

@article {pmid42046721,
year = {2026},
author = {Deng, M and Wang, Y},
title = {Ocular Symptoms in Long COVID: A Cross-Sectional Study [Letter].},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {20},
number = {},
pages = {616430},
pmid = {42046721},
issn = {1177-5467},
}

@article {pmid42040088,
year = {2026},
author = {Onik, G},
title = {A health resort-based intervention reduces insomnia with minimal changes in quality of life in COVID-19 survivors and non-COVID-19 controls.},
journal = {Frontiers in public health},
volume = {14},
number = {},
pages = {1803380},
pmid = {42040088},
issn = {2296-2565},
mesh = {Humans ; *Sleep Initiation and Maintenance Disorders/therapy ; *Quality of Life ; *COVID-19/complications/psychology ; Male ; Female ; Middle Aged ; *Health Resorts ; Adult ; *Survivors/psychology/statistics & numerical data ; Aged ; SARS-CoV-2 ; },
abstract = {BACKGROUND: Persistent post-COVID-19 symptoms, especially insomnia, are common and markedly impair quality of life. While some patients improve over time, many experience long-lasting complaints. Health resort treatment has shown potential benefits in long COVID, but its effects on sleep and quality of life remain unclear. This study aimed to evaluate the impact of comprehensive health resort treatment on insomnia and quality of life in post-COVID-19 individuals and to compare outcomes with those without prior SARS-CoV-2 infection.

METHODS: A total of 101 participants, including 30 post-COVID-19 individuals, underwent comprehensive health resort treatment. Propensity score matching was used to compare post-COVID-19 and non-COVID groups. Insomnia and health-related quality of life were assessed using the Athens Insomnia Scale and EQ-5D-5L, respectively, before and after the sanatorium stay.

RESULTS: The Athens Insomnia Score significantly decreased in post-COVID-19 individuals following sanatorium treatment (6.24 ± 5.93 vs. 3.97 ± 4.19 points; p = 0.0005). The EQ index did not change significantly after treatment (p = 0.08). Overall health status, assessed using the visual analog scale (VAS), significantly improved in individuals with a history of COVID-19 (76.03 ± 12.70 vs. 88.45 ± 7.80 points; p < 0.0001). Treatment effectiveness did not differ significantly between the patient groups.

CONCLUSIONS: Comprehensive health resort treatments may improve insomnia and self-reported health in COVID-19 survivors. Effects on overall quality of life appear limited, and outcomes are similar to those in individuals without prior COVID-19. Further research is needed to clarify the clinical utility of this approach.},
}

Humans
*Sleep Initiation and Maintenance Disorders/therapy
*Quality of Life
*COVID-19/complications/psychology
Male
Female
Middle Aged
*Health Resorts
Adult
*Survivors/psychology/statistics & numerical data
Aged
SARS-CoV-2

@article {pmid42040552,
year = {2026},
author = {Srinivasan, M and Joseph, PV},
title = {A hypothesis connecting dysgeusia due to defects in ATP-P2X3 signaling and fatigue in myalgic encephalomyelitis/chronic fatigue syndrome: lessons learned from long-COVID.},
journal = {Frontiers in medicine},
volume = {13},
number = {},
pages = {1808646},
pmid = {42040552},
issn = {2296-858X},
abstract = {Myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) is a neuroimmune disease characterized by debilitating post-exertional malaise (PEM), brain-fog/cognitive problems, and dysregulation of the autonomic nervous system. Currently, there are no objective biomarkers for ME/CFS despite decades of research. Here, we compile evidence from literature that supports taste dysfunction, particularly alterations of taste perception mediated by Type II taste receptor cells, may be a critical underrecognized feature of ME/CFS. The impetus is drawn from the emerging evidence of clinicopathological similarities between long-COVID and ME/CFS. We discuss in parallel the mechanisms of cellular metabolism, inflammation, vascular dysfunction, and autonomic dysregulation in ME/CFS and long-COVID pathophysiology. We postulate that mechanistically, dysregulation of ATP signaling through P2X2/P2X3 purinergic receptors underlies both gustatory impairment and core ME/CFS symptoms. Adopting information from the NIH-RECOVER shared resources, we present evidence that suggests chemosensory dysfunction as a potential indicator of progression/severity of PEM. We discuss standardized taste testing as a non-invasive screening tool complementary to molecular biomarkers for ME/CFS. Notwithstanding, we acknowledge the limitations, confounding and contributing factors such as medications and deficiencies that may exacerbate or independently cause taste-related symptoms in ME/CFS. In conclusion, we present a compelling case for the multi-factorial role of taste dysfunction in ME/CFS and suggest specific research priorities for investigating the relationship between chemosensory function and post-viral chronic illness.},
}

@article {pmid42041273,
year = {2026},
author = {Silveira, JM and Nakaishi, APM and da Silva, MG and Dos Santos, DO and Gastaldi, AC},
title = {Effects of Exercise-Based Pulmonary Rehabilitation in Patients with Long COVID: A Systematic Review and Meta-Analysis.},
journal = {Advances in respiratory medicine},
volume = {94},
number = {2},
pages = {},
doi = {10.3390/arm94020025},
pmid = {42041273},
issn = {2543-6031},
mesh = {Humans ; *COVID-19/rehabilitation/complications/physiopathology ; *Exercise Therapy/methods ; Quality of Life ; Exercise Tolerance ; SARS-CoV-2 ; Randomized Controlled Trials as Topic ; },
abstract = {Background/Objective: A substantial proportion of infected individuals develop persistent symptoms after the acute phase of COVID-19, regardless of initial disease severity. Long COVID (LC) remains a public health challenge characterized by impaired functional exercise capacity (FEC) and quality of life (QoL). We systematically synthesized evidence on the effects of in-person outpatient pulmonary rehabilitation (OPR) with individualized and supervised exercise in adults with LC. Methods: Following PROSPERO (CRD42023389365), this study reviewed randomized controlled trials (RCTs) and observational cohort studies (OCSs) published between November 2019 and January 2026 in MEDLINE/PubMed, Web of Science, PEDro, and EMBASE. Results: Fifteen studies (n = 803) were included. OPR improved FEC (6MWT; MD: 53.72 m, 95% CI 43.69-63.75) and 30″SST (MD: 4.68, 95% CI 3.59-5.77) and reduced exertional dyspnea. RCTs showed benefits in physical (MD: 8.04, 95% CI 3.02-13.05) and mental QoL (MD: 6.60, 95% CI 2.01-11.18) and dyspnea impact, with inconsistent PF findings. Fatigue showed a trend toward improvement but was measured using heterogeneous patient-reported tools in RCTs and OCSs. Conclusions: Supervised PR improves FEC, QoL, and dyspnea in individuals with LC. In patients with fatigue/PEM, systematic assessment and continuous symptom monitoring are essential. High-quality controlled studies are needed to strengthen evidence and clinical guide.},
}

Humans
*COVID-19/rehabilitation/complications/physiopathology
*Exercise Therapy/methods
Quality of Life
Exercise Tolerance
SARS-CoV-2
Randomized Controlled Trials as Topic

@article {pmid42041818,
year = {2026},
author = {Moore, AL and Jedlicka, EJ and Patterson, JC and Ledbetter, CR},
title = {LearningRx Cognitive Training for Workplace Self-Efficacy in Adults with Post-COVID-19 Brain Fog: A Mixed-Methods Pilot Study.},
journal = {Brain sciences},
volume = {16},
number = {4},
pages = {},
doi = {10.3390/brainsci16040410},
pmid = {42041818},
issn = {2076-3425},
support = {Louisiana State University Health Sciences Center Shreveport Research Council Intramural Grants Program Center for Brain Health (CBH) Grant-in-Aid Award.//Louisiana State University/ ; },
abstract = {BACKGROUND/OBJECTIVES: Cognitive dysfunction, or "brain fog", following COVID-19 viral infection is strongly associated with diminished work capacity which disproportionality affects working-age adults. This study examined an existing method of cognitive rehabilitation training applied to adults struggling with workplace functioning and self-efficacy due to post-COVID-19 brain fog.

METHODS: Nine adults with post-COVID-19 cognitive dysfunction participated in this single arm pilot trial of a severity-adaptive cognitive training program. The participants completed 45-90 h of clinician-delivered cognitive training exercises delivered remotely in 60- to 90-min sessions, two or three times per week. The primary outcome measure was overall workplace self-efficacy with subskills of perceived workplace functioning, perception of cognitive functioning, and perception of home functioning assessed through pre and post surveys and qualitative interviews. The secondary outcome was cognitive function operationalized by an IQ score administered before and after the intervention.

