Tag: long covid risk factors

A multidimensional immunological perspective on long COVID

Highlights:

  • Inflammaging may predispose to and be amplified by Long COVID.
  • SARS-CoV-2 may trigger autoantibodies disrupting neuroimmune balance.
  • Long COVID involves persistent immune system and autonomic dysregulation.
  • Biomarkers reflect immune and autonomic imbalance in Long COVID.
  • Biological clocks may help identify Long COVID vulnerability and guide care.

Abstract

Long COVID is a chronic condition that arises after SARS-CoV-2 infection and is characterized by persistent and often debilitating symptoms, such as fatigue, cognitive dysfunction (“brain fog”), dyspnea, and autonomic disturbances. Increasing evidence suggests that Long COVID shares key immunopathological mechanisms with autoimmune diseases, primarily sustained immune dysregulation.

In individuals with genetic or immunological susceptibility, SARS-CoV-2 infection can trigger the production of autoantibodies targeting cytokines, membrane receptors, and components of the autonomic nervous system (ANS), thereby disrupting neuroimmune homeostasis. This immune imbalance may impair anti-inflammatory regulatory pathways, such as the cholinergic anti-inflammatory pathway (CAP), and may contribute to a chronic state of inflammation and autoimmunity. One proposed contributor to this process is inflammaging – a chronic, low-grade inflammation associated with aging – which may not only predispose individuals to Long COVID but may also be amplified by the persistent immune activation seen in this condition.

In this perspective, we propose a conceptual framework in which inflammaging, immune-tolerance breakdown, and autonomic dysfunctions interact to sustain the pathophysiology of Long COVID. We discuss emerging biomarkers across these axes, including inflammatory cytokines, circulating autoantibodies, immune cell phenotypes, epigenetic modifications, and heart rate variability. Advances in inflammaging-related biomarkers and biological clocks may support early identification of individuals at higher risk for persistent immune and autonomic dysregulation, ultimately informing more precise diagnostic and therapeutic strategies for Long COVID.

Source: Giunta S, Giuliani A, Sabbatinelli J, Olivieri F. A multidimensional immunological perspective on long COVID. Cytokine Growth Factor Rev. 2025 Aug;84:1-11. doi: 10.1016/j.cytogfr.2025.07.001. Epub 2025 Jul 5. PMID: 40640033. https://pubmed.ncbi.nlm.nih.gov/40640033/

Reinfection with SARS-CoV-2 in the Omicron Era is Associated with Increased Risk of Post-Acute Sequelae of SARS-CoV-2 Infection: A RECOVER-EHR Cohort Study

Abstract:

Importance: Post-acute sequelae of SARS-CoV-2 infection (PASC) remains a major public health challenge. While previous studies have focused on characterizing PASC and identifying its subphenotypes in children and adolescents following an initial SARS-CoV-2 infection, the risks of PASC with Omicron-variant reinfections remain unclear. Using a real-world data approach, this study investigates the risks of PASC following reinfections during the Omicron phase in the pediatric population.

Objective: To investigate the risks of PASC diagnosis and 24 PASC symptoms and conditions after reinfection of SARS-CoV-2 during Omicron period in the pediatric population.

Design setting and participants: This retrospective cohort study used data from the RECOVER consortium comprising 40 children’s hospitals and health institutions in U.S. between January 2022 and October 2023.

Exposures: A second SARS-CoV-2 infection, confirmed by a positive polymerase-chain-reaction (PCR) or antigen tests, or a diagnose of COVID-19, occurring at least 60 days after the initial infection, compared to the initial infection.

Main outcomes and measures: PASC was identified using two approaches: (1) the ICD-10-CM diagnosis code U09.9 and (2) a symptom-based definition including 24 physician-identified symptoms and conditions. Absolute risks of incident PASC were reported, and relative risks (RRs) were calculated by comparing the second infection episode with the first infection episode groups using a modified Poisson regression model, adjusting for demographic, clinical, and healthcare utilization factors through exact matching and propensity scoring matching.

