@article {pmid41873548,
year = {2026},
author = {Joseph, R and Rabelo, L and Do Nascimento, EB},
title = {Evidence of impaired processing speed and cognitive control in recovered COVID-19 patients: The role of cognitive slowing in long COVID memory impairment.},
journal = {Applied neuropsychology. Adult},
volume = {},
number = {},
pages = {1-16},
doi = {10.1080/23279095.2026.2649334},
pmid = {41873548},
issn = {2327-9109},
abstract = {Cognitive impairment is among the most reported symptoms in post-acute sequelae of SARS-CoV-2 infection. These impairments, often termed "brain fog" include difficulties in memory, attention, executive function, and processing speed, significantly impacting individuals' quality of life and daily functioning. This study investigates the hypothesis that survivors may exhibit impaired processing speed (PS) and cognitive control (CC), crucial components of cognitive functioning that potentially underlie learning and memory disturbances. An observational study was conducted with 61 participants (mean age: 35.7 ± 8.7 years, 53% female, 47% male), categorized into three groups: control (CTL), COVID symptomatic (COV-S), and hospitalized (COV-H). Participants were recruited through a sociodemographic and screening questionnaire and assessed using various cognitive and psychological evaluation tools, including the Five-Digit Test (FDT) and Rey Auditory Verbal Learning Test (RAVLT). Results indicate that declines in processing speed and cognitive control are related to the clinical condition of COVID-19, with greater severity observed in hospitalized individuals. The study provides robust evidence that COVID-19 affects processing speed and cognitive control, directly leading to slowed learning stages and impairments in the RAVLT encoding stage, due to increased interference during memory formation, affecting episodic-semantic memory tasks.},
}

@article {pmid41873998,
year = {2026},
author = {Goh, GK and Foster, JA and Uversky, VN},
title = {Clues to Long COVID Linked to Virulence and Infectivity Found in Shell Proteins.},
journal = {Advances in respiratory medicine},
volume = {94},
number = {2},
pages = {},
doi = {10.3390/arm94020018},
pmid = {41873998},
issn = {2543-6031},
mesh = {Humans ; *COVID-19/virology ; *SARS-CoV-2/pathogenicity ; Virulence ; Animals ; },
abstract = {Clinical, experimental, and computational evidence of COVID-19 virulence and infectivity has been linked to SARS-CoV-2 shell disorder. A strong link was first discovered using an AI disorder-predicting tool, which detected an unusually hard (low disorder) outer shell among all SARS-CoV-2-related viruses but not in the 2003 SARS-CoV-1. This could account for the high infectivity found in SARS-CoV-2-but not in SARS-CoV-1-as it is believed that hard shells protect viral particles from the onslaught of the antimicrobial enzymes present in the respiratory system and saliva. As a result, much larger quantities of particles are shed by COVID-19 patients. Abnormally hard outer shells (M) are associated with burrowing animals, e.g., pangolins, and SARS-CoV-2 likely acquired these shells due to its long-term evolutionary interactions with pangolins. As for virulence, the inner shell of SARS-CoV-2 (N) has been found to exhibit lower disorder than that of SARS-CoV-1. This lower disorder is consistent with the fact that SARS-CoV-2 is less virulent than SARS-CoV-1, as higher disorder in the inner shell is associated with more efficient protein-protein binding during replication. The link between N/M disorder and virulence or infectivity falls under the umbrella of shell disorder models (SDMs), which can connect virulence, infectivity, and long COVID under one coherent concept. Evidence of the reliability and reproducibility of SDMs as applied to COVID-19 is examined. The hard M that is resisting the antimicrobial enzymes in the respiratory system can be extended to immunological enzymes, especially those found in phagocytes such as macrophages, which can therefore become a reservoir for the virus.},
}

Humans
*COVID-19/virology
*SARS-CoV-2/pathogenicity
Virulence
Animals

@article {pmid41875425,
year = {2026},
author = {Lerma-Irureta, D and Méndez-López, F and Navarro-Matías, E and Lerma-Puertas, D and Magallón-Botaya, R},
title = {Differential Factors Associated With the Presence of Persistent Symptoms in Individuals Diagnosed With Long COVID: Protocol for a Longitudinal Matched Case-Control Study.},
journal = {JMIR research protocols},
volume = {15},
number = {},
pages = {e67133},
doi = {10.2196/67133},
pmid = {41875425},
issn = {1929-0748},
mesh = {Humans ; *COVID-19/complications/epidemiology/physiopathology/diagnosis ; Case-Control Studies ; Longitudinal Studies ; Spain/epidemiology ; Quality of Life ; SARS-CoV-2 ; Adult ; Female ; Male ; Post-Acute COVID-19 Syndrome ; Middle Aged ; Research Design ; },
abstract = {BACKGROUND: Long COVID (postacute sequelae of SARS-CoV-2 infection) is a heterogeneous condition with persistent multisystem symptoms and substantial functional burden. Integrative longitudinal studies combining clinical phenotyping, lifestyle factors, and immunobiological markers are needed to clarify determinants of symptom persistence and inform risk stratification and targeted interventions.

OBJECTIVE: This study aims to identify clinical, biological/immunological, and sociodemographic factors associated with Long COVID status by comparing individuals with persistent symptoms to matched recovered controls, and to evaluate longitudinal changes in symptoms and secondary outcomes over follow-up.

METHODS: ARALongCOV is a longitudinal matched case-control observational study conducted in Aragón, Spain, including adults (≥18 years of age) with confirmed SARS-CoV-2 infection. Participants are recruited through 3 sources: the Long COVID Aragón Patient Association, the Aragón Health Service database, and primary care consultations. Long COVID and recovered participants are individually matched 1:1 (without replacement) on sex/gender (exact), age (±3 years), and date of acute COVID-19 diagnosis (±30 days). Outcomes include persistent symptoms and functioning and patient-reported outcomes (quality of life, physical activity, diet, sleep, mental health, functional status, cognitive performance, pain catastrophizing, and fatigue), alongside clinical variables and biochemical/immunological markers (including inflammatory and cytokine profiles, SARS-CoV-2 antispike immunoglobulin G serology, and viral reactivation serologies). Measurements are obtained at baseline (T0) and repeated at follow-up (T1) using standardized procedures.

RESULTS: The study received ethics approval from the Clinical Research Ethics Committee of Aragón (PI21/278). Funding was provided by Instituto de Salud Carlos III through project PI22/01070 (cofunded by the European Union) for the period 2023-2027. Baseline assessments (T0) were initiated in late 2022/early 2023. As of February 2026, a total of 200 participants have been enrolled (n=100 Long COVID; n=100 recovered controls) and have completed T0; T1 assessments are scheduled for late 2025/early 2026 (~3-year follow-up for the earliest enrolled participants). Primary analyses will be conducted after completion of T1 assessments, with dissemination planned from the second half of 2026 and continuing through 2027.

CONCLUSIONS: This protocol describes a comprehensive, multidimensional longitudinal study designed to clarify determinants of Long COVID by integrating clinical, functional, lifestyle, and immunobiological data in matched cohorts. Findings are expected to support risk stratification, phenotype discovery, and identification of prognostic markers to inform preventive, diagnostic, and rehabilitative strategies.

TRIAL REGISTRATION: ISRCTN Registry ISRCTN27312680; https://tinyurl.com/33cbysrk.

DERR1-10.2196/67133.},
}

Humans
*COVID-19/complications/epidemiology/physiopathology/diagnosis
Case-Control Studies
Longitudinal Studies
Spain/epidemiology
Quality of Life
SARS-CoV-2
Adult
Female
Male
Post-Acute COVID-19 Syndrome
Middle Aged
Research Design

@article {pmid41875623,
year = {2026},
author = {Vianna, CM and de Figueiredo, AM and Camacho, LAB and Marques, CMC and Xavier, JR and da Gama, VC and Pizzini, GLC and Braga, RM and Santos, EAPD and Maia, MLS},
title = {Risk factors for post-COVID-19 condition: A case-control study in municipalities of Paraíba and Rio de Janeiro, Brazil.},
journal = {The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases},
volume = {30},
number = {2},
pages = {105807},
doi = {10.1016/j.bjid.2026.105807},
pmid = {41875623},
issn = {1678-4391},
abstract = {INTRODUCTION: Post-COVID-19 condition, refers to one or multiple symptoms that continue for several weeks or months following the COVID-19 infection. This study aims to assess the factors associated with post-COVID-19 condition in the Brazilians regions of Paraiba and Rio de Janeiro. Understanding this factor is crucial to public policies and improving care for high-risk individuals.

METHODS: This is a multicenter, retrospective case-control study. Cases were classified as individuals experiencing persistent symptoms for over 12-weeks following a confirmed COVID-19 diagnosis, whereas controls were those who recovered. Data on sociodemographic characteristics, medical history, lifestyle factors, and vaccination status were gathered, and logistic regression was used to analyze the relationship between these variables and the onset of post-COVID-19 condition.

RESULTS: Of the 1.350 participants, 734 were cases and 616 were controls, with a 54% frequency of post-COVID-19 condition. The study found significant associations between the syndrome and female sex (OR = 2.09; 95% CI 1.6‒2.74), middle age (OR = 2.03; 95% CI 1.31‒3.15 for 40- to 60-years) and over 60 (OR=1.84; 95% CI 1.06‒3.2), white people (OR = 1.41; 95% CI 1.07‒1.86), hypercholesterolemia (OR = 1.66; 95% CI 1.18‒2.32), chronic lung diseases (OR = 5.60; 95% CI 1.18‒26.65), mental illness such as anxiety and panic disorder (OR = 2.52; 95% CI 1.64‒3.87), family history of long COVID syndrome (OR = 2.07; 95% CI 1.45‒2.97), hospitalization (OR = 5.89; 95% CI 3.92‒8.86) and good pre-COVID health perception (OR = 0.69; 95% CI 0.53‒0.9).

CONCLUSIONS: The findings reinforce the importance of identifying groups more frequently affected by post-COVID-19 condition and supporting follow-up strategies aimed at mitigating its impact on individuals and health services.},
}

@article {pmid41876107,
year = {2026},
author = {Brierley, M and Vakilian, F and Rostami, M},
title = {When High Scores Hide Realities: Enhancing Patient Survey Data Through Joint Display.},
journal = {Annals of family medicine},
volume = {24},
number = {2},
pages = {153-158},
doi = {10.1370/afm.250474},
pmid = {41876107},
issn = {1544-1717},
mesh = {Humans ; *Patient Satisfaction/statistics & numerical data ; Alberta ; *COVID-19/epidemiology ; Surveys and Questionnaires ; Qualitative Research ; SARS-CoV-2 ; Female ; *Health Care Surveys/methods ; },
abstract = {PURPOSE: Patient surveys often include closed- and open-ended responses that are usually reported separately, and links between them rarely explored, limiting interpretive depth. We outline a strategy that integrates quantitative and qualitative survey data in a joint display which enables combined analysis and findings to inform and improve programs for patients.

METHODS: Data were drawn from a patient experience survey implemented in Alberta's long COVID Inter-professional Outpatient Program (IPOP). A joint display of Likert-scale satisfaction ratings and themed open-text feedback was developed to examine connections between the structured responses and qualitative insights.

RESULTS: We integrated quantitative survey satisfaction ratings with themes from the qualitative analysis of open-text comments in a joint display. Examining these data sets together added an analytical layer and uncovered nuanced experiences not evident in Likert-scale responses alone. By aligning satisfaction scores with themes, the joint display surfaced contradictory and paradoxical findings that would otherwise be hidden.

CONCLUSIONS: Aligning Likert-scale responses with thematic analysis of open-text reveals subtleties that may be obscured by scores alone. Understanding the narratives behind ratings is essential to evaluate health care programming, particularly when surveys are the primary mechanism for incorporating patient voices into service planning and delivery.},
}

Humans
*Patient Satisfaction/statistics & numerical data
Alberta
*COVID-19/epidemiology
Surveys and Questionnaires
Qualitative Research
SARS-CoV-2
Female
*Health Care Surveys/methods

@article {pmid41869098,
year = {2026},
author = {Becker, KN and Hagood, M and Creeden, JF and Heck, H and Haak, PT and Larder, C and Tipton, C and Schroeder, J and Eisenmann, KM},
title = {Baseline Clinician Attitudes and Practices Regarding Long-Term Neurological Follow-Up for COVID-19 Patients: Early Pandemic Insights With Contemporary Relevance.},
journal = {Cureus},
volume = {18},
number = {2},
pages = {e103837},
pmid = {41869098},
issn = {2168-8184},
abstract = {OBJECTIVES: This study aimed to investigate clinician opinions and practices regarding long-term neurological follow-up for COVID-19 patients during the early pandemic period (June-August 2020), before formal long COVID recognition, and identify the gaps between clinician awareness and clinical practice implementation.

METHODS:  We conducted a cross-sectional survey of 199 physicians and advanced practice providers (APPs; including nurse practitioners, physician assistants, certified registered nurse anesthetists (CRNAs), and similar roles) across Northwest Ohio and Southeast Michigan healthcare systems (June-August 2020). The survey assessed clinician awareness of long-term neurological risks, screening behaviors, referral practices, and attitudes toward long-term neurological follow-up using an original adaptive questionnaire administered via Qualtrics. Bivariate associations were tested using Pearson's chi-square and Fisher's exact test (p ≤ 0.05). This study was approved by the University of Toledo Institutional Review Board (Protocol #300681, exempt status).

RESULTS:  Most respondents (54/96, 56.3%) believed that more than 50% of COVID-19 patients should receive long-term neurological follow-up, primarily by neurology specialists (66/134, 49.3%). However, only 13/93 (14.0%) were actively referring more than 50% of their COVID-19 patients for such care. Average referral rates increased modestly from 14.1% pre-pandemic to 19.9% during the pandemic, with 100/130 (76.9%) reporting no change in practices. Self-reported familiarity with neurological manifestations of COVID-19 (114/179, 63.7%) was substantially lower than general COVID-19 familiarity (178/180, 98.9%).

CONCLUSIONS:  Substantial disconnect existed between clinician beliefs about appropriate care and actual referral practices, revealing infrastructure barriers, including inadequate specialty capacity and lack of standardized protocols. These baseline findings document the state of clinical practice before formal long COVID guidelines were established.

POLICY IMPLICATIONS:  Healthcare systems require enhanced infrastructure for long-term neurological monitoring of COVID-19 survivors, including increased specialty capacity and standardized protocols, informing pandemic preparedness for chronic disease complications.},
}

@article {pmid41870866,
year = {2026},
author = {di Filippo, L and Terenzi, U and Bolamperti, S and Bechini, C and Bossoni, S and Campaniolo, M and Gifuni, L and Doga, M and Giustina, A},
title = {Chronic cholecalciferol supplementation and adequate vitamin D status are associated with reduced risk of Long COVID.},
journal = {Journal of endocrinological investigation},
volume = {},
number = {},
pages = {},
pmid = {41870866},
issn = {1720-8386},
support = {ABIONC06//ABIOGEN SPA/ ; },
}

@article {pmid41870982,
year = {2026},
author = {Fernández, GA and Baratta, MSG and Klajn, DS},
title = {Long COVID in children and adolescents: Incidence and clinical characteristics in Buenos Aires, 2021-2023.},
journal = {Archivos argentinos de pediatria},
volume = {},
number = {},
pages = {e202510958},
doi = {10.5546/aap.2025-10958.eng},
pmid = {41870982},
issn = {1668-3501},
abstract = {Introduction. Long COVID affects approximately 8.5% of the pediatric and adolescent population after SARS-CoV-2 infection, and vaccination could reduce its incidence. Objectives. To determine the incidence of long COVID in children and adolescents aged 5 to 18 years, describe symptoms and duration, analyze differences by age and sex, estimate reinfections and school absenteeism, and evaluate its relationship with vaccination. Population and methods. Prospective cohort study conducted between August 1, 2021, and February 1, 2023. To calculate incidence, patients with COVID-19 treated at a general acute care hospital in the Autonomous City of Buenos Aires were included; for characterization, cases referred from other centers were included as well. Descriptive and comparative analyses were performed, estimating incidence with 95% CI; STATA 14.0 was used (p <0.05). The study was approved by the Ethics Committee. Results. Of 496 patients, 475 were included, and 21 were excluded due to severe comorbidities. The incidence of long COVID was 7.79% (95% CI 5.37-10.21). Those affected had a higher mean age (12.57 vs. 11.20 years; p = 0.02) and a higher incidence in unvaccinated or partially vaccinated individuals (11.48% vs. 5.48%; p = 0.018). The most common symptoms were fatigue, cough, and myalgia. Conclusion. The incidence of long COVID was comparable to that reported in other pediatric series. A lower incidence was observed in children and adolescents with complete vaccination schedules, and fatigue was the most frequent clinical manifestation. These findings reinforce the need to continue generating evidence.},
}

@article {pmid41864480,
year = {2026},
author = {Rauf, M and Naveed, A and Asghar, MU},
title = {Post-acute sequelae of COVID-19: A disorder of impaired innate immune resolution - A narrative review.},
journal = {Clinical immunology (Orlando, Fla.)},
volume = {285},
number = {},
pages = {110701},
doi = {10.1016/j.clim.2026.110701},
pmid = {41864480},
issn = {1521-7035},
abstract = {Post-acute sequelae of COVID-19 (PASC) affect millions of people worldwide and are increasingly recognized as a disorder of failed innate immune resolution rather than a persistent viral infection. Emerging evidence shows that residual SARS-CoV-2 antigens, host-derived alarmins, reactivated latent viruses, and mucosal microbiome-derived products from oral-nasopharyngeal and gut reservoirs sustain the chronic activation of pattern-recognition receptors, inflammasomes, and complement pathways. In parallel, deficits in specialized pro-resolving mediators, impaired efferocytosis, and persistent tissue injury prevent physiological termination of inflammation. These unresolved cues drive long-lasting epigenetic and metabolic reprogramming of hematopoietic stem cells and myeloid lineages, creating maladaptive trained immunity states characterized by hyper-responsiveness or exhaustion of these cells. Thromboinflammatory processes, including aberrant NETosis and sustained interface signalingling, further reinforce self-perpetuating inflammatory circuits. Together, these pathways give rise to reproducible molecular endotypes, including thromboinflammatory, interferon-driven, and neuroinflammatory phenotypes, which explain clinical heterogeneity. Framing PASC as a disorder of impaired immune resolution within a mucosal microbial viral context provides a unifying mechanistic scaffold for biomarker identification and host-directed therapies. This review proposes that restoring active resolution programs, rebalancing metabolic-epigenetic networks, and dismantling pathogenic innate feedback loops are promising strategies for reversing the chronic immune imprint of PASC.},
}

@article {pmid41862909,
year = {2026},
author = {Khalid, K and Abdullah, ADI and Lim, HX and Ali, RAR},
title = {Pharmacological and non-pharmacological management of long COVID.},
journal = {Virology journal},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12985-025-02991-5},
pmid = {41862909},
issn = {1743-422X},
abstract = {Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a major global health burden in terms of acute infection and long-term consequences. Approximately 10% of infected experience autonomic dysfunction, cardiovascular complications, and neurological impairments. While immune dysregulation, persistent viral reservoirs, chronic inflammation, gut dysbiosis, and vascular dysfunction are implicated, the exact pathophysiological mechanisms of Long COVID remain unclear. Additionally, treatment options are limited and challenging to prescribe due to symptom heterogeneity. Non-pharmacological interventions such as increased salt intake, elimination diets for gastrointestinal symptoms, and cognitive pacing for fatigue may not be sufficient for severe symptoms. Moreover, pharmacological interventions such as β-blockers, calcium channel blockers, pyridostigmine, antihistamines, and low-dose naltrexone can improve tachycardia, fatigue, and brain fog but there are no standardized guidelines. In light of evidence supporting a strong association of Long COVID with gut dysbiosis, probiotics have emerged as a promising intervention. Clinical studies have shown that Bacillus coagulans, Bacillus subtilis, Lactobacillus acidophilus, and Bifidobacterium species can improve fatigue, gastrointestinal health, and overall physical and mental well-being in Long COVID patients. Large-scale randomized controlled trials are warranted to validate probiotic efficacy in Long COVID and reduce burden on individual health and healthcare institutions.},
}

@article {pmid41862917,
year = {2026},
author = {Luo, S and Zheng, Z and Karimi, L and Plebanski, M and Lankatillake, C and Sheahan, J and Anderson, K and Jovanovski, N and Seal, EL and Cockshaw, W and Wollersheim, D and Cleary, S and El-Ansary, D and Flanagan, KL and Jessup, R and Abrahamson, S and Whyler, N and Fineberg, D and Scoullar, MJL and Seeley, MC and Tippett, E and Xenos, S and Itsiopoulos, C},
title = {Between silence and solutions: a global guideline review of long COVID care and services in Australia.},
journal = {BMC health services research},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12913-026-14268-w},
pmid = {41862917},
issn = {1472-6963},
}

@article {pmid41857005,
year = {2026},
author = {Gandhi, MM and Moser, C and Currier, JS and Ritz, J and Eron, JJ and Daar, ES and Wohl, DA and Fischer, WA and Singh, U and Hughes, MD and Smith, DM and Evering, TH and Chew, KW and , },
title = {Association of long COVID with health-related quality-of-life outcomes.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-36189-8},
pmid = {41857005},
issn = {2045-2322},
support = {UM1AI068634//National Institute of Allergy and Infectious Diseases/ ; UM1AI068636//National Institute of Allergy and Infectious Diseases/ ; },
abstract = {The association of long COVID with health-related quality-of-life (HrQOL) has not been well-characterized. Participants who received blinded placebo in the ACTIV-2/A5401 outpatient COVID-19 treatment trial were included in an analysis of the association of long COVID with HrQOL (both pre-specified exploratory trial endpoints) 9 months after acute COVID-19. Long COVID was defined as presence of self-assessed COVID-19 symptoms and HrQOL was assessed with EQ-5D-5L and SF-36v2 questionnaires. Associations were evaluated by Fisher's exact tests and Wilcoxon rank-sum tests. Of 546 participants, 13% had long COVID. Long COVID was associated with greater risk of reported problems in the EQ-5D-5L dimensions of mobility, usual activities, pain/discomfort, and anxiety/depression (risk ratios 3.45-6.00, all p < 0.001) and worse self-reported health scores (median 80 vs. 95, p < 0.001). Participants with long COVID also had worse SF-36v2 composite physical and mental component scores (both p < 0.001) and individual SF-36 domain scores (physical functioning, physical role, bodily pain, general health, vitality, social functioning, emotional role, and mental health; all p < 0.001). Associations were similar regardless of baseline (pre-COVID-19) medical history. Long COVID is associated with impaired HrQOL across multiple domains, highlighting the need to develop preventative and therapeutic interventions for this protean condition.},
}

@article {pmid41857445,
year = {2026},
author = {Friedberg, A and McConnell, E and Stanwick, S and Perez, L and MacEwan, S and Rush, LJ and Bowman-Burpee, S and Smith, RM and Joshi, S and Woschkolup, K and Grandominico, J and McAlearney, AS and Schamess, A},
title = {Outcomes of Patients with Neurocognitive Symptoms Attending a Long COVID Clinic: A Longitudinal Cohort Study.},
journal = {Journal of general internal medicine},
volume = {},
number = {},
pages = {},
pmid = {41857445},
issn = {1525-1497},
abstract = {BACKGROUND: Data are lacking on longitudinal outcomes of patients treated in primary care-led long COVID (LC) clinics.

OBJECTIVE: Assess changes in health-related quality of life (HRQoL) in patients with LC and neurocognitive symptoms from enrollment in a LC clinic to 6 months post-enrollment.

DESIGN: Observational cohort study.

SETTING: Primary care-led LC clinic at an academic medical center.

PARTICIPANTS: One hundred fifty patients with long COVID and neurocognitive symptoms who completed the PROMIS29 inventory at clinic enrollment and 6 months post-enrollment.

INTERVENTIONS: Multimodality care consisting of disease education and behavioral management, rehabilitative therapies, and pharmacotherapy for LC symptoms.

MAIN MEASURES: Treatments received and change in PROMIS29 t-scores from enrollment to 6-month follow-up.

KEY RESULTS: T-scores (mean, SE) at clinic entry were worse than the population mean (50) for fatigue (65.6, 1.05), sleep disturbance (57.3, 1.00), anxiety (60.0, 1.26), physical function (37.9, 0.87), social role participation (40.2, 0.84), pain (60.1, 1.24), and depression (57.3, 1.11). Patients received multimodality treatment consisting of disease education and behavioral management (all patients), combined rehabilitation and pharmacotherapy (44%), rehabilitation only (22%), or pharmacotherapy only (16%). There were statistically significant improvements in mean t-scores in all PROMIS29 domains at 6 months. Clinically significant improvement (change in t-score of ≥ 2.5) was seen for physical functioning (+ 2.9, 0.58), fatigue (- 4.9, 0.80), social functioning (+ 3.4, 0.68), and pain (- 2.8, 0.88). Change in t-score > 5 was seen in fatigue with symptom-titrated physical rehabilitation, in fatigue and pain with amantadine and memantine, and in sleep disturbance and pain with trazodone and amitriptyline.

CONCLUSION: Multimodal symptom-directed interventions incorporating rehabilitation alongside targeted pharmacotherapy were associated with significantly improved HRQoL in patients with LC and neurological symptoms.},
}

@article {pmid41859298,
year = {2026},
author = {Blitshteyn, S and Doherty, TA and Steinman, L},
title = {Postural Orthostatic Tachycardia Syndrome, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID as Neuroimmune Disorders.},
journal = {ImmunoTargets and therapy},
volume = {15},
number = {},
pages = {581262},
pmid = {41859298},
issn = {2253-1556},
abstract = {Postural orthostatic tachycardia syndrome (POTS), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long COVID are heterogeneous disorders with overlapping complex, multi-factorial and multi-systemic pathophysiology. POTS and ME/CFS are the most common phenotypes of Long COVID that can lead to significant disability and functional impairment. The exact pathophysiologic mechanisms of these disorders alone or in combination are still being investigated, but important mechanistic factors have been identified, such as autonomic dysfunction, immune dysregulation, autoimmunity, mitochondrial dysfunction, cerebral hypoperfusion, and neuroinflammation. To this end, we believe that these conditions should be viewed as neuroimmune disorders and should be included in the field of neuroimmunology, with its educational curriculum, training, and clinical care pathways. Including these disorders as part of neuroimmunology subspecialty is the key to advancing the science and clinical care of this underserved patient population with these complex and disabling conditions.},
}

@article {pmid41860011,
year = {2026},
author = {Houchen-Wolloff, L and Bell, J and Pritchard, R and Poinasamy, K and Holmes, K and Walker, S and Smith, N and Hastie, C and Rogers, N and Adams, D and Nathu, R and Gill, R and Bunker, J and Staunton, L and Chalmers, J and Ho, LP and Harris, V and Horsley, A and Marks, M and Raman, B and Wain, LV and Brightling, C and Evans, R},
title = {Consortium-Based Patient and Public Involvement and Engagement for Long COVID Research: A Pirit-Focused Impact Evaluation of the PHOSP-COVID Study.},
journal = {Health expectations : an international journal of public participation in health care and health policy},
volume = {29},
number = {2},
pages = {e70591},
doi = {10.1111/hex.70591},
pmid = {41860011},
issn = {1369-7625},
support = {+ MRC: MR/V027859/1//National Institute for Health and Care Research/ ; COV0319//National Institute for Health and Care Research/ ; },
mesh = {Humans ; *COVID-19/epidemiology ; *Patient Participation ; *Community Participation ; SARS-CoV-2 ; *Survivors ; Pandemics ; },
abstract = {BACKGROUND: At the start of the coronavirus disease-2019 (COVID-19) pandemic in early 2020, the long-term outcomes for survivors of COVID-19 were unknown. The PHOSP-COVID cohort study was set up at scale and pace in Spring 2020 to determine the short- to long-term health consequences of COVID-19 in post-hospitalisation survivors; to understand the impact of interventions during and after the acute illness on these long-term sequelae and to build the foundation for multiple in-depth studies. A consortium infrastructure of hospital trusts, academic partners, industry, patients and charities was created. From the study inception, patients were central to the PHOSP-COVID consortium, whereby a Patient and Public involvement and Engagement (PPIE) group was convened, including charity groups, people with lived experience recruited through clinical care from NHS sites, and patient support groups through Long Covid Support. Embedding high-quality, meaningful PPIE within a large consortium brings challenges and benefits. In this article, we describe our experiences of setting up and sustaining the PHOSP-COVID Consortium PPIE group, including a PIRIT-focussed evaluation of the impact of our PPIE work and provide top tips for researchers to take forward when embedding PPIE in future consortium research.