RESULTS: The participants achieved significant improvements in workplace self-efficacy and cognition following cognitive training. The main qualitative themes of self-reported improvements were in executive function, health and energy, daily living activities, productivity, and socioemotional functioning. A cross-case synthesis of pre-intervention struggles, and post-intervention improvements revealed subthemes at work or school in cognitive processing and comprehension, memory, executive function, fatigue, emotional distress, confidence in work or academics, and work/academic performance impairment. As a group, the mean gain in IQ score was 10.5 points.

CONCLUSIONS: This study adds to the growing body of literature examining the possibility of using cognitive rehabilitation for post-COVID-19 cognitive dysfunction impacting workplace self-efficacy and work functioning.},
}

@article {pmid42043247,
year = {2026},
author = {Mahajan, S and Mahajan, S and Kaushik, N},
title = {Integrative Insights into the Immunopathogenesis and Organ-Specific Immunological Mechanisms of Long COVID: A Narrative Review.},
journal = {Viruses},
volume = {18},
number = {4},
pages = {},
doi = {10.3390/v18040458},
pmid = {42043247},
issn = {1999-4915},
mesh = {Humans ; *COVID-19/immunology/pathology/complications/virology ; *SARS-CoV-2/immunology ; Post-Acute COVID-19 Syndrome ; Immunity, Innate ; Adaptive Immunity ; Organ Specificity ; Autoimmunity ; },
abstract = {Long COVID (LC), also referred to as post-acute sequelae of SARS-CoV-2 infection, is characterized by persistent symptoms originating 3 months following acute COVID-19, lasting for at least two months and frequently affecting individuals who initially experienced mild to moderate disease. The clinical spectrum is heterogeneous, involving respiratory, cardiovascular, neurological, renal, gastrointestinal, and endocrine systems, thereby posing substantial diagnostic and therapeutic challenges. Despite extensive investigation, the precise immunopathogenic mechanisms underlying LC remain incompletely defined. Accumulating evidence suggests that LC is driven by a multifactorial interplay of persistent viral antigen reservoirs, chronic immune activation, dysregulated innate and adaptive immune responses, autoimmunity, endothelial dysfunction, microvascular injury, and aberrant tissue repair. These systemic immune perturbations manifest variably across different organs, contributing to the diverse clinical phenotypes observed. However, mechanistic clarity is hindered by heterogeneity in study designs, limited longitudinal data, and the absence of standardized immunological profiling. This narrative review provides integrative insights into the immunopathogenesis of LC, synthesizing current evidence on systemic immune dysregulation and organ-specific immunological mechanisms. A conceptual framework is proposed to facilitate a structured understanding of this complex syndrome and to guide future research toward targeted immunomodulatory strategies.},
}

Humans
*COVID-19/immunology/pathology/complications/virology
*SARS-CoV-2/immunology
Post-Acute COVID-19 Syndrome
Immunity, Innate
Adaptive Immunity
Organ Specificity
Autoimmunity

@article {pmid42043604,
year = {2026},
author = {Camara, B and Buonsenso, D},
title = {Response to letter: Methodological considerations for interpreting a scoping review of pediatric long COVID biomarkers.},
journal = {European journal of pediatrics},
volume = {185},
number = {5},
pages = {},
doi = {10.1007/s00431-026-06992-6},
pmid = {42043604},
issn = {1432-1076},
}

@article {pmid42043629,
year = {2026},
author = {Selvakumar, JP and Wyller, VBB},
title = {Methodological considerations for interpreting a scoping review of pediatric long COVID biomarkers.},
journal = {European journal of pediatrics},
volume = {185},
number = {5},
pages = {},
pmid = {42043629},
issn = {1432-1076},
}

@article {pmid42043742,
year = {2026},
author = {Tomaskovic, A and Weber, V and Ochmann, DT and Hillen, B and Neuberger, EWI and Brahmer, A and Lachtermann, E and Lieb, K and Simon, P},
title = {Cardiopulmonary Exercise Testing Reveals Functional Limitations and Work Disability in Severe Post-COVID-19 and ME/CFS Patients.},
journal = {Sports medicine - open},
volume = {12},
number = {1},
pages = {},
pmid = {42043742},
issn = {2199-1170},
abstract = {BACKGROUND: Patients severely affected by post-COVID-19 condition (PCC) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) often experience long-term work incapacity, contributing to a growing economic burden. Organ-centered clinical diagnostics frequently fail to explain their work disability.

OBJECTIVES: We aimed to objectively assess physical work ability using cardiopulmonary exercise testing (CPET) in a cohort of long-standing and severely affected PCC patients. We hypothesized: (1) patients with ME/CFS exhibit lower peak oxygen uptake (VO₂peak [mL/min/kg]) and peak power output (PPO [W/kg]) than those without; (2) most patients demonstrate objective work disability, closely aligned with subjective perception of disability; (3) oxygen pulse (O2 pulse [mL/bpm]) is reduced in ME/CFS, independent of comorbidity.

METHODS: The study was conducted in the Department of Sports Medicine, Prevention and Rehabilitation at Johannes Gutenberg-University Mainz (Mainz, Germany). Between July 31, 2023, and March 31, 2025, a total of 92 PCC patients with suspected occupational disease underwent symptom-limited CPET and completed the Canadian Consensus Criteria, Bell Disability Scale (Bell-Score), and DePaul Symptom Questionnaire (Post-Exertional Malaise) Short Form (DSQ-PEM).

RESULTS: Nearly half of the patients (49%) met ME/CFS criteria and 79% screened positive on the DSQ-PEM. ME/CFS patients showed significantly lower VO₂peak (13.0 ± 3.1 vs. 15.4 ± 4.9, p = 0.012), PPO (0.9 ± 0.3 vs. 1.1 ± 0.5, p = 0.014), and O₂ pulse (7.7 ± 2.0 vs. 8.5 ± 1.9, p = 0.047) compared to those without ME/CFS. Overall, 66% of patients met objective thresholds for work disability (VO₂peak < 15 mL/min/kg or PPO < 1 W/kg). Forty-five patients (51%) had a Bell-Score ≤ 30 and 82% from those had VO₂peak < 15 and/or PPO < 1. VO₂peak and PPO significantly correlated with Bell-Score (r = 0.3, p = 0.005 and r = 0.3, p = 0.003) and were the lowest among patients on medical sick leave (13.3 ± 3.3 and 0.9 ± 0.3), compared to those in occupational reintegration (16.0 ± 3.9, p = 0.04 and 1.2 ± 0.5, p = 0.024) or currently working (18.0 ± 7.1, p = 0.036 and 1.2 ± 0.5, p = 0.015).

CONCLUSIONS: Severely affected PCC patients exhibit objective work disability, particularly those with ME/CFS. VO₂peak and PPO are associated with subjective disability and occupational status. Therefore, early integration of CPET into clinical and occupational evaluations can inform individualized therapy planning and return-to-work decisions. Trial registration DRKS, DRKS00032394. Registered 28 July 2023, https://drks.de/search/de/trial/DRKS00032394.},
}

@article {pmid42045916,
year = {2026},
author = {Li, S and Zhao, H and Zhang, M and Yuan, T and Li, X and Shen, Z and Qin, C and Li, Y and Pan, M},
title = {Long-term health outcomes in elderly COPD patients with long COVID: a 2-year prospective cohort study.},
journal = {Respiratory research},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12931-026-03689-0},
pmid = {42045916},
issn = {1465-993X},
}

@article {pmid42035205,
year = {2026},
author = {Yuan, MQ and Pan, YF and Zhang, ZY and Wu, YX and Zhu, KD and Wang, ZR and Zhang, ZY and Xiong, JQ and Xu, Z and Huang, L and Wang, FS and Shi, L},
title = {Therapeutic potential of mesenchymal stromal cells in COVID-19: a meta-analysis of clinical trials conducted since the pandemic onset.},
journal = {Stem cell research & therapy},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13287-026-05020-6},
pmid = {42035205},
issn = {1757-6512},
support = {No. 2022YFA1105604//National Key Research and Development Program of China/ ; },
abstract = {BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can induce immune dysregulation and multi-organ injury; mesenchymal stromal cell (MSC) therapy has shown promise in clinical trials for COVID-19 and may have broader applicability to pneumonia induced by respiratory viruses (e.g., the influenza virus). This meta-analysis synthesized the available comparative clinical evidence on the safety and efficacy of MSCs in patients with moderate to critical COVID-19 and examined the reported outcomes relevant to Long-COVID.