Results: A total of 465,717 individuals under 21 years old (mean [SD] age 8.17 [6.58] years; 52% male) were included. Compared to the first infection, a second infection was associated with significantly increased risk of an overall PASC diagnosis (RR, 2.08; 95% confidence interval [CI], 1.68-2.59), and with many specific conditions including: myocarditis (RR, 3.60; 95% CI, 1.46-8.86); changes in taste and smell (RR, 2.83; 95% CI, 1.41-5.67); thrombophlebitis and thromboembolism (RR, 2.28; 95% CI, 1.71-3.04); heart disease (RR, 1.96; 95% CI, 1.69 to 2.28); acute kidney injury (RR, 1.90; 95% CI, 1.38 to 2.61); fluid and electrolyte (RR, 1.89; 95% CI, 1.62 to 2.20); generalized pain (RR, 1.70; 95% CI, 1.48 to ; arrhythmias (RR, 1.59; 95% CI, 1.45-1.74); abnormal liver enzyme (RR, 1.56; 95% CI, 1.24 to ; fatigue and malaise (RR, 1.50; 95% CI, 1.38 to 1.64); musculoskeletal pain (RR, 1.45; 95% CI, 1.37 to 1.54); abdominal pain (RR, 1.42; 95% CI, 1.34 to 1.50); postural orthostatic tachycardia syndromes (POTS)/dysautonomia (RR, 1.35; 95% CI, 1.20 to 1.51); cognitive functions (RR, 1.32; 95% CI, 1.15 to 1.50); and respiratory signs and symptoms (RR, 1.29; 95% CI, 1.25 to 1.33). The risks were consistent across various organ systems, including cardiovascular, respiratory, gastrointestinal, neurological, and musculoskeletal systems.

Conclusions and relevance: Children and adolescents face significantly higher risk of various PASC outcomes after reinfection with SARS-CoV-2. These findings suggest a cumulative risk of PASC and highlight the urgent need for targeted prevention strategies to reduce reinfections, which includes an increased emphasis on initial or re-vaccination of children.

Source: Zhang B, Wu Q, Jhaveri R, Zhou T, Becich MJ, Bisyuk Y, Blanceró F, Chrischilles EA, Chuang CH, Cowell LG, Fort D, Horowitz CR, Kim S, Ladino N, Liebovitz DM, Liu M, Mosa ASM, Schwenk HT, Suresh S, Taylor BW, Williams DA, Morris JS, Forrest CB, Chen Y. Reinfection with SARS-CoV-2 in the Omicron Era is Associated with Increased Risk of Post-Acute Sequelae of SARS-CoV-2 Infection: A RECOVER-EHR Cohort Study. medRxiv [Preprint]. 2025 Mar 30:2025.03.28.25324858. doi: 10.1101/2025.03.28.25324858. PMID: 40196285; PMCID: PMC11974971. https://pmc.ncbi.nlm.nih.gov/articles/PMC11974971/ (Full text)

Long COVID Incidence Proportion in Adults and Children Between 2020 and 2024: An Electronic Health Record-Based Study From the RECOVER Initiative

Abstract:

Background: Incidence estimates of post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, also known as long COVID, have varied across studies and changed over time. We estimated long COVID incidence among adult and pediatric populations in 3 nationwide research networks of electronic health records (EHRs) participating in the RECOVER (Researching COVID to Enhance Recovery) Initiative using different classification algorithms (computable phenotypes).

Methods: This EHR-based retrospective cohort study included adult and pediatric patients with documented acute SARS-CoV-2 infection and 2 control groups: contemporary coronavirus disease 2019 (COVID-19)-negative and historical patients (2019). We examined the proportion of individuals identified as having symptoms or conditions consistent with probable long COVID within 30-180 days after COVID-19 infection (incidence proportion). Each network (the National COVID Cohort Collaborative [N3C], National Patient-Centered Clinical Research Network [PCORnet], and PEDSnet) implemented its own long COVID definition. We introduced a harmonized definition for adults in a supplementary analysis.

Results: Overall, 4% of children and 10%-26% of adults developed long COVID, depending on computable phenotype used. Excess incidence among SARS-CoV-2 patients was 1.5% in children and ranged from 5% to 6% among adults, representing a lower-bound incidence estimation based on our control groups. Temporal patterns were consistent across networks, with peaks associated with introduction of new viral variants.

Conclusions: Our findings indicate that preventing and mitigating long COVID remains a public health priority. Examining temporal patterns and risk factors for long COVID incidence informs our understanding of etiology and can improve prevention and management.