METHODS: This article outlines the set-up and sustainability of the PHOSP-COVID study PPIE group, in consultation with the National Institute for Health and Care Research (NIHR) guidance. To evaluate PPIE impact, we used PIRIT (Public Involvement in Research Impact Tool, 2023- Cardiff), and we provide our honest reflections of our PPIE work according to the PIRIT planning tool. The results highlight the benefits of a consortium approach to PPIE as well as the challenges, with quotes from PPIE contributors and academics. In addition, we have created top tips for researchers to take forward when embedding PPIE in future consortium research, linked to the NIHR standards.

LEARNING AND REFLECTION: This manuscript has identified gaps in PPIE considerations for the PHOSP-COVID study and specific challenges around a consortium-based approach for PPIE. These are largely due to time scale (i.e. the pace of setting up the study within a pandemic) and communication factors (diverse and large numbers of people to include/inform). Through reflection on the challenges and successes experienced in the PHOSP-COVID consortium PPIE via a PIRIT-focused impact evaluation, we have developed recommendations to support future good practice.

Patients and members of the public were involved in all aspects of this work from idea inception, design and conduct of the work, analysis and interpretation of the data. Eight patients prepared the manuscript and are included as co-authors.},
}

Humans
*COVID-19/epidemiology
*Patient Participation
*Community Participation
SARS-CoV-2
*Survivors
Pandemics

@article {pmid41860534,
year = {2026},
author = {Anderer, S},
title = {Long COVID Prevalence Decreases as Recovery Rates Improve.},
journal = {JAMA},
volume = {},
number = {},
pages = {},
doi = {10.1001/jama.2026.1021},
pmid = {41860534},
issn = {1538-3598},
}

@article {pmid41861144,
year = {2026},
author = {Oehlke, SM and Goreis, A and Lozar, A and Klinger, D and Plener, PL and Zeiler, M and Kothgassner, OD},
title = {Understanding the role of psychological factors in long COVID: a network analysis approach.},
journal = {European journal of public health},
volume = {36},
number = {2},
pages = {},
doi = {10.1093/eurpub/ckag038},
pmid = {41861144},
issn = {1464-360X},
support = {//European Economic and Social Committee (EWSA)-Fund/ ; },
mesh = {Humans ; *COVID-19/psychology/epidemiology/complications ; Female ; Male ; Adult ; Middle Aged ; Anxiety/epidemiology/psychology ; Depression/epidemiology/psychology ; Self Efficacy ; SARS-CoV-2 ; Surveys and Questionnaires ; Post-Acute COVID-19 Syndrome ; Aged ; },
abstract = {Long COVID (LC) is a heterogeneous, multisystem condition that persists beyond the acute phase of SARS-CoV-2 infection. Psychological symptoms are highly prevalent and may influence the course and severity of LC. However, their specific role within the broader symptom structure remains insufficiently understood. This study applied a psychological network approach to examine how psychological factors contribute to the overall symptom structure of LC and to identify central and bridging variables that may serve as promising targets for intervention. A sample of 283 individuals with LC (nfemale = 235, nmale = 47, ndiverse = 1; age: M = 39.48, SD = 13.29) completed an online survey assessing post-viral physical symptoms and psychological factors, including depression, anxiety, COVID-19-related traumatic stress, and lack of self-efficacy. A regularized partial correlation network was estimated based on ten variables. The network revealed a dense degree of connectivity, with psychological factors integrated into the broader symptom structure. Depression emerged as the most central variable. Cardiovascular and respiratory symptoms, neurological symptoms, and depression served as key bridge variables. Lack of self-efficacy showed moderate associations with COVID-19-related traumatic stress and anxiety. Female gender was linked to greater gastrointestinal symptom burden, while older age was associated with more pronounced cardiovascular and respiratory symptoms. This study underscores the central role of psychological factors-particularly depression-as key targets for intervention in LC. By advancing the understanding of factors shaping health outcomes in LC, our findings support the integration of psychological approaches into the clinical management of affected individuals.},
}

Humans
*COVID-19/psychology/epidemiology/complications
Female
Male
Adult
Middle Aged
Anxiety/epidemiology/psychology
Depression/epidemiology/psychology
Self Efficacy
SARS-CoV-2
Surveys and Questionnaires
Post-Acute COVID-19 Syndrome
Aged

@article {pmid41861186,
year = {2026},
author = {Kawamura, T and Kohno, J and Kikuchi, A and Arita, R and Takayama, S and Ishii, T},
title = {Factors involved in the improvement of prolonged symptoms in patients with COVID-19 treated with Japanese traditional (Kampo) medicine: A single-center, prospective, observational study.},
journal = {Medicine},
volume = {105},
number = {12},
pages = {e48084},
doi = {10.1097/MD.0000000000048084},
pmid = {41861186},
issn = {1536-5964},
support = {none//Department of Kampo and Integrative Medicine, Tohoku University Graduate School of Medicine/ ; },
mesh = {Humans ; Male ; Female ; Prospective Studies ; Middle Aged ; *Medicine, Kampo/methods ; Fatigue/etiology ; *COVID-19/complications/therapy ; Aged ; Japan/epidemiology ; *COVID-19 Drug Treatment ; Adult ; SARS-CoV-2 ; Treatment Outcome ; *Drugs, Chinese Herbal/therapeutic use ; East Asian People ; },
abstract = {Patients with prolonged symptoms of COVID-19 (PSC) show various symptoms, especially fatigue, which affect their activities of daily living and inhibit their return to social life. As there is no standard treatment for PSC, we developed a treatment regimen that includes Japanese traditional (Kampo) medicine according to patient symptoms and condition. This study aimed to investigate the progression of symptoms in patients with PSC using this treatment regimen and to assess differences in background factors that affect the improvement of symptoms in patients. We conducted a prospective, observational study and collected data from patients with PSC who visited a hospital in Japan between May 2022 and December 2023. The patient performance status (PS, 0-9) and 16 symptoms on a numerical rating scale (NRS, 0-10) were recorded at each visit. A total of 114 patients were analyzed. The group with a first visit general fatigue score equal to or greater than the median (GMGF group) took more time to achieve PS ≤ 2 (hazard ratio [95% confidence interval (CI)], 0.405 [0.253-0.650], P < .001) and the end of visit milestone (0.283 [0.150-0.532], P < .001) compared to the group with a first visit general fatigue score less than the median (LMGF group). The group with ≥90 days from the onset to the first visit (≥90 days group) reached the end of visit milestone significantly later (0.510 [0.267-0.974], P = .041) than the group with <90 days from the onset (the <90 days group). The odds ratios (95% CI) for achieving PS ≤ 2 and the end of visit milestone within 3 months of the first visit in the GMGF group were 0.140 (0.046-0.425, P < .001) and 0.148 (0.058-0.380, P < .001), respectively. The ≥90 days group experienced difficulty in achieving the end of visit milestone within 3 months of the first visit (odds ratio [95% CI], 0.430 [0.179-1.035], P = .06). Patients with PSC who have a high general fatigue score at their first visit may have difficulty improving their symptoms. Early treatment, including Kampo medicine, can promote the improvement of PSC symptoms.},
}

Humans
Male
Female
Prospective Studies
Middle Aged
*Medicine, Kampo/methods
Fatigue/etiology
*COVID-19/complications/therapy
Aged
Japan/epidemiology
*COVID-19 Drug Treatment
Adult
SARS-CoV-2
Treatment Outcome
*Drugs, Chinese Herbal/therapeutic use
East Asian People

@article {pmid41851212,
year = {2026},
author = {Kukreti, S and Yeh, CY and Lu, MT and Imteyaz, K and Strong, C and Ko, NY},
title = {Post-acute sequelae of SARS-CoV-2 infection symptom network centrality analysis of Taiwan population to unveil intricate symptomatology patterns.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-41991-5},
pmid = {41851212},
issn = {2045-2322},
support = {114-2811-B-006-028//National Science and Technology Council/ ; },
}

@article {pmid41851917,
year = {2026},
author = {Allen, AJ and Ward, M},
title = {Long COVID should be a public health concern.},
journal = {Perspectives in public health},
volume = {},
number = {},
pages = {17579139261429368},
doi = {10.1177/17579139261429368},
pmid = {41851917},
issn = {1757-9147},
}

@article {pmid41852583,
year = {2026},
author = {Ramer, V and van Montfrans, GA},
title = {Persistent prostaglandin E2 upregulation and hormonal multi-resistance: A hypothesis for long COVID.},
journal = {Biochemistry and biophysics reports},
volume = {46},
number = {},
pages = {102518},
pmid = {41852583},
issn = {2405-5808},
abstract = {An explanation for long COVID (LC) and its many symptoms remains elusive, and no unifying upstream mediator of its pathophysiology has yet been identified. Viral infections, including COVID-19, upregulate Prostaglandin E2 (PGE2), - the principal lipid mediator of inflammation. PGE2 has broad paracrine effects, including modulation of autoantibodies, nervous systems, blood pressure, glucose levels, and apoptosis. Upregulated, PGE2 may drive multiple pathological processes through its four receptors: EP1-EP4. Through EP3, PGE2 stimulates characteristic viral sickness symptoms. Both severe and mild disease may precede LC, possibly reflecting either excessive or insufficient EP3 activity, which we term "EP3 up" and "EP3 down", respectively. In individuals with "EP3 up" or "EP3 down" states, elevated PGE2 levels may disrupt homeostasis. Diverse physical and mental stressors upregulate PGE2. Data suggest that multiple hormones and agents stimulate PGE2 production, while PGE2 reportedly antagonizes these agents, possibly functioning as a homeostatic limiter. Sufficiently elevated PGE2, "PGE2 dominance", may interfere with their activity through inhibiting their release, overlapping subcellular signaling pathways or by stimulating phosphorylation and autoantibodies. Homeostatic elevations of PGE2-stimulating hormones, together with other PGE2-raising factors, may promote resistance to these hormones, resulting in persistent PGE2 upregulation. Literature suggests that PGE2 overactivity, mediated by imbalanced EP receptor signaling, aligns with the diverse symptomatology of LC. Based on our literature analysis, we propose that persistent upregulation of PGE2 plays a pivotal role in the development of LC. Consequently, validation of elements of this framework may help guide exploration of therapeutic strategies targeting PGE2 pathways or EP receptor regulation.},
}

@article {pmid41852926,
year = {2026},
author = {Gutzeit, J and Weiß, M and Bahmer, T and Lieb, W and Schreiber, S and Vehreschild, JJ and Nürnberger, C and Pütz, SM and Heim, E and Ruß, AK and Dempfle, A and Krawczak, M and Poick, S and Schäfer, A and Morbach, C and Lehmann, C and Polidori, MC and Reese, JP and Zoller, T and Krist, L and Heyckendorf, J and Reinke, LM and Deckert, J and Hein, G and , },
title = {Long-term trends in Post-COVID severity: a machine learning analysis from the POP/COVIDOM cohort of the German NAPKON Cohort Network.},
journal = {EClinicalMedicine},
volume = {93},
number = {},
pages = {103822},
pmid = {41852926},
issn = {2589-5370},
abstract = {BACKGROUND: Post-COVID syndrome (PCS) affects many survivors with varying symptom profiles driven by acute disease severity (PCS-S) or individual resilience (PCS-R). While cross-sectional studies have identified risk factors and gender differences, long-term trajectories remain unclear. This study investigates the stability and progression of PCS-S and PCS-R scores after 9, 24 and 36 months from initial diagnosis, identifying key predictive factors stratified by gender.

METHODS: We analyzed data from 1526 participants of the German National Pandemic Cohort Network (NAPKON), modeling symptom-based PCS-score trajectories over time with linear mixed-effects models. Data were split into training (n = 944), test (n = 233), and two-site external validation (n = 349) sets. Gender-stratified elastic-net regression used nine-month clinical and psychosocial measures to predict PCS scores at 24 and 36 months. All data were collected between November 2020 and February 2024. The study is registered on ClinicalTrials.gov (NCT04679584) and in the German Registry for Clinical Studies (DRKS00023742).

FINDINGS: PCS-S and PCS-R scores showed small but significant declines between 9 and 36 months (β = -0.054 and -0.065, respectively; p < 0.001), indicating persistent symptom burden despite gradual improvement. Predictive models explained 16.7-52.6% of variance in later PCS severity. Fatigue after 9 months and age predicted later PCS-S; quality of life and depression added predictive value in females. Fatigue and sleep issues predicted PCS-R, with living/employment status relevant in females and cognitive deficits in males.

INTERPRETATION: The severity of PCS subtype manifest after 9 months remains relatively stable over time, with distinct gender-specific predictors shaping symptom progression. Tailored interventions are essential for long-term management of PCS pathways.

FUNDING: The COVIDOM study is funded by the Network University Medicine as part of the NAPKON.},
}

@article {pmid41855420,
year = {2026},
author = {Deng, J and Tao, L and Liu, N and Li, J and Qin, C and Yan, W and Wang, Y and Du, M and Liu, Q and Liu, J},
title = {Rehabilitation status and preference for medical choice behaviours of long COVID-19 in China: a national cross-sectional study and discrete choice experiment.},
journal = {Journal of global health},
volume = {16},
number = {},
pages = {04081},
doi = {10.7189/jogh.16.04081},
pmid = {41855420},
issn = {2047-2986},
mesh = {Humans ; Cross-Sectional Studies ; *COVID-19/rehabilitation/epidemiology/psychology ; Male ; Female ; China/epidemiology ; Middle Aged ; Adult ; *Choice Behavior ; *Patient Preference/statistics & numerical data ; Aged ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Health Status ; },
abstract = {BACKGROUND: Long COVID-19 has emerged as a growing global public health challenge requiring patient-centred responses, yet its prevalence and management are often underestimated. We aimed to investigate the rehabilitation status and medical choice behaviours among patients with long COVID-19 in China during the Omicron wave.

METHODS: We conducted a national cross-sectional study and a discrete choice experiment (DCE) in China from 4 July to 11 August 2023. We used the modified COVID-19 Yorkshire Rehabilitation Scale (C19-YRSm) to assess rehabilitation status. We collected preferences for medical choice behaviours of long COVID-19, demographics, health-related factors, and COVID-19 history. We assessed preferences for medical choice behaviours among people with long COVID-19 using mixed logit models.

RESULTS: Among 2942 participants health status was significantly poorer than before COVID-19 infection. The prevalence of common symptoms assessed by C19-YRSm ranged from 21.52% to 72.67%, with fatigue (72.67%) being the most common, followed by breathlessness on walking up a flight of stairs (64.96%) and sleep problems (62.95%). Of these symptoms, the majority of participants (15.06-47.65%) reported mild problems. Of the five functional limitations, difficulty with other activities of daily living (31.03%) was the most common, followed by difficulty with communication (28.04%), while difficulty with personal care (9.65%) was the least common. The DCE results showed that the strongest attribute affecting preferences was medical distance (β = -1.135). While seeking healthcare for long COVID-19, people preferred lower out-of-pocket costs, a closer distance, a higher hospital level, nutritional supportive therapies or rehabilitation training, and medical services that integrate traditional Chinese and Western medicine.

CONCLUSIONS: A substantial proportion of individuals developed long COVID-19 symptoms and functional limitations, most of which were mild. These findings highlight the importance of ongoing screening and comprehensive, tailored rehabilitation services to promote recovery and avert a public health crisis of long COVID-19.},
}

Humans
Cross-Sectional Studies
*COVID-19/rehabilitation/epidemiology/psychology
Male
Female
China/epidemiology
Middle Aged
Adult
*Choice Behavior
*Patient Preference/statistics & numerical data
Aged
SARS-CoV-2
Post-Acute COVID-19 Syndrome
Health Status

@article {pmid41856437,
year = {2026},
author = {Perez-Mazzali, M and Pérez-Cózar, F and Cal-Sabater, P and Rybakowska, P and Tellería, P and Gamazo, J and De Vicuña, MG and Arribas-Rodríguez, E and Fiz-López, A and de Castro, CG and García-Blesa, A and Rello, SR and De Prado, Á and Pérez, C and Tamayo, E and Orduña, A and Dueñas, C and Marañón, C and Bernardo, D and Cuesta-Sancho, S},
title = {Persistent T cell phenotypic alterations and early innate immune dysregulation as potential biomarkers of Long COVID.},
journal = {The Journal of infection},
volume = {},
number = {},
pages = {106731},
doi = {10.1016/j.jinf.2026.106731},
pmid = {41856437},
issn = {1532-2742},
abstract = {Long COVID is a complex condition characterized by a broad spectrum of persistent, multisystemic symptoms that often impair daily activities and cause disability with significant socioeconomic impact. Although several hypotheses have been proposed to explain its pathophysiology-including immune dysregulation-the underlying mechanisms remain poorly understood. Indeed, there are no current treatments for this condition. Therefore, we aimed to characterize immune alterations induced by SARS-CoV-2 during the acute phase of infection and three months post-hospital discharge in a cohort of patients who later developed Long COVID, referred to a matched cohort who did not. We performed high-dimensional immune profiling of peripheral blood mononuclear cells using a 40-marker mass cytometry panel. Data analysis combined classical hierarchical gating strategies with unsupervised computational approaches. Our results revealed distinct immune signatures between Long COVID and non-Long COVID patients, affecting both the innate and adaptive immune compartments. Notably, individuals who subsequently developed Long COVID exhibited early abnormalities at infection in innate immunity, particularly involving dendritic cells and γδ T cells. Moreover, three months post-discharge, persistent alterations were observed in several adaptive immune cell subsets in patients who next developed Long COVID over time. In summary, our findings suggest that early immune dysregulation following viral infection may predispose individuals to persistent post-viral pathology.},
}

@article {pmid41856465,
year = {2026},
author = {Malakooti, SK and Abboud, M and Murphy, JE and Singer, NG and McComsey, GA},
title = {Autoimmune Disease is Associated with Heightened Long COVID Risk but Prior Immunization is Protective.},
journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases},
volume = {},
number = {},
pages = {108540},
doi = {10.1016/j.ijid.2026.108540},
pmid = {41856465},
issn = {1878-3511},
abstract = {OBJECTIVES: Patients with autoimmune disease (AD) may be predisposed to Long COVID, yet the impact of primary autoantibody-associated AD and prior immunization remains unclear.

METHODS: TriNetX, a global electronic health database, identified adults with confirmed SARS-CoV-2 infection between January 1, 2020 and September 21, 2023 and at least one follow-up visit >90 days later. Long COVID was defined as persistent or new symptoms ≥90 days after infection. Patients with and without pre-existing AD were propensity-score-matched on demographics and comorbidities. Logistic regression assessed odds of Long COVID, with additional sensitivity analyses performed.

RESULTS: Among 2,472,196 patients with SARS-CoV-2, 289,206 had AD (+AD). After matching, baseline characteristics were similar. +AD patients had higher odds of all Long COVID symptoms compared with -AD patients. The highest odds were observed for disturbance to smell/taste (OR:1.99;95%CI:1.88-2.11), hair loss (OR:1.96;95%CI:1.89-2.04), abnormal movements/tremors (OR:1.93;95%CI:1.88-1.98), and body aches (OR:1.85;95%CI:1.81-1.89). Unvaccinated +AD patients had higher odds of all symptoms compared with matched unvaccinated -AD. Within +AD, primary autoantibody-associated AD demonstrated higher odds of most symptoms.

CONCLUSION: Pre-existing AD increases the risk of Long COVID, with the highest risk in primary autoantibody-associated AD. Prior vaccination mitigates the risk of most Long COVID symptoms in +AD patients, with heightened protection observed in primary autoantibody-associated AD.},
}

@article {pmid41856572,
year = {2026},
author = {Cao, B and Soriano, JB and Wang, Q and Al-Aly, Z and Gu, X and Wang, G and Leo, YS and Jin, Y and Shi, Q and Ohmagari, N and Liu, E and Paredes, R and Lu, H and Kim, ES and Zhang, D and Estill, J and Li, L and Spruyt, K and Yang, W and Wang, Y and Ran, M and Luo, X and Zhang, H and Xu, J and Zhang, R and Zhao, J and Zhao, J and Evans, RA and Jeon, J and Peluso, MJ and Errett, LE and Zhang, W and Chalmers, JD and Chen, Y and , },
title = {Clinical practice guideline for long COVID prevention and treatment.},
journal = {The European respiratory journal},
volume = {},
number = {},
pages = {},
doi = {10.1183/13993003.02611-2025},
pmid = {41856572},
issn = {1399-3003},
abstract = {BACKGROUND: This guideline aims to address key clinical questions of long COVID, and to provide evidence-base recommendations. The target population is adults with long COVID. The primary users of the guideline are clinical physicians, clinical pharmacists, nurses, and general practitioners in community healthcare institutions worldwide.

METHODS: The guideline was registered at the Practice guideline REgistration for transPAREncy platform (PREPARE-2024CN123) and followed a pre-specified protocol. A multidisciplinary working group was established and comprised 60 members from 10 countries and 10 area of expertise, with a strong background in long COVID research and clinical practice, and methodology of guideline development. Through a two-step process, we determined the 8 PICO questions focusing on prevention and treatment of long COVID. After comprehensively searching literature, conducting systematic reviews, and investigating patients' values and preferences, three rounds of Delphi survey were conducted among 24 international experts to reach consensus. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was applied to rate the certainty of evidence and determine the strength of recommendations.

RESULTS: The guideline presents 10 specific recommendations, each supported by existing, updated, or newly conducted systematic reviews. The key recommendations are pertinent to the following issues: 1) suggestion of vaccination or use of antiviral agents during the acute phase of COVID-19 to prevent long COVID; 2) suggestions against the use of nirmatrelvir-ritonavir and glucocorticoids (patients with persistent respiratory symptoms and olfactory disorders) for long COVID treatment; 3) suggestions supporting the use of multi-species probiotics, cognitive behavioral therapy (patients with fatigue), and personalized rehabilitation after excluding post-exertional malaise for long COVID treatment.

CONCLUSIONS: This guideline provides evidence-based recommendations for the prevention and treatment of long COVID. Given the limited and often low-methodological quality evidence, all recommendations are supported by very low to moderate certainty. Further high-quality studies are needed to strengthen the evidence base.},
}

@article {pmid41845161,
year = {2026},
author = {Saurer, P and Ballouz, T and Cusini, A and Haile, SR and Kahlert, CR and von Kietzell, M and Kuster, SP and Rütti, M and Schlegel, M and Strahm, C and Stocker, R and Vuichard-Gysin, D and Risch, L and Puhan, MA and Dörr, T and Kohler, P and , },
title = {Persistence of Post-Acute COVID-19 Sequelae (PASC) symptoms in healthcare workers four years after ancestral SARS-CoV-2 infection: a prospective multicentre cohort.},
journal = {Infection},
volume = {},
number = {},
pages = {},
pmid = {41845161},
issn = {1439-0973},
support = {31CA30_196544//Swiss National Sciences Foundation SNSF/ ; },
abstract = {PURPOSE: Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), or long COVID (LC), remains a significant burden for public health, with limited long-term data. This study aimed to assess the prevalence and evolution of PASC symptoms after ancestral SARS-CoV-2 (aSCV2) infection in a longitudinal healthcare worker (HCW) cohort.

METHODS: A multicentre cohort study involving HCWs from 14 institutions was conducted in Switzerland. Infection status was based on self-reported positive swabs, with additional serology used to confirm uninfected controls. Baseline was defined as the first survey conducted in 2022 (median 18.5 months post-infection), with follow-up surveys every 6 months through November 2024. To identify PASC-specific symptoms, 24 chronic symptoms were compared between 456 aSCV2-infected and 571 uninfected participants using chi-square tests at baseline. In aSCV2-infected individuals reporting PASC-specific symptoms, symptom trajectories and subjective LC were analyzed across follow-up surveys. Functional limitations were assessed using the Post-COVID Functional Status (PCFS) scale.

RESULTS: Thirteen of 24 symptoms were more common in aSCV2-infected individuals, with fatigue (22.8%), loss of smell/taste (11.4%), and brain fog (8.3%) being most prevalent. At baseline, 186/456 (40.8%) infected participants reported ≥ 1 PASC-specific symptom. Most symptoms declined in prevalence up to the last survey (median 47.5 months post-infection), although 41/70 (58.6%) remaining participants still reported ≥ 1 PASC symptom. Subjective LC was reported by 70/186 (37.6%) and was associated with higher symptom burden. PCFS scores showed slight impairments in most cases, although moderate-to-severe limitations often persisted.

CONCLUSIONS: PASC symptoms persisted up to four years after aSCV2 infection in a substantial proportion of HCWs.},
}

@article {pmid41847505,
year = {2026},
author = {Chagay, N and Tamadon, A and Kim, S and Dossimov, A and Issanguzhina, Z and Tulegenova, G and Kuldeeva, G and Puxovikova, N and Kim, I and Mussin, NM and Sharoffidin, RS},
title = {Pediatric-related post-COVID condition (long COVID) research and its foundational influences: a bibliometric analysis (2020-2025).},
journal = {Frontiers in pediatrics},
volume = {14},
number = {},
pages = {1677983},
pmid = {41847505},
issn = {2296-2360},
abstract = {BACKGROUND: The COVID-19 pandemic significantly influenced healthcare systems worldwide. The long-term consequences of the infection in children, the phenomenon of post-COVID-19 syndrome, have been attracting increasing attention of the scientific community. The present study is a bibliometric analysis of publications addressing post-COVID (long COVID) complications in pediatric population over the period 2020-2025.

METHODS AND MATERIALS: The analysis covers 1,292 records retrieved from Scopus and Web of Science (search date: June 2025). Records were retrieved using post-COVID condition/long COVID terminology combined with pediatric-related keywords; therefore, the corpus includes pediatric-focused studies as well as influential general PCC publications indexed with pediatric terms and frequently cited in pediatric research. The search strategy combined post-COVID condition/long COVID terminology with pediatric terms (child/infant/adolescent), applying filters for English language, publication years 2020-2025, and document type (articles and reviews). Data were merged and analyzed in R using bibliometrix/Biblioshiny to describe productivity, collaboration, citations, and thematic structure.

RESULTS: The retrieved corpus included 1,292 publications from 84 countries/regions. The United States led productivity with 270 publications (20.9%), followed by the United Kingdom (114; 8.8%) and China (90; 7.0%). The most frequent author keywords included "COVID-19" (n = 900) and "long COVID" (n = 818). Highly cited items predominantly consisted of general or mixed-age PCC frameworks, indicating that foundational long COVID literature substantially shapes citation patterns within pediatric-tagged publications. Thematic mapping showed symptom-focused clusters as dominant, while MIS-C and cognitive impairment were less prominent in author-keyword frequency and thematic clustering within the retrieved dataset.

CONCLUSION: The findings describe the pediatric-term-indexed PCC research landscape and highlight substantial gaps in pediatric-specific evidence, definitions, and longitudinal data.},
}

@article {pmid41848128,
year = {2025},
author = {Hajji, H and Kalai, A and Chaabeni, A and Migaou, H and Jebali, B and Ben Salah Frih, Z and Ben Saad, H and Jellad, A},
title = {Beyond the basics: exploring non-conventional treatment for fatigue in post-acute COVID-19 syndrome.},
journal = {La Tunisie medicale},
volume = {103},
number = {9},
pages = {1265-1271},
doi = {10.62438/tunismed.v103i9.5926},
pmid = {41848128},
issn = {2724-7031},
mesh = {Humans ; *COVID-19/complications/therapy ; Post-Acute COVID-19 Syndrome ; *Fatigue/therapy/etiology ; SARS-CoV-2 ; Dietary Supplements ; Acupuncture Therapy/methods ; },
abstract = {INTRODUCTION: Post-acute 2019 coronavirus disease syndrome (PACS) is a multifaceted, multisystem disorder affecting an estimated 75 million individuals globally (in May 2024). Defined by symptoms persisting beyond four weeks post-infection, PACS manifests in subacute (4-12 weeks) and chronic (>12 weeks) phases, with fatigue being a prominent and debilitating feature. Comprehensive management of PACS-associated fatigue needs diverse therapeutic strategies extending beyond conventional rehabilitation.

AIM: This narrative review explored non-conventional interventions for PACS-related fatigue, focusing on treatments involving nutritional rehabilitation, physical modalities, and other innovative therapies.

METHODS: Narrative review.