METHODS: We searched the PubMed, Embase, and CNKI databases for original, comparative studies in moderate, severe, or critical COVID-19 published up to September 2, 2024. Twenty-four eligible studies (13 RCTs and 11 non-randomized controlled trials; n = 1080) were included in the mortality meta-analysis. Patients were assigned to either the intervention group (MSC therapy plus standard care) or the control group (standard care with or without placebo). The primary efficacy outcome was all-cause mortality, while the primary safety outcomes were adverse events (AEs) and serious adverse events (SAEs). Secondary outcomes included clinical recovery, hospitalization metrics, chest imaging, and inflammatory biomarkers. We performed a pooled meta-analysis on mortality with subgroup analyses (by disease severity, administration route, dosing frequency, and study design), assessment of publication bias (using funnel plots and Egger's test), and evaluation of the quality of evidence via the GRADE approach. AEs/SAEs were analyzed using meta-analysis and descriptive statistics, while other secondary outcomes were summarized descriptively.

RESULTS: MSC therapy significantly reduced all-cause mortality (MSC: 26.4% vs control: 31.9%; fixed-effect OR = 0.74, 95% CI 0.55-0.99), with low heterogeneity (I[2] = 2.8%, P =0.422[Q-test]) and no publication bias. The quality of evidence was moderate (according to the GRADE assessment). The subgroup analysis revealed a significant survival benefit in severe/critical patients (OR = 0.73, 95% CI 0.54-0.98) but not in studies that included moderate cases (OR = 0.91, 95% CI 0.23-3.65). No significant heterogeneity was found across study designs, administration routes, or dosing frequencies, which confirmed the robustness of the primary findings while indicating insufficient evidence to determine the optimal regimen. The secondary outcomes suggested improvements in clinical recovery, pulmonary function, and pro-/anti-inflammatory cytokine balance in patients that received MSC therapy. Limited studies with long-term follow-up indicated potential benefits for Long-COVID outcomes (e.g., fatigue, quality of life, residual CT abnormalities, and exercise tolerance). No significant differences were observed in AEs or SAEs post-MSC infusion, which suggested that MSC therapy was well tolerated.

CONCLUSION: This meta-analysis indicated that MSC therapy may reduce mortality in patients with severe or critical COVID-19, demonstrating a favorable safety profile and potential benefits for Long-COVID and other viral pneumonias. Further large-scale, rigorous RCTs and mechanistic studies are warranted to strengthen the evidence base and standardize MSC administration regimens (source, dosing, frequency, and intervals) for managing COVID-19, Long-COVID, and other viral pneumonias.},
}

@article {pmid39668387,
year = {2025},
author = {Savith, A and Meah, A and Murthy, RSS and Phal, NB},
title = {Long-term Health Implications of Coronavirus Disease 2019: A Prospective Study on Post-coronavirus Disease 2019 Symptoms.},
journal = {Annals of African medicine},
volume = {24},
number = {1},
pages = {167-172},
pmid = {39668387},
issn = {0975-5764},
mesh = {Humans ; *COVID-19/complications/epidemiology/physiopathology/diagnosis ; Prospective Studies ; Male ; Female ; Middle Aged ; Cross-Sectional Studies ; Adult ; SARS-CoV-2 ; Severity of Illness Index ; Aged ; Post-Acute COVID-19 Syndrome ; Hospitalization ; Prevalence ; Fatigue/epidemiology ; Dyspnea/epidemiology ; },
abstract = {CONTEXT: Patients recovering from coronavirus disease 2019 (COVID-19) infection continue to have some persistent symptoms or develop new symptoms, resulting in impairment of everyday activities beyond the initial acute period. The current study was undertaken to understand the long term health implications of covid 19 and to analyse the correlation of post covid symptoms with the severity of infection and inflammatory markers at the time of hospitalisation.

AIMS: (1) To estimate the prevalence of post covid symptoms at the end of 1 month,3 months and 12 months after discharge, (2) To correlate post covid symptoms with the severity of infection and inflammatory markers at the time of hospitalisation.

SETTINGS AND DESIGN: The study design was a cross-sectional study.

SUBJECTS AND METHODS: A prospective observational study was done on 150 COVID-19 reverse transcription-polymerase chain reaction-positive patients aged 18 years and above recovering from acute infection discharged from Vydehi Institute of Medical Sciences and Research Centre. All the patients were followed up for 1 year, during which telephonic interviews were conducted, and a systematic enquiry was made regarding post-COVID-19 symptoms.

STATISTICAL ANALYSIS USED: Data were entered in MS Excel and analyzed in SPSS V25. Descriptive statistics are represented with percentages, mean with standard deviation, or median with interquartile range depending on the nature of the data. The Kolmogorov-Smirnov test was applied to find normality. The Chi-square test, Independent t -test, or Mann-Whitney U -test were calculated depending on normality; P < 0.05 was considered statistically significant.

RESULTS: A total of 150 COVID-19-positive patients discharged from the hospital were included in the study. Sixty-seven percent of patients had symptoms at 1 month, 39% at 3 months, and 31% of patients persisted to have symptoms at 1 year. The most common symptoms at 1 year were fatigue (5%), breathlessness (5%), and insomnia (5%). No statistically significant correlation was found with the severity of infection, inflammatory markers, and other variables.

CONCLUSIONS: Approximately one-third of patients who recover from acute COVID-19 infection may continue to have post-COVID-19 symptoms at 1 year after infection. Fatigue is the most common post-COVID-19 symptom. Post-COVID-19 symptoms can affect COVID-19 survivors regardless of the severity of the infection.},
}

Humans
*COVID-19/complications/epidemiology/physiopathology/diagnosis
Prospective Studies
Male
Female
Middle Aged
Cross-Sectional Studies
Adult
SARS-CoV-2
Severity of Illness Index
Aged
Post-Acute COVID-19 Syndrome
Hospitalization
Prevalence
Fatigue/epidemiology
Dyspnea/epidemiology

@article {pmid42026739,
year = {2026},
author = {Thomas, C and Ashton, RE and Owen, R and McNeil-Angopa, E and Carr, J and Bewick, T and Faghy, MA},
title = {Impaired peripheral oxygen delivery during submaximal exercise in adults with long COVID.},
journal = {Physiological reports},
volume = {14},
number = {8},
pages = {e70873},
doi = {10.14814/phy2.70873},
pmid = {42026739},
issn = {2051-817X},
support = {IN-UK-983-6080//Gilead Sciences (Gilead)/ ; },
mesh = {Humans ; *COVID-19/physiopathology/metabolism/complications ; Male ; Female ; Middle Aged ; *Muscle, Skeletal/metabolism/physiopathology ; *Exercise/physiology ; Exercise Test ; Adult ; *Oxygen Consumption ; *Oxygen/metabolism ; Spectroscopy, Near-Infrared ; SARS-CoV-2 ; },
abstract = {Long COVID (LC) is a multisystem condition that is linked to distinct pathologies including viral persistence, immunological dysfunction, endothelial damage, and mitochondrial dysfunction. To date, limited research has assessed peripheral tissue hypoxia to better understand LC symptom exacerbation. Forty-six people with LC and 10 controls (CON) completed two submaximal cardiopulmonary exercise tests (CPETs), separated by 24-h. Near-infrared spectroscopy (NIRS)-derived signals from the left gastrocnemius muscle were continuously monitored before, during, and after 2-day incremental CPET. CPET outcomes demonstrated impaired physical function on day 2 compared with day 1 for the LC cohort at rest and VT1. LC tissue saturation index (TSI%) remained elevated above rest for a shorter duration of exercise compared to CON on day 1 (2nd minute vs. 5th minute). On day 2, this response worsened for LC (Rest vs. 1st exercise minute: 63 ± 5% vs. 65 ± 5%; p < 0.05); meanwhile, CON exhibited sustained TSI% elevation throughout exercise above rest (Rest vs. 12th exercise minute: 62 ± 5% vs. 67 ± 4%; p < 0.05). LC TSI% remained elevated above rest for a shorter duration of exercise compared to CON, worsening for LC on day 2. LC showed rapid normalization of TSI%, suggesting impaired muscle oxygenation and recovery during repeated exercise.},
}