Source: Mandel H, Yoo YJ, Allen AJ, Abedian S, Verzani Z, Karlson EW, Kleinman LC, Mudumbi PC, Oliveira CR, Muszynski JA, Gross RS, Carton TW, Kim C, Taylor E, Park H, Divers J, Kelly JD, Arnold J, Geary CR, Zang C, Tantisira KG, Rhee KE, Koropsak M, Mohandas S, Vasey A, Mosa ASM, Haendel M, Chute CG, Murphy SN, O’Brien L, Szmuszkovicz J, Guthe N, Santana JL, De A, Bogie AL, Halabi KC, Mohanraj L, Kinser PA, Packard SE, Tuttle KR, Hirabayashi K, Kaushal R, Pfaff E, Weiner MG, Thorpe LE, Moffitt RA. Long COVID Incidence Proportion in Adults and Children Between 2020 and 2024: An Electronic Health Record-Based Study From the RECOVER Initiative. Clin Infect Dis. 2025 Jul 18;80(6):1247-1261. doi: 10.1093/cid/ciaf046. PMID: 39907495; PMCID: PMC12272849. https://pubmed.ncbi.nlm.nih.gov/39907495/

Gastrointestinal Barrier Disruption in Post-COVID Syndrome Fatigue Patients

Abstract:

Background: Post-COVID Syndrome (PCS) is the term for a condition with persistent symptoms in a proportion of COVID-19 patients after asymptomatic, mild, or severe disease courses. Numbers vary, but the current estimate is that after COVID-19 approximately 10% develop PCS. The aim of our study was to evaluate the impact of SARS-CoV-2 infection on the gastrointestinal (GI) tract and associations with the development of PCS with fatigue, post-exertional malaise (PEM), orthostatic dysregulation, autonomous dysregulation, and/or neurocognitive dysregulation.

Methods: By combining medical record data from a prospective observational study with symptom analysis before, during, and after SARS-CoV-2 infection, we aimed to identify potential risk factors and predictive markers for PCS. Additionally, we analyzed blood, saliva, and stool samples from this well-characterized PCS patient cohort to biologically validate our findings.

Results: We identified significant associations between pre-existing GI complaints and the development of PCS Fatigue. PCS patients showed higher LBP/sCD14 ratios, lower IL-33 levels, and higher IL-6 levels compared to control groups. Our results highlight the critical role of the GI tract in PCS development of post-viral Fatigue.

Conclusion: We propose that the viral infection disrupts pathways related to the innate immune response and GI barrier function, evidenced by intestinal low-grade inflammation and GI barrier leakage. Monitoring GI symptoms and markers before, during, and after SARS-CoV-2 infection is crucial for identifying predictive clinical phenotypes in PCS. Understanding the interaction between viral infections, immune responses, and gut integrity could lead to more effective diagnostic and treatment strategies, ultimately reducing the burden on PCS patients.

Source: Rohrhofer J, Wolflehner V, Schweighardt J, Koidl L, Stingl M, Zehetmayer S, Séneca J, Pjevac P, Untersmayr E. Gastrointestinal Barrier Disruption in Post-COVID Syndrome Fatigue Patients. Allergy. 2025 May 15. doi: 10.1111/all.16593. Epub ahead of print. PMID: 40372110. https://onlinelibrary.wiley.com/doi/10.1111/all.16593 (Full text)

Impact of COVID-19 on myalgic encephalomyelitis/chronic fatigue syndrome-like illness prevalence: A cross-sectional survey

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) can be triggered by infectious agents including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the impact of the coronavirus disease 2019 (COVID-19) pandemic on ME/CFS prevalence is not well characterized.

Methods: In this population-based cross-sectional study, we enrolled a stratified random sample of 9,825 adult participants in the Kaiser Permanente Northern California (KPNC) integrated health system from July to October 2022 to assess overall ME/CFS-like illness prevalence and the proportion that were identified following COVID-19 illness. We used medical record and survey data to estimate the prevalence of ME/CFS-like illness based on self-reported symptoms congruent with the 2015 Institute of Medicine ME/CFS criteria. History of COVID-19 was based on a positive SARS-CoV-2 nucleic acid amplification test or ICD-10 diagnosis code in the medical record, or self-report of prior COVID-19 on a survey.