RESULTS: Treatments reported in the literature include melatonin, QingjinYiqi, nutritional supplements, aromatherapy, antioxidants, Tai Chi, acupuncture, yoga, singing, hyperbaric oxygen therapy (HBOT), pulsed electromagnetic field therapy, and whole-body vibration. Melatonin and QingjinYiqi have shown notable improvements in fatigue and overall health. Nutritional supplements such as vitamin-minerals combinations have demonstrated enhancements in muscle strength, physical performance, and quality of life. Tai Chi, acupuncture, and yoga have shown positive effects on fatigue, muscle strength, and overall well-being. Aromatherapy, singing, HBOT, pulsed electromagnetic field therapy, and whole-body vibration effectively reduce fatigue while enhancing physical and cognitive functions.

CONCLUSION: These non-conventional treatments offer promising supplementary benefits to conventional rehabilitation.},
}

Humans
*COVID-19/complications/therapy
Post-Acute COVID-19 Syndrome
*Fatigue/therapy/etiology
SARS-CoV-2
Dietary Supplements
Acupuncture Therapy/methods

@article {pmid41849004,
year = {2026},
author = {Gebetsroither, P and Ettenauer, T and Likar, R},
title = {Treatment of post-COVID symptoms with auricular vagus nerve stimulation.},
journal = {Wiener medizinische Wochenschrift (1946)},
volume = {},
number = {},
pages = {},
pmid = {41849004},
issn = {1563-258X},
abstract = {We present a retrospective analysis of nine long COVID patients undergoing auricular vagus nerve stimulation for 4 weeks. Questionnaires screening for 35 symptoms and 22 aspects of quality of life showed improvements in 28/35 symptoms immediately after treatment, of which 19 persisted at the 12-week follow-up. Most benefits were reported with regards to pain, fatigue, post-exertional malaise, sleep and dysautonomia. Furthermore, the vast majority (19 out of 22) of aspects of quality of life were reported to have improved to various degrees.},
}

@article {pmid41849271,
year = {2026},
author = {Pham, ANQ and Smith, J and Byers, KA and Card, KG},
title = {Associations between demographic, clinical, and socioeconomic factors and mental health in long COVID: A clinic-based cross-sectional study.},
journal = {PloS one},
volume = {21},
number = {3},
pages = {e0342516},
doi = {10.1371/journal.pone.0342516},
pmid = {41849271},
issn = {1932-6203},
mesh = {Humans ; Female ; Male ; *COVID-19/psychology/epidemiology/complications ; Middle Aged ; Cross-Sectional Studies ; *Mental Health ; Adult ; Socioeconomic Factors ; *Anxiety/epidemiology ; *Depression/epidemiology ; British Columbia/epidemiology ; Aged ; SARS-CoV-2/isolation & purification ; Chronic Disease ; },
abstract = {BACKGROUND: Long COVID is associated with persistent symptoms, including the onset of new mental health challenges such as anxiety and depression, as well as the worsening of pre-existing conditions. While previous research has examined the impact of demographic factors, chronic conditions, and traumatic events on mental health, little is known about how these factors interact to shape mental health outcomes in individuals with Long COVID. This study investigates the relationship between selected demographics characteristics, social determinants of health - specifically living settings, place of living, employment status, and working hours - and chronic health conditions on mental health outcomes among individuals with Long COVID.

METHODS: This is a secondary analysis using previously collected survey data from 3,611 individuals, who were diagnosed, referred to and admitted at Post-COVID Recovery Clinics, British Columbia, Canada at the time of their admission. The dataset includes demographic variables (sex, age, living situation, employment status, occupation, ethnicity), history of chronic conditions, and mental health outcomes (anxiety and depression) of patients. Univariable and multivariable Generalized Linear Regression analyses were conducted to examine associations between SDoH and mental health outcomes, adjusting for potential confounders.

RESULTS: The cohort had a mean age of 50 years, and 62% of participants were female. Overall, 38% screened positive for anxiety, 35% for depression, and 26% for both conditions following COVID-19 infection. In multivariable analyses, younger age, cognitive issues, and activity limitations were significantly associated with symptoms of anxiety, while younger age, cognitive issues, and physical impairments were significantly associated with symptoms of depression. In the multivariable model, individuals with cognitive issues were more likely to report anxiety (RR = 1.45, 95% CI: 1.34-1.56) and depression (RR = 1.54, 95% CI: 1.42-1.68). Activity limitations were also associated with anxiety (RR = 1.12, 95% CI: 1.01-1.24), and physical impairments with depression (RR = 1.43, 95% CI: 1.24-1.65). Overall, 38% of patients reported symptoms of anxiety, 35% reported depression, and 26% experienced both following COVID-19 infection.

CONCLUSION: These findings highlight important associations between mental health symptoms and clinical factors among individuals with Long COVID and underscore the need for further longitudinal research to clarify causal pathways and inform mental health support strategies, particularly among those with activity limitations, cognitive and physical impairments.

The data collection and questionnaire were designed and conducted by the Post-COVID Integrated Clinic Network in British Columbia, Canada.},
}

Humans
Female
Male
*COVID-19/psychology/epidemiology/complications
Middle Aged
Cross-Sectional Studies
*Mental Health
Adult
Socioeconomic Factors
*Anxiety/epidemiology
*Depression/epidemiology
British Columbia/epidemiology
Aged
SARS-CoV-2/isolation & purification
Chronic Disease

@article {pmid41850429,
year = {2026},
author = {Kraus, T and Napierala, H and Schrimpf, A and Joos, S and Blaschke, S and Hanses, F and Vehreschild, MJGT and Hamelmann, E and Schmidt, J and Scheer, CS and Römmele, C and Göpel, S and Almahfoud, M and Dahl, E and Hamprecht, A and Kaasch, AJ and Wendel, J and Ole Jensen, BE and Tepasse, PR and Dashti, H and Vehreschild, JJ and Scherer, M and Bröhl, I and Raquib, S and Nürnberger, C and Reese, JP and Appel, KS and Krefting, D and Förster, C and , },
title = {Impact of COVID-19 vaccination on post-COVID syndrome across clinical definitions and phenotypes: a prospective multicenter cohort study.},
journal = {Mayo Clinic proceedings},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.mayocp.2026.02.018},
pmid = {41850429},
issn = {1942-5546},
abstract = {OBJECTIVES: To assess the impact of COVID-19 vaccination on distinct clinical definitions and phenotypes of post-COVID syndrome (PCS) and identify risk factors for PCS despite vaccination.

METHODS: Data were drawn from the German National Pandemic Cohort Network (NAPKON), including adult COVID-19 patients with known vaccination status recruited between December 2, 2020, and February 13, 2023. PCS prevalence was assessed using 3 clinical definitions: the broad WHO definition (any sequelae at 3 months), symptom clusters (Fatigue, Respiratory, Cognitive), and a symptom-based PCS score reflecting clinical severity. Multivariable logistic regression was employed to estimate the protective effect of vaccination.

RESULTS: Among 756 patients, 26% were fully vaccinated (≥2 doses) before infection. Vaccination was associated with a significantly reduced risk of PCS according to the WHO definition (OR 0.555, 95% CI 0.339-0.906), the PCS score (OR 0.536, 95% CI 0.335-0.856), the Respiratory Cluster (OR 0.508, 95% CI 0.295-0.875), and the Cognitive Cluster (OR 0.443, 95% CI 0.213-0.923). In contrast, no protective association was observed for the Fatigue Cluster (OR 0.917, 95% CI 0.554-1.519). The favorable association with vaccination was particularly observed in patients with mild acute symptoms, regardless of hospitalization. The protective effect of vaccination persisted at 12-month follow-up, although fatigue remained unaffected.

CONCLUSION: Findings indicate that broader PCS definitions may mask clinically relevant heterogeneity and support the need for differentiated, phenotype-oriented definitions that reflect clinical presentations of PCS, including differential responses to vaccination. Such refined clinical definitions may facilitate exploration of whether these phenotypes reflect distinct underlying pathophysiological mechanisms.},
}

@article {pmid41840045,
year = {2026},
author = {Boever, J and Jakob, A and Paetzold, C and Gomes, D and Birzele, LT and Baalmann, K and Haas, NA and Nussbaum, C},
title = {Microcirculatory impairment and increased arterial stiffness in pediatric Long COVID patients.},
journal = {European journal of pediatrics},
volume = {185},
number = {4},
pages = {},
pmid = {41840045},
issn = {1432-1076},
mesh = {Humans ; *Microcirculation/physiology ; Female ; *Vascular Stiffness/physiology ; *COVID-19/physiopathology/complications ; Male ; Child ; Adolescent ; SARS-CoV-2 ; Endothelium, Vascular/physiopathology ; Case-Control Studies ; Post-Acute COVID-19 Syndrome ; Cohort Studies ; },
abstract = {PURPOSE: The exact pathogenesis of Long COVID remains unclear. Microvascular and endothelial dysfunction, established contributors to SARS-CoV-2-related conditions, appear to play a role in pediatric Long COVID.

METHODS: At the Children's University Hospital of LMU Munich, we conducted a comparative cohort study including pediatric Long COVID patients. Microcirculation was assessed using sublingual sidestream dark field (SDF) imaging, analyzing the microvascular flow index (MFI), the total vessel density (TVD), and the proportion of perfused vessels (PPV). Endothelial function and arterial stiffness were evaluated using peripheral arterial tonometry (EndoPAT), measuring reactive hyperemia index (RHI) and augmentation index (AIx@75).

RESULTS: We analyzed 37 pediatric Long COVID patients (13.5 ± 2.6 years; 22 females) with persisting symptoms (> 4 weeks) and 46 healthy controls (12.4 ± 4.8 years; 21 females). Patients exhibited significant microcirculatory alterations, with reduced MFI (2.59 [IQR, 2.38-2.75] vs. 2.83 [IQR, 2.69-2.96]; p = .003), TVD (16.12 [IQR, 15.24-17.86] mm/mm2 vs. 19.38 [IQR, 17.58-20.57] mm/mm2; p < .001), and PPV (13.58 [IQR, 12.72-14.89]% vs. 17.67 [IQR, 16.60-19.32]%; p < .001). Microcirculatory changes varied with clinical phenotype and were most pronounced in patients presenting with dyspnea.We analyzed 37 pediatric Long COVID patients (13.5 ± 2.6 years; 22 females) with persisting symptoms (> 4 weeks) and 46 healthy controls (12.4 ± 4.8 years; 21 females). Patients exhibited significant microcirculatory alterations, with reduced MFI (2.59 [IQR, 2.38-2.75] vs. 2.83 [IQR, 2.69-2.96]; p = .003), TVD (16.12 [IQR, 15.24-17.86] mm/mm2 vs. 19.38 [IQR, 17.58-20.57] mm/mm2; p < .001), and PPV (13.58 [IQR, 12.72-14.89]% vs. 17.67 [IQR, 16.60-19.32]%; p < .001). Microcirculatory changes varied with clinical phenotype and were most pronounced in patients presenting with dyspnea.

CONCLUSION: We demonstrate measurable vascular alterations in pediatric Long COVID, including microvessel reduction and increased arterial stiffness. Our findings support a role of vascular changes in Long COVID and highlight the importance of integrating cardiovascular monitoring and follow-up into the management of affected children.

WHAT IS KNOWN: • Microvascular and endothelial dysfunction appear to play a role in SARS-CoV-2-related diseases. • Adults with Long COVID show persistent capillary rarefaction and endothelial impairment supporting a vascular mechanism underlying ongoing symptoms.

WHAT IS NEW: • Pediatric Long COVID is likewise associated with significant microvascular damage and furthermore with increased arterial stiffness. • Children with dyspnea exhibit a distinct vascular phenotype characterized by marked capillary loss, indicating a potential microvascular origin of persistent respiratory symptoms.},
}

Humans
*Microcirculation/physiology
Female
*Vascular Stiffness/physiology
*COVID-19/physiopathology/complications
Male
Child
Adolescent
SARS-CoV-2
Endothelium, Vascular/physiopathology
Case-Control Studies
Post-Acute COVID-19 Syndrome
Cohort Studies

@article {pmid41840047,
year = {2026},
author = {Bonnefoy, PB and Pascal, P and Ceyrat, Q and Burg, S and Razzouk-Cadet, M and Moreau Triby, C and Biancheri Mounicq, I and Bourre, JC and Salaun, PY and Le Roux, PY},
title = {Functional alterations due to post-COVID-19 lung lesions - lessons from a multicenter V/Q SPECT/CT based registry.},
journal = {European journal of nuclear medicine and molecular imaging},
volume = {},
number = {},
pages = {},
pmid = {41840047},
issn = {1619-7089},
}

@article {pmid41840532,
year = {2026},
author = {He, S and Liu, Y and Li, Y and Ji, L and Liu, Y and Yan, J and Zhang, Z and Sun, H and Gao, M and Wu, S},
title = {Immune-inflammatory mediators of frailty and long COVID in older adults: a prospective cohort study.},
journal = {BMC geriatrics},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12877-026-07328-7},
pmid = {41840532},
issn = {1471-2318},
support = {LKZ2023007//Jiangsu Geriatric Health Research Project/ ; BE2023704//Project of Jiangsu Province Science and Technology Plan Special Fund/ ; },
}

@article {pmid41840550,
year = {2026},
author = {Schmidt, L and Feddern, S and Kossow, A and Niessen, J and Grüne, B and Schmidt, N and Haberstock, L and Rost, S and Joisten, C and , },
title = {Severe acute COVID-19 and early long COVID signals in paediatric cohorts: an analysis of real-world data from two health departments, Germany.},
journal = {BMC pediatrics},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12887-026-06724-7},
pmid = {41840550},
issn = {1471-2431},
}

@article {pmid41841761,
year = {2026},
author = {Ward, B and Bindels, LB and Balligand, J-L and Bearzatto, B and Bommer, G and Cani, PD and De Greef, J and Dewulf, JP and Gatto, L and Haufroid, V and Jodogne, S and Kabamba, B and Pyr Dit Ruys, S and Vertommen, D and Yombi, JC and Belkhir, L and Elens, L},
title = {Association of nasopharyngeal Dolosigranulum pigrum and Corynebacterium species with post-acute sequelae of SARS-CoV-2 in a longitudinal cohort.},
journal = {Microbiology spectrum},
volume = {},
number = {},
pages = {e0231325},
doi = {10.1128/spectrum.02313-25},
pmid = {41841761},
issn = {2165-0497},
abstract = {This longitudinal study investigated the differential composition of the nasopharyngeal microbiome in patients presenting different COVID-19 infectious phenotypes and its evolution during convalescence, with a focus on post-acute sequelae of SARS-CoV-2 (PASC) and its potential microbiome-related mechanisms. Microbiota composition was assessed for a cohort of healthy participants (n = 25), influenza patients (n = 24), and patients with moderate (n = 50) and severe (n = 57) COVID-19. Samples were collected at two time points: during the acute infection phase and at approximately 3-month follow-up. From collected nasopharyngeal swab samples, metagenomics using shotgun sequencing was performed and the microbiota composition was analyzed. Alpha and beta diversity analyses revealed no significant differences in overall community diversity between patient groups across visits. However, differential abundance testing identified specific species, such as Dolosigranulum pigrum and various Corynebacterium species, whose profiles correlated with PASC development. Furthermore, the analysis of microbial co-associations identifies commensal species, including D. pigrum and Corynebacterium species, which are less abundant in patients who develop PASC, consistent with a potential protective role suggested by experimental studies but not proven by our observational data. Antibiotic use was associated with lower levels of key protective taxa, which may increase susceptibility to PASC in case of superinfection. These findings highlight the potential importance of the nasopharyngeal microbiome in acute COVID-19 disease outcomes and suggest that preserving or restoring a balanced respiratory microbiome could mitigate the risk of COVID-19 persistent symptoms and PASC development. Our results may set the stage for future clinical interventions involving probiotics or microbial-derived metabolites to promote respiratory health post-COVID-19.IMPORTANCEThis study highlights the importance of bacteria naturally found in the upper respiratory tract, particularly the nasopharynx (the nasopharyngeal microbiome), in shaping how severely COVID-19 affects patients and whether they experience persistent symptoms, also called long-COVID or post-acute sequelae of SARS-CoV-2 (PASC). By examining microbiome samples from healthy people, influenza patients, and individuals with COVID-19 during acute and convalescent phases, we found that certain commensal bacteria, namely, Dolosigranulum pigrum and Corynebacterium species, were less abundant in individuals who developed long-COVID and more abundant in those who fully recovered. We also observed that antibiotic treatment was associated with lower abundances of these commensal taxa, in turn coinciding with a higher frequency of PASC. These findings suggest that the composition of the nasopharyngeal microbiome is associated with recovery trajectories after COVID-19 and motivate future research into treatments aimed toward the microbiome to improve respiratory health following infection.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT05557539.},
}

@article {pmid41835098,
year = {2026},
author = {Dos Santos, LPM and Leão, JV and Silva, KYBM and Dos Santos, DL and Batista, CN and Barros, JA and Paranhos, ACM and Dias, ÁRN and Falcão, LFM},
title = {Transcranial stimulation as a possible therapeutic proposal in long COVID.},
journal = {Frontiers in rehabilitation sciences},
volume = {7},
number = {},
pages = {1766757},
pmid = {41835098},
issn = {2673-6861},
abstract = {The COVID-19 pandemic triggered an unprecedented global health crisis, with significant repercussions on the mental and neurological health of millions of individuals. Long COVID, characterized by persistent and debilitating symptoms, including chronic fatigue, pain, cognitive impairment, and mood swings, represents a substantial therapeutic challenge. In this context, neuromodulation emerges as a promising therapeutic strategy, offering new perspectives for the management of refractory neurological symptoms. This article aims to critically review the current evidence on the use of neuromodulation in patients with long COVID.},
}

@article {pmid41836412,
year = {2026},
author = {Korobova, ZR and Totolian, AA},
title = {Principal component analysis of cytokine signature in COVID-19 and Long COVID.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1717107},
doi = {10.3389/fimmu.2026.1717107},
pmid = {41836412},
issn = {1664-3224},
mesh = {Humans ; *COVID-19/immunology/blood ; *Cytokines/blood/immunology ; *SARS-CoV-2/immunology ; Male ; Middle Aged ; Female ; Principal Component Analysis ; Adult ; Aged ; Biomarkers/blood ; },
abstract = {INTRODUCTION: Despite the activity of the COVID-19 pandemic being lower in the recent years, COVID-associated threat, long COVID (LC). Its clinical presentation includes nearly 200 symptoms affecting cardiovascular, respiratory, nervous systems, endocrine organs, urinary tract, and gastrointestinal systems. Cytokines serve as important biomarkers for assessing the level of immune system involvement and dysregulation in LC. Most studies on cytokine network and cytokine interactions usually address more traditional methods of statistical analysis with comparison criteria, discriminant analysis, regression. But multiplex cytokine analysis includes dozens of parameters, and requires complex assessment of the network as a whole.

METHODS: We analyzed data of cytokine multiplex analysis of 289 patients with COVID-19, 44 patients with LC and 51 healthy donors. PCA we identified cyotkines with the highest importance rate, and further investigated between them with the use of 3D mapping.

RESULTS: Three key clusters were identified: cluster A - IL-13, CCL7/MCP-3, IL-4; cluster B - IL-18, CCL2/MCP-1, CCL4/MIP-1β, CXCL8/IL-8, M-CSF, and cluster C - sCD40L, CXCL1/GROα, PDGF-AA, EGF, FGF-2, FLT-3L, IL-7, IL-17F.

DISCUSSION: The coordinated interactions within these clusters reveal a complex immunopathology behind LC: clsuter A repsresenting local immune responses, cluster B for neuroinflammatory processes, and cluster C for changes in the blood vessels. The results, however, leave an opening for further investigatoin and interpretation.},
}

Humans
*COVID-19/immunology/blood
*Cytokines/blood/immunology
*SARS-CoV-2/immunology
Male
Middle Aged
Female
Principal Component Analysis
Adult
Aged
Biomarkers/blood

@article {pmid41836919,
year = {2026},
author = {Aguzin Parrilli, LJ and Belzunce, MA},
title = {Bias and generalizability of brain age prediction models: A multi-cohort evaluation with anatomical and interpretability insights.},
journal = {Imaging neuroscience (Cambridge, Mass.)},
volume = {4},
number = {},
pages = {},
doi = {10.1162/IMAG.a.1164},
pmid = {41836919},
issn = {2837-6056},
abstract = {Brain age prediction from T1-weighted MRI and its associated brain age gap (BAG) has emerged as a promising neuroimaging biomarker for assessing deviations from normative aging. However, the robustness, bias, and interpretability of existing models across external datasets remain poorly understood, limiting clinical translation. In this study, we evaluated four publicly available brain age models (ENIGMA, DeepBrainNet, Pyment, and BrainAgeNeXt) across four independent MRI datasets (ADNI, UNSAM Long COVID, and two OpenNeuro cohorts), comprising 1,634 subjects with diverse demographic and clinical profiles. Models were tested using their original preprocessing pipelines, and performance was assessed using mean absolute error (MAE), mean error (ME), and BAG variability metrics, with additional analyses of biases related to age, dataset, ethnicity, and education. Interpretability was evaluated using Layer-wise Relevance Propagation, and anatomical correlates were explored using BrainChart-derived centile scores. Group-level comparisons were performed between cognitively normal (CN) individuals and patients with Mild Cognitive Impairment (MCI), Alzheimer's disease (AD), or Long COVID (LC). Models based on 3D convolutional neural networks (Pyment and BrainAgeNeXt) outperformed the DeepBrainNet 2D CNN and the ENIGMA ridge regression model in both accuracy (MAE: 3.9-3.7 vs. 6.2-12.4 years respectively) and stability (ASTD: 3.2-2.9 vs. 4.6-8.3 years). Dataset-specific BAG differences were largely explained by age distributions, whereas ethnicity showed a statistically significant but small effect on BAG in some models. Relevance maps highlighted the lateral ventricles as the most consistently relevant anatomical region, with additional cerebellar contributions emerging in older adults for BrainAgeNeXt. Group-level analyses confirmed elevated BAG in MCI and AD patients compared to CN, while no significant differences were observed in Long COVID participants. These findings suggest that, while BAG is a promising biomarker for group-level analyses, current models are required to address age and demographic biases to enable individual-level clinical application.},
}

@article {pmid41836927,
year = {2026},
author = {Baptista, SN and Atkins, T and Chakraborty, S and Bakhit, M and Glasziou, P and Byambasuren, O},
title = {Candidate treatments for long COVID: a narrative review of expert and patient-driven priorities.},
journal = {Frontiers in medicine},
volume = {13},
number = {},
pages = {1734600},
doi = {10.3389/fmed.2026.1734600},
pmid = {41836927},
issn = {2296-858X},
abstract = {OBJECTIVE: To map the existing evidence for candidate treatments for long COVID that were prioritised by clinicians and people with lived experience, and to characterise their feasibility, acceptability and safety.

STUDY DESIGN: The study was conducted as a narrative review using pragmatic methods including iterative stakeholder-informed decision-making a monthly-updated evidence search, rapid lay evidence summaries and a structured research prioritisation process.

DATA SOURCES: Potential candidate treatments were identified via a combination of database and trial registry searches. These were then ranked by clinicians and people with lived experience using surveys. Evidence summaries for the top 14 interventions (low-dose naltrexone, antivirals, metformin, nicotine, vagus nerve stimulation, antihistamines, guanfacine, colchicine, nattokinase, intravenous immunoglobulins, monoclonal antibodies, coenzyme Q10, multicomponent rehabilitation packages, and exercise training) were created. Prioritised treatments were collated first by searching a collaborative living evidence database (updated monthly) of relevant systematic reviews and randomised controlled trials and then by conducting supplementary searches of other study designs.

DATA SYNTHESIS: Six of 14 interventions had long-COVID-specific randomised controlled trial (RCT) evidence (exercise [16 RCTs], multicomponent packages [5 RCTs], coenzyme Q10 [2 RCTs], antivirals [1 RCT], vagus nerve stimulation [1 pilot RCT], monoclonal antibodies [1 small RCT]); the remainder relied on indirect or very low-certainty data (e.g., uncontrolled studies or mechanistic rationale). Across interventions, evidence certainty was mostly low to very low, and safety/feasibility varied.

CONCLUSION: This review prioritises and maps candidate treatments for long COVID. There was insufficient direct evidence to inform clinical recommendations. Rather, the treatments presented in this review represent those that could be rigorously tested in clinical trials as they show biological plausibility and/or are feasible and acceptable to people with lived experience and clinicians.