Humans
*COVID-19/physiopathology/metabolism/complications
Male
Female
Middle Aged
*Muscle, Skeletal/metabolism/physiopathology
*Exercise/physiology
Exercise Test
Adult
*Oxygen Consumption
*Oxygen/metabolism
Spectroscopy, Near-Infrared
SARS-CoV-2

@article {pmid42028736,
year = {2026},
author = {Samet, M and Aghaei-Meybodi, FA and Hosseini, S and Meidany, A and Fateh, A},
title = {Lung autopsy findings in 44 COVID-19 deceased patients:pathological and radiological insights.},
journal = {Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace},
volume = {},
number = {},
pages = {},
doi = {10.4081/monaldi.2026.3412},
pmid = {42028736},
issn = {2532-5264},
abstract = {This study presents a detailed histopathological analysis of lung tissue from 44 deceased COVID19 patients, aiming to elucidate the mechanisms driving severe disease progression. Postmortem biopsies were systematically examined, revealing diffuse alveolar damage in 95.5% of cases, predominantly in the acute/exudative phase. Characteristic features included extensive hyaline membrane formation, alveolar septal thickening, fibrin deposition, and red blood cell extravasation. Notably, advanced fibrosis, indicative of ongoing tissue remodeling, was observed in 86.4% of cases, highlighting the chronic pathological impact of the disease. Patient demographics showed a predominance of older males with comorbidities such as hypertension and diabetes, aligning with known high-risk profiles. The methodology involved meticulous autopsy procedures and standardized histopathological assessments to ensure the reliability of findings. This study provides key insight into histological changes in the lungs of COVID-19 patients, helping to clarify the disease's progression. It provides valuable insights that may contribute to a better understanding of long COVID and the potential long-term pulmonary complications in these patients. These findings may ultimately support improved management approaches and therapeutic strategies for COVID-19 care.},
}

@article {pmid42028925,
year = {2026},
author = {Silva, LI and Gonzalez-Zambrano, CM and Ferreira, VCMP and Corrêa, FC and Dias-Melicio, LA},
title = {MicroRNAs in Acute COVID-19 and Long COVID: Dysregulation, Pathogenic Roles, and Clinical Implications.},
journal = {Journal of immunology research},
volume = {2026},
number = {1},
pages = {e5862241},
doi = {10.1155/jimr/5862241},
pmid = {42028925},
issn = {2314-7156},
support = {001//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; },
mesh = {Humans ; *COVID-19/genetics/immunology/virology/pathology ; *MicroRNAs/genetics ; *SARS-CoV-2/physiology/immunology ; Post-Acute COVID-19 Syndrome ; Extracellular Vesicles ; Gene Expression Regulation ; Biomarkers ; Inflammation ; },
abstract = {MicroRNAs (miRNAs) are key post-transcriptional regulators of gene expression with central roles in immune responses, inflammation, and viral pathogenesis. Increasing evidence indicates that severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection induces marked dysregulation of host and viral miRNAs (v-miRNAs), contributing to disease severity during acute COVID-19 and to the persistent manifestations observed in long COVID (LC). This narrative review critically synthesizes current evidence on miRNA dysregulation across the acute and post-acute phases of COVID-19, highlighting their pathogenic roles, clinical relevance, and existing knowledge gaps. During acute infection, altered miRNA profiles-including those associated with immune activation, endothelial dysfunction, and immunothrombosis-reflect both host responses and viral strategies of immune modulation, including miRNAs carried by extracellular vesicles (EVs) and SARS-CoV-2-derived v-miRNAs. In LC, emerging data suggest that persistent miRNA alterations are associated with unresolved inflammation, pulmonary dysfunction, neurological symptoms, and vascular injury, although available studies remain limited and heterogeneous. Overall, miRNAs represent promising biomarkers and potential therapeutic targets in COVID-19; however, robust longitudinal and mechanistic studies are urgently needed to clarify their causal roles and translational utility in post-acute disease.},
}

Humans
*COVID-19/genetics/immunology/virology/pathology
*MicroRNAs/genetics
*SARS-CoV-2/physiology/immunology
Post-Acute COVID-19 Syndrome
Extracellular Vesicles
Gene Expression Regulation
Biomarkers
Inflammation

@article {pmid42029517,
year = {2026},
author = {Couto, NMS and Bernal, JVM and Facioli, TP and Dos Santos, D and de Souza, HCD},
title = {The Severity of COVID-19 Is Associated with Greater Impairment of Cardiac Autonomic Modulation-Physical Training as a Countermeasure.},
journal = {Journal of functional morphology and kinesiology},
volume = {11},
number = {2},
pages = {},
doi = {10.3390/jfmk11020149},
pmid = {42029517},
issn = {2411-5142},
support = {2023/17422-7//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; 001//Coordenação de Aperfeicoamento de Pessoal de Nível Superior/ ; },
abstract = {Background: COVID-19 has been associated with persistent impairments in autonomic modulation of heart rate variability (HRV). However, whether disease severity during the acute phase influences the magnitude of these impairments remains insufficiently explored. In turn, aerobic physical training (APT) has been proposed as a countermeasure to autonomic dysfunction of HRV in different conditions, although its effects in individuals with COVID-19 are not yet well established. To address these gaps, this study investigated the consequences of COVID-19 on autonomic modulation of HRV according to disease severity and evaluated the effects of APT on this parameter. Methods: One hundred and sixteen individuals (58 men and 58 women) aged between 30 and 55 years were included, allocated into three groups according to the severity of the disease in the acute phase: Mild group (n = 38, mean age: 48 ± 7 years); Moderate group (n = 52, mean age: 43 ± 5 years); and Severe group (n = 26, mean age: 45 ± 6 years). All groups had anthropometric and hemodynamic parameters evaluated before and after the 16-week APT period, as well as parameters of autonomic modulation of HRV analyzed using linear (time and frequency domain) and non-linear (symbolic analysis) methods obtained from R-R interval (RRi) recordings in the supine position for 30 min. Results: Initially, all groups presented similar anthropometric and hemodynamic values. In contrast, the Moderate and Severe groups presented lower values for standard deviation of normal RRi (SDNN; Moderate: 38 ± 14 ms; Severe: 33 ± 12 ms vs. Mild: 55 ± 28 ms; p < 0.001), root mean square difference between adjacent normal RRi (RMSSD; Moderate: 28 ± 13 ms; Severe: 22 ± 7 ms vs. Mild: 47 ± 38 ms; p < 0.001), total variance (Moderate: 203 ± 127 ms[2]; Severe: 303 ± 157 ms[2] vs. Mild: 526 ± 347 ms[2]; p < 0.001), and high-frequency (HF) oscillations in absolute units (Moderate: 259 ± 270 ms[2]; Severe: 153 ± 74 ms[2] vs. Mild: 438 ± 421 ms[2]; p < 0.001), both compared to the Mild group. In turn, the Severe group, when compared to the other groups, also presented lower HF oscillations (Severe: 29 ± 12 nu vs. Mild: 44 ± 17 nu and Moderate: 42 ± 17 nu; p < 0.001) and higher low-frequency (LF) oscillations (Severe: 71 ± 12 nu vs. Mild: 60 ± 17 nu and Moderate: 58 ± 17 nu; p < 0.001), but in normalized units. After the 16-week APT, all groups showed increases in HF oscillations (Mild: -206 ms[2] and -19.12 nu; Moderate: -236 ms[2] and -26.7 nu; Severe: -211 ms[2] and -31.0 nu; p < 0.001) and reductions in LF oscillations (Mild: 198 ms[2] and 19.01 nu; Moderate: 98 ms[2] and 26.7 nu; Severe: 218 ms[2] and 31.1 nu; p < 0.001), both in absolute and normalized units. In this case, there were no further differences in LF and HF oscillations between the groups. Conclusions: Individuals who had COVID-19 and developed moderate to severe cases showed greater impairments in the autonomic modulation of HRV, characterized by increased sympathetic autonomic modulation and reduced vagal modulation. In turn, APT as a countermeasure appears to increase vagal autonomic modulation and reduce sympathetic autonomic modulation of HRV, regardless of the previous severity of COVID-19.},
}

@article {pmid42021271,
year = {2026},
author = {Sommen, SL and Segtnan, S and Selvakumar, J and Havdal, LB and Stiansen-Sonerud, T and Gjerstad, J and Mjaaland, S and Nygaard, UC and Wyller, VBB and Mukherjee, R and Berven, LL},
title = {Long COVID: Deep single-cell immunophenotyping and machine learning reveal a general signature for fatigue.},
journal = {Journal of translational medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12967-026-08149-3},
pmid = {42021271},
issn = {1479-5876},
}