Results: Of 2,745,374 adults in the eligible population, an estimated 45,892 (95% confidence interval [CI]: 32,869, 58,914) or 1.67% (CI 1.20%, 2.15%) had ME/CFS-like illness. Among those with ME/CFS-like illness, an estimated 14.12% (CI 3.64%, 24.6%) developed the illness after COVID-19. Among persons who had COVID-19, those with ME/CFS-like illness after COVID-19 were more likely to be unvaccinated and to have had COVID-19 before June 1, 2021. All persons with ME/CFS-like illness had significant impairment in physical, mental, emotional, social, and occupational functioning compared to persons without ME/CFS-like illness.

Conclusions: In a large, integrated health system, 1.67% of adults had ME/CFS-like illness and 14.12% of all persons with ME/CFS-like illness developed it after COVID-19. Though COVID-19 did not substantially increase ME/CFS-like illness in the KPNC population during the study time period, ME/CFS-like illness nevertheless affects a notable portion of this population and is consistent with estimates of ME/CFS prevalence in other populations. Additional attention is needed to improve awareness, diagnosis, and treatment of ME/CFS.

Source: Wood MS, Halmer N, Bertolli J, Amsden LB, Nugent JR, Lin JS, Rothrock G, Nadle J, Chai SJ, Cope JR, Champsi JH, Yang J, Unger ER, Skarbinski J; for STOP-ME/CFS and COVID-SELECT. Impact of COVID-19 on myalgic encephalomyelitis/chronic fatigue syndrome-like illness prevalence: A cross-sectional survey. PLoS One. 2024 Sep 18;19(9):e0309810. doi: 10.1371/journal.pone.0309810. PMID: 39292671; PMCID: PMC11410243. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11410243/ (Full text)

Characteristics and predictors of Long Covid in children: a 3-year prospective cohort study

Summary:

Background: Children can develop Long Covid, however long term outcomes and their predictors are poorly described in these patients. The primary aim is to describe characteristics and predictors of Long Covid in children assessed in-clinics up to 36 months post-SARS-CoV-2 infection, as well as investigate the role of vaccines in preventing Long Covid, risk of reinfections and development of autoimmune diseases.

Methods: Children aged 0–18 years old with confirmed SARS-CoV-2 infection were invited for a prospective follow-up assessment at a peadiatric post-covid clinic in Rome, Italy, at serial intervals (3-, 6-, 12-, 18-, 24- and 36-months post-infection onset, between 01/02/2020 and 28/02/2024). Long Covid was defined as persistence of otherwise unexplained symptoms for at least three months after initial infection.

Findings: 1319 patients were initially included, 1296 reached the 3 months follow-up or more. Of the patients who underwent multiple follow-ups, 23.2% (301), 169 (13.2%), 89 (7.9%), 67 (6.1%), 47 (7.1%) were diagnosed with Long Covid at 3-6-12-18-24 months, respectively For the primary outcome of Long Covid at three months, age >12 years (P < 0.001, OR 11.33, 95% CI 4.2; 15.15), comorbidities (P = 0.008, OR 1.83, 95% CI 1.06; 2.44), being infected with original variants (P < 0.001, OR 4.77, 95% CI 2.46; 14.47), female sex (P < 0.001, OR 1.62, 95% CI 1.02; 1.89) were statistically significant risk factors. Age >12 years (P = 0.002, OR 9.37, 95% CI 1.58; 8.64), and infection with original (P = 0.012, OR 3.52, 95% CI 1.32; 8.64) and alfa (P < 0.001, OR 4.09, 95% CI 2.01; 8.3) SARS-CoV-2 variants remained statistically significant risk factors for Long Covid duration for at least 18 months. Vaccination was associated with a lower risk of long covid at 3, 6 and 12 months for older children and a lower risk of reinfections. Being infected with the original SARS-CoV-2 variant was associated with a higher risk of new-onset autoimmune diseases ((P = 0.035, 95% CI 1.12; 2.4). One patient was diagnosed with Long Covid after a re-infection.

Interpretation: This is the longest follow-up study of children with SARS-CoV-2 infection, showing a significant and long-lasting burden of Long Covid in the pediatric population. Our findings highlight the urgent need of investing in pediatric Long Covid in order to find effective diagnostic and therapeutic approaches, as well can inform preventive strategies in case of future pandemics.