REGISTRATION: A review protocol was not prospectively registered because the review adopted an iterative approach to support priority setting rather than clinical guidance.},
}

@article {pmid41830160,
year = {2026},
author = {Cataldo, SA and Horovitz, SG and Margulis, L and Micciulli, A and Sarmiento, F and Monteleone, M and Brocco, M and Belzunce, MA},
title = {Spatial Coefficient of Variation (sCOV) From ASL MRI Reveals Global Cerebrovascular Dysfunction in Long COVID.},
journal = {NMR in biomedicine},
volume = {39},
number = {4},
pages = {e70264},
doi = {10.1002/nbm.70264},
pmid = {41830160},
issn = {1099-1492},
support = {IW-8320273708//International Brain Research Organization/ ; FITBA-B06//Ministerio de la Producción, Ciencia y Tecnología/ ; PICT-PRH-2022-01//Agencia Nacional de Promoción Científica y Tecnológica/ ; },
mesh = {Humans ; Male ; Female ; *COVID-19/physiopathology/diagnostic imaging/complications ; Middle Aged ; *Magnetic Resonance Imaging/methods ; *Cerebrovascular Circulation ; Spin Labels ; *Cerebrovascular Disorders/diagnostic imaging/physiopathology ; Adult ; Aged ; Brain/diagnostic imaging/blood supply ; SARS-CoV-2 ; },
abstract = {Long COVID is increasingly associated with persistent neurological and cognitive symptoms, yet its underlying mechanisms remain unclear. Vascular dysregulation, endothelial dysfunction, and microvascular injury have been proposed as potential contributors. Arterial spin labeling (ASL) MRI allows noninvasive quantification of cerebral blood flow (CBF) and assessment of vascular function. Previous studies have reported hypoperfusion in long COVID patients, but few have accounted for delayed arterial transit time, which can affect ASL quantification. The spatial coefficient of variation (sCOV) has been previously used as a proxy of arterial transit time, providing a noninvasive marker of global cerebrovascular function. We examined 186 adults from an Argentine cohort (145 long COVID and 41 controls), approximately 2 years postinfection. Three-dimensional pulsed ASL data were processed with ExploreASL to quantify CBF and sCOV in gray matter and lobar regions. Group comparisons were performed using multivariate models adjusted for age, sex, and white matter hyperintensity (WMH) volume. Long COVID participants showed significantly higher global gray matter sCOV compared with controls (p = 0.02), with consistent regional trends across the frontal (L: p = 0.05; R: p = 0.07), temporal (L: p = 0.05; R: p = 0.08), parietal (L: p = 0.07; R: p = 0.06), occipital (L: p = 0.08; R: p = 0.05), and insular (L: p = 0.01; R: p = 0.15) lobes after FDR correction. Mean global, lobar, and regional gray matter CBF and WMH volumes did not differ significantly between groups. Increased sCOV, reflecting delayed arterial transit and reduced vascular efficiency, indicates widespread cerebrovascular dysfunction in the absence of perfusion deficits and not associated with white matter hyperintensities. These findings provide evidence of global vascular impairment in long COVID and support sCOV as a sensitive, noninvasive biomarker of cerebrovascular health.},
}

Humans
Male
Female
*COVID-19/physiopathology/diagnostic imaging/complications
Middle Aged
*Magnetic Resonance Imaging/methods
*Cerebrovascular Circulation
Spin Labels
*Cerebrovascular Disorders/diagnostic imaging/physiopathology
Adult
Aged
Brain/diagnostic imaging/blood supply
SARS-CoV-2

@article {pmid41828637,
year = {2026},
author = {Menário, CVB and Silva-Aguiar, RP and Teixeira, DE and Nascimento, GS and Visconti, NRGR and Andrade, LS and Mello, FCQ and Lapa-E-Silva, JR and Rocha, NN and Martins, CM and Cruz, FF and Pinheiro, AAS and Silva, PL and Rocco, PRM and Caruso-Neves, C},
title = {Tubular Damage Biomarkers Are a Useful Tool for Identifying Early Renal Injury in Long COVID.},
journal = {International journal of molecular sciences},
volume = {27},
number = {5},
pages = {},
doi = {10.3390/ijms27052420},
pmid = {41828637},
issn = {1422-0067},
support = {grants 465656/2014-5 (to P.M.R.R. and C.C.-N.), 306433/2022-2 and 444068/2024-4 (to A.A.S.P.), and 309112/2021-4 and 406836/2024-8 (to C.C.-N.)//Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)/ ; grants E-26/210.181/2020 (to P.M.R.R. and C.C.-N.), E-26/203.926/2024 and E-26/210.046/2023 (to C.C.-N.), E-26/200.564/2023 (to A.A.S.P.), and E-26/210.824/2021 (to all authors)//Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)/ ; Finance Code 001 and CAPES/PRINT 88887.508141/2020-00//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)/ ; },
mesh = {Humans ; *COVID-19/complications ; Male ; Female ; *Biomarkers/urine ; Middle Aged ; Glomerular Filtration Rate ; Cross-Sectional Studies ; Aged ; *Acute Kidney Injury/diagnosis/etiology ; Albuminuria ; *Kidney Tubules/pathology/metabolism ; SARS-CoV-2 ; Adult ; },
abstract = {Patients without overt glomerular dysfunction may develop tubular injury, referred to as subclinical acute kidney injury. The burden of COVID-19-related renal damage may therefore be underestimated, as current KDIGO criteria do not include tubular damage biomarkers (TDBs). This study evaluated kidney injury in patients with long COVID by assessing TDBs alongside glomerular biomarkers, proteinuria (UPCr) and albuminuria (UACr). In this cross-sectional study, 75 patients without prior chronic kidney disease were recruited from a long COVID outpatient clinic and stratified according to the time since SARS-CoV-2 infection into 6-, 12-, and 24-month post-COVID-19 groups (referred to as 6-, 12-, and 24-MPC, respectively). Overall, 49.3% of patients had normal estimated glomerular filtration rate (eGFR >90 mL/min/1.73 m[2]), 34.7% showed mildly reduced eGFR (90-60), and 16% exhibited marked eGFR reduction (<60). Among patients with normal eGFR, the combined mean prevalence (mean ± SD) of abnormal TDBs, UACr, and UPCr was 29.7 ± 4.9%, indicating early tubular injury. Temporal analysis revealed a higher prevalence of TDB abnormalities at 6-MPC, whereas glomerular dysfunction was more pronounced at 24-MPC. These findings suggest that renal injury in long COVID is more prevalent than previously recognized and that TDB assessment may improve early detection of kidney damage.},
}

Humans
*COVID-19/complications
Male
Female
*Biomarkers/urine
Middle Aged
Glomerular Filtration Rate
Cross-Sectional Studies
Aged
*Acute Kidney Injury/diagnosis/etiology
Albuminuria
*Kidney Tubules/pathology/metabolism
SARS-CoV-2
Adult

@article {pmid41827411,
year = {2026},
author = {Guzmán-Gurrola, AL and González-López, L and Chávez-Íñiguez, JS and Verduzco Vázquez, M and Flores-Hernández, EI and Novoa-Burquez, JA and Zavala-Cerna, MG},
title = {Sex-Specific Differences in Nutritional Status and Olfaction in Association with Cognitive Impairment Amongst Older Adults with Long COVID Syndrome.},
journal = {Journal of clinical medicine},
volume = {15},
number = {5},
pages = {},
doi = {10.3390/jcm15051994},
pmid = {41827411},
issn = {2077-0383},
abstract = {Background/Objectives: Long COVID has emerged as a significant public health concern, characterized by persistent symptoms following SARS-CoV-2 infection. Cognitive impairment is a common sequela, particularly among older adults (OAs). Although olfactory dysfunction and malnutrition have been previously associated with cognitive decline, it remains elusive to what extent sex-specific variations in these and additional factors will be pivotal to guiding targeted interventions in a sex-specific manner. To fill this gap in knowledge, we undertook a study with the purpose of investigating the contribution of sex-specific risk factors to the development of cognitive impairment (CI) in a cohort of OAs hospitalized with long COVID. Methods: We undertook a cross-sectional study among OAs hospitalized at a geriatric care unit. Olfactory function was assessed using the Sniffin' Stick Test. Cognitive impairment was evaluated by the Mini-Mental State Examination, and nutritional status was assessed with the Mini Nutritional Assessment (MNA). Statistical analyses included linear regression. Results: A total of 45 patients with long COVID were included, of whom 51% were female. The prevalence of CI was lower in men compared to women. In the single variable analysis, nutritional factors were associated with CI only in women; importantly, the loss of olfactory function was associated with CI in the whole group and to CI in women after multivariate analysis. Conclusions: Olfactory dysfunction is a potential biomarker for cognitive impairment in OAs with long COVID in a sex-specific manner. In our study nutritional status and probable obesity could be additional factors associated with CI; nevertheless, this was not confirmed in our multivariate analysis; therefore, this hypothesis would need to be tested in larger studies.},
}

@article {pmid41827401,
year = {2026},
author = {Tremblay, C and Bauer, UMM and Beudt, J and Orwat, S and Diller, GP and Pfitzer, C and Helm, PC},
title = {The Impact of Acute COVID-19 Infection and Long COVID in Patients with Congenital Heart Disease: A Longitudinal Study by the German National Register for Congenital Heart Disease.},
journal = {Journal of clinical medicine},
volume = {15},
number = {5},
pages = {},
doi = {10.3390/jcm15051986},
pmid = {41827401},
issn = {2077-0383},
abstract = {Background: Patients with congenital heart disease (CHD) were considered to belong to a vulnerable group at risk for COVID-19 infection. Our aim was to investigate the severity of acute COVID-19 infection in this patient group as well as the occurrence of sequelae. Methods: We performed telephone interviews with all accessible COVID positive CHD patients from our online COVID-19 patient survey. Baseline information was extracted from our nationwide data bank, with further details from hospital discharge letters. Results: Ninety-nine patients (or parents) were interviewed (male 50.5%): 28 children, 32 young adults (up to 29 years), and 39 adults (30 years and above). Twenty patients had simple, 38 moderate, and 41 complex CHD (10.1% were cyanotic). In twelve patients the CHD was native, ten underwent univentricular palliation, and the rest had corrective cardiac treatment. Thirty patients had additional non-cardiac risk factors. The acute course of COVID-19 was mild in 50, moderate in 38, and severe in three patients, requiring hospitalization. No deaths occurred. Long COVID symptoms (persisting ≥ 12 weeks) were reported by 31 patients. Conclusions: Despite underlying CHD, the severity of the acute course of COVID-19 in our cohort is comparable to that in the general population. Even patients with cyanotic CHD, complex CHD after univentricular palliation, or those with pulmonary hypertension, usually had a mild to moderate course, so that hospitalization was rarely necessary. The percentage of CHD patients reporting Long COVID symptoms (31%) was higher than in the general population. The long-term impact of COVID-19 and Long COVID in CHD patients is unknown and remains to be investigated.},
}

@article {pmid41826684,
year = {2026},
author = {Pérez Chacón, G and Mascaro, S and Estcourt, MJ and Phetsouphanh, C and Nicholson, AE and Snelling, T and Wu, Y},
title = {Developing a general research framework for long COVID using causal modelling.},
journal = {Communications medicine},
volume = {},
number = {},
pages = {},
doi = {10.1038/s43856-026-01488-8},
pmid = {41826684},
issn = {2730-664X},
abstract = {BACKGROUND: Long COVID is an infection-associated chronic condition with uncertain evolution, leading to ambiguity in case definitions and various hypotheses about its pathophysiology. Despite this diversity, causal models may offer a unified understanding of post-acute COVID-19 mechanisms. This study aimed to examine whether dynamic Bayesian networks could facilitate inferences on long COVID.

METHODS: Using a causal engineering approach, we developed directed acyclic graphs and qualitatively parametrised them as Bayesian networks to depict the hypothesised mechanisms of long COVID in a theory-agnostic manner. Based on the literature and expert knowledge, we created a general modelling framework summarising biological pathways from mild or severe COVID-19 to the development of respiratory symptoms and fatigue over four key periods (t1 to t4). We used qualitative parametrisation for design and validation, and tested the framework against four scenarios: A) mild COVID-19 at t1 (start of acute infection); B) severe acute COVID-19 at t1; C) symptoms reported at t1 (acute COVID-19 disease); and D) symptoms reported at t1 and t3 (e.g., 3-to-6 months post-acute infection), indicating long COVID.

RESULTS: Here we show that, in scenario A, the probability of progressing to severe disease and developing persistent organ dysfunction 1-to-2 years post-acute COVID-19 was lower than in scenario C. Those reporting symptoms at t1 and t3 have the highest probability of developing persistent organ dysfunction beyond the acute infection period.

CONCLUSIONS: Our findings lay the foundations for a better understanding of the progression of long COVID syndromes. Illustrative simulations support the use of causal models to help address both diagnostic and prognostic questions in long COVID research.},
}

@article {pmid41826107,
year = {2026},
author = {Ganmaa, D and Cook, KA and Khudyakov, P and Enkhjargal, D and Bilegtsaikhan, T and Mayer, KH and Clar, A and Rueschman, M and Balasubramanian, R and Hazra, A and Sesso, HD and Stone, VE and Copeland, P and Friedenberg, G and Smith, DC and Lei, Q and Lee, T and McDonald, EG and Enkhtsetseg, T and Sumiya, E and Narankhuu, Y and Erdenetuya, M and Tserendagva, D and Landberg, R and Roxhed, N and Lagerström, SR and Manson, JE},
title = {A Randomized Trial of Vitamin D Supplementation and COVID-19 Clinical Outcomes and Long COVID: The Vitamin D for COVID-19 Trial.},
journal = {The Journal of nutrition},
volume = {},
number = {},
pages = {101398},
doi = {10.1016/j.tjnut.2026.101398},
pmid = {41826107},
issn = {1541-6100},
abstract = {BACKGROUND: Data from randomized controlled trials of vitamin D3 supplementation in modifying the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are sparse.

OBJECTIVES: We evaluated the effect of vitamin D3 supplementation on healthcare utilization and other clinical outcomes among adults with coronavirus disease 2019 (COVID-19) and their close contacts.

METHODS: We conducted a parallel 2-group randomized controlled double-blinded trial targeting free-living adults in the United States and Mongolia. Index participants with newly diagnosed COVID-19 were cluster-randomized with up to one of their cohabiting contacts either to an oral vitamin D3 loading dose of 9600 IU/d for 2 d followed by 3200 IU/d for 4 wk or to placebo. Participants completed weekly questionnaires on healthcare utilization, disease severity, and long COVID (index participants) or new SARS-CoV-2 infection (household contacts). The primary outcome was ≥1 healthcare visits (including hospitalization) or death within 4 wk among the index participants.

RESULTS: Index participants (n = 1747) were a median of 38.0 y old (IQR: 31.1-47.0), 65.6% female/other sex, 4.2% Black non-Hispanic, 4.8% Hispanic/Latinx, 43.2% Asian, 44.3% non-Hispanic White, and 44.9% vitamin D deficient or insufficient (25-hydroxyvitamin D3 <20 ng/mL). Baseline characteristics for the household contacts (n = 277) were similar. The 4-wk cumulative incidence of healthcare utilization in index participants did not significantly differ between the vitamin D3 (n = 863) and placebo (n = 884) groups [cumulative incidences, 0.28 compared with 0.29; odds ratio (OR), 0.97; 95% confidence interval (CI): 0.75, 1.24]. Similar nonsignificant results were observed for the prespecified secondary treatment and prevention outcomes, though per-protocol analyses showed a nonsignificant trend toward benefit of vitamin D3 on the prevalence of long COVID at 8 wk (OR, 0.78; 95% CI: 0.59, 1.03). No safety concerns were identified.

CONCLUSIONS: Among adults with newly diagnosed SARS-CoV-2 infections, vitamin D3 supplementation did not significantly change the 4-wk cumulative incidence of healthcare utilization or COVID-19-related outcomes compared with placebo. Promising results for long COVID warrant further study. This study was registered at clinicaltrials.gov as NCT04536298. First registered on 1 September, 2020.},
}

@article {pmid41825703,
year = {2026},
author = {Boniface, ER and Alvergne, A and Darney, BG and Benhar, E and van Lamsweerde, A and Edelman, A},
title = {Menstrual cycle patterns during acute and long COVID-19 infection among a cohort of individuals with regular menstrual cycles.},
journal = {American journal of obstetrics and gynecology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajog.2026.03.001},
pmid = {41825703},
issn = {1097-6868},
}

@article {pmid41825193,
year = {2026},
author = {Costantino, V and Notaras, A and MacIntyre, CR},
title = {Long COVID in children in Australia and the potential impact of vaccination.},
journal = {Vaccine},
volume = {79},
number = {},
pages = {128442},
doi = {10.1016/j.vaccine.2026.128442},
pmid = {41825193},
issn = {1873-2518},
abstract = {Long COVID (LC) or Post-COVID condition (PCC) is a serious illness that can result in chronic conditions in all ages, including children. We used SARS-CoV-2 infection-induced data to find monthly seroprevalence in 6 months to 11 year olds in 2021-2022 to estimate the proportion experiencing PCC. A non-dynamic model using age-specific PCC rates, in accordance with the WHO definition of LC and the National Academies of Sciences, Engineering, and Medicine (NASEM) definition of PCC, was applied to estimate the burden of LC in children during 2021-2023 and to evaluate the impact of vaccination under different coverage and vaccine effectiveness (VE) scenarios. By the end of 2022, seroprevalence was higher among children aged 5-11 years (85.6%) than among those aged 6 months-4 years (77.9%). However, a higher proportion of the youngest age experienced LC (approximately 0.8%), compared with children aged 5-11 year (approximately 0.3%). The low vaccination coverage achieved in the 5-11 age group (40%) averted approximately 9% of infections and reduced LC prevalence by 13% at the end of 2022 under the assumption of no waning VE. If children aged 6 months-4 years age group, who were ineligible for routine vaccination, had been vaccinated at the same uptake level, infections and LC prevalence could have been reduced by approximately 5% and 10%, respectively. Achieving coverage comparable to that of adults aged 70 years and older (94%) would have resulted in substantially larger reductions in infections (∼ 32%-55%) and LC prevalence (∼34%) in both paediatric age groups. However, assuming VE waning 12% per month, the reduction in seroprevalence and LC prevalence are limited to 2-4%, depending on coverage. These findings suggest that vaccination can reduce LC burden in children, which should be considered in vaccine policy.},
}

@article {pmid41824763,
year = {2026},
author = {Bachelet, VC and Jiménez-Paneque, R and Gomolán, P and Silva-Ayarza, I and López Nitsche, M and Andrades, CO and Carroza, B and Morgado, B},
title = {Validation of the cultural adaptation of the "Long Coronavirus Disease (COVID) Symptom and Impact Tools" for the Chilean population.},
journal = {Medwave},
volume = {26},
number = {2},
pages = {e3205},
doi = {10.5867/medwave.2026.02.3205},
pmid = {41824763},
issn = {0717-6384},
mesh = {Humans ; Chile ; *COVID-19/diagnosis/physiopathology/complications ; Reproducibility of Results ; Male ; Female ; Middle Aged ; Adult ; Translations ; Aged ; Surveys and Questionnaires ; Post-Acute COVID-19 Syndrome ; },
abstract = {INTRODUCTION: The Long Coronavirus Disease (COVID) Symptom and Impact Tools (ST and IT) are self-administered instruments designed to monitor symptoms and the impact of long COVID. We translated and culturally adapted these tools for use in Chile. This study evaluated internal consistency and test-retest reliability for the IT, described reported symptoms with the ST, and explored changes over time.

METHODS: The first phase, previously published, involved translation and cultural adaptation. The second phase included 28 patients with persistent COVID-19 symptoms; 20 completed a second assessment. The IT assesses impact using six items, each scored 0-10 (total 0-60). The ST lists 53 symptoms across ten categories. Internal consistency of the IT was assessed using Cronbach's alpha and item-consistency indicators. Test-retest reliability was evaluated using the intraclass correlation coefficient (ICC, 95% CI) and a Bland-Altman analysis. ST responses were summarized with absolute and relative frequencies and confidence intervals.

RESULTS: The IT showed excellent internal consistency (Cronbach's alpha 0.945; 95% CI 0.906-0.971). Test-retest reliability was acceptable (ICC 0.72; 95% CI 0.43-0.88), with minimal bias in the Bland-Altman plot. General, neurological, thoracic, and ear-nose-throat symptoms were the most frequent. Participants reported a mean of 19 symptoms, with no significant differences between visits.

CONCLUSIONS: The adapted tools demonstrated acceptable psychometric properties and appear suitable for use in Chile. Symptom reporting was extensive, underscoring the need for larger studies to confirm these findings.},
}

Humans
Chile
*COVID-19/diagnosis/physiopathology/complications
Reproducibility of Results
Male
Female
Middle Aged
Adult
Translations
Aged
Surveys and Questionnaires
Post-Acute COVID-19 Syndrome

@article {pmid41824149,
year = {2026},
author = {M van der Feltz-Cornelis, C},
title = {Cognition and Long COVID: a Review.},
journal = {Current neurology and neuroscience reports},
volume = {26},
number = {1},
pages = {},
pmid = {41824149},
issn = {1534-6293},
}

@article {pmid41823222,
year = {2026},
author = {Shapira, S and Vishnevsky, G and Yaakobi, H and Shenberg, G and Motlaq, M and Liberman, E and Kalisky, A and Benari, G and Tsiodras, S and Adi, N and Lötvall, J and Arber, N},
title = {Reduced Mortality in COVID-19 Patients Treated With Inhaled Extracellular Vesicles Expressing CD24.},
journal = {Journal of extracellular vesicles},
volume = {15},
number = {3},
pages = {e70253},
doi = {10.1002/jev2.70253},
pmid = {41823222},
issn = {2001-3078},
support = {74260//Israel Innovation Authority/ ; },
mesh = {Humans ; Male ; Female ; *Extracellular Vesicles/metabolism ; *COVID-19/mortality/therapy ; Middle Aged ; Retrospective Studies ; *CD24 Antigen/administration & dosage/therapeutic use/metabolism ; Aged ; Administration, Inhalation ; SARS-CoV-2 ; Quality of Life ; *COVID-19 Drug Treatment ; },
abstract = {BACKGROUND: Severe COVID-19, and other systemic infections, can trigger hyperinflammation leading to lung injury. EXO-CD24, an inhaled extracellular vesicle therapy with anti-inflammatory properties, has shown acute clinical benefit, but long-term effects on survival remain unknown.

METHODS: We compared the mortality in 35 patients with moderate-to-severe COVID-19 treated with inhaled EXO-CD24 on five consecutive days in 2020, versus 105 matched controls receiving standard care (1:3 ratio). This 'real life' study was a retrospective follow-up extended to 4.6 years after infection, evaluating all-cause mortality as well as health-related quality of life in survivors (HRQoL).

RESULTS: No deaths occurred in the EXO-CD24 group (0/35) versus 14 deaths (13.3%) among the matched controls (p < 0.05). The survival difference was most marked in the first month but persisted over time. At the end of the follow-up, theEXO-CD24 patients reported significantly better HRQoL, including well-being, physical function, and mobility.

CONCLUSIONS: Repeated inhalations with EXO-CD24 is associated with improved survival and HRQoL up to 4.6 years post-treatment. These findings suggest durable benefits and support further evaluation of EXO-CD24 as an immunomodulatory therapy in severe inflammatory conditions.

TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04657497.},
}

Humans
Male
Female
*Extracellular Vesicles/metabolism
*COVID-19/mortality/therapy
Middle Aged
Retrospective Studies
*CD24 Antigen/administration & dosage/therapeutic use/metabolism
Aged
Administration, Inhalation
SARS-CoV-2
Quality of Life
*COVID-19 Drug Treatment

@article {pmid41822694,
year = {2026},
author = {Butzin-Dozier, Z and Kumar, M and Ji, Y and Wang, LC and Anzalone, AJ and Hurwitz, E and Patel, RC and Wong, R and Bramante, C and Sines, B},
title = {IL-6 Receptor Antagonists and Severe Post-COVID-19 Outcomes: An Emulated Target Trial.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.02.27.26347274},
pmid = {41822694},
abstract = {BACKGROUND: Interleukin-6 (IL-6) is a cytokine that plays a key role in systemic hyperinflammation and may mediate the relationship between acute COVID-19 and severe long-term outcomes such as Long COVID or death. IL-6 modulating drugs may reduce patients' risk of severe post-COVID-19 outcomes.

METHODS: We conducted an emulated target trial in a retrospective cohort of patients with moderate-to-severe rheumatoid arthritis who were prescribed IL-6 receptor antagonists (sarilumab or tocilizumab, pooled treatment) or other biologic agents (anakinra or baricitinib, pooled comparator) in 2022. We compared the 12-month cumulative incidence of mortality and Long COVID (diagnosed and probable) between groups using Super Learner and targeted maximum likelihood estimation, adjusting for covariates of interest.

RESULTS: In our cohort of 3,553 patients, we found that prescription of IL-6 receptor antagonists was associated with a lower 12-month cumulative mortality (adjusted relative risk (aRR) 0.40, 95% CI 0.27, 0.59), diagnosed Long COVID aRR 0.42, 95% CI 0.23, 0.78), and probable Long COVID (aRR 0.71, 95% CI 0.61, 0.83), compared to prescription of other biologic agents, among rheumatoid arthritis patients.

CONCLUSIONS: IL-6 receptor antagonists may prevent the incidence of severe post-COVID-19 outcomes, such as Long COVID or mortality. This supports the hypothesis that IL-6 may be a mechanistic biomarker of COVID-19 sequelae and that acute COVID-19 severity may mediate this relationship.},
}

@article {pmid41822518,
year = {2026},
author = {Shahbaz, S and Bozorgmehr, N and Rahmati, A and Abouda, A and Syed, H and Osman, M and Elahi, S},
title = {Single-cell analysis reveals immune remodeling of monocytes, NK cells, T cell exhaustion, and Galectin-9-associated depletion of gamma delta and mucosal-associated invariant T cells in Long COVID with ME/CFS.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1745933},
pmid = {41822518},
issn = {1664-3224},
mesh = {Humans ; *Killer Cells, Natural/immunology ; *COVID-19/immunology/complications ; Female ; Single-Cell Analysis ; *Mucosal-Associated Invariant T Cells/immunology ; *Monocytes/immunology ; *SARS-CoV-2/immunology ; *Galectins/immunology/metabolism ; Middle Aged ; Adult ; Receptors, Antigen, T-Cell, gamma-delta/immunology/metabolism ; T-Cell Exhaustion ; },
abstract = {INTRODUCTION: The cellular mechanisms underlying Long COVID (LC) associated with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) remain poorly understood.

METHODS: We performed single-cell RNA sequencing (scRNA-seq) on peripheral blood mononuclear cells collected 12 months after acute COVID-19 infection from female individuals with LC-ME/CFS and recovered (R) individuals. Comparative analysis was also performed using publicly available scRNA-seq datasets from idiopathic ME/CFS patients.

RESULTS: Based on transcriptional signatures, LC-ME/CFS patients exhibited a marked reduction in naïve CD4[+] and CD8[+] T cells, regulatory T cells, MAIT cells, and γδ T cells, accompanied by an expansion of effector T cells. NK cells displayed reduced frequency and altered activation-associated transcriptional factors, consistent with impaired cytotoxic potentials. B cells in LC patients exhibited gene expression profiles indicative of heightened activation, while plasma cells revealed a distinct transcriptional subset expressing NK-associated genes. Platelets and low-density neutrophils were expanded and exhibited enrichment of activated-related transcripts. Monocyte subsets demonstrated transcriptional skewing characterized by reduced expression of phagocytosis-associated genes and increased expression of pro-inflammatory cytokine-related genes/pathways. In contrast, idiopathic ME/CFS patients exhibited less pronounced immune alterations at the transcriptional level: while T cell activation was evident, there was no reduction in MAIT or NK cells, nor signs of T cell exhaustion. Notably, FOXP3 expression was upregulated, and B cells and platelets demonstrated dysregulated signatures in idiopathic ME/CFS. Mechanistically, we identify Galectin-9-TIM-3 interaction as a potential pathway driving γδ and MAIT cell depletion in LC.

CONCLUSION: Our results reveal extensive peripheral immune remodeling in LC-ME/CFS, distinct from idiopathic ME/CFS, and support a model of chronic immune activation and dysregulation. Our findings offer a cellular framework for understanding LC pathogenesis and point to potential biomarkers and therapeutic targets for intervention.},
}

Humans
*Killer Cells, Natural/immunology
*COVID-19/immunology/complications
Female
Single-Cell Analysis
*Mucosal-Associated Invariant T Cells/immunology
*Monocytes/immunology
*SARS-CoV-2/immunology
*Galectins/immunology/metabolism
Middle Aged
Adult
Receptors, Antigen, T-Cell, gamma-delta/immunology/metabolism
T-Cell Exhaustion

@article {pmid41822471,
year = {2026},
author = {Currey, J and Wang, C and Mayer, MG and Chen, Y and Nisperuza Vidal, AK and Allen, MJ and Khatun, MS and Ellsworth, CR and Islamuddin, M and Evangelista, J and Minor, SM and Golden, N and Zwezdaryk, KJ and Maness, NJ and Blair, RV and Kolls, JK and Pociask, DA and Fischer, T and Qin, X},
title = {Characterization of subchronic lung and brain consequences caused by mouse-adapted SARS-CoV-2 and influenza A infection of C57BL6 mice.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1755141},
pmid = {41822471},
issn = {1664-3224},
mesh = {Animals ; Mice ; *SARS-CoV-2/physiology ; Mice, Inbred C57BL ; *Lung/pathology/virology/immunology/metabolism ; *COVID-19/pathology/immunology/virology ; *Brain/virology/pathology/immunology/metabolism ; *Influenza A virus/physiology ; *Orthomyxoviridae Infections/pathology/immunology/virology ; Disease Models, Animal ; Female ; },
abstract = {INTRODUCTION: SARS-CoV-2 and, to a lesser extent, influenza A can lead to long-term complications in the respiratory and nervous systems. However, the mechanisms driving post-viral sequelae remain poorly understood.

METHODS: To address this gap, we longitudinally characterized C57BL/6 mice infected with sublethal doses of mouse-adapted SARS-CoV-2 (MA30) or influenza A (PR8). Lung and brain tissues were analyzed at 14-, 21-, and 28-days post-infection (DPI) using histological analysis and bulk-RNA sequencing.

RESULTS: In the lungs, both infections caused prolonged inflammation and fibrosis. MA30-infected lungs showed persistent upregulation of inflammation, coagulation, complement, as well as fibrotic, and extracellular matrix (ECM) remodeling pathways at 21 DPI, alongside downregulation of epithelial junction and metabolic program pathways. In contrast, PR8-infected lungs exhibited a strong acute interferon response and chronic upregulation of basal epithelial markers (e.g., Krt5, Krt14), consistent with epithelial regeneration. Notably, only PR8-infected mice displayed KRT5+ progenitor cell migration into damaged lung regions, indicating divergence in repair mechanisms. Neither MA30-infected, nor PR8-infected mice had detectable brain infection. However, MA30 mice, but not PR8-infected mice exhibited an elevated frequency of microhemorrhages at early timepoints and marked neuroinflammation at all timepoints. Transcriptomic profiling of MA30-infected brains showed enrichment for up-regulation of ECM remodeling, vascular dysfunction, IL6-signaling pathways along with a virus-specific disruption of the hypothalamic-pituitary axis with MA30 infection not seen in PR8-infected brains. These included genes linked to neuroinflammation, sensory processing disruption, and microvascular injury, mirroring clinical features of Long COVID.