@article {pmid42022303,
year = {2025},
author = {Tabarsi, P and Mohamadnia, A and Shahabinejad, P and Haseli, S and Askari, E and Bahrami, N and Shafaghi, S and Hajimoradi, M},
title = {Long COVID in Patients with Multiple Sclerosis Treated with Rituximab: A Report of Two Cases.},
journal = {Tanaffos},
volume = {24},
number = {1},
pages = {106-110},
pmid = {42022303},
issn = {1735-0344},
abstract = {COVID-19 symptoms may persist for more than 12 weeks in some infected patients, a condition described as long COVID-19 in these cases. These patients have symptoms attributed to impairment of multiple organs. Scientists have discovered the lengthy COVID-19 etiology, risk factors, and treatments. It has been observed that immunosuppression may prolong COVID-19 symptoms. Patients with multiple sclerosis (pwMS) are generally treated with disease-modifying treatments, which suppress the immune system and predispose patients to infections like COVID-19. Also, these drugs may increase not only the morbidity and mortality of infection but also the risk of developing long COVID-19 in these patients. We have described two cases of multiple sclerosis patients who were diagnosed with long COVID-19. Both patients were under treatment with rituximab, so we discussed treatment choices and strategies for pwMS patients under rituximab who had symptoms of long COVID. Our data would further add to the information on managing long COVID-19 in pwMS under treatment with rituximab.},
}

@article {pmid42022621,
year = {2026},
author = {Obeagu, EI},
title = {Taming the Cytokine Storm: Therapeutic Strategies for Post-Acute Sequelae of SARS-CoV-2 Infection.},
journal = {Health science reports},
volume = {9},
number = {3},
pages = {e72174},
pmid = {42022621},
issn = {2398-8835},
abstract = {BACKGROUND AND AIM: Post-acute sequelae of SARS-CoV-2 infection (PASC), commonly referred to as long COVID, has emerged as a significant global health concern, marked by persistent symptoms and chronic inflammation following recovery from acute COVID-19. A central driver of PASC pathogenesis is the sustained cytokine storm-an exaggerated and prolonged pro-inflammatory response that leads to ongoing tissue injury and multisystem dysfunction. This review aims to synthesize current knowledge on cytokine dysregulation in PASC and evaluate emerging therapeutic strategies targeting these immunopathological mechanisms.

METHODS: A narrative review methodology was employed, drawing from recent peer-reviewed publications, clinical trial databases, and immunological studies published between 2020 and 2025. Articles focusing on cytokine profiles in PASC, immune reprogramming, and immunomodulatory therapies were included. Mechanistic studies, biomarker research, and translational trials involving corticosteroids, cytokine inhibitors, Janus kinase (JAK) inhibitors, and novel biologics were critically analyzed.

RESULTS: The literature reveals that elevated levels of IL-6, IL-1β, TNF-α, and IFN-γ persist in a subset of PASC patients, contributing to chronic systemic and organ-specific inflammation. Emerging therapies-including IL-6 and IL-1 receptor antagonists, JAK inhibitors, and CNS-penetrant anti-inflammatory agents-demonstrate promise in modulating cytokine storms and improving clinical outcomes. Recent insights into cytokine profiling, trained immunity, and neuroimmune crosstalk suggest potential for precision-based interventions tailored to distinct inflammatory phenotypes in PASC.

CONCLUSION: Persistent cytokine dysregulation underlies the pathophysiology of PASC and offers actionable targets for therapeutic intervention. Immunomodulatory strategies, when guided by biomarker profiling and systems biology approaches, hold promise for mitigating long-term complications of COVID-19. Future research should prioritize personalized treatment algorithms to address the heterogeneity of PASC and enhance patient recovery.},
}

@article {pmid42026280,
year = {2026},
author = {Stanley, HB and Bensafi, M},
title = {The characteristics of chemosensory losses in the symptomatology of long-COVID.},
journal = {European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery},
volume = {},
number = {},
pages = {},
pmid = {42026280},
issn = {1434-4726},
support = {964529//Horizon 2020 Framework Programme/ ; Human Chemosensation IRP project//CNRS/ ; },
}

@article {pmid42002663,
year = {2026},
author = {Stervbo, U and Anft, M and Paniskaki, K and Blazquez-Navarro, A and Doevelaar, A and Skrzypczyk, S and Kohut, E and Kurek, J and Wehler, P and Kaliszczyk, S and Rosiewicz, K and Seibert, FS and Hölzer, B and Thieme, CJ and Roch, T and Konik, MJ and Berger, MM and Brenner, T and Kölsch, U and Adamzik, M and Schmueck-Henneresse, M and Scheibenbogen, C and Dolff, S and Dittmer, U and Witzke, O and Westhoff, TH and Babel, N},
title = {Acute COVID-19 is associated with altered CD8 T-cells indicative of impaired ability to control Epstein-Barr virus reactivation.},
journal = {Medical microbiology and immunology},
volume = {215},
number = {1},
pages = {},
pmid = {42002663},
issn = {1432-1831},
abstract = {UNLABELLED: Increasing evidence suggests that reactivation of latent EBV in patients with COVID-19 may be linked to the development of post-acute sequelae of COVID-19, colloquially known as Long COVID. However, the reason for this co-occurrence of primary infection and reactivation of latent viruses remains elusive. During the first wave of COVID-19, we assessed all major immune cell populations by flow cytometry in a cohort of 61 patients with moderate to critical COVID-19 at the time of hospitalization. Additional blood samples from these patients were biobanked for later analysis. Using these biobanked samples, we evaluated the co-occurrence of CMV, EBV, as well as HHV-6A and -6B by qPCR. EBV was found to be reactivated not only in patients with critical or severe COVID-19 (24/33 patients; 72.72%), but also in patients with moderate COVID-19 disease (19/28; 67.86%) at the time of hospital admission. In contrast, HHV-6A was not detected among any patients, whereas CMV and HHV-6B only occurred in low frewuencies (7.1–12.1% and 10.7–15.2%, respectively). In COVID-19 patients with EBV reactivation, the degree of expression of the T-cell co-stimulatory CD28 and co-expression of CD28 and the integrin CD11a was diminished on CD8 T-cells. In contrast, the frequency of CD8 T-cells expressing the proliferative exhaustion marker CD57 increased. Collectively, these data point to an altered activation phenotype of circulating CD8 T cells and that higher replicative senescence is associated with EBV reactivation. The data presented here suggests an alteration in the CD8 T-cell compartment with impaired ability to control the EBV reactivation in COVID patients.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00430-026-00873-3.},
}

@article {pmid42015188,
year = {2026},
author = {Sardell, JM and Das, S and Pearson, M and Kolobkov, D and Malinowski, AR and Fullwood, LM and Sanna, M and Baxter, H and McLellan, K and Natt, M and Lamirel, D and Chowdhury, S and Strivens, MA and Gardner, S},
title = {Identification of novel reproducible combinatorial genetic risk factors for myalgic encephalomyelitis in the DecodeME patient cohort and commonalities with long COVID.},
journal = {Journal of translational medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12967-026-08167-1},
pmid = {42015188},
issn = {1479-5876},
support = {10083274//Innovate UK/ ; },
}

@article {pmid42016647,
year = {2026},
author = {Wetmore, E and Grach, S and Boes, C and Lanzino, G and Kissoon, N},
title = {Long COVID Syndrome and Associated New Daily Persistent Headache (NDPH) Presenting With Crossed Clonus Response.},
journal = {Clinical case reports},
volume = {14},
number = {3},
pages = {e72386},
pmid = {42016647},
issn = {2050-0904},
abstract = {Evaluating patients following a COVID-19 infection with multiple chronic, progressive symptoms can be challenging, but easy to navigate by using the temporal profile obtained from the clinical history, findings from the neurological exam, and screening for red flag symptoms.},
}

@article {pmid42017188,
year = {2026},
author = {Alvarez-Pedrerol, M and Polo-Alonso, S and Ramos, R and Martí-Lluch, R and Pinsach-Abuin, ML and Dégano, IR and Elosua, R and Subirana, I and Hernáez, Á and Selga, E and Puigdecanet, E and Pruneda-Paz, J and Solà-Richarte, C and Puigmulé, M and Pérez, A and Nogués, X and Masclans, JR and Güerri-Fernández, R and Cubero-Gallego, H and Tizon-Marcos, H and Vaquerizo, B and Brugada, R and Camps-Vilaró, A and Marrugat, J},
title = {Sex Differences in Long COVID Prevalence Over One year After the Acute Phase, and Related Risk Factors. The GINA-COVID Cohort Study.},
journal = {International journal of women's health},
volume = {18},
number = {},
pages = {538491},
pmid = {42017188},
issn = {1179-1411},
abstract = {BACKGROUND: This 1-year cohort study aimed to track long COVID prevalence, identify associated risk factors, and assess its association with hospitalization.