Source: Camporesi, Anna et al. Characteristics and predictors of Long Covid in children: a 3-year prospective cohort study.  eClinicalMedicine, Volume 76, 102815 https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(24)00394-8/fulltext

The Effect of Sex on the Risk of Long-COVID and Cardiovascular Complications in Healthy Patients without Comorbidities: Data from a Polish Long-COVID Cardiovascular (PoLoCOV-CVD) Study

Abstract:

Background: The prevalence of long-COVID (LC) presents a significant challenge to healthcare systems globally. There are still some discrepancies on the role of sex as an independent risk factor of LC complications. Thus, we aimed to determine the differences in clinical and cardiovascular complications between males and females without comorbidities after COVID-19.
Methods: Clinical data on the course of the disease with the accompanying symptoms and post-COVID-19 symptoms were compiled from both male and female subjects with a minimum 12-week interval after COVID-19 recovery. Next, the patients were followed for 12 months. ECG, echocardiography, 24 h ECG monitoring, 24 h ambulatory blood pressure monitoring (ABPM), and selected biochemical tests were performed. LC was diagnosed based on the World Health Organization (WHO) definition. To reduce the impact of confounders, i.e., body mass index (BMI) and age, on the results of the study, the nearest neighbour (NN) propensity score matching (PSM) method with a 1:1 ratio was used.
Results: The results were obtained following the removal of cases with comorbidities from the database consisting of 1237 males and 2192 females, and PSM of the new database included 886 cases (443 males and 443 females). At both the 3-month and 1-year post-recovery marks, females consistently reported a higher frequency of LC symptoms compared to males (p < 0.001 for both comparisons). Moreover, after 1 year of follow-up, females exhibited a higher prevalence of LC compared to males, with rates of 14% versus 8.3%, respectively (p = 0.013).
The symptoms that significantly differed between females and males in the 12-month follow-up were hair loss (5.4 vs. 0.7%, p < 0.001), memory and concentration disturbances (8.4 vs. 4.3%, p = 0.013), and headaches (4.3 vs. 1.4%, p = 0.008). Females presented lower mean arterial pressure (MAP) [89 (83–95) mmHg versus (vs.) 94 (89–100); p < 0.001] and lower pulse pressure (PP) [46 (42–52) mmHg vs. 51 (48–57); p < 0.001] in 24 h ABPM and more elevated heart rates (HRs) in 24 h ECG monitoring as well as arrhythmia (p < 0.001 and p = 0.018, respectively). Males had a higher occurrence of ECG abnormalities such as QRS >= 120 ms, ST-T changes, T inversion, arrhythmia, and QRS fragmentation (27.3% vs. 19.2%; p = 0.004). No significant differences were observed between males and females concerning physical activity levels, stress, fatigue, alcohol consumption, and smoking habits.
Conclusions: One year post-COVID-19 recovery, regardless of age and BMI, healthy females more often suffered from LC symptoms than males. They had lower MAP and PP in 24 h ABPM, more often had higher HRs and arrhythmia in 24 h ECG monitoring, and fewer ECG abnormalities than males.
Source: Bielecka-Dabrowa A, Sakowicz A, Gryglewska-Wawrzak K, Kapusta J, Banach M, Jankowski P, Chudzik M. The Effect of Sex on the Risk of Long-COVID and Cardiovascular Complications in Healthy Patients without Comorbidities: Data from a Polish Long-COVID Cardiovascular (PoLoCOV-CVD) Study. Journal of Clinical Medicine. 2024; 13(6):1559. https://doi.org/10.3390/jcm13061559 https://www.mdpi.com/2077-0383/13/6/1559 (Full text)

Role of the complement system in Long COVID

Abstract:

Long COVID, or Post-Acute COVID Syndrome (PACS), may develop following SARS-CoV-2 infection, posing a substantial burden to society. Recently, PACS has been linked to a persistent activation of the complement system (CS), offering hope for both a diagnostic tool and targeted therapy. However, our findings indicate that, after adjusting proteomics data for age, body mass index and sex imbalances, the evidence of complement system activation disappears.

Furthermore, proteomic analysis of two orthogonal cohorts—one addressing PACS following severe acute phase and another after a mild acute phase—fails to support the notion of persistent CS activation. Instead, we identify a proteomic signature indicative of either ongoing infections or sustained immune activation similar to that observed in acute COVID-19, particularly within the mild-PACS cohort.