DISCUSSION: Together, these findings establish distinct tissue-specific trajectories of long-term pathology following SARS-CoV-2 and influenza infection and provide a foundation for dissecting the mechanisms of post-viral lung and brain disease.},
}

Animals
Mice
*SARS-CoV-2/physiology
Mice, Inbred C57BL
*Lung/pathology/virology/immunology/metabolism
*COVID-19/pathology/immunology/virology
*Brain/virology/pathology/immunology/metabolism
*Influenza A virus/physiology
*Orthomyxoviridae Infections/pathology/immunology/virology
Disease Models, Animal
Female

@article {pmid41820938,
year = {2026},
author = {Zhang, Z and Xue, Y and Gao, L and Guan, L and Zhang, H and Ma, H and Li, X and Li, J and Yang, H and Tong, Z},
title = {Associated factors and predictive nomogram of long COVID: a cross-sectional study in China.},
journal = {BMC pulmonary medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12890-026-04221-2},
pmid = {41820938},
issn = {1471-2466},
support = {2023YFC0872500//Ministry of Science and Technology of the People's Republic of China/ ; BJRID2024-008//Beijing Research Center for Respiratory Infectious Diseases Projec/ ; 062//Beijing Scholars Program/ ; },
}

@article {pmid41820731,
year = {2026},
author = {Su, H and Keller, B and Danesh, V and McPeake, J and Boehm, LM and Eaton, TL and Mart, MF and Patel, MB and Ely, EW},
title = {Long COVID and the Challenge of Long-Term Employment: An Ecological, Sequential Explanatory Mixed-Methods Approach.},
journal = {Journal of occupational rehabilitation},
volume = {},
number = {},
pages = {},
pmid = {41820731},
issn = {1573-3688},
abstract = {PURPOSE: To identify and contextualize the determinants of long-term employment, health, and financial outcomes among individuals affected by Long COVID.

METHODS: Sequential explanatory mixed-methods study design guided by the social-ecological model. Adults with Long COVID who were employed before infection and returned to work during the three-year follow-up were recruited through in-person and virtual outpatient venues: ResearchMatch, a Long COVID clinic, and a peer support group affiliated with a medical center. Participants completed validated surveys assessing factors influencing sustained employment. Stratified semi-structured interviews were then conducted to explore how these factors shaped sustained employment. Quantitative data were analyzed using descriptive and inferential statistical methods, while qualitative data were analyzed through content analysis.

RESULTS: Among 79 participants who returned to work, 58% (n = 46) remained employed after a mean follow-up of 1,077 days. Those still employed reported reduced capacity and persistent uncertainty. Those no longer employed experienced worse physical health (p < 0.002), greater comorbidity burden (p = 0.01), more environmental barriers (p = 0.02), and increased financial hardship (p = 0.03). Qualitative analyses identified nonlinear return-to-work trajectories shaped by fluctuating and often invisible symptoms, alongside multilevel themes influencing employment sustainability, including misalignment between functional capacity and job demands, challenges obtaining workplace accommodations, stigma, limited policies, and labor market barriers.

CONCLUSIONS: Employment sustainability among individuals with Long COVID is shaped by complex, multilevel barriers, with job loss further worsening health and financial hardship. Investment in comprehensive Long COVID care, including multidisciplinary clinical services, vocational rehabilitation, clinician education, public awareness initiatives, employer training, and policy reform, is critical to support long-term recovery and employment sustainability.},
}

@article {pmid41819071,
year = {2026},
author = {He, K and Simmonds, AJ},
title = {Gut check: Peroxisomes as a missing link in long COVID intestinal repair.},
journal = {Developmental cell},
volume = {61},
number = {3},
pages = {466-467},
doi = {10.1016/j.devcel.2026.02.011},
pmid = {41819071},
issn = {1878-1551},
mesh = {*Peroxisomes/metabolism ; Humans ; Animals ; *COVID-19/virology/pathology/metabolism ; *SARS-CoV-2 ; *Intestines/virology/pathology ; Signal Transduction ; },
abstract = {Long COVID is often associated with persistent gastrointestinal dysfunction. In this issue of Developmental Cell, Wang et al. reveal that intestinal SARS-CoV-2 reservoirs disrupt VLCFA-mediated peroxisome signaling needed for epithelial repair. Patient studies, combined with Drosophila and mammalian models, identify an underlying mechanism and FDA-approved peroxisome activators as potential therapeutics.},
}

*Peroxisomes/metabolism
Humans
Animals
*COVID-19/virology/pathology/metabolism
*SARS-CoV-2
*Intestines/virology/pathology
Signal Transduction

@article {pmid41816409,
year = {2026},
author = {Chai, X and Qi, H and Liu, X and Zhou, F and Jiang, Y and Wu, M and Lian, S and Wang, L and Bao, Y},
title = {A narrative review of SARS-CoV-2 variants and long COVID.},
journal = {Journal of thoracic disease},
volume = {18},
number = {2},
pages = {164},
pmid = {41816409},
issn = {2072-1439},
abstract = {BACKGROUND AND OBJECTIVE: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since the onset of the pandemic, there has been a continuous rise in cases of both COVID-19 and long COVID. It is acknowledged that long COVID is a multisystem disorder with a wide range of symptoms; its primary symptoms and indicators include fatigue, dyspnea, anosmia, myalgia, cough, and hyposmia. SARS-CoV-2 has continuously evolved since the wild strain first appeared, resulting in numerous genetic variants. These strains exhibit significant differences in terms of pathogenicity and immune evasion. Key scientific questions remain regarding whether and how these variations influence the development and clinical course of long COVID. This review aims to examine associations between SARS-CoV-2 strains and long COVID, synthesize current evidence, identify research gaps, and provide recommendations for subsequent rehabilitation treatments.

METHODS: Literature searches were conducted using PubMed, focusing on publications from January 2020 to August 2025. Relevant literature on long COVID and SARS-CoV-2 variants was systematically reviewed and summarized, and included in this review.

KEY CONTENT AND FINDINGS: This review highlights the ongoing genetic evolution of SARS-CoV-2 as a key temporal dynamic during the pandemic. Different SARS-CoV-2 variants result in varying severity of long COVID. Anti-inflammatory treatments demonstrate significant efficacy for long COVID patients. COVID-19 vaccination prior to SARS-CoV-2 infection reduces the risk of long COVID, and another successful treatment option for persistent COVID symptoms is physical therapy.

CONCLUSIONS: Long COVID remains a significant public health challenge. The relationship between SARS-CoV-2 variants and long COVID requires further elucidation. This condition may cause significant economic and medical burdens in the future. To completely protect the physical and mental health of long COVID patients, it is essential to broaden therapeutic options and create individualized therapy programs. Therefore, understanding the connection between long COVID and SARS-CoV-2 variants is crucial. Based on this knowledge, effective strategies must be designed to empower individuals in proactively addressing and managing long COVID.},
}

@article {pmid41816007,
year = {2026},
author = {Park, J and Hwang, W and Lee, S and Lee, HC and MacMahon, M and Zilbauer, M and Han, N},
title = {Advancing understanding of long COVID pathophysiology through quantum walk-based network analysis.},
journal = {Bioinformatics advances},
volume = {6},
number = {1},
pages = {vbag050},
pmid = {41816007},
issn = {2635-0041},
abstract = {MOTIVATION: Long COVID is a multisystem condition characterized by persistent symptoms such as fatigue, cognitive impairment, and systemic inflammation following COVID-19 infection. However, its mechanisms remain poorly understood. In this study, we applied the quantum walk, a computational approach leveraging quantum interference, to explore large-scale SARS-CoV-2-induced protein networks.

RESULT: Compared to the conventional random walk with restart method, the quantum walk demonstrated superior capacity to traverse deeper regions of the network, uncovering proteins and pathways implicated in Long COVID. Key findings include mitochondrial dysfunction, thromboinflammatory responses, and neuronal inflammation as central mechanisms. Quantum walk uniquely identified the CDGSH iron-sulfur domain-containing protein family and VDAC1, a mitochondrial calcium transporter, as critical regulators of these processes. VDAC1 emerged as a potential biomarker and therapeutic target, supported by FDA-approved compounds such as cannabidiol. These findings highlight quantum walk as a powerful tool for elucidating complex biological systems and identifying novel therapeutic targets for conditions like Long COVID.

The code and input data that were used for this study are available at https://github.com/Namshik-Han-Lab/QuantumWalk-LongCovid.},
}

@article {pmid41814585,
year = {2026},
author = {Caliman-Sturdza, OA and Gheorghita, R and Lobiuc, A and Filip, R and Soldanescu, I and Mangul, S and Dimian, M},
title = {Management of long COVID-19 in children and adolescents: from diagnosis to therapeutically approaches.},
journal = {Annals of medicine},
volume = {58},
number = {1},
pages = {2642510},
doi = {10.1080/07853890.2026.2642510},
pmid = {41814585},
issn = {1365-2060},
mesh = {Humans ; *COVID-19/therapy/complications/diagnosis ; Child ; Adolescent ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; },
abstract = {INTRODUCTION: Long Coronavirus disease 2019 (COVID-19), also termed post-acute sequelae of severe acute respiratory syndrome coronavirus 2 infection (PASC), has emerged as a complex multisystem condition in children and adolescents worldwide. It can occur even after mild or asymptomatic acute infections, with symptoms that may persist, fluctuate, or relapse over time. This review aims to comprehensively explore the characteristic manifestations, management and current therapeutic possibilities of pediatric Long COVID-19 (L-C19).

METHODS: A systematic search was conducted in multiple databases such as PubMed, Scopus, Web of Science, and Google Scholar, for literature published between January 2020 and October 2025.

RESULTS: Diagnosing pediatric L-C19 is challenging due to the heterogeneity of symptoms and lack of specific diagnostic biomarkers. Most young patients experience gradual improvement over months, but a significant subset remains symptomatic for >1 year with substantial disability, underscoring the need for timely diagnosis and intervention. Current clinical consensus emphasizes an individualized, multidisciplinary management approach focused on symptom relief and functional rehabilitation. No definitive cure exists for L-C19; thus, care is tailored to each patient's predominant issues. Therapeutic strategies combine supportive self-management (e.g. energy conservation and pacing) with both non-pharmacological and pharmacological interventions. Multimodal rehabilitation programs - including graded exercise therapy and cognitive behavioral therapy - have shown promise in improving fatigue, mental health, and overall quality of life. Targeted treatments for specific sequelae (such as autonomic dysfunction or chronic pain) are applied on a case-by-case basis, although high-quality evidence for medications remains limited. Globally, interdisciplinary collaborations have been established to provide harmonized diagnostic and treatment protocols, and major research initiatives are underway to evaluate novel therapies and include children in L-C19 clinical trials.

CONCLUSION: Ongoing international efforts to develop standardized diagnostic tools, outcome measures, and evidence-based interventions are crucial to optimize care and long-term outcomes for children and adolescents affected by L-C19.},
}

Humans
*COVID-19/therapy/complications/diagnosis
Child
Adolescent
SARS-CoV-2
Post-Acute COVID-19 Syndrome

@article {pmid41814565,
year = {2026},
author = {Clarke, Z and Cowan, H and Rhodes, T and Fernes, P and Haines, A and Leal, L},
title = {Vital yet Fragile: Informal Networks of Support Among Young People Navigating Long Covid.},
journal = {Health expectations : an international journal of public participation in health care and health policy},
volume = {29},
number = {2},
pages = {e70611},
doi = {10.1111/hex.70611},
pmid = {41814565},
issn = {1369-7625},
support = {13515//National Institute for Health and Social Care Research/ ; },
mesh = {Humans ; *COVID-19/psychology ; Adolescent ; Female ; Male ; Young Adult ; Qualitative Research ; *Social Support ; Adult ; United Kingdom ; Interviews as Topic ; SARS-CoV-2 ; Health Services Accessibility ; },
abstract = {INTRODUCTION: Young people living with Long Covid face challenges accessing health care and social support. Previous qualitative research in the UK has described the 'invalidation' of Long Covid illness experience. It has been said that there is a 'double invisibility' produced by narratives that minimise the effects of Covid-19 among young people, which combine with a generalised lack of awareness of Long Covid itself. In this analysis, we look beyond the well-documented networks of online self-help and advocacy to trace how young people navigate, connect and maintain multi-sited alternative care networks to manage their everyday experiences of Long Covid.

METHODS: We draw on the analysis of qualitative interviews with 54 young people aged 15-25 with long-term health impacts from Covid-19, of whom 30 also participated in follow-up interviews. The sample includes young people with multiple genders, who identify with a range of ethnic identities, and who have experience of neurodiversity or additional disabilities. Interview transcripts were analysed to identify key themes, in collaboration with a group of peer researchers who are co-authors on this study.

RESULTS: We find that the informal networks that are navigated and created by young people play a vital role, but that they are also fragile. We present our findings across four themes-how informal networks afford young people validation in different ways; the material differences informal networks bring to young people's lives; the work that young people do to build and maintain these networks; and the fragility of support networks. We show that informal networks are not simply identified and found, but that they are 'made to work' by young people who do the work that brings informal networks together and that holds them in place.

CONCLUSION: We conclude that there is a need to strengthen the vital work of informal care that is done by young people, but that alternative care networks should not be seen simply as a means of 'filling the gaps' of inadequate care. There is a need to build infrastructures that properly integrate formal with informal care in direct response to young people's experiences of Long Covid.

This qualitative study was undertaken in close collaboration with community partners and co-produced with young people affected by Long Covid, using participatory methods. Young people affected by Long Covid were involved in a series of consultations, workshops and meetings focused on the analysis of data and their development into project outputs, including as authors of this paper.},
}

Humans
*COVID-19/psychology
Adolescent
Female
Male
Young Adult
Qualitative Research
*Social Support
Adult
United Kingdom
Interviews as Topic
SARS-CoV-2
Health Services Accessibility

@article {pmid41813046,
year = {2026},
author = {Njøten, KL and Magnussen, LH and Haugstvedt, A and Jürgensen, M and Kvale, G and Frisk, B},
title = {Exploring experiences following participation in a concentrated micro-choice-based rehabilitation programme for long covid: a focus group study.},
journal = {BMJ open},
volume = {16},
number = {3},
pages = {e105215},
doi = {10.1136/bmjopen-2025-105215},
pmid = {41813046},
issn = {2044-6055},
abstract = {OBJECTIVES: To explore how individuals with long covid experienced various aspects of a micro-choice-based rehabilitation programme and if these experiences could facilitate behaviour change.

DESIGN: A qualitative study with three focus groups was conducted, in mean 9.8 months after completing the rehabilitation programme. Data were analysed using systematic text condensation.

SETTING: The study was conducted in a university setting.

PARTICIPANTS: 19 participants (aged 23-55 years, 15 women) were included between Spring 2021 and Autumn 2022.

INTERVENTION: The participants in this study had participated in a 3-day concentrated micro-choice-based rehabilitation programme. One of the main features of this intervention was to support participants in shifting their focus from targeting symptoms to choosing alternative actions aimed at improving everyday functioning, referred to as micro-choices.

RESULTS: Five themes were identified: (1) reduction in uncertainty achieved through reassurance and motivation; (2) 'in the same boat': sharing experiences and supporting each other; (3) knowledge about the body's stress responses and micro-choices; (4) shifting between individual practice and close collaboration with the therapists; and (5) sustaining behaviour change is challenging. These themes illustrated how participants' experiences with different aspects of the rehabilitation programme facilitated both the initiation and maintenance of behaviour change. The participants highlighted the importance of acknowledging their challenges, reducing fear, sharing experiences with peers, feeling understood and supported, collaborating with a skilled team, receiving personalised guidance and gaining insights through the exploration and implementation of micro-choices. Participants also highlighted that behaviour change is an ongoing process requiring sustained effort.

CONCLUSION: The findings showed how participants experienced various aspects of a concentrated micro-choice-based rehabilitation programme as supportive of behaviour change. The findings indicate that a concentrated rehabilitation programme may facilitate self-management and improve everyday function in individuals with long covid.

TRIAL REGISTRATION NUMBER: NCT05234281.},
}

@article {pmid41812698,
year = {2026},
author = {Naghibosadat, M and Hahn, E and Molinaro, S and Babuadze, G and Kozak, R},
title = {Comparison of SARS-CoV-2 Variant Pathogenicity in a Long-COVID Syrian Hamster Model.},
journal = {Virus research},
volume = {},
number = {},
pages = {199711},
doi = {10.1016/j.virusres.2026.199711},
pmid = {41812698},
issn = {1872-7492},
abstract = {The SARS-CoV-2 pandemic has infected over 700 million people, and a substantial proportion develop post-acute sequelae of COVID-19, a disorder marked by persistent, multi-organ symptoms. Elucidating the underlying pathophysiology; and how it varies by viral lineage; is critical for guiding therapy. Syrian golden hamsters develop transient but non-lethal illness that parallels human disease and are therefore a model to investigate post-acute phase pathology with different viral variants. Hamsterswere infection with WT (B1), Alpha (B.1.1.7) or Beta (B.1.351) variants and monitored for 28 days for clinical signs and viral shedding. Lungs, nasal turbinates, heart, kidneys and spleen were collected at 14- and 28-days post-infection for quantitative histopathological analysis. All viral variants produced similar acute disease, with peak viral loads on day 3 and maximal weight loss on day 7. Inflammation and fibrosis were evident in every infected group. Notably, WT and Alpha variants caused greater lung, cardiac, and renal fibrosis than the Beta variant, while splenic germinal-center expansion was most pronounced in animals infected with the Alpha variant. These findings establish that SARS-CoV-2 leaves variant-dependent post-acute multi-organ damage in hamsters, with WT and Alpha inducing the most severe pathology. This model captures variant-dependent post-acute organ injury and provides a quantitative framework for evaluating anti-fibrotic interventions.},
}

@article {pmid41810370,
year = {2026},
author = {Azhir, A and Cheng, J and Tian, J and Bassett, IV and Patel, CJ and Klann, JG and Murphy, SN and Estiri, H},
title = {The age paradox in post-infectious sequelae: physiological reserve outweighs chronological age in Long COVID susceptibility.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.02.24.26346989},
pmid = {41810370},
abstract = {BACKGROUND: Older age is widely considered a risk factor for post-acute sequelae of SARS-CoV-2 infection (PASC), typically attributed to immunosenescence and inflammaging. However, whether this association reflects intrinsic biological ageing or accumulated comorbidity burden remains unclear, with implications for clinical risk stratification.

METHODS: We conducted a retrospective cohort study using the Precision PASC Research Cohort (P2RC) from Mass General Brigham, comprising 133,792 COVID-19 patients from 12 hospitals and 20 community health centres in Massachusetts (March 2020-May 2024). PASC was ascertained using a validated computational phenotyping algorithm. We used generalised estimating equations with cluster-robust variance to model PASC risk, causal mediation analysis to decompose age effects through comorbidity burden and acute severity, and specification curve analysis across 768 analytical specifications to assess robustness.

FINDINGS: After adjustment for comorbidity burden, each decade of age was associated with 6% lower odds of PASC (OR 0.94; 95% CI 0.93-0.95). Causal mediation analysis revealed that comorbidities accounted for 145% of the total age effect, indicating inconsistent mediation wherein age's direct protective effect was masked by its indirect harm through chronic disease accumulation. This protection was age-dependent: adults younger than 65 years retained robust resilience independent of comorbidities (ADE:-0.0042, p<0.001), whereas adults 65 years and older showed complete loss of this protection (ADE: +0.0020, p=0.14).

INTERPRETATION: Long COVID susceptibility is driven by physiological reserve rather than chronological age until approximately age 65, beyond which age-related protective mechanisms become exhausted. Risk stratification should prioritise comorbidity burden over birth year in younger adults.

FUNDING: National Institute of Allergy and Infectious Diseases (NIAID).},
}

@article {pmid41809272,
year = {2026},
author = {Zarkadi, A and Katotomichelakis, M and Chaidas, K},
title = {Long-Term Olfactory Dysfunction in COVID-19 Patients: A Systematic Review.},
journal = {Cureus},
volume = {18},
number = {2},
pages = {e103143},
pmid = {41809272},
issn = {2168-8184},
abstract = {Olfactory dysfunction (OD) emerged early in the COVID-19 pandemic as a prevalent and often persistent symptom. While most individuals recover within weeks, a significant proportion continue to suffer from long-term impairments, including both quantitative and qualitative sensory deficits. Our review aimed to summarize current evidence on long-term post-COVID-19 OD with a duration of at least three months, including prevalence, recovery trajectory, and prognostic factors. The PubMed and Scopus databases were searched for relevant studies up to August 2024 following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Twenty-one studies were ultimately included, involving over 4,000 individuals. A remarkable proportion of patients continue to experience persistent dysfunction post-infection for a period ranging from several months to over two years. Qualitative disorders, such as parosmia and phantosmia, frequently appeared during recovery. Prognosis seemed to be related to age, initial severity, duration of OD, co-existing symptoms, and potentially sex. A consistent discrepancy between subjective reports and objective psychophysical test results was observed. Methodological heterogeneity limited comparability across studies. Olfactory dysfunction is a significant and often overlooked long-term complication of COVID-19. Standardized diagnostic criteria, validated outcome measures, and prospective longitudinal research are urgently needed to guide evidence-based management and improve patient outcomes.},
}

@article {pmid41808916,
year = {2026},
author = {Jackson, ML and Weaver, MD and Varma, P and Czeisler, MÉ and Booker, LA and McDonald, CF and Robbins, R and Ridgers, A and Lane, R and Rajaratnam, SMW and Czeisler, CA and Quan, SF and Howard, ME},
title = {Presentation and temporal nature of postacute sequelae of SARS-CoV-2 infection in a US national cohort.},
journal = {Brain, behavior, & immunity - health},
volume = {53},
number = {},
pages = {101205},
pmid = {41808916},
issn = {2666-3546},
abstract = {BACKGROUND: Postacute Sequelae of SARS-CoV-2 Infection (PASC) is a novel illness emerging from SARS-CoV-2 infection, characterized by the persistence of symptoms beyond resolution of the initial illness. Understanding the phenotypes and trajectory of PASC is critical for diagnosis and development of personalized management approaches for specific PASC syndromes, to ultimately improve quality of life. The aim of this study was to examine the prevalence and duration, and characterize patterns of specific PASC symptoms in a community-based cohort.

METHOD: A non-probabilistic, weighted, cross-sectional survey of 14,964 adults from the US general population from the COVID-19 Outbreak Public Evaluation (COPE) Initiative between March 10, 2022 and June 2, 2022.

RESULTS: At 1-month post-infection, 44% of individuals with a history of SARS-CoV-2 infection reported at least one physical symptom, 47% reported at least one mental health symptom and 33% reported at least one cognitive symptom (14%, 10%, and 17% in controls, respectively). The prevalence of specific physical, cognitive and mental health symptoms declined between 1- and 12-months post-infection, to a prevalence rate similar to non-infected controls by 12 months. Cluster analysis revealed the persistence of symptom groups, with loss of taste and smell, psychosocial symptoms, respiratory and cardiovascular symptoms, and brain fog the most prominent at 12 months. Although cognitive symptom clusters persisted to 6 months post-infection, mental health clusters were transient.

CONCLUSIONS: The prevalence of most common PASC symptoms fell to general population levels within 12 months. Persisting physical and cognitive symptom clusters provide insights into potentially distinct disease pathways, and are essential for guiding clinical management strategies, rehabilitation programs, and public health interventions aimed at mitigating long-term impacts of COVID-19.},
}

@article {pmid41806535,
year = {2026},
author = {Sansa, A and Cardesín, A and Campos, M and Rovira, C and de Haro, J and Yuste, E and Caballero-Borrego, M},
title = {Long COVID-19 olfactory dysfunction: discrepancy between psychophysical tests and self-perception.},
journal = {Brazilian journal of otorhinolaryngology},
volume = {92},
number = {3},
pages = {101797},
doi = {10.1016/j.bjorl.2026.101797},
pmid = {41806535},
issn = {1808-8686},
abstract = {OBJECTIVES: To evaluate the discrepancies between psychophysical olfactory tests and self-perceived smell function in consecutive patients with long COVID-19-related olfactory dysfunction, and to compare the characteristics of this impairment with those observed in other nasal conditions, in order to improve diagnostic accuracy and guide targeted treatment strategies.

METHODS: An observational study of 86 long COVID-19 patients assessed by the Barcelona Smell Test (BAST-24 Plus), Visual Analogue Scale (VAS), and the quality-of-life Sino-Nasal Outcome Test (SNOT-22). Results were compared with 120 healthy controls and 121 patients with chronic rhinosinusitis with Nasal Polyps (CRSwNP).

RESULTS: Long COVID-19 patients reported a mean VAS score of 6.34 and a SNOT-22 score of 26.43, with question 21 (smell) accounting for 12.67% of the total. No correlation was found between VAS and total SNOT-22 score, but a moderate positive correlation was observed with question 21 (r = 0.488, p < 0.001). BAST-24 Plus scores were significantly lower than in controls for Detection, Identification, and Correct Answer (p < 0.001). Compared to the CRSwNP group, long COVID-19 patients showed less impairment in Detection and Identification (p < 0.001). A stronger negative correlation was observed between VAS and Identification (r = -0.629, p < 0.0001) than with Detection (r = -0.482, p < 0.0001), suggesting that odor identification dysfunction has a greater impact on subjective perception.

CONCLUSIONS: The subjective perception of olfactory dysfunction does not correlate with psychophysical test results in long COVID-19 patients and is characterized by a predominantly identification-dominant quantitative impairment, which differs from other disorders showing detection-dominant impairment. These findings highlight the need for specific diagnostic and therapeutic strategies.

LEVEL OF EVIDENCE: III.},
}

@article {pmid41803812,
year = {2026},
author = {Wang, K and Ma, CH and Khoramjoo, M and Kung, JY and Oudit, GY},
title = {Taurine supplementation as a therapeutic strategy for cellular senescence and chronic inflammation in long COVID: a systematic review and meta-analysis.},
journal = {BMC infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12879-026-13009-y},
pmid = {41803812},
issn = {1471-2334},
}

@article {pmid41803387,
year = {2026},
author = {Leitner, M and Ropele, S and Fellner, M and Koini, M},
title = {Intra and inter-network functional connectivity among long-Covid patients with ongoing disease duration.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-42000-5},
pmid = {41803387},
issn = {2045-2322},
}

@article {pmid41798842,
year = {2026},
author = {Duan, J and Zhang, J and Li, C and Li, Y and Yu, D and Chen, Y and Yang, Q and Lin, X and Cai, X},
title = {Fecal short-chain fatty acids and serum metabolites: the impact of COVID-19 infection on dialysis patients.},
journal = {Frontiers in nutrition},
volume = {13},
number = {},
pages = {1772671},
pmid = {41798842},
issn = {2296-861X},
abstract = {INTRODUCTION: Patients undergoing dialysis are particularly susceptible to severe COVID-19 outcomes owing to pre-existing metabolic and immunological dysregulation, which may exacerbate clinical severity and elevate the risk of long COVID (LC). Nevertheless, the precise metabolic pathways implicated remain poorly characterized. This study aimed to characterize fecal short-chain fatty acids (SCFAs) and serum metabolomic signatures in dialysis patients with acute COVID-19 and to explore their association with LC.

METHODS: Targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) quantified fecal SCFAs in 27 infected patients and 28 non-infected controls, and untargeted gas chromatography-mass spectrometry (GC-MS)-based metabolomics profiled serum samples from 23 infected patients and all 40 controls in partially overlapping patient subsets, with repeat serum sampling at 3 months and stratification into LC and non-LC groups. Multivariate analyses, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and Pearson correlation analyses between differential metabolites and routine clinical indicators were performed.

RESULTS: Infected patients exhibited significantly lower fecal levels of six SCFAs, including propionate and butyrate, compared with controls. Serum metabolomics identified 54 infection-related differential metabolites enriched in amino acid, energy, carbohydrate, and nucleotide metabolism, and 77 LC-associated metabolites predominantly mapping to amino acid and energy pathways. Pearson correlation analysis showed that amino acids and energy-supporting metabolites (e.g., glutamine, aspartate, methionine, cystine, taurine) were inversely correlated with C-reactive protein, leukocyte and neutrophil counts, and aspartate aminotransferase, but positively correlated with albumin, serum potassium, and lymphocyte or eosinophil counts, whereas purine degradation products and organic acids (e.g., uric acid, hypoxanthine, pyruvate, glycolate) exhibited the opposite pattern.

DISCUSSION: COVID-19 infection in dialysis patients is associated with marked depletion of fecal SCFAs and broad perturbations of systemic metabolism, with persistent amino-acid-centered alterations among patients who develop LC. These findings offer a novel metabolic framework supporting the implementation of prolonged follow-up strategies to monitor and ameliorate persistent sequelae in this high-risk population.},
}

@article {pmid41797113,
year = {2026},
author = {Shukla, A and Brahma, PK and Rajput, DS},
title = {Comment on "Association of Symptoms of neuropsychological long COVID with imaging and plasma biomarkers".},
journal = {Journal of the neurological sciences},
volume = {484},
number = {},
pages = {125841},
doi = {10.1016/j.jns.2026.125841},
pmid = {41797113},
issn = {1878-5883},
}

@article {pmid41796425,
year = {2026},
author = {Peñaherrera-Vásquez, D and Reina, A and Merlo, F and Fajardo-Loaiza, T and Zambrano-Sánchez, G and Rivadeneira, J and Fuenmayor-González, L},
title = {Unveiling the genitourinary phenotype of long COVID: a systematic review and meta-analysis.},
journal = {International urology and nephrology},
volume = {},
number = {},
pages = {},
pmid = {41796425},
issn = {1573-2584},
abstract = {IMPORTANCE: Long COVID has been associated with persistent multisystemic manifestations. However, genitourinary alterations have not been formally recognized as a distinct phenotype despite growing reports suggesting their relevance for long-term morbidity and quality of life.