METHODS: The GINA-COVID cohort study included 2698 COVID-19 patients from Spain, who reported persistent symptoms spontaneously mentioned in an open questionnaire one year after infection. We recorded symptom onset, duration, and recovery rates at 12 months. Hospitalization data were collected from the Catalan Health System. We performed descriptive statistics and logistic regression models stratified by sex to identify factors associated with long COVID, using multiple imputation for missing values and model selection via stepwise regression based on the Akaike Information Criterion.

RESULTS: Significant sex differences appeared, with females showing a two-fold higher risk of developing long COVID compared to males (OR=1.95; 95% CI, 1.68-2.29). Females reported higher prevalence and a greater number of persistent symptoms, with fatigue being the most common in both sexes (36% in females, 26% in males at 3 months). The recovery rate at 12 months was lower in females (23% vs. 34%, p<0.001). Hypertension emerged as the most significant protective factor for long COVID in females (OR=0.64; 95% CI, 0.48-0.84), whereas COVID-19 severity was the most influential risk factor in males (OR=2.34; 95% CI, 1.79-3.08). Despite these differences, the trajectory of persistent symptoms over time was similar between the sexes. Importantly, long COVID did not increase hospital admissions.

CONCLUSION: Findings underscore the importance of sex-specific approaches in managing long COVID and suggest further investigation into hypertension's protective role in females and disease severity's impact in males.},
}

@article {pmid42017426,
year = {2026},
author = {Krzyzanowski, MC and Pan, H and Glaze, I and Hwang, S and Williams, D and Engle, M and Waterfield, J and Ives, C and Armson, S and Huggins, W and Hamilton, CM},
title = {The PhenX Toolkit: Long COVID Collection of Standard Protocols.},
journal = {Current protocols},
volume = {6},
number = {4},
pages = {e70317},
doi = {10.1002/cpz1.70317},
pmid = {42017426},
issn = {2691-1299},
support = {/HG/NHGRI NIH HHS/United States ; (U41HG007050)//Genomic Research/ ; (U24HG012556)//Biomedical Knowledgebase/ ; /CD/ODCDC CDC HHS/United States ; /HL/NHLBI NIH HHS/United States ; /NS/NINDS NIH HHS/United States ; /MD/NIMHD NIH HHS/United States ; /CA/NCI NIH HHS/United States ; /DA/NIDA NIH HHS/United States ; //Office of Behavioral and Social Sciences Research/ ; /ES/NIEHS NIH HHS/United States ; //Disaster Research Response (DR2)/ ; },
mesh = {Humans ; *COVID-19/complications/epidemiology ; SARS-CoV-2 ; *Data Collection/methods ; Crowdsourcing/methods ; },
abstract = {Because of the urgent need to better understand the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission mechanism and clinical outcomes resulting from infection, health organizations and research institutes developed data collection instruments to assess coronavirus disease 2019 (COVID-19) symptoms, treatments, and associated impacts on behaviors and risks, treatment and outcomes, information available, psychosocial and mental health, and socioeconomic effects across demographic groups. The PhenX team developed the COVID-19 Protocol Library to share data collection instruments, methods, and protocols in use by investigators and to reduce proliferation of similar protocols. The Office of Behavioral and Social Sciences Research and the National Human Genome Research Institute sponsored the effort, in collaboration with the NIH Disaster Research Response Program. As the COVID-19 library was being established, crowdsourcing was used to identify key topics related to the pandemic, which formed the basis of the COVID-19 Research Collection, and was released in the PhenX Toolkit. Long COVID continues to have an impact on human health. Long COVID is a chronic condition that occurs after SARS-CoV-2 infection and is present for at least 3 months, encompassing a variety of symptoms or conditions that may improve, worsen, or be ongoing. Not surprisingly, submissions to the COVID-19 library began to address Long COVID symptoms. After discussions with its Steering Committee, the PhenX team established a collection of Long COVID measurement protocols. Also, there was significant interest in assessing the amount of overlap among all instruments submitted to the COVID-19 library. The intent was to develop a tool that could identify potential for cross-study analyses. The COVID-19 Variable Compare Tool (VCT) integrates all COVID-19 Research Collection protocols and a prioritized subset of instruments from the COVID-19 library. The Long COVID Specialty Collection and the VCT support investigators' needs to combine and analyze data related to COVID-19 prospectively and retrospectively by identifying compatibility with other studies. © 2026 RTI International. Current Protocols published by Wiley Periodicals LLC. Basic Protocol: Exploring Long COVID through PhenX Toolkit Specialty Collections and the Variable Compare Tool.},
}

Humans
*COVID-19/complications/epidemiology
SARS-CoV-2
*Data Collection/methods
Crowdsourcing/methods

@article {pmid42017829,
year = {2026},
author = {Sun, H and Dang, R and Li, P and Xiao, W and Scott-Sutherland, J and Sassower, KC and Westover, MB and Felsenstein, D and Thomas, RJ and Haack, M and Mullington, JM},
title = {Facility-Measured Sleep Electroencephalographic Microstructures in Long COVID.},
journal = {Sleep},
volume = {},
number = {},
pages = {},
doi = {10.1093/sleep/zsag090},
pmid = {42017829},
issn = {1550-9109},
abstract = {STUDY OBJECTIVES: Sleep electroencephalographic (EEG) microstructures are related to brain functions, providing a window into the unrefreshing, non-restorative sleep and daytime fatigue symptoms in long COVID (LC) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). We aim to characterize sleep EEG microstructural differences in individuals with LC and age-sex-matched healthy controls (HC), and also ME/CFS, using overnight in-lab facility-measured polysomnography (PSG).

METHODS: 28 LC and 28 HC participants came from a single-center research study. 19 ME/CFS participants came from a single clinical center. Sleep EEG was processed to extract spectral band powers, spindles, slow oscillations (SO, 0.5-1 Hz), spindle-SO coupling, brain age index (BAI), alpha-delta patterns, and infraslow oscillation relative band power (ISO, 0.005-0.03 Hz).

RESULTS: Compared to HC, LC had higher SO power during wake before sleep and REM sleep. In N2 and N3, LC showed a faster within-spindle frequency drop (chirp) and shorter SO peak duration in the frontal region. LC showed widespread, early spindle-SO coupling phase at SO trough for both fast and slow spindles, with early fast spindle-SO coupling associated with worse sleep quality. ME/CFS shared some differences with LC but had higher SO-uncoupled slow spindle densities in frontal and central regions, more alpha-delta patterns in the first half of the night, and widespread elevated ISO power in the slow sigma band (11-13 Hz).

CONCLUSIONS: These findings suggest that LC and ME/CFS are associated with plausibly pathological sleep EEG microstructure changes, illuminating the pathobiology of post-infectious processes on brain activity.CLINICAL TRIAL INFORMATIONTrial 1: Sleep and Inflammatory Resolution Pathway, https://clinicaltrials.gov/study/NCT03377543, NCT03377543.Trial 2: Pain in Long COVID-19: the Role of Sleep, https://clinicaltrials.gov/study/NCT05606211, NCT05606211.},
}

@article {pmid42018978,
year = {2026},
author = {Gesell, D and Lienesch, P and Shi, Y and Strobl, R and Tauscher, M and Gerlach, R and Grill, E and Koller, D},
title = {Care Pathways and Patient Experiences Among Patients With Post COVID-19 Condition: Study Protocol for a Mixed-Methods Study in Germany.},
journal = {JMIR research protocols},
volume = {15},
number = {},
pages = {e91976},
doi = {10.2196/91976},
pmid = {42018978},
issn = {1929-0748},
mesh = {Humans ; Germany/epidemiology ; *COVID-19/therapy/complications/epidemiology ; Retrospective Studies ; SARS-CoV-2 ; Qualitative Research ; *Patient Acceptance of Health Care/statistics & numerical data ; *Critical Pathways ; Research Design ; Female ; Male ; Focus Groups ; Post-Acute COVID-19 Syndrome ; Pandemics ; },
abstract = {BACKGROUND: The COVID-19 pandemic has a lasting impact on health care utilization, as both the acute infection and post COVID condition (PCC) can lead to increased demand for medical services due to ongoing symptoms.