Source: Vadim Farztdinov, Boris Zühlke, Franziska Sotzny, Fridolin Steinbeis, Martina Seifert, Claudia Kedor, Kirsten Wittke, Pinkus Tober-Lau, Thomas Zoller, Kathrin Textoris-Taube, Daniela Ludwig, Clemens Dierks, Dominik Bierbaum, Leif Erik Sander, Leif G Hanitsch, Martin Witzenrath, Florian Kurth, Michael Mülleder, Carmen Scheibenbogen, Markus Ralser. Role of the complement system in Long COVID. medRxiv 2024.03.14.24304224; doi: https://doi.org/10.1101/2024.03.14.24304224 https://www.medrxiv.org/content/10.1101/2024.03.14.24304224v1.full-text (Full text)

Headache or Disturbed Smell and Taste During Acute COVID-19 as Predictors of Long COVID at One Year

Abstract:

Purpose: Long coronavirus disease (COVID) poses a significant health concern for a substantial proportion of COVID-19 patients. Viral pathogenesis studies suggest the potential of central nervous system (CNS) affection in the acute phase of COVID-19 predicting long COVID.

This study investigates whether acute COVID-19 symptoms, particularly headache and disturbed smell and taste, predict manifestations of long COVID.

Methods: This prospective cohort study included COVID-19 patients hospitalized between March 2020, and May 2021. One year after discharge, patients responded to a symptom questionnaire. Logistic regression analysis was used to determine the odds ratio (OR) for these outcomes.

Results: Of 288 eligible patients, 111 responded to the follow-up questionnaire. At 1 year follow-up, disturbed smell and taste during acute COVID-19 did not elevate the risk of long COVID. However, patients with acute headache demonstrated a tendency towards an elevated risk of CNS-related long COVID. Notably, this risk significantly increased in patients reporting dizziness (adjusted OR=4.20; 95% confidence interval (CI) 1.19 – 14.85). Neither disturbed smell and taste nor headache during acute COVID-19 indicated a statistically significant risk of worsening in fatigue, health, or total symptom score at 1-year follow-up.

Conclusion: Headache, and not disturbed smell and taste, predicted CNS-related long COVID. Further research is warranted to clarify pathways connecting CNS-related symptoms during acute COVID-19 with long COVID, aiding the efforts of addressing the range of symptoms observed among long COVID patients and developing effective interventions.

Source: Jane Agergaard. Headache or Disturbed Smell and Taste During Acute COVID-19 as Predictors of Long COVID at One Year, 07 February 2024, PREPRINT (Version 1) available at Research Square [https://doi.org/10.21203/rs.3.rs-3930891/v1] https://www.researchsquare.com/article/rs-3930891/v1 (Full text)

SSRI Use During Acute COVID-19 Infection Associated with Lower Risk of Long COVID Among Patients with Depression

Abstract:

Background Long COVID, also known as post-acute sequelae of COVID-19 (PASC), is a poorly understood condition with symptoms across a range of biological domains that often have debilitating consequences. Some have recently suggested that lingering SARS-CoV-2 virus in the gut may impede serotonin production and that low serotonin may drive many Long COVID symptoms across a range of biological systems. Therefore, selective serotonin reuptake inhibitors (SSRIs), which increase synaptic serotonin availability, may prevent or treat Long COVID. SSRIs are commonly prescribed for depression, therefore restricting a study sample to only include patients with depression can reduce the concern of confounding by indication.

Methods In an observational sample of electronic health records from patients in the National COVID Cohort Collaborative (N3C) with a COVID-19 diagnosis between September 1, 2021, and December 1, 2022, and pre-existing major depressive disorder, the leading indication for SSRI use, we evaluated the relationship between SSRI use at the time of COVID-19 infection and subsequent 12-month risk of Long COVID (defined by ICD-10 code U09.9). We defined SSRI use as a prescription for SSRI medication beginning at least 30 days before COVID-19 infection and not ending before COVID-19 infection. To minimize bias, we estimated the causal associations of interest using a nonparametric approach, targeted maximum likelihood estimation, to aggressively adjust for high-dimensional covariates.

Results We analyzed a sample (n = 506,903) of patients with a diagnosis of major depressive disorder before COVID-19 diagnosis, where 124,928 (25%) were using an SSRI. We found