OBJECTIVES: To determine the frequency and characteristics of genitourinary manifestations in patients with long COVID and to evaluate the evidence supporting the possible emergence of a genitourinary phenotype within long COVID.

DATA SOURCES: For this Systematic review and meta-analysis, a comprehensive search was conducted in PubMed (MEDLINE), Scopus, Web of Science, Embase, SciELO, and Bireme-BvS from inception to October 2025, without language or publication date restrictions. Observational studies (cross-sectional, cohort, or case-control) assessing individuals with one or more genitourinary symptoms-such as menstrual alterations, erectile dysfunction, urinary tract symptoms, or renal function decline-persisting ≥ 12 weeks after SARS-CoV-2 infection were included. Studies addressing only acute-phase manifestations, vaccine-related effects, or pre-existing genitourinary conditions were excluded.

DATA EXTRACTION AND SYNTHESIS: Data extraction was performed independently by two reviewers following PRISMA guidelines. Risk of bias (RoB) was assessed using the Joanna Briggs Institute checklist for prevalence studies. A random-effects meta-analysis using the Freeman-Tukey double arcsine transformation was applied to estimate pooled proportions, and heterogeneity was quantified using the I[2] statistic, Cochran's Q test, and the between-study variance (τ[2]).

MAIN OUTCOMES AND MEASURES: The primary outcomes were the pooled frequencies of genitourinary manifestations in long COVID, including menstrual disorders, erectile dysfunction, and renal function decline.

RESULTS: Nine primary studies encompassing 2332 participants from eight countries were included. Most studies (88.9%) presented a low RoB. The pooled frequency of menstrual disorders was 49% (95% CI 24-74), erectile dysfunction 21% (95% CI 16-28), and renal function decline 29% (95% CI 20-39).

CONCLUSIONS AND RELEVANCE: This systematic review and meta-analysis provide evidence supporting the possible emergence of a genitourinary phenotype of long COVID, encompassing menstrual irregularities, erectile dysfunction, cystitis-like symptoms, and renal impairment. Recognition of this potential phenotype is crucial for improving diagnostic accuracy, patient follow-up, and multidisciplinary management. Further high-quality studies are warranted to elucidate the underlying mechanisms and long-term clinical implications.},
}

@article {pmid41747471,
year = {2026},
author = {Szwarcwald, CL and de Almeida, WDS and de Souza Junior, PRB and de Castilho, EA and Damacena, GN and Gomes, CS and Malta, DC},
title = {Impact of the COVID-19 pandemic on the health situation of the Brazilian population.},
journal = {The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases},
volume = {30},
number = {2},
pages = {105790},
pmid = {41747471},
issn = {1678-4391},
abstract = {INTRODUCTION: The analysis of COVID-19 mortality revealed that the Brazilian population was critically impacted by the pandemic. However, many knowledge gaps remain regarding COVID-19 morbidity in the country. This article aims to analyze the consequences of the coronavirus disease on health situation of the Brazilian population.

METHODS: This was a cross-sectional epidemiological online survey using an electronic questionnaire between July and December 2023. The sampling method used was the virtual Respondent Driven Sampling (RDS). Changes in socioeconomic conditions were assessed in the post-pandemic period. Anti-COVID-19 vaccination coverage, prevalence of SARS-CoV-2 infection were estimated, as well as of sequelae lasting three months or more (Long COVID) among confirmed cases. Associations of Long COVID with self-reported heath status, sleep disorders, and depressive symptoms were analyzed.

RESULTS: The sample included 3805 individuals 18-years or older. Regarding vaccination, 61.5 % (95 % CI: 58.0 %-65.0 %) stated they had received 3‒4 doses. In the post-pandemic period, 41.6 % faced financial difficulties. Prevalence of confirmed SARS-CoV-2 infection was 40.2 %, 6.4 % of respondents reported having had COVID-19, although not confirmed by test, and 15.3 % did not know if they had been infected with the coronavirus. Among those infected, 32.0 % (95 % CI: 28.8 %-35.3 %) reported Long COVID, 21.4 % reported a COVID-19-related illness, and 5.2 % needed and obtained hospitalization. Long COVID was associated with worsening self-rated health, sleep disorders, feelings of depression and 27.7 % were unable to perform their usual activities for one month or more.

CONCLUSION: The results of this study showed that Brazil was severely affected by the COVID-19 pandemic, both in terms of mortality and morbidity. The availability of timely post-pandemic data, as presented in this study, may be highly relevant to inform public policies aimed at promoting healthy behaviors, controlling NCDs, improving mental health care, and supporting specialized care for Long COVID within the public health system.},
}

@article {pmid41286257,
year = {2025},
author = {Staab, KR and McIntosh, MJ and Puliyakote, ASK and Hahn, AD and AlArab, N and Percy, JL and Lanning, T and Theeler, J and Linkenmeyer, C and Wharff, CJ and Bruening, E and Sieren, JC and Hoffman, EA and Comellas, AP and Hoth, KF and Fain, SB},
title = {Long COVID: lung pathophysiology and its relationship with cognitive dysfunction.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {42595},
pmid = {41286257},
issn = {2045-2322},
support = {R01 HL126771/HL/NHLBI NIH HHS/United States ; S10 OD026960/OD/NIH HHS/United States ; P30 ES005605/ES/NIEHS NIH HHS/United States ; R01 HL169765/HL/NHLBI NIH HHS/United States ; COVID-19 and Emerging Respiratory Viruses Research Award//American Lung Association/ ; NIH NCATS S10OD026960, NIH CTSA program grant UM1TR004403, NIH NHLBI R01HL169765, NIH NHLBI R01HL126771/NH/NIH HHS/United States ; UM1 TR004403/TR/NCATS NIH HHS/United States ; },
mesh = {Humans ; Female ; Male ; *COVID-19/physiopathology/complications ; Middle Aged ; *Cognitive Dysfunction/physiopathology/etiology ; *Lung/physiopathology ; Magnetic Resonance Imaging ; Aged ; Post-Acute COVID-19 Syndrome ; Adult ; SARS-CoV-2 ; Respiratory Function Tests ; Anxiety ; Sleep Wake Disorders/physiopathology ; },
abstract = {Post-acute sequelae of COVID-19 (Long COVID) includes physical and cognitive symptoms that can last long after acute infection. Links between lung pathophysiology and cognitive dysfunction in Long COVID remain largely unexplored. Long COVID participants were recruited from a post-COVID-19 clinic. Participants completed Patient-Reported Outcomes Measurement Information System (PROMIS) symptom questionnaires for Sleep Disturbance, Anxiety, Depression, and Cognitive Function, the National Institute of Health Toolbox Cognition Battery (NIHTB-CB), pulmonary function tests (spirometry, diffusion capacity of the lung), structural and functional brain magnetic resonance imaging (MRI), and [129]Xe MRI for ventilation and regional pulmonary gas exchange evaluation, at the same study visit. Bivariate relationships between lung and cognitive function in Long COVID were assessed using Spearman partial correlations, adjusted for age. Twelve participants (age = 54 ± 11 yrs.; 10 females) that were 32 ± 5 months from infection were evaluated. PROMIS symptom scores indicated reduced perceived cognitive function in everyday life along with increased fatigue, anxiety, depressive symptoms, and sleep disturbance. However, objective cognitive function performance on NIHTB-CB were broadly within normal limits. Lower [129]Xe MRI gas exchange was correlated with more severe symptoms of sleep disturbance, reduced executive functioning performance, and elevated cerebral perfusion via brain MRI. These results are suggestive of a link between lung pathophysiology and cognitive dysfunction in this Long COVID population with enduring respiratory and cognitive symptoms more than two years after infection.},
}

Humans
Female
Male
*COVID-19/physiopathology/complications
Middle Aged
*Cognitive Dysfunction/physiopathology/etiology
*Lung/physiopathology
Magnetic Resonance Imaging
Aged
Post-Acute COVID-19 Syndrome
Adult
SARS-CoV-2
Respiratory Function Tests
Anxiety
Sleep Wake Disorders/physiopathology

@article {pmid40720834,
year = {2025},
author = {Feldman, CH and Santacroce, L and Bassett, IV and Thaweethai, T and Alicic, R and Atchley-Challenner, R and Chung, A and Goldberg, MP and Horowitz, CR and Jacobson, KB and Kelly, JD and Knight, S and Lutrick, K and Mudumbi, P and Parthasarathy, S and Prendergast, H and Quintana, Y and Sharareh, N and Shellito, J and Sherif, ZA and Taylor, BD and Taylor, E and Tsevat, J and Wiley, Z and Williams, NJ and Yee, L and Aponte-Soto, L and Baissary, J and Berry, J and Charney, AW and Costantine, MM and Duven, AM and Erdmann, N and Ernst, KC and Feuerriegel, EM and Flaherman, VJ and Go, M and Hawkins, K and Jacoby, V and John, J and Kelly, S and Kindred, E and Laiyemo, A and Levitan, EB and Levy, BD and Logue, JK and Marathe, JG and Martin, JN and McComsey, GA and Metz, TD and Minor, T and Montgomery, AP and Mullington, JM and Ofotokun, I and Okumura, MJ and Peluso, MJ and Pogreba-Brown, K and Raissy, H and Rosas, JM and Singh, U and VanWagoner, T and Clark, CR and Karlson, EW},
title = {Social Determinants of Health and Risk for Long COVID in the U.S. RECOVER-Adult Cohort.},
journal = {Annals of internal medicine},
volume = {178},
number = {9},
pages = {1287-1297},
pmid = {40720834},
issn = {1539-3704},
support = {OT2 HL156812/HL/NHLBI NIH HHS/United States ; OT2 HL161841/HL/NHLBI NIH HHS/United States ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; P30 ES006694/ES/NIEHS NIH HHS/United States ; },
mesh = {Humans ; *Social Determinants of Health ; *COVID-19/epidemiology ; Female ; Male ; United States/epidemiology ; Prospective Studies ; Adult ; Middle Aged ; Risk Factors ; SARS-CoV-2 ; Aged ; Poverty ; Post-Acute COVID-19 Syndrome ; },
abstract = {BACKGROUND: Social determinants of health (SDoH) contribute to disparities in SARS-CoV-2 infection, but their associations with long COVID are unknown.

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

DESIGN: Prospective observational cohort study.

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

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

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

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

LIMITATION: Selection bias may influence observed associations and generalizability.

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

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

Humans
*Social Determinants of Health
*COVID-19/epidemiology
Female
Male
United States/epidemiology
Prospective Studies
Adult
Middle Aged
Risk Factors
SARS-CoV-2
Aged
Poverty
Post-Acute COVID-19 Syndrome

@article {pmid40554463,
year = {2025},
author = {Gross, RS and Thaweethai, T and Salisbury, AL and Kleinman, LC and Mohandas, S and Rhee, KE and Snowden, JN and Tantisira, KG and Warburton, D and Wood, JC and Kinser, PA and Milner, JD and Rosenzweig, EB and Irby, K and Flaherman, VJ and Karlson, EW and Chibnik, LB and Pant, DB and Krishnamoorthy, A and Gallagher, R and Lamendola-Essel, MF and Hasson, DC and Katz, SD and Yin, S and Dreyer, BP and Blancero, F and Carmilani, M and Coombs, K and Fitzgerald, ML and Letts, RJ and Peddie, AK and Aschner, JL and Atz, AM and Banerjee, D and Bogie, A and Bukulmez, H and Clouser, K and Cottrell, LA and Cowan, K and D'Sa, VA and Dozor, A and Elliott, AJ and Faustino, EVS and Fiks, AG and Gaur, S and Gennaro, ML and Gordon, S and Hasan, UN and Hester, CM and Hogan, A and Hsia, DS and Kaelber, DC and Kosut, JS and Krishnan, S and McCulloh, RJ and Michelow, IC and Nolan, SM and Oliveira, CR and Olson, LM and Pace, WD and Palumbo, P and Raissy, H and Reyes, A and Ross, JL and Salazar, JC and Selvarangan, R and Stein, CR and Stevenson, MD and Teufel, RJ and Werzberger, A and Westfall, JM and Zani, K and Zempsky, WT and Zimmerman, E and Bind, MC and Chan, J and Guan, Z and Morse, RE and Reeder, HT and Metz, TD and Newburger, JW and Truong, DT and Foulkes, AS and Stockwell, MS and , and , },
title = {Characterizing Long COVID Symptoms During Early Childhood.},
journal = {JAMA pediatrics},
volume = {179},
number = {7},
pages = {781-792},
pmid = {40554463},
issn = {2168-6211},
support = {K23 AI159518/AI/NIAID NIH HHS/United States ; OT2 HL161841/HL/NHLBI NIH HHS/United States ; R01 HL162373/HL/NHLBI NIH HHS/United States ; },
abstract = {IMPORTANCE: Recent studies have identified characteristic symptom patterns of long COVID (LC) in adults and children older than 5 years. However, LC remains poorly characterized in early childhood. This knowledge gap limits efforts to identify, care for, and prevent LC in this vulnerable population.

OBJECTIVES: To identify symptoms that had the greatest difference in frequency comparing children with a history of SARS-CoV-2 infection to those without, to identify differences in the types of symptoms by age group (infants/toddlers [0-2 years] vs preschool-aged children [3-5 years]), and to derive an index that can be used in research studies to identify young children with LC.

This was a multisite longitudinal cohort study with enrollment from over 30 US health care and community settings, including infants, toddlers, and preschool-aged children with and without SARS-CoV-2 infection history. Study data were analyzed from May to December 2024.

EXPOSURE: SARS-CoV-2 infection.

MAIN OUTCOMES AND MEASURES: LC and 41 symptoms among infants/toddlers and 75 symptoms among preschool-aged children.

RESULTS: The study included 472 infants/toddlers (mean [SD] age, 12 [9] months; 278 infected with SARS-CoV-2; 194 uninfected; 234 male [50%]; 73 Black or African American [16%]; 198 Hispanic, Latino, or Spanish [43%]; 242 White [52%]) and 539 preschool-aged children (mean [SD] age, 48 [10] months; 399 infected with SARS-CoV-2; 140 uninfected; 277 female [51%]; 70 Black or African American [13%]; 210 Hispanic, Latino, or Spanish [39%]; 287 White [54%]). The median (IQR) time between first infections and completion of symptom surveys was 318 (198-494) days for infants/toddlers and 520 (330-844) days for preschool-aged children. A research index was derived for each age group based on symptoms most associated with infection history. The index is calculated by summing scores assigned to each prolonged symptom that was present, where higher scores indicate greater magnitude of association with history of SARS-CoV-2 infection: poor appetite (5 points), trouble sleeping (3.5 points), wet cough (3.5 points), dry cough (3 points), and stuffy nose (0.5 points) for infants/toddlers, and daytime tiredness/sleepiness/low energy (6.5 points) and dry cough (3 points) for preschool-aged children. Among infants/toddlers with infection, 40 of 278 (14%) were classified as having probable LC by having an index of at least 4 points. Among preschool-aged children, 61 of 399 (15%) were classified as having probable LC by having an index of at least 3 points. Participants with higher indices often had poorer overall health, lower quality of life, and perceived delays in developmental milestones.

CONCLUSIONS AND RELEVANCE: This cohort study identified symptom patterns and derived research indices that were distinct between the 2 age groups and differed from those previously identified in older ages, demonstrating the need to characterize LC separately across age ranges.},
}

@article {pmid40210368,
year = {2025},
author = {Verduzco-Gutierrez, M and Fleming, TK and Azola, AM},
title = {Considerations for Long COVID Rehabilitation in Women.},
journal = {Physical medicine and rehabilitation clinics of North America},
volume = {36},
number = {2},
pages = {371-387},
doi = {10.1016/j.pmr.2024.11.009},
pmid = {40210368},
issn = {1558-1381},
mesh = {Humans ; *COVID-19/rehabilitation/epidemiology ; Female ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Sex Factors ; },
abstract = {The coronavirus disease 2019 (COVID-19) pandemic has given rise to long COVID, a prolonged manifestation of severe acute respiratory syndrome coronavirus 2 infection, which presents with varied symptoms and conditions lasting beyond expected acute illness. Despite efforts, diagnostic and treatment approaches remain insufficient, particularly for women who experience higher prevalence rates. Rehabilitation professionals have played a crucial role during the pandemic. Individualized rehabilitation plans, encompassing various therapies and interdisciplinary collaborations, are essential. Addressing disparities and biological sex differences is paramount, requiring increased research, understanding, and advocacy for effective rehabilitative care tailored to all individuals affected by long COVID.},
}

Humans
*COVID-19/rehabilitation/epidemiology
Female
SARS-CoV-2
Post-Acute COVID-19 Syndrome
Sex Factors

@article {pmid39947217,
year = {2025},
author = {Proal, AD and Aleman, S and Bomsel, M and Brodin, P and Buggert, M and Cherry, S and Chertow, DS and Davies, HE and Dupont, CL and Deeks, SG and Ely, EW and Fasano, A and Freire, M and Geng, LN and Griffin, DE and Henrich, TJ and Hewitt, SM and Iwasaki, A and Krumholz, HM and Locci, M and Marconi, VC and Mehandru, S and Muller-Trutwin, M and Painter, MM and Pretorius, E and Price, DA and Putrino, D and Qian, Y and Roan, NR and Salmon, D and Tan, GS and VanElzakker, MB and Wherry, EJ and Van Weyenbergh, J and Yonker, LM and Peluso, MJ},
title = {Targeting the SARS-CoV-2 reservoir in long COVID.},
journal = {The Lancet. Infectious diseases},
volume = {25},
number = {5},
pages = {e294-e306},
pmid = {39947217},
issn = {1474-4457},
support = {K23 AI157875/AI/NIAID NIH HHS/United States ; R01 HL173059/HL/NHLBI NIH HHS/United States ; R01 NS136197/NS/NINDS NIH HHS/United States ; },
mesh = {Humans ; *COVID-19/virology/complications ; *SARS-CoV-2/physiology/drug effects ; Antiviral Agents/therapeutic use ; COVID-19 Drug Treatment ; Clinical Trials as Topic ; },
abstract = {There are no approved treatments for post-COVID-19 condition (also known as long COVID), a debilitating disease state following SARS-CoV-2 infection that is estimated to affect tens of millions of people. A growing body of evidence shows that SARS-CoV-2 can persist for months or years following COVID-19 in a subset of individuals, with this reservoir potentially driving long-COVID symptoms or sequelae. There is, therefore, an urgent need for clinical trials targeting persistent SARS-CoV-2, and several trials of antivirals or monoclonal antibodies for long COVID are underway. However, because mechanisms of SARS-CoV-2 persistence are not yet fully understood, such studies require important considerations related to the mechanism of action of candidate therapeutics, participant selection, duration of treatment, standardisation of reservoir-associated biomarkers and measurables, optimal outcome assessments, and potential combination approaches. In addition, patient subgroups might respond to some interventions or combinations of interventions, making post-hoc analyses crucial. Here, we outline these and other key considerations, with the goal of informing the design, implementation, and interpretation of trials in this rapidly growing field. Our recommendations are informed by knowledge gained from trials targeting the HIV reservoir, hepatitis C, and other RNA viruses, as well as precision oncology, which share many of the same hurdles facing long-COVID trials.},
}

Humans
*COVID-19/virology/complications
*SARS-CoV-2/physiology/drug effects
Antiviral Agents/therapeutic use
COVID-19 Drug Treatment
Clinical Trials as Topic

@article {pmid39489523,
year = {2024},
author = {Holmes, A and Emerson, L and Irving, LB and Tippett, E and Pullin, JM and Young, J and Watters, DA and Hamilton, A},
title = {Persistent symptoms after COVID-19: an Australian stratified random health survey on long COVID.},
journal = {The Medical journal of Australia},
volume = {221 Suppl 9},
number = {},
pages = {S12-S17},
doi = {10.5694/mja2.52473},
pmid = {39489523},
issn = {1326-5377},
mesh = {Humans ; *COVID-19/epidemiology/psychology ; Female ; Male ; Middle Aged ; Adult ; *Post-Acute COVID-19 Syndrome ; *Health Surveys ; *SARS-CoV-2 ; Aged ; Quality of Life ; Australia/epidemiology ; Victoria/epidemiology ; Young Adult ; Depression/epidemiology ; Adolescent ; Anxiety/epidemiology ; Fatigue/epidemiology/etiology ; },
abstract = {OBJECTIVE: To determine the impact of persistent symptoms after coronavirus disease 2019 (COVID-19) in an Australian population.

DESIGN, SETTING, PARTICIPANTS: We conducted a statewide health survey of a stratified random sample of adults who had had a confirmed acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19-positive group) and their close contacts (control group). The sample was drawn from Victoria's COVID-19 database between January 2020 and October 2022. Data were collected from 12 688 survey respondents between September 2022 and April 2023 (11 174 in the COVID-19-positive group and 1514 in the control group).

MAIN OUTCOME MEASURES: Persistent new symptoms, recovery, and daily function using validated questionnaires for fatigue, neurocognitive symptoms, anxiety, depression and quality of life.

RESULTS: At a mean of 12.6 months after infection, 4560 respondents in the COVID-19-positive group (39.1%; 95% CI, 37.9-40.3%) reported at least one persistent new symptom, compared with 216 respondents in the control group (20.8%; 95% CI, 18.5-23.1%). A total of 1656 respondents (14.2%; 95% CI, 13.4-15.0%) were classified as having clinical long COVID using the criteria of at least one persistent new symptom and less than 80% recovery three months after the infection. Of the respondents with clinical long COVID, 535 (3.2%; 95% CI, 2.6-3.8%) reported at least moderate problems with usual activities at 12 months after their infection. The proportion of respondents with clinical long COVID was lower for those with more recent infections. The risk factors for clinical long COVID were female sex, age 40-49 years, infection severity, chronic illness, and past anxiety or depression. Factors associated with a decreased risk of having clinical long COVID included infection when the Omicron strain was dominant and infection when the Delta strain was dominant, as compared with when the ancestral strain of the virus was dominant.

CONCLUSION: Persistent symptoms after COVID-19 are common, though with a lower incidence following infection from less virulent strains. Although long COVID can be largely managed in primary care, a minority of people who have persistent symptoms and impaired function may require specialist care pathways, the effectiveness of which should be a focus of future research.},
}

Humans
*COVID-19/epidemiology/psychology
Female
Male
Middle Aged
Adult
*Post-Acute COVID-19 Syndrome
*Health Surveys
*SARS-CoV-2
Aged
Quality of Life
Australia/epidemiology
Victoria/epidemiology
Young Adult
Depression/epidemiology
Adolescent
Anxiety/epidemiology
Fatigue/epidemiology/etiology

@article {pmid38343863,
year = {2025},
author = {Preiss, A and Bhatia, A and Aragon, LV and Baratta, JM and Baskaran, M and Blancero, F and Brannock, MD and Chew, RF and Díaz, I and Fitzgerald, M and Kelly, EP and Zhou, A and Carton, TW and Chute, CG and Haendel, M and Moffitt, R and Pfaff, E},
title = {EFFECT OF PAXLOVID TREATMENT DURING ACUTE COVID-19 ON LONG COVID ONSET: AN EHR-BASED TARGET TRIAL EMULATION FROM THE N3C AND RECOVER CONSORTIA.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {38343863},
support = {UL1 TR002649/TR/NCATS NIH HHS/United States ; UL1 TR002548/TR/NCATS NIH HHS/United States ; UL1 TR001433/TR/NCATS NIH HHS/United States ; UL1 TR001422/TR/NCATS NIH HHS/United States ; UL1 TR001860/TR/NCATS NIH HHS/United States ; UL1 TR001427/TR/NCATS NIH HHS/United States ; U54 GM104942/GM/NIGMS NIH HHS/United States ; UL1 TR001420/TR/NCATS NIH HHS/United States ; UL1 TR001439/TR/NCATS NIH HHS/United States ; UL1 TR002243/TR/NCATS NIH HHS/United States ; UL1 TR001445/TR/NCATS NIH HHS/United States ; UL1 TR003096/TR/NCATS NIH HHS/United States ; U01 DA055358/DA/NIDA NIH HHS/United States ; U54 GM104938/GM/NIGMS NIH HHS/United States ; UL1 TR002537/TR/NCATS NIH HHS/United States ; UL1 TR001857/TR/NCATS NIH HHS/United States ; UL1 TR001412/TR/NCATS NIH HHS/United States ; U54 GM133807/GM/NIGMS NIH HHS/United States ; UL1 TR001872/TR/NCATS NIH HHS/United States ; UL1 TR001878/TR/NCATS NIH HHS/United States ; UL1 TR002529/TR/NCATS NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; UL1 TR002494/TR/NCATS NIH HHS/United States ; UL1 TR002736/TR/NCATS NIH HHS/United States ; U54 GM115516/GM/NIGMS NIH HHS/United States ; UL1 TR002369/TR/NCATS NIH HHS/United States ; UL1 TR002541/TR/NCATS NIH HHS/United States ; U54 GM115371/GM/NIGMS NIH HHS/United States ; UL1 TR002001/TR/NCATS NIH HHS/United States ; UL1 TR002538/TR/NCATS NIH HHS/United States ; U54 GM115458/GM/NIGMS NIH HHS/United States ; UL1 TR001442/TR/NCATS NIH HHS/United States ; UL1 TR002535/TR/NCATS NIH HHS/United States ; UL1 TR001866/TR/NCATS NIH HHS/United States ; UL1 TR003167/TR/NCATS NIH HHS/United States ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; UL1 TR001409/TR/NCATS NIH HHS/United States ; UL1 TR001449/TR/NCATS NIH HHS/United States ; UL1 TR001453/TR/NCATS NIH HHS/United States ; UL1 TR002489/TR/NCATS NIH HHS/United States ; U54 GM104940/GM/NIGMS NIH HHS/United States ; UL1 TR003107/TR/NCATS NIH HHS/United States ; INV-018455/GATES/Gates Foundation/United States ; UL1 TR003015/TR/NCATS NIH HHS/United States ; UL1 TR002733/TR/NCATS NIH HHS/United States ; U24 TR002306/TR/NCATS NIH HHS/United States ; UL1 TR002003/TR/NCATS NIH HHS/United States ; UL1 TR001876/TR/NCATS NIH HHS/United States ; UL1 TR001436/TR/NCATS NIH HHS/United States ; UL1 TR002378/TR/NCATS NIH HHS/United States ; UL1 TR002384/TR/NCATS NIH HHS/United States ; UL1 TR002553/TR/NCATS NIH HHS/United States ; UL1 TR002389/TR/NCATS NIH HHS/United States ; UL1 TR001414/TR/NCATS NIH HHS/United States ; U54 GM104941/GM/NIGMS NIH HHS/United States ; UL1 TR002014/TR/NCATS NIH HHS/United States ; UM1 TR004528/TR/NCATS NIH HHS/United States ; UL1 TR002550/TR/NCATS NIH HHS/United States ; UL1 TR002319/TR/NCATS NIH HHS/United States ; UL1 TR001855/TR/NCATS NIH HHS/United States ; UL1 TR001425/TR/NCATS NIH HHS/United States ; UL1 TR002373/TR/NCATS NIH HHS/United States ; UL1 TR002240/TR/NCATS NIH HHS/United States ; UL1 TR002556/TR/NCATS NIH HHS/United States ; UL1 TR003017/TR/NCATS NIH HHS/United States ; UL1 TR001998/TR/NCATS NIH HHS/United States ; UL1 TR001873/TR/NCATS NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; UL1 TR002645/TR/NCATS NIH HHS/United States ; UL1 TR001450/TR/NCATS NIH HHS/United States ; UL1 TR002366/TR/NCATS NIH HHS/United States ; U54 GM115428/GM/NIGMS NIH HHS/United States ; UL1 TR002345/TR/NCATS NIH HHS/United States ; UL1 TR002377/TR/NCATS NIH HHS/United States ; U54 GM115677/GM/NIGMS NIH HHS/United States ; UL1 TR002544/TR/NCATS NIH HHS/United States ; UL1 TR003098/TR/NCATS NIH HHS/United States ; UL1 TR001430/TR/NCATS NIH HHS/United States ; UL1 TR003142/TR/NCATS NIH HHS/United States ; },
abstract = {BACKGROUND: Preventing and treating post-acute sequelae of SARS-CoV-2 infection (PASC), commonly known as Long COVID, has become a public health priority. Researchers have begun to explore whether Paxlovid treatment in the acute phase of COVID-19 could help prevent the onset of PASC.