OBJECTIVE: The aim of this study is to systematically examine health care utilization among individuals after acute SARS-CoV-2 infection in Bavaria, Germany, with a particular focus on PCC. The study combines claims data analysis with qualitative interviews to improve the understanding of objective care pathways and patients' subjective experiences within the health care system.

METHODS: The research project 'SOLongCOVID' employs a mixed-methods design consisting of two subprojects: (1) a retrospective cohort study using claims data from the Bavarian Association of Statutory Health Insurance Physicians (KVB) to analyze care pathways through state sequence analysis, (2) a qualitative study based on semistructured interviews and focus groups with patients with PCC concerning their subjective care experiences. A synthesis process involving a focus group discussion will combine the information from the two subprojects, providing a comprehensive understanding of the care processes of patients with PCC.

RESULTS: The study was funded by the German Federal Joint Committee Innovation Fund in October 2024. Statutory health insurance claims data cover the period from 2019 to 2022, and qualitative interview data collection is planned from May 2025 to August 2026. As of manuscript submission, study preparation and ethics approvals have been completed, and 14 participants have been recruited for the qualitative interviews. Study findings are anticipated to be published from July 2026 to August 2027.

CONCLUSIONS: The results are expected to enhance the understanding of existing barriers and challenges and to support evidence-based recommendations for improving care pathways for patients with specific care needs.},
}

Humans
Germany/epidemiology
*COVID-19/therapy/complications/epidemiology
Retrospective Studies
SARS-CoV-2
Qualitative Research
*Patient Acceptance of Health Care/statistics & numerical data
*Critical Pathways
Research Design
Female
Male
Focus Groups
Post-Acute COVID-19 Syndrome
Pandemics

@article {pmid42019647,
year = {2026},
author = {Nieuwland, JM and Scaramuzza, A and Bugiani, M and van de Berg, WDJ and Middeldorp, J},
title = {Human brain matters: Navigating the neuropathology of COVID-19.},
journal = {Brain pathology (Zurich, Switzerland)},
volume = {},
number = {},
pages = {e70101},
doi = {10.1111/bpa.70101},
pmid = {42019647},
issn = {1750-3639},
support = {//European research project NEUROCOV, funded by Horizon Europe (EU)/ ; },
abstract = {Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused millions of deaths worldwide. Although the incidence of severe acute cases has declined, the prevalence of long COVID, also known as post-acute sequelae of COVID-19 (PASC), is rising. The pathological mechanisms underlying severe COVID-19, along with the relationship to neurological disorders and potential risk for neurodegeneration, remain poorly understood. The aim of this narrative review is to summarize neuropathological features described in postmortem human COVID-19 brains (n = 352). Furthermore, analysis of biofluids and neuroimaging from PASC patients underline long-term changes in the proteome and CNS response following the infection. Postmortem brain studies from severe COVID-19 patients highlight disruption of the fluid-brain barriers and vascular dysregulation defined by endothelial inflammation and disruption, hemorrhages, and hypoxic-ischemic damage. Neuroinflammation, including astrogliosis, microglia nodules and infiltration of adaptive immune cells, has been reported in the olfactory bulb, medulla oblongata, midbrain and cerebellum. Neuronal damage was demonstrated in the hippocampus, midbrain and cerebellum in severe COVID-19 and protein aggregation was observed in the midbrain and entorhinal cortex. Neuropathological burden and elevated blood and/or cerebrospinal fluid (CSF) levels of proinflammatory cytokines (e.g. IL-6) and neuro-axonal proteins (e.g. NfL) correlated with severity of anosmia, memory deficits, and cerebellar ataxia. Elderly patients and/or patients with underlying neurological diseases were more susceptible and had worsened symptoms. Potential disease mechanisms underlying neurological symptoms observed in severe COVID-19 are vascular and fluid-brain barrier abnormalities, chronic neuroinflammation, persistent axonal damage and protein aggregation. In PASC patients, an altered biofluid proteome with increased neuronal proteins and pro-inflammatory cytokines was observed. The pathological burden in affected brain regions may contribute to manifestations such as anosmia, memory deficits, and cerebellar ataxia.},
}

@article {pmid42020802,
year = {2026},
author = {Steifman, CB and Alvarez-Carcamo, B and Verma, S and McCarthy, R and Guthrie, LB and Gill, KK and Swank, Z and Walt, DR and Grabowski, EF and Fasano, A and VanElzakker, MB and Irimia, D and Yonker, LM},
title = {Endovascular profiles linked to neutrophil activation in children and young adults with long COVID.},
journal = {Pediatric research},
volume = {},
number = {},
pages = {},
pmid = {42020802},
issn = {1530-0447},
abstract = {BACKGROUND: Endovascular symptoms are among the most debilitating long COVID symptoms; however, underlying mechanisms are unclear. Children and young adults with long COVID, an understudied population, offer key insight into long COVID pathology.

METHODS: Eighty-four children and young adults ≤25 years from the U.S. and Canada were enrolled; 61 with long COVID and 23 healthy pediatric controls. We assessed symptom burden, quantified fibrin amyloid microclots, endovascular cytokines, cell-free DNA, and conducted in vitro assays to assess Spike-related neutrophil-mediated endothelial cell injury.

RESULTS: Cardiovascular symptoms were prevalent among participants with long COVID. Microclot burden was increased (p = 0.0003), as were markers of angiogenesis and endothelial remodeling, including FGF-2, which correlated with microclots (p = 0.04). Cytokines involved in leukocyte trafficking (sVCAM-1, L-selectin, α-2-macroglobulin) were reduced while cell-free DNA, a marker of intravascular neutrophil extracellular trap (NET) formation, was increased (p = 0.003) and positively correlated with microclot component serum amyloid A (p = 0.004). Co-culture assays revealed that NETosis, triggered by Spike immune complexes, contributes to endothelial injury in long COVID.

CONCLUSIONS: Children and young adults with long COVID with cardiovascular symptoms display increased microclots, endothelial injury, and neutrophil inflammation, which warrant further evaluation and suggest intravascular NETosis as a key driver of endovascular pathology in long COVID.

IMPACT: Children and young adults with long COVID display elevated endothelial biomarkers, underscoring disease-related rather than age-related endovascular profiles following SARS-CoV-2 infection. Children and young adults with long COVID exhibit increased microclot burden in blood. Neutrophil activation may contribute to ongoing endovascular injury in long COVID. A combination of microclots, neutrophil markers, and endothelial cytokines could serve as biomarkers for Long COVID.},
}

@article {pmid42008509,
year = {2026},
author = {Ortega-Martin, E and Alvarez-Galvez, J},
title = {Understanding quality-of-life patterns in long COVID: How Symptoms and socioeconomic conditions shape patient wellbeing.},
journal = {PloS one},
volume = {21},
number = {4},
pages = {e0347743},
doi = {10.1371/journal.pone.0347743},
pmid = {42008509},
issn = {1932-6203},
mesh = {Humans ; *Quality of Life ; Male ; Female ; Middle Aged ; *COVID-19/epidemiology/psychology/pathology ; Cross-Sectional Studies ; Adult ; Aged ; Spain/epidemiology ; Socioeconomic Factors ; SARS-CoV-2/isolation & purification ; Surveys and Questionnaires ; Fatigue ; Social Support ; },
abstract = {OBJECTIVE: To characterize the heterogeneity of Long COVID (LC) by identifying distinct patient profiles based on symptoms and quality of life (QoL), and to examine the sociodemographic and clinical predictors associated with these profiles.

STUDY DESIGN: A cross-sectional observational study was conducted.

METHODS: We recruited 363 patients with LC in Spain via an online survey. Symptom patterns were identified through latent class analysis of 15 binary symptoms. QoL was assessed with the patient-derived LC-6D-QoL across six dimensions, and cluster analysis defined QoL subgroups. Logistic regression was applied to examine clinical and sociodemographic predictors of QoL profiles.

RESULTS: Two symptom profiles emerged: a low-burden profile, dominated by fatigue and cognitive problems, and a high-burden profile with multisystem involvement. QoL clustered into three profiles-high, middle, and low QoL-with more than half of participants in the low QoL group. Symptom burden and employment status were the strongest predictors of poor QoL, whereas age, sex, education, and income showed limited associations. Social support was more frequently reported among participants with low QoL.

CONCLUSIONS: LC is characterized by distinct clinical and QoL profiles, with strong interactions between multisystem symptom burden and social determinants. Identifying patients at greatest risk of poor QoL can inform stratified interventions and integrated policies that combine medical care, psychosocial support, and workplace reintegration.},
}

Humans
*Quality of Life
Male
Female
Middle Aged
*COVID-19/epidemiology/psychology/pathology
Cross-Sectional Studies
Adult
Aged
Spain/epidemiology
Socioeconomic Factors
SARS-CoV-2/isolation & purification
Surveys and Questionnaires
Fatigue
Social Support

@article {pmid42010131,
year = {2026},
author = {Floridia, M and Weimer, LE and Bonfanti, P and Forte, AL and Cogliandro, V and Bottaro, V and Andreozzi, P and Zucco, S and Vagheggini, G and Onder, G},
title = {Cognitive impairment in long-COVID: frequency, trajectories and risk factors in a cohort study from Italy.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {47},
number = {5},
pages = {},
pmid = {42010131},
issn = {1590-3478},
support = {I85F21003410005//Ministero della Salute/ ; },
}

@article {pmid42010493,
year = {2026},
author = {Köhrer, S and Brand, ML and Leidner, V and Zimmer, H and Langel, A and Langel, J and Michl, P and Mohr, I},
title = {Exploratory longitudinal cohort study of modest bilirubin-driven biochemical liver alterations after SARS-CoV-2 infection in a selected subgroup of patients with Wilson's disease and liver cirrhosis.},
journal = {BMC gastroenterology},
volume = {26},
number = {1},
pages = {},
pmid = {42010493},
issn = {1471-230X},
}

@article {pmid42011141,
year = {2026},
author = {Lloyd-Jones, G and Santamarina, M and Alcock, R and Oudkerk, M},
title = {Acute COVID-19 lung disease and long COVID vascular pathophysiology modelling: the relevance of medical imaging in building multidisciplinary understanding.},
journal = {The British journal of radiology},
volume = {},
number = {},
pages = {},
doi = {10.1093/bjr/tqag056},
pmid = {42011141},
issn = {1748-880X},
abstract = {In this review, imaging features of COVID-19 lung disease are analysed in the context of pathophysiological processes in different phases of the disease. Radiological evidence is presented for the central role of vasculopathic phenomena in both the acute and post-acute phases of COVID-19. Radiologists have a central role in building understanding of many diseases. In multidisciplinary settings, medical imaging has a role in diagnosing, assessing severity, monitoring progress and delineating anatomy involved in diseases. Imaging also helps to elucidate models of disease pathogenesis. At the outset of the COVID-19 pandemic many groups worked together informally to gain understanding of pathogenesis, but no centralised system for formal interdisciplinary collaboration existed. In hindsight, the absence of formalised radiological involvement in building models of pathophysiology potentially contributed to the use of terminology which may be considered inappropriate or misleading. We reflect on the use of certain terminology commonly used to describe the lung disease. In conclusion, imaging is essential to multidisciplinary understanding of COVID-19 vascular pathophysiology both in the acute and post-acute phases of disease. Formation of collaborative systems to build interdisciplinary understanding of disease pathogenesis across all medical and scientific specialties should be a priority at the outset of any future pandemic.},
}

@article {pmid42011214,
year = {2026},
author = {Tan, C and Meng, J and Dai, X and He, B and Liu, P and Wu, Y and Xiong, Y and Yin, H and Wang, S and Gao, S},
title = {Corrigendum to 'Effects of therapeutic interventions on long COVID: a meta-analysis of randomized controlled trials'.},
journal = {EClinicalMedicine},
volume = {94},
number = {},
pages = {103887},
pmid = {42011214},
issn = {2589-5370},
abstract = {[This corrects the article DOI: 10.1016/j.eclinm.2026.103883.][This corrects the article DOI: 10.1016/j.eclinm.2026.103882.][This corrects the article DOI: 10.1016/j.eclinm.2025.103412.].},
}

@article {pmid42013972,
year = {2026},
author = {Sagoo, R and Sagoo, NS and Nguyen, K and Sathyamoorthy, M},
title = {Sex-Based Differences in Cardiovascular Diagnoses, Mortality, and Resource Utilization in Long COVID Hospitalizations: A National Inpatient Sample Analysis.},
journal = {The American journal of cardiology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.amjcard.2026.04.027},
pmid = {42013972},
issn = {1879-1913},
abstract = {Long COVID refers to persistent sequelae following SARS-CoV-2 infection, and sex-specific cardiovascular outcomes among hospitalized patients remain incompletely characterized. We queried the 2022 National Inpatient Sample (NIS) to identify adult hospitalizations with a diagnosis of long COVID (ICD-10 U09.9), excluding patients younger than 18 years or with missing outcome data. Analyses incorporated NIS discharge weights to generate national estimates. Multivariable (survey-weighted) logistic regression was used to estimate adjusted odds ratios (aORs) for cardiovascular diagnoses and in-hospital mortality. Among 87,415 weighted hospitalizations for long COVID, 49.4% were male and 50.6% were female. Males had more complicated hypertension, coagulopathy, and alcohol use disorder, whereas females had higher rates of obesity, depression, and hypothyroidism (all p<0.05). Males had a higher in-hospital mortality rate (5.9% vs. 4.7%, p<0.001). In adjusted analyses, females had lower odds of in-hospital mortality (aOR: 0.874 [95% CI, 0.819-0.932]), cardiac arrhythmias (aOR: 0.652 [0.629-0.677]), venous thromboembolism (aOR: 0.846 [0.807-0.887]), and myocardial infarction (aOR: 0.767 [0.720-0.817]). Adjusted odds of ischemic cerebrovascular accident were not significantly different (aOR: 0.955 [0.795-1.146]). Females had higher odds of transient ischemic attack (aOR: 1.441 [1.067-1.945]). Median length of stay (5 vs. 4 days) and total hospital charges ($50,447 vs. $43,839) were lower in females (all p<0.001). In conclusion, in this nationally representative analysis of long COVID hospitalizations, sex-based differences were observed in cardiovascular diagnoses, mortality, and healthcare utilization, and these findings support sex-sensitive risk stratification and hypothesis generation for post-COVID care.},
}

@article {pmid42001973,
year = {2026},
author = {Mery, V and Albacar, N and Matute-Villacís, M and Dalmases, M and Sibila, O and Agustí, À and Embid, C},
title = {"High prevalence of obstructive sleep apnea in patients with Long-COVID".},
journal = {Respiratory medicine},
volume = {},
number = {},
pages = {108848},
doi = {10.1016/j.rmed.2026.108848},
pmid = {42001973},
issn = {1532-3064},
abstract = {BACKGROUND: Long-COVID (LC) is defined as the persistence of symptoms 12 weeks after the acute COVID infection not explained by any other alternative diagnosis. Its pathophysiology is poorly understood. Obstructive Sleep Apnea (OSA) shares several clinical manifestations with LC, such as fatigue and low-quality sleep, however, thus far, their potential coexistence has been poorly addressed.

OBJECTIVE: To investigate the prevalence of OSA in patients with LC.

METHODS: Observational, prospective study. Patients with LC were recruited from a dedicated ambulatory hospital clinic. All patients underwent a comprehensive clinical evaluation, including standardized questionnaires to evaluate persistent symptoms, lung function tests and full polysomnography.

RESULTS: We studied 73 patients with LC. Their mean age was 57.4 ± 10.5 years, they were predominantly male (56.2%), 73.9% of whom were hospitalized during the acute COVID episode. Median AHI was 17.2 (24.14) events/h with a proportion of mild (27.4%), moderate (24.6%) and severe OSA (31.5%). Objective questionnaires identified poor sleep quality and fatigue as the most prevalent symptoms and daytime sleepiness as the least prevalent. Self-reported symptoms were frequent, with dyspnea, fatigue, and insomnia being the most commonly reported. Neither objective nor subjective symptoms correlated with OSA severity, with the exception of insomnia.

CONCLUSION: In this single-center, clinic-based LC cohort, OSA diagnosed by in-lab PSG was highly common. Given that OSA is treatable, a sleep study should be considered in LC patients even in the absence of daytime sleepiness or in the presence of insomnia.},
}