METHODS AND FINDINGS: We used electronic health records from the National Clinical Cohort Collaborative (N3C) to define a cohort of 410,026 patients who had COVID-19 since April 1, 2022, and were eligible for Paxlovid treatment due to risk for progression to severe COVID-19. We used the target trial emulation framework to estimate the effect of Paxlovid treatment on PASC incidence. The treatment group was defined as outpatients prescribed Paxlovid within five days of COVID-19 index, and the control group was defined as all patients meeting eligibility criteria not in the treatment group. The follow-up period was 180 days. We estimated overall PASC incidence using a computable phenotype. We also measured incident cognitive, fatigue, and respiratory symptoms in the post-acute period. Paxlovid treatment had a small effect on overall PASC incidence (relative risk [RR] 0.94; 95% CI [0.90, 0.99]; p=0.011). It had a slightly stronger protective effect against cognitive (RR 0.86; 95% CI [0.77, 0.95]; p<0.001) and fatigue (RR 0.92; 95% CI [0.86, 0.97]; p=0.002) symptoms.

CONCLUSIONS: In this study, Paxlovid had a weaker preventative effect on PASC than in prior observational studies, suggesting that Paxlovid is unlikely to become a definitive solution for preventing PASC. Differing effects by symptom cluster suggest that the etiology of cognitive and fatigue symptoms may be more closely related to viral load than that of respiratory symptoms. Future research should explore potential heterogeneous treatment effects across PASC subphenotypes.},
}

@article {pmid36748919,
year = {2023},
author = {Hicks, SD},
title = {Comparison of Symptom Duration Between Children With SARS-CoV-2 and Peers With Other Viral Illnesses During the COVID-19 Pandemic.},
journal = {Clinical pediatrics},
volume = {62},
number = {9},
pages = {1101-1108},
pmid = {36748919},
issn = {1938-2707},
support = {R33 HD105610/HD/NICHD NIH HHS/United States ; R61 HD105610/HD/NICHD NIH HHS/United States ; UL1 TR002014/TR/NCATS NIH HHS/United States ; },
mesh = {Child ; Humans ; Child, Preschool ; Adolescent ; *COVID-19/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Pandemics ; Cross-Sectional Studies ; Pain ; },
abstract = {Some children and young people (CYP) with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) experience persistent symptoms, commonly called "long COVID." It remains unclear whether symptoms of SARS-CoV-2 persist longer than those of other respiratory viruses, particularly in young children. This cross-sectional study involved 372 CYP (0-15 years) tested for SARS-CoV-2. Character and duration of symptoms (cough, runny nose, sore throat, rash, diarrhea, vomiting, sore muscles, fatigue, fever, loss of smell) were compared between CYP with a positive test (n = 100) and those with a negative test (n = 272), while controlling for medical/demographic covariates. The average duration of symptoms for CYP with a positive SARS-CoV-2 test (8.5 ± 10 days) did not differ from that of CYP with a negative test (7.2 ± 5 days, P = .71, d = 0.046). A positive SARS-CoV-2 test did not increase the risk (36/372, 10%) of symptoms persisting for ≥3 weeks (odds ratio = 0.96, 95% confidence interval = 0.45-2.0). These results suggest CYP with non-SARS-CoV-2 infections experience a similar duration of symptoms as peers with SARS-CoV-2 infection.},
}

Child
Humans
Child, Preschool
Adolescent
*COVID-19/epidemiology
SARS-CoV-2
Post-Acute COVID-19 Syndrome
Pandemics
Cross-Sectional Studies
Pain

@article {pmid35227568,
year = {2022},
author = {Serhan, CN and Libreros, S and Nshimiyimana, R},
title = {E-series resolvin metabolome, biosynthesis and critical role of stereochemistry of specialized pro-resolving mediators (SPMs) in inflammation-resolution: Preparing SPMs for long COVID-19, human clinical trials, and targeted precision nutrition.},
journal = {Seminars in immunology},
volume = {59},
number = {},
pages = {101597},
pmid = {35227568},
issn = {1096-3618},
support = {K99 HL153673/HL/NHLBI NIH HHS/United States ; R35 GM139430/GM/NIGMS NIH HHS/United States ; },
mesh = {Animals ; Humans ; *COVID-19 ; Docosahexaenoic Acids/therapeutic use ; *Eicosapentaenoic Acid/therapeutic use ; Inflammation ; Inflammation Mediators/metabolism ; Metabolome ; Pandemics ; Post-Acute COVID-19 Syndrome ; Clinical Trials as Topic ; },
abstract = {The COVID-19 pandemic has raised international awareness of the importance of rigorous scientific evidence and the havoc caused by uncontrolled excessive inflammation. Here we consider the evidence on whether the specialized pro-resolving mediators (SPMs) are ready to meet this challenge as well as targeted metabololipidomics of the resolution-inflammation metabolomes. Specific stereochemical mechanisms in the biosynthesis of SPMs from omega-3 essential fatty acids give rise to unique local-acting lipid mediators. SPMs possess stereochemically defined potent bioactive structures that are high-affinity ligands for cognate G protein-coupled surface receptors that evoke the cellular responses required for efficient resolution of acute inflammation. The SPMs biosynthesized from the major omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are coined Resolvins (resolution phase interaction products; E series and D-series), Protectins and Maresins (macrophage mediators in resolving inflammation). Their biosynthesis and stereochemical assignments are established and confirmed (>1,441 resolvin publications in PubMed.gov) as well as their functional roles on innate immune cells and adaptive immune cells (both lymphocyte T-cell subsets and B-cells). The resolution of a protective acute inflammatory response is governed mainly by phagocytes that actively clear apoptotic cells, debris, blood clots and pathogens. These resolution phase functions of the acute inflammatory response are enhanced by SPMs, which together prepare the inflammatory loci for homeostasis and stimulate tissue regeneration via activating stem cells and the biosynthesis of novel cys-SPMs (e.g. MCTRs, PCTRs and RCTRs). These cys-SPMs also activate regeneration, are organ protective and stimulate resolution of local inflammation. Herein, we review the biosynthesis and functions of the E-series resolvins, namely resolvin E1 (the first n-3 resolvin identified), resolvin E2, resolvin E3 and resolvin E4 biosynthesized from their precursor eicosapentaenoic acid (EPA), and the critical role of total organic synthesis in confirming SPM complete stereochemistry, establishing their potent functions in resolution of inflammation, and novel structures. The physical properties of each biologically derived SPM, i.e., ultra-violet (UV) absorbance, chromatographic behavior, and tandem mass spectrometry (MS[2]) fragmentation, were matched to SPMs biosynthesized and prepared by stereospecific total organic synthesis. We briefly review this approach, also used with the endogenous D-series resolvins, protectins and maresins confirming their potent functions in resolution of inflammation, that paves the way for their rigorous evaluation in human tissues and clinical trials. The assignment of complete stereochemistry for each of the E and D series Resolvins, Protectins and Maresins was a critical and required step that enabled human clinical studies as in SPM profiling in COVID-19 infections and experimental animal disease models that also opened the promise of resolution physiology, resolution pharmacology and targeted precision nutrition as new areas for monitoring health and disease mechanisms.},
}

Animals
Humans
*COVID-19
Docosahexaenoic Acids/therapeutic use
*Eicosapentaenoic Acid/therapeutic use
Inflammation
Inflammation Mediators/metabolism
Metabolome
Pandemics
Post-Acute COVID-19 Syndrome
Clinical Trials as Topic

@article {pmid41795913,
year = {2026},
author = {Thorpe, DW and Jones, LA and Martin, AM and Coleman, RA and Allman, C and Peterson, RA and Keating, DJ},
title = {The role of peripheral serotonin in SARS-CoV-2 infectivity, COVID-19 treatment and long COVID.},
journal = {Immunology and cell biology},
volume = {},
number = {},
pages = {},
doi = {10.1111/imcb.70097},
pmid = {41795913},
issn = {1440-1711},
abstract = {Gastrointestinal symptoms have emerged as a common, but underappreciated, cause of morbidity in relation to SARS-CoV-2 infection and the COVID-19 pandemic. This manifests as a range of indications including diarrhea, anorexia, nausea, vomiting and abdominal pain. In addition, the gastrointestinal tract may represent a route of viral entry via the epithelial cell layer lining the gut wall. This route of entry could be a significant component of disease pathogenesis, including effects on the nervous system via the gut-brain axis. In this review, we provide an assessment of the effects of COVID-19 on the gastrointestinal system, its involvement in disease severity and potential pathways for viral entry and infection in the gastrointestinal tract. We also examine evidence that gut-derived serotonin is affected by SARS-CoV-2 infection, how this may link to symptoms and disease pathogenesis and the potential link to the efficacy of selective serotonin reuptake inhibitors in reducing COVID-19 severity.},
}

@article {pmid41795493,
year = {2026},
author = {Amitani, H and Sakato, T and Asakawa, A},
title = {Resolution of Long COVID and myalgic encephalomyelitis/chronic fatigue syndrome symptoms following kanshoho, a low-pressure muscle relaxation technique: A case report.},
journal = {Explore (New York, N.Y.)},
volume = {22},
number = {3},
pages = {103374},
doi = {10.1016/j.explore.2026.103374},
pmid = {41795493},
issn = {1878-7541},
abstract = {Post-COVID-19 condition (Long COVID) can cause persistent multi-system symptoms such as fatigue, pain, and cognitive dysfunction ("brain fog"), and a subset of patients meet diagnostic criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Treatment options remain limited, particularly when post-exertional malaise (PEM) restricts exercise-based rehabilitation. A 41-year-old woman developed refractory symptoms after acute SARS-CoV-2 infection, including severe fatigue, posterior neck and shoulder pain, bilateral upper extremity numbness, brain fog, and insomnia. Despite up-titration of sertraline to 50 mg/day by a previous physician and trials of other symptomatic medications, her symptoms did not show meaningful improvement. After exclusion of alternative organic causes, she was diagnosed with Long COVID and met diagnostic criteria for ME/CFS. Kanshoho, a low-pressure muscle relaxation technique, was administered as the primary intervention, with brief advice on activity pacing; sertraline (50 mg/day) was continued initially and later tapered at the patient's request, without clear symptom worsening, and subsequently discontinued. After 10 sessions over 2.5 months, all symptoms resolved at the final assessment. Fatigue visual analog scale (VAS) improved from 79 mm to 0 mm, performance status improved from 7 to 0, and the Profile of Mood States, Second Edition Total Mood Disturbance raw score decreased from 136 to -19. Although causality cannot be inferred from a single case, this low-load approach may warrant evaluation in controlled studies, especially for patients in whom PEM limits conventional rehabilitation.},
}

@article {pmid41754151,
year = {2026},
author = {Caliman-Sturdza, OA and Gheorghita, RE and Soldanescu, I and Dimian, M and Mangul, S},
title = {Vitamin D in Infectious Diseases: A Narrative Review Focusing on COVID-19, Long COVID, and Influenza.},
journal = {Nutrients},
volume = {18},
number = {4},
pages = {},
pmid = {41754151},
issn = {2072-6643},
mesh = {Humans ; *Vitamin D/therapeutic use/blood/administration & dosage/analogs & derivatives ; *COVID-19/immunology/complications ; *Influenza, Human/immunology/drug therapy ; *Vitamin D Deficiency/immunology/complications/drug therapy ; Dietary Supplements ; SARS-CoV-2 ; Immunity, Innate/drug effects ; Vitamins ; },
abstract = {Vitamin D is a secosteroid hormone traditionally recognized for its role in bone and mineral metabolism, but it is increasingly understood to also function as an important immunomodulator influencing susceptibility to and outcomes of infectious diseases. This narrative review summarizes current evidence on the immunological, clinical, and preventive effects of vitamin D in the context of novel coronavirus disease (COVID-19), post-acute sequelae of SARS-CoV-2 infection (long COVID), and influenza. Mechanistically, vitamin D enhances innate immune defenses through the induction of antimicrobial peptides, including cathelicidin and defensins, and modulates adaptive immunity by suppressing maladaptive Th1/Th17 responses while promoting regulatory T-cell activity. Observational studies have frequently associated vitamin D deficiency with more severe COVID-19 outcomes; however, these associations may be influenced by confounding factors and reverse causality. Some meta-analyses suggest that vitamin D supplementation reduced rates of intensive care unit admission and ventilatory support, particularly among older adults and individuals with low baseline serum 25-hydroxyvitamin D concentrations. Emerging evidence also indicates that inadequate vitamin D status may be associated with an increased risk and symptom burden of long COVID, although causality has not been established. In the case of influenza, a limited number of randomized controlled trials (RCTs) and meta-analyses report a modest but statistically significant reduction in infection risk, especially with daily or weekly vitamin D supplementation in populations with low baseline vitamin D levels. Clinical guidelines consistently recommend maintaining adequate vitamin D status for general health but do not endorse high-dose vitamin D as a treatment for COVID-19 due to inconsistent trial findings. Overall, vitamin D should not be considered a standalone therapeutic agent; rather, maintaining sufficient vitamin D levels represents a low-risk, potentially beneficial strategy to support immune resilience against respiratory viral infections.},
}

Humans
*Vitamin D/therapeutic use/blood/administration & dosage/analogs & derivatives
*COVID-19/immunology/complications
*Influenza, Human/immunology/drug therapy
*Vitamin D Deficiency/immunology/complications/drug therapy
Dietary Supplements
SARS-CoV-2
Immunity, Innate/drug effects
Vitamins

@article {pmid41532554,
year = {2026},
author = {Liao, TL and Liu, PY and Chen, YM and Tang, KT and Liu, HJ and Chen, DY},
title = {Extracellular Vesicle-Delivered tRF-His-GTG-1 Reprograms Neutrophil Lipophagy and Triggers Inflammation in COVID-19.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {13},
number = {13},
pages = {e08695},
pmid = {41532554},
issn = {2198-3844},
support = {NSTC 112-2314-B-075A-002-MY3//National Science and Technology Council/ ; TCVGH-1137305C//Taichung Veterans General Hospital/ ; TCVGH-1133902E//Taichung Veterans General Hospital/ ; TCVGH-1143918C//Taichung Veterans General Hospital/ ; },
mesh = {*COVID-19/immunology/metabolism/pathology ; *Neutrophils/metabolism/immunology ; Humans ; Animals ; *Extracellular Vesicles/metabolism ; *Inflammation/metabolism/immunology ; Extracellular Traps/metabolism/immunology ; SARS-CoV-2 ; Male ; rab GTP-Binding Proteins/metabolism ; *Autophagy ; rab7 GTP-Binding Proteins ; Female ; Toll-Like Receptor 8/metabolism ; Middle Aged ; TOR Serine-Threonine Kinases/metabolism ; Signal Transduction ; Disease Models, Animal ; },
abstract = {Immunometabolism and neutrophil extracellular traps (NETs) play pivotal roles in the pathogenesis of coronavirus disease 2019 (COVID-19) and its postacute sequelae. However, the upstream regulators that reprogram neutrophil lipid metabolism and trigger excessive NET formation remain largely undefined. This study identifies a transfer RNA-derived fragment, tRF-His-GTG-1, enriched in platelet-derived extracellular vesicles, as a key driver of neutrophil lipophagy dysfunction and inflammation in COVID-19. The use on neutrophils from 60 patients and 20 healthy controls, a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected hamster model, and multiple in vitro assays shows that severe COVID-19 and long COVID are characterized by increased lipid droplet (LD) accumulation and NET release. Mechanistically, tRF-His-GTG-1 activates Toll-like receptor 8 (TLR8)-mammalian target of rapamycin (mTOR) signaling and suppresses RAB7A expression, changes that impair lipophagic flux. This dual pathway impairs lipophagy and promotes NET formation and proinflammatory cytokine secretion. Importantly, ex vivo treatment with a tRF-His-GTG-1 inhibitor restores lipophagy, reduces LD and NET levels, and suppresses interleukin 1beta (IL-1β)/IL-8 production in patient-derived neutrophils. These findings reveal a novel EV-mediated immunometabolic axis linking platelets to neutrophil dysfunction, and position tRF-His-GTG-1 as a promising RNA-based therapeutic target for COVID-19-associated hyperinflammation.},
}

*COVID-19/immunology/metabolism/pathology
*Neutrophils/metabolism/immunology
Humans
Animals
*Extracellular Vesicles/metabolism
*Inflammation/metabolism/immunology
Extracellular Traps/metabolism/immunology
SARS-CoV-2
Male
rab GTP-Binding Proteins/metabolism
*Autophagy
rab7 GTP-Binding Proteins
Female
Toll-Like Receptor 8/metabolism
Middle Aged
TOR Serine-Threonine Kinases/metabolism
Signal Transduction
Disease Models, Animal

@article {pmid41396732,
year = {2026},
author = {Asghar, AF and Enderle, J and Salazar, JH and Esani, M},
title = {Predictors of post-acute sequelae of coronavirus disease 2019 and long COVID in adults and children: a retrospective cohort study using us electronic health record data.},
journal = {Journal of public health (Oxford, England)},
volume = {48},
number = {1},
pages = {185-194},
doi = {10.1093/pubmed/fdaf157},
pmid = {41396732},
issn = {1741-3850},
mesh = {Humans ; *COVID-19/complications/epidemiology ; Retrospective Studies ; Male ; Female ; Child ; Adult ; Electronic Health Records/statistics & numerical data ; Middle Aged ; Adolescent ; United States/epidemiology ; Child, Preschool ; Young Adult ; SARS-CoV-2 ; Risk Factors ; Infant ; Post-Acute COVID-19 Syndrome ; Aged ; Comorbidity ; Incidence ; },
abstract = {OBJECTIVE: This study examined the incidence and predictors of post-acute sequelae of COVID-19 (PASC) and Long COVID in adults and children with confirmed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Associations assessed included demographic factors, comorbidities, lab markers, and patient clinical complications.

METHOD: A retrospective cohort of 13,940 patients with confirmed SARS-CoV-2 infection (7836 adults and 6104 children) from the Optum® COVID-19 Electronic Health Record dataset was analyzed (1 June 2020-30 June 2021). PASC was defined as symptoms lasting <3 months postinfection and Long COVID as symptoms ≥3 months. Inclusion criteria were patients of all ages with a confirmed SARS-CoV-2 infection. Excluded from the study were patients in the Texas Department of Criminal Justice system and patients with active HIV, malignancy, or respiratory viral/bacterial infection. Statistical analyses (chi-square, Mann-Whitney U, multivariable logistic regression) were performed using Microsoft Excel and IBM Statistical Package for the Social Sciences statistics V.25.

RESULTS: Symptoms consistent with PASC were reported by 21.5% of adult patients, with 8.8% reporting Long COVID; 10.5% of pediatric patients reported PASC, with 9% reporting Long COVID (P < .05). In adults, predictors of PASC included age ≥54, female sex, non-Caucasian race, smoking, obesity, pneumonia, and multiple comorbidities; higher red blood cell count was protective. Predictors of Long COVID in adults was associated with female sex, obesity, and heart disease. In children, predictors of PASC included female sex and comorbidities. Younger age (≤10 years) was a significant predictor of Long COVID in children.

Protocols that include targeted follow-up and early intervention are needed for post-COVID conditions in high-risk individuals across age groups. Integrating predictive markers into routine care could enhance preparedness and resilience against future waves of post-viral syndromes.},
}

Humans
*COVID-19/complications/epidemiology
Retrospective Studies
Male
Female
Child
Adult
Electronic Health Records/statistics & numerical data
Middle Aged
Adolescent
United States/epidemiology
Child, Preschool
Young Adult
SARS-CoV-2
Risk Factors
Infant
Post-Acute COVID-19 Syndrome
Aged
Comorbidity
Incidence

@article {pmid39804551,
year = {2025},
author = {Vernon, SD and Zheng, T and Do, H and Marconi, VC and Jason, LA and Singer, NG and Natelson, BH and Sherif, ZA and Bonilla, HF and Taylor, E and Mullington, JM and Ashktorab, H and Laiyemo, AO and Brim, H and Patterson, TF and Akintonwa, TT and Sekar, A and Peluso, MJ and Maniar, N and Bateman, L and Horwitz, LI and Hess, R and , },
title = {Incidence and Prevalence of Post-COVID-19 Myalgic Encephalomyelitis: A Report from the Observational RECOVER-Adult Study.},
journal = {Journal of general internal medicine},
volume = {40},
number = {5},
pages = {1085-1094},
pmid = {39804551},
issn = {1525-1497},
support = {P30 AI050409/AI/NIAID NIH HHS/United States ; UM1 TR004409/TR/NCATS NIH HHS/United States ; OTA OT2HL161841/HL/NHLBI NIH HHS/United States ; OT2HL156812/HL/NHLBI NIH HHS/United States ; OT2 HL161841/HL/NHLBI NIH HHS/United States ; OT2HL161847/HL/NHLBI NIH HHS/United States ; OT2 HL156812/HL/NHLBI NIH HHS/United States ; },
mesh = {Humans ; *COVID-19/epidemiology/complications/diagnosis ; Female ; Incidence ; Male ; Adult ; Middle Aged ; Prevalence ; Longitudinal Studies ; *Fatigue Syndrome, Chronic/epidemiology/diagnosis/etiology ; United States/epidemiology ; Cohort Studies ; Aged ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; },
abstract = {BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) may occur after infection. How often people develop ME/CFS after SARS-CoV-2 infection is unknown.

OBJECTIVE: To determine the incidence and prevalence of post-COVID-19 ME/CFS among adults enrolled in the Researching COVID to Enhance Recovery (RECOVER-Adult) study.

RECOVER-Adult is a longitudinal observational cohort study conducted across the U.S. We included participants who had a study visit at least 6 months after infection and had no pre-existing ME/CFS, grouped as (1) acute infected, enrolled within 30 days of infection or enrolled as uninfected who became infected (n=4515); (2) post-acute infected, enrolled greater than 30 days after infection (n=7270); and (3) uninfected (1439).

MEASUREMENTS: Incidence rate and prevalence of post-COVID-19 ME/CFS based on the 2015 Institute of Medicine ME/CFS clinical diagnostic criteria.

RESULTS: The incidence rate of ME/CFS in participants followed from time of SARS-CoV-2 infection was 2.66 (95% CI 2.63-2.70) per 100 person-years while the rate in matched uninfected participants was 0.93 (95% CI 0.91-10.95) per 100 person-years: a hazard ratio of 4.93 (95% CI 3.62-6.71). The proportion of all RECOVER-Adult participants that met criteria for ME/CFS following SARS-CoV-2 infection was 4.5% (531 of 11,785) compared to 0.6% (9 of 1439) in uninfected participants. Post-exertional malaise was the most common ME/CFS symptom in infected participants (24.0%, 2830 of 11,785). Most participants with post-COVID-19 ME/CFS also met RECOVER criteria for long COVID (88.7%, 471 of 531).

LIMITATIONS: The ME/CFS clinical diagnostic criteria uses self-reported symptoms. Symptoms can wax and wane.

CONCLUSION: ME/CFS is a diagnosable sequela that develops at an increased rate following SARS-CoV-2 infection. RECOVER provides an unprecedented opportunity to study post-COVID-19 ME/CFS.},
}

Humans
*COVID-19/epidemiology/complications/diagnosis
Female
Incidence
Male
Adult
Middle Aged
Prevalence
Longitudinal Studies
*Fatigue Syndrome, Chronic/epidemiology/diagnosis/etiology
United States/epidemiology
Cohort Studies
Aged
SARS-CoV-2
Post-Acute COVID-19 Syndrome

@article {pmid39693079,
year = {2025},
author = {Geng, LN and Erlandson, KM and Hornig, M and Letts, R and Selvaggi, C and Ashktorab, H and Atieh, O and Bartram, L and Brim, H and Brosnahan, SB and Brown, J and Castro, M and Charney, A and Chen, P and Deeks, SG and Erdmann, N and Flaherman, VJ and Ghamloush, MA and Goepfert, P and Goldman, JD and Han, JE and Hess, R and Hirshberg, E and Hoover, SE and Katz, SD and Kelly, JD and Klein, JD and Krishnan, JA and Lee-Iannotti, J and Levitan, EB and Marconi, VC and Metz, TD and Modes, ME and Nikolich, JŽ and Novak, RM and Ofotokun, I and Okumura, MJ and Parthasarathy, S and Patterson, TF and Peluso, MJ and Poppas, A and Quintero Cardona, O and Scott, J and Shellito, J and Sherif, ZA and Singer, NG and Taylor, BS and Thaweethai, T and Verduzco-Gutierrez, M and Wisnivesky, J and McComsey, GA and Horwitz, LI and Foulkes, AS and , },
title = {2024 Update of the RECOVER-Adult Long COVID Research Index.},
journal = {JAMA},
volume = {333},
number = {8},
pages = {694-700},
pmid = {39693079},
issn = {1538-3598},
support = {OT2 HL156812/HL/NHLBI NIH HHS/United States ; P30 AI050409/AI/NIAID NIH HHS/United States ; R21 DC021054/DC/NIDCD NIH HHS/United States ; R01 HL151508/HL/NHLBI NIH HHS/United States ; R01 DC013277/DC/NIDCD NIH HHS/United States ; UM1 TR004528/TR/NCATS NIH HHS/United States ; OT2 HL161841/HL/NHLBI NIH HHS/United States ; R01 DC017397/DC/NIDCD NIH HHS/United States ; R01 HL162373/HL/NHLBI NIH HHS/United States ; UM1 TR004409/TR/NCATS NIH HHS/United States ; F31 DC006764/DC/NIDCD NIH HHS/United States ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; R03 DC010267/DC/NIDCD NIH HHS/United States ; },
mesh = {Adult ; Female ; Humans ; Male ; Middle Aged ; *Post-Acute COVID-19 Syndrome/classification/complications/diagnosis/virology ; Prospective Studies ; Puerto Rico ; SARS-CoV-2/pathogenicity ; United States ; Quality of Life ; },
abstract = {IMPORTANCE: Classification of persons with long COVID (LC) or post-COVID-19 condition must encompass the complexity and heterogeneity of the condition. Iterative refinement of the classification index for research is needed to incorporate newly available data as the field rapidly evolves.

OBJECTIVE: To update the 2023 research index for adults with LC using additional participant data from the Researching COVID to Enhance Recovery (RECOVER-Adult) study and an expanded symptom list based on input from patient communities.

Prospective, observational cohort study including adults 18 years or older with or without known prior SARS-CoV-2 infection who were enrolled at 83 sites in the US and Puerto Rico. Included participants had at least 1 study visit taking place 4.5 months after first SARS-CoV-2 infection or later, and not within 30 days of a reinfection. The study visits took place between October 2021 and March 2024.

EXPOSURE: SARS-CoV-2 infection.

MAIN OUTCOMES AND MEASURES: Presence of LC and participant-reported symptoms.

RESULTS: A total of 13 647 participants (11 743 with known SARS-CoV-2 infection and 1904 without known prior SARS-CoV-2 infection; median age, 45 years [IQR, 34-69 years]; and 73% were female) were included. Using the least absolute shrinkage and selection operator analysis regression approach from the 2023 model, symptoms contributing to the updated 2024 index included postexertional malaise, fatigue, brain fog, dizziness, palpitations, change in smell or taste, thirst, chronic cough, chest pain, shortness of breath, and sleep apnea. For the 2024 LC research index, the optimal threshold to identify participants with highly symptomatic LC was a score of 11 or greater. The 2024 index classified 20% of participants with known prior SARS-CoV-2 infection and 4% of those without known prior SARS-CoV-2 infection as having likely LC (vs 21% and 5%, respectively, using the 2023 index) and 39% of participants with known prior SARS-CoV-2 infection as having possible LC, which is a new category for the 2024 model. Cluster analysis identified 5 LC subtypes that tracked quality-of-life measures.

CONCLUSIONS AND RELEVANCE: The 2024 LC research index for adults builds on the 2023 index with additional data and symptoms to help researchers classify symptomatic LC and its symptom subtypes. Continued future refinement of the index will be needed as the understanding of LC evolves.},
}

Adult
Female
Humans
Male
Middle Aged
*Post-Acute COVID-19 Syndrome/classification/complications/diagnosis/virology
Prospective Studies
Puerto Rico
SARS-CoV-2/pathogenicity
United States
Quality of Life

@article {pmid39402206,
year = {2024},
author = {Thomas, D and Noishiki, C and Gaddam, S and Wu, D and Manhas, A and Liu, Y and Tripathi, D and Kathale, N and Adkar, SS and Garhyan, J and Liu, C and Xu, B and Ross, EG and Dalman, RL and Wang, KC and Oro, AE and Sallam, K and Lee, JT and Wu, JC and Sayed, N},
title = {CCL2-mediated endothelial injury drives cardiac dysfunction in long COVID.},
journal = {Nature cardiovascular research},
volume = {3},
number = {10},
pages = {1249-1265},
pmid = {39402206},
issn = {2731-0590},
support = {K99 HL163443-01//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; 869015//American Heart Association (American Heart Association, Inc.)/ ; R01 HL161002/HL/NHLBI NIH HHS/United States ; R01 AR054780/AR/NIAMS NIH HHS/United States ; K01 HL135455/HL/NHLBI NIH HHS/United States ; R01 HL150693/HL/NHLBI NIH HHS/United States ; R01 AR073170/AR/NIAMS NIH HHS/United States ; K99 HL163443/HL/NHLBI NIH HHS/United States ; R01 HL141851/HL/NHLBI NIH HHS/United States ; R01 HL158641/HL/NHLBI NIH HHS/United States ; },
mesh = {Humans ; *COVID-19/metabolism/complications ; Animals ; *Angiotensin-Converting Enzyme 2/metabolism/genetics ; *Chemokine CCL2/metabolism/genetics ; *SARS-CoV-2 ; *Endothelial Cells/metabolism/virology/pathology ; Mice, Transgenic ; Mice ; Male ; Female ; Induced Pluripotent Stem Cells/metabolism ; Oxidative Stress ; Post-Acute COVID-19 Syndrome ; Middle Aged ; Aged ; Myocytes, Cardiac/metabolism/virology/pathology ; Organoids/metabolism ; Spike Glycoprotein, Coronavirus/metabolism/genetics ; Heart Diseases/metabolism/pathology/virology/etiology ; },
abstract = {Evidence linking the endothelium to cardiac injury in long coronavirus disease (COVID) is well documented, but the underlying mechanisms remain unknown. Here we show that cytokines released by endothelial cells (ECs) contribute to long-COVID-associated cardiac dysfunction. Using thrombotic vascular tissues from patients with long COVID and induced pluripotent stem cell-derived ECs (iPSC-ECs), we modeled endotheliitis and observed similar dysfunction and cytokine upregulation, notably CCL2. Cardiac organoids comprising iPSC-ECs and iPSC-derived cardiomyocytes showed cardiac dysfunction after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure, driven by CCL2. Profiling of chromatin accessibility and gene expression at a single-cell resolution linked CCL2 to 'phenotype switching' and cardiac dysfunction, validated by high-throughput proteomics. Disease modeling of cardiac organoids and exposure of human ACE2 transgenic mice to SARS-CoV-2 spike proteins revealed that CCL2-induced oxidative stress promoted post-translational modification of cardiac proteins, leading to cardiac dysfunction. These findings suggest that EC-released cytokines contribute to cardiac dysfunction in long COVID, highlighting the importance of early vascular health monitoring in patients with long COVID.},
}

Humans
*COVID-19/metabolism/complications
Animals
*Angiotensin-Converting Enzyme 2/metabolism/genetics
*Chemokine CCL2/metabolism/genetics
*SARS-CoV-2
*Endothelial Cells/metabolism/virology/pathology
Mice, Transgenic
Mice
Male
Female
Induced Pluripotent Stem Cells/metabolism
Oxidative Stress
Post-Acute COVID-19 Syndrome
Middle Aged
Aged
Myocytes, Cardiac/metabolism/virology/pathology
Organoids/metabolism
Spike Glycoprotein, Coronavirus/metabolism/genetics
Heart Diseases/metabolism/pathology/virology/etiology

@article {pmid39196964,
year = {2024},
author = {Gross, RS and Thaweethai, T and Kleinman, LC and Snowden, JN and Rosenzweig, EB and Milner, JD and Tantisira, KG and Rhee, KE and Jernigan, TL and Kinser, PA and Salisbury, AL and Warburton, D and Mohandas, S and Wood, JC and Newburger, JW and Truong, DT and Flaherman, VJ and Metz, TD and Karlson, EW and Chibnik, LB and Pant, DB and Krishnamoorthy, A and Gallagher, R and Lamendola-Essel, MF and Hasson, DC and Katz, SD and Yin, S and Dreyer, BP and Carmilani, M and Coombs, K and Fitzgerald, ML and Güthe, N and Hornig, M and Letts, RJ and Peddie, AK and Taylor, BD and Balaraman, V and Bogie, A and Bukulmez, H and Dozor, AJ and Eckrich, D and Elliott, AJ and Evans, DN and Farkas, JS and Faustino, EVS and Fischer, L and Gaur, S and Harahsheh, AS and Hasan, UN and Hsia, DS and Huerta-Montañez, G and Hummel, KD and Kadish, MP and Kaelber, DC and Krishnan, S and Kosut, JS and Larrabee, J and Lim, PPC and Michelow, IC and Oliveira, CR and Raissy, H and Rosario-Pabon, Z and Ross, JL and Sato, AI and Stevenson, MD and Talavera-Barber, MM and Teufel, RJ and Weakley, KE and Zimmerman, E and Bind, MC and Chan, J and Guan, Z and Morse, RE and Reeder, HT and Akshoomoff, N and Aschner, JL and Bhattacharjee, R and Cottrell, LA and Cowan, K and D'Sa, VA and Fiks, AG and Gennaro, ML and Irby, K and Khare, M and Guttierrez, JL and McCulloh, RJ and Narang, S and Ness-Cochinwala, M and Nolan, S and Palumbo, P and Ryu, J and Salazar, JC and Selvarangan, R and Stein, CR and Werzberger, A and Zempsky, WT and Aupperle, R and Baker, FC and Banich, MT and Barch, DM and Baskin-Sommers, A and Bjork, JM and Bookheimer, SY and Brown, SA and Casey, BJ and Chang, L and Clark, DB and Dale, AM and Dapretto, M and Ernst, TM and Fair, DA and Feldstein Ewing, SW and Foxe, JJ and Freedman, EG and Friedman, NP and Garavan, H and Gee, DG and Gonzalez, R and Gray, KM and Heitzeg, MM and Herting, MM and Jacobus, J and Laird, AR and Larson, CL and Lisdahl, KM and Luciana, M and Luna, B and Madden, PAF and McGlade, EC and Müller-Oehring, EM and Nagel, BJ and Neale, MC and Paulus, MP and Potter, AS and Renshaw, PF and Sowell, ER and Squeglia, LM and Tapert, S and Uddin, LQ and Wilson, S and Yurgelun-Todd, DA and Foulkes, AS and Stockwell, MS and , and , },
title = {Characterizing Long COVID in Children and Adolescents.},
journal = {JAMA},
volume = {332},
number = {14},
pages = {1174-1188},
pmid = {39196964},
issn = {1538-3598},
support = {U24 DA041147/DA/NIDA NIH HHS/United States ; U01 DA041120/DA/NIDA NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; K23 AI159518/AI/NIAID NIH HHS/United States ; U01 DA041156/DA/NIDA NIH HHS/United States ; R01 DA057567/DA/NIDA NIH HHS/United States ; U01 DA041117/DA/NIDA NIH HHS/United States ; OT2 HL161841/HL/NHLBI NIH HHS/United States ; R01 HL162373/HL/NHLBI NIH HHS/United States ; },
abstract = {IMPORTANCE: Most research to understand postacute sequelae of SARS-CoV-2 infection (PASC), or long COVID, has focused on adults, with less known about this complex condition in children. Research is needed to characterize pediatric PASC to enable studies of underlying mechanisms that will guide future treatment.

OBJECTIVE: To identify the most common prolonged symptoms experienced by children (aged 6 to 17 years) after SARS-CoV-2 infection, how these symptoms differ by age (school-age [6-11 years] vs adolescents [12-17 years]), how they cluster into distinct phenotypes, and what symptoms in combination could be used as an empirically derived index to assist researchers to study the likely presence of PASC.

Multicenter longitudinal observational cohort study with participants recruited from more than 60 US health care and community settings between March 2022 and December 2023, including school-age children and adolescents with and without SARS-CoV-2 infection history.

EXPOSURE: SARS-CoV-2 infection.

MAIN OUTCOMES AND MEASURES: PASC and 89 prolonged symptoms across 9 symptom domains.

RESULTS: A total of 898 school-age children (751 with previous SARS-CoV-2 infection [referred to as infected] and 147 without [referred to as uninfected]; mean age, 8.6 years; 49% female; 11% were Black or African American, 34% were Hispanic, Latino, or Spanish, and 60% were White) and 4469 adolescents (3109 infected and 1360 uninfected; mean age, 14.8 years; 48% female; 13% were Black or African American, 21% were Hispanic, Latino, or Spanish, and 73% were White) were included. Median time between first infection and symptom survey was 506 days for school-age children and 556 days for adolescents. In models adjusted for sex and race and ethnicity, 14 symptoms in both school-age children and adolescents were more common in those with SARS-CoV-2 infection history compared with those without infection history, with 4 additional symptoms in school-age children only and 3 in adolescents only. These symptoms affected almost every organ system. Combinations of symptoms most associated with infection history were identified to form a PASC research index for each age group; these indices correlated with poorer overall health and quality of life. The index emphasizes neurocognitive, pain, and gastrointestinal symptoms in school-age children but change or loss in smell or taste, pain, and fatigue/malaise-related symptoms in adolescents. Clustering analyses identified 4 PASC symptom phenotypes in school-age children and 3 in adolescents.

CONCLUSIONS AND RELEVANCE: This study developed research indices for characterizing PASC in children and adolescents. Symptom patterns were similar but distinguishable between the 2 groups, highlighting the importance of characterizing PASC separately for these age ranges.},
}

@article {pmid38630952,
year = {2024},
author = {McAlpine, L and Zubair, AS and Joseph, P and Spudich, S},
title = {Case-Control Study of Individuals With Small Fiber Neuropathy After COVID-19.},
journal = {Neurology(R) neuroimmunology & neuroinflammation},
volume = {11},
number = {3},
pages = {e200244},
pmid = {38630952},
issn = {2332-7812},
support = {K23 NS133488/NS/NINDS NIH HHS/United States ; L30 NS139301/NS/NINDS NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; },
mesh = {Humans ; Female ; Middle Aged ; Male ; *Small Fiber Neuropathy ; Case-Control Studies ; Retrospective Studies ; *Fatigue Syndrome, Chronic ; Post-Acute COVID-19 Syndrome ; Immunoglobulins, Intravenous ; *COVID-19 ; *Autonomic Nervous System Diseases ; },
abstract = {OBJECTIVES: To report a case-control study of new-onset small fiber neuropathy (SFN) after COVID-19 with invasive cardiopulmonary exercise testing (iCPET). SFN is a critical objective finding in long COVID and amenable to treatment.

METHODS: A retrospective chart review was conducted on patients seen in the NeuroCOVID Clinic at Yale who developed new-onset SFN after a documented COVID-19 illness. We collected demographics, symptoms, skin biopsy, iCPET testing, treatments, and clinical response to treatment or no intervention.

RESULTS: Sixteen patients were diagnosed with SFN on skin biopsy (median age 47, 75% female, 75% White). 92% of patients reported postexertional malaise characteristic of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and 7 patients underwent iCPET, which demonstrated neurovascular dysregulation and dysautonomia consistent with ME/CFS. Nine patients underwent treatment with IVIG, and 7 were not treated with IVIG. The IVIG group experienced significant clinical response in their neuropathic symptoms (9/9) compared with those who did not receive IVIG (3/7; p = 0.02).

DISCUSSION: Here, we present preliminary evidence that after COVID-19, SFN is responsive to treatment with IVIG and linked with neurovascular dysregulation and dysautonomia on iCPET. A larger clinical trial is indicated to further demonstrate the clinical utility of IVIG in treating postinfectious SFN.

CLASSIFICATION OF EVIDENCE: This study provides Class III evidence. It is a retrospective cohort study.},
}

Humans
Female
Middle Aged
Male
*Small Fiber Neuropathy
Case-Control Studies
Retrospective Studies
*Fatigue Syndrome, Chronic
Post-Acute COVID-19 Syndrome
Immunoglobulins, Intravenous
*COVID-19
*Autonomic Nervous System Diseases

@article {pmid37748514,
year = {2023},
author = {Klein, J and Wood, J and Jaycox, JR and Dhodapkar, RM and Lu, P and Gehlhausen, JR and Tabachnikova, A and Greene, K and Tabacof, L and Malik, AA and Silva Monteiro, V and Silva, J and Kamath, K and Zhang, M and Dhal, A and Ott, IM and Valle, G and Peña-Hernández, M and Mao, T and Bhattacharjee, B and Takahashi, T and Lucas, C and Song, E and McCarthy, D and Breyman, E and Tosto-Mancuso, J and Dai, Y and Perotti, E and Akduman, K and Tzeng, TJ and Xu, L and Geraghty, AC and Monje, M and Yildirim, I and Shon, J and Medzhitov, R and Lutchmansingh, D and Possick, JD and Kaminski, N and Omer, SB and Krumholz, HM and Guan, L and Dela Cruz, CS and van Dijk, D and Ring, AM and Putrino, D and Iwasaki, A},
title = {Distinguishing features of long COVID identified through immune profiling.},
journal = {Nature},
volume = {623},
number = {7985},
pages = {139-148},
pmid = {37748514},
issn = {1476-4687},
support = {R35 GM143072/GM/NIGMS NIH HHS/United States ; R01 AI157488/AI/NIAID NIH HHS/United States ; U01 FD005938/FD/FDA HHS/United States ; T32 GM007205/GM/NIGMS NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; T32 GM136651/GM/NIGMS NIH HHS/United States ; },
mesh = {Humans ; *Antibodies, Viral/blood/immunology ; Biomarkers/blood ; Cross-Sectional Studies ; *Herpesvirus 4, Human/immunology ; *Hydrocortisone/blood ; Immunophenotyping ; *Lymphocytes/immunology ; Machine Learning ; *Myeloid Cells/immunology ; *Post-Acute COVID-19 Syndrome/diagnosis/immunology/physiopathology/virology ; *SARS-CoV-2/immunology ; },
abstract = {Post-acute infection syndromes may develop after acute viral disease[1]. Infection with SARS-CoV-2 can result in the development of a post-acute infection syndrome known as long COVID. Individuals with long COVID frequently report unremitting fatigue, post-exertional malaise, and a variety of cognitive and autonomic dysfunctions[2-4]. However, the biological processes that are associated with the development and persistence of these symptoms are unclear. Here 275 individuals with or without long COVID were enrolled in a cross-sectional study that included multidimensional immune phenotyping and unbiased machine learning methods to identify biological features associated with long COVID. Marked differences were noted in circulating myeloid and lymphocyte populations relative to the matched controls, as well as evidence of exaggerated humoral responses directed against SARS-CoV-2 among participants with long COVID. Furthermore, higher antibody responses directed against non-SARS-CoV-2 viral pathogens were observed among individuals with long COVID, particularly Epstein-Barr virus. Levels of soluble immune mediators and hormones varied among groups, with cortisol levels being lower among participants with long COVID. Integration of immune phenotyping data into unbiased machine learning models identified the key features that are most strongly associated with long COVID status. Collectively, these findings may help to guide future studies into the pathobiology of long COVID and help with developing relevant biomarkers.},
}

Humans
*Antibodies, Viral/blood/immunology
Biomarkers/blood
Cross-Sectional Studies
*Herpesvirus 4, Human/immunology
*Hydrocortisone/blood
Immunophenotyping
*Lymphocytes/immunology
Machine Learning
*Myeloid Cells/immunology
*Post-Acute COVID-19 Syndrome/diagnosis/immunology/physiopathology/virology
*SARS-CoV-2/immunology

@article {pmid37667052,
year = {2023},
author = {Proal, AD and VanElzakker, MB and Aleman, S and Bach, K and Boribong, BP and Buggert, M and Cherry, S and Chertow, DS and Davies, HE and Dupont, CL and Deeks, SG and Eimer, W and Ely, EW and Fasano, A and Freire, M and Geng, LN and Griffin, DE and Henrich, TJ and Iwasaki, A and Izquierdo-Garcia, D and Locci, M and Mehandru, S and Painter, MM and Peluso, MJ and Pretorius, E and Price, DA and Putrino, D and Scheuermann, RH and Tan, GS and Tanzi, RE and VanBrocklin, HF and Yonker, LM and Wherry, EJ},
title = {SARS-CoV-2 reservoir in post-acute sequelae of COVID-19 (PASC).},
journal = {Nature immunology},
volume = {24},
number = {10},
pages = {1616-1627},
pmid = {37667052},
issn = {1529-2916},
support = {K08 HL143183/HL/NHLBI NIH HHS/United States ; L30 AI147159/AI/NIAID NIH HHS/United States ; R01 DK123749/DK/NIDDK NIH HHS/United States ; R01 HL173059/HL/NHLBI NIH HHS/United States ; },
mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; RNA, Viral/genetics ; SARS-CoV-2 ; Antiviral Agents ; Disease Progression ; },
abstract = {Millions of people are suffering from Long COVID or post-acute sequelae of COVID-19 (PASC). Several biological factors have emerged as potential drivers of PASC pathology. Some individuals with PASC may not fully clear the coronavirus SARS-CoV-2 after acute infection. Instead, replicating virus and/or viral RNA-potentially capable of being translated to produce viral proteins-persist in tissue as a 'reservoir'. This reservoir could modulate host immune responses or release viral proteins into the circulation. Here we review studies that have identified SARS-CoV-2 RNA/protein or immune responses indicative of a SARS-CoV-2 reservoir in PASC samples. Mechanisms by which a SARS-CoV-2 reservoir may contribute to PASC pathology, including coagulation, microbiome and neuroimmune abnormalities, are delineated. We identify research priorities to guide the further study of a SARS-CoV-2 reservoir in PASC, with the goal that clinical trials of antivirals or other therapeutics with potential to clear a SARS-CoV-2 reservoir are accelerated.},
}

Humans
*COVID-19
Post-Acute COVID-19 Syndrome
RNA, Viral/genetics
SARS-CoV-2
Antiviral Agents
Disease Progression

@article {pmid41791802,
year = {2026},
author = {Morsa, M and Dothée, L and Cabello, C and Lesoinne, A and Collette, F and Willems, S},
title = {Psychoeducational interventions for patients with Long COVID and neuropsychological difficulties: A qualitative process evaluation of the COVCOG clinical trial.},
journal = {Neuropsychological rehabilitation},
volume = {},
number = {},
pages = {1-27},
doi = {10.1080/09602011.2026.2640067},
pmid = {41791802},
issn = {1464-0694},
abstract = {Between 2022 and 2024, the COVCOG randomized controlled trial evaluated two psychoeducation interventions for people living with Long COVID: one addressing cognitive difficulties and the other affective difficulties. While the results showed small to moderate improvements in both groups, we still lack information on the individual and contextual mechanisms that facilitated or hindered the benefits of the intervention. Our research aimed to understand how, under what circumstances, and for whom the intervention generates changes. A qualitative process evaluation was conducted with patients and clinicians involved in COVCOG. Semi-structured individual interviews were conducted and analysed through reflexive thematic analysis. Sixteen patients and ten clinicians participated. Five themes were developed, helping to better understand the conditions for intervention success: Being recognized as a person with Long COVID, Learning to manage Long COVID on a daily basis, Changing as a person, Considering life after the intervention, and Adapting the clinical protocol. Our findings highlight the importance of both institutional and interpersonal recognition as a foundational mechanism for engagement and perceived effectiveness. Psychoeducation for people living with Long COVID should be designed as part of a broader, adaptive, and evolving care pathway, by supporting patients in navigating its biographical and functional consequences over time.},
}

@article {pmid41791507,
year = {2026},
author = {Cintron, SA and Diaz, FJ and Krebill, R and Hitchcock, SR and Kasuske, L and Yang, FM and Pierce, J},
title = {Prevalence and Symptoms of Post-COVID-19 Syndrome in Active-Duty Military Personnel.},
journal = {The American journal of the medical sciences},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.amjms.2026.03.001},
pmid = {41791507},
issn = {1538-2990},
abstract = {BACKGROUND: Post-acute COVID-19 is a syndrome characterized by the persistence of clinical symptoms beyond 4 weeks from the onset of acute symptoms. Over 250,000 Department of Defense service members have recovered or are recovering from acute COVID-19, and the range of symptoms and physiological changes can impact the medical readiness of military service members. Understanding the chronic illness among some of the active-duty personnel with this virus is needed to begin finding treatments to reduce their symptoms and improve their health outcomes.

METHODS: This was a longitudinal, descriptive study designed to examine the prevalence and persistence of the symptoms of active-duty military persons who have post-COVID-19 syndrome. We obtained data from electronic health records (EHRs) of clinics and hospitals of the armed services from U.S. military bases. The de-identified data set came from the Department of Defense Military Health System Data Repository (MDR) which is a centralized data repository established to capture, archive, validate, integrate, and distribute Defense Health Agency (DHA) data worldwide.

RESULTS: The most prevalent symptom was pulmonary related, affecting 22.4% of individuals with post-COVID-19 syndrome. The second most prevalent symptom was neurological problems (14.6%), followed by fatigue (13.5%), digestive issues (12.5%), and fever (11.5%). Approximately 3.7% of military personnel with post-COVID-19 experienced cognitive symptoms however, they had the greatest persistence, followed by pulmonary related, fatigue, and neurological symptoms.

CONCLUSIONS: Based on the symptoms identified, finding treatments for post-COVID-19 syndrome is needed particularly for military personnel to maintain fitness and readiness.},
}

@article {pmid41790803,
year = {2026},
author = {Silva, IVTC and Inoue, LH and Brito, FAM and Baccon, WC and Pesce, GB and Höring, CF and Theodoro, MDS and Inoue, DCME and Dores, LS and Batista, NA and Charlo, PB and Baldissera, VDA and Moura, DRO and Salci, MA and Carreira, L},
title = {Prevalence and factors associated with long Covid in older people in the State of Paraná.},
journal = {Revista da Escola de Enfermagem da U S P},
volume = {60},
number = {},
pages = {e20240429},
doi = {10.1590/1980-220X-REEUSP-2024-0429en},
pmid = {41790803},
issn = {1980-220X},
mesh = {Humans ; Brazil/epidemiology ; *COVID-19/epidemiology/complications ; Cross-Sectional Studies ; Aged ; Male ; Female ; Aged, 80 and over ; Prevalence ; Middle Aged ; Risk Factors ; Polypharmacy ; Smoking/epidemiology ; Time Factors ; Post-Acute COVID-19 Syndrome ; },
abstract = {OBJECTIVE: To analyze the factors associated with long Covid in older people 18 months after the acute phase of the disease.

METHOD: This cross-sectional and analytical study was conducted with older individuals who had Covid-19 in 2020 and survived the disease in the state of Paraná, Brazil. Sociodemographic, lifestyle habits, health and treatment information, as well as information on signs, symptoms and sequelae of the disease were collected through telephone interviews conducted 18 months after notification or hospital discharge. For the analyses, descriptive measures, association tests, and Poisson regression models with robust variance were used.

RESULTS: Of the 345 older people who participated in the study, 224 (65%) still had some symptom or sequelae of Covid-19 18 months after the illness. Being a smoker or former smoker (PR = 2.21; 95% CI = 1.06;3.36), self-reported sleep quality (PR = 0.32; 95% CI = 0.16-0.47), and the use of continuous medication (RP = 5.24; 95% CI = 2.64-7.85; p < 0.0001) were associated with long-term Covid.

CONCLUSION: Morbidity and polypharmacy rates are high in this population, contributing to the persistence of symptoms. In this context, it becomes essential to align health services, together with professionals, to meet the needs arising from the sequelae in older people.},
}

Humans
Brazil/epidemiology
*COVID-19/epidemiology/complications
Cross-Sectional Studies
Aged
Male
Female
Aged, 80 and over
Prevalence
Middle Aged
Risk Factors
Polypharmacy
Smoking/epidemiology
Time Factors
Post-Acute COVID-19 Syndrome

@article {pmid41790576,
year = {2026},
author = {Morcos, ZL and Theoharides, TC},
title = {Long COVID neuropathy: The role of mast cells.},
journal = {Journal of neuropathology and experimental neurology},
volume = {},
number = {},
pages = {},
doi = {10.1093/jnen/nlag016},
pmid = {41790576},
issn = {1554-6578},
abstract = {Postacute sequelae of SARS-CoV-2 infection (PASC), or Long COVID, is estimated to affect over 60 million individuals globally, with almost half of COVID-19 survivors experiencing persistent symptoms such as neuropathic pain, fatigue, and autonomic dysfunction. Despite its prevalence, the pathophysiology of PASC remains poorly understood. This narrative review highlights activation of mast cells (MCs), the unique tissue immune cells as a central contributor to neuropathic manifestations in PASC. Mast cell locations near nerves and vessels allows them to regulate neuroimmune and neurovascular processes. Mast cell activation mirrors patterns seen in small-fiber neuropathy and myalgic encephalomyelitis/chronic fatigue syndrome, suggesting a shared immune-mediated etiology. The SARS-CoV-2 spike protein has been shown to activate MCs via angiotensin-converting enzyme 2 and toll-like receptor 4, triggering release of pro-inflammatory and neurotoxic mediators, including interleukin-1β, interleukin-6, tumor necrosis factor alpha, histamine, and tryptase. Such mediators sensitize peripheral nerves, disrupt the blood-brain barrier, and recruit microglia, ultimately contributing to small-fiber injury, neuroinflammation, and dysautonomia. Emerging reports suggest benefit from MC-directed treatments although responses remain variable. Understanding the role of MCs in PASC may offer a plausible mechanism of pathogenesis and guide targeted therapies. Future studies are needed to validate these findings and improve PASC patient outcomes.},
}

@article {pmid41790479,
year = {2026},
author = {Al-Jassas, HK and Al-Hakeim, HK},
title = {The Principal Component of the Inflammatory Biomarkers is the Best Predictor of Neuropsychiatric Disorders in Long COVID Patients.},
journal = {Clinical neuropharmacology},
volume = {},
number = {},
pages = {},
pmid = {41790479},
issn = {1537-162X},
abstract = {OBJECTIVES: Long COVID (LC) is associated with neuropsychiatric disorders (anxiety, depression, and fatigue), an insulin resistance (IR) state, and inflammatory biomarkers. In the present study, IR and inflammatory biomarkers were used to predict the scores of neuropsychiatric disorders.

METHODS: The ELISA method was used for measurements of IL-1β, IL-10, IL-18, C-reactive protein (CRP), and insulin in the sera of LC and control subjects. Glucose levels were measured spectrophotometrically. The Hamilton scale for anxiety (HAMA) and depression (HAMD), and the fibro fatigue scale (FFtotal) were used for scoring the neuropsychiatric symptoms. The homeostatic model assessment 2 (HOMA2) calculator was used for computing IR (HOMA2IR), insulin sensitivity (HOMA%S), and pancreatic β-cell function (HOMA%B).

RESULTS: LC is associated with neuropsychiatric diseases (FFtotal, HAMAtotal, and HAMDtotal), insulin resistance biomarkers, and inflammatory biomarkers. These biomarkers are correlated with each other in LC patients. The building of principal components for inflammatory biomarkers (PC_Inflam) and insulin resistance (PC_IR) creates vectors that could surpass individual biomarkers in neuropsychiatric issue prediction in liver cirrhosis patients. Out of the biomarkers investigated, PC_Inflam is the most important predictor for FFtotal (sensitivity and specificity of 71.4%), HAMAtotal (sensitivity and specificity of 70%), and HAMDtotal (sensitivity of 71.2% and specificity of 71.5%).

CONCLUSIONS: Neuropsychiatric disorders can be predicted by the principal component built from inflammatory biomarkers (IL-1β, IL-10, IL-18, and CRP). In contrast, PC_IR has a lower predictive value for the neuropsychiatric disorders compared with PC_Inflam. These results indicated the significant role of inflammation in the main symptoms of LC.},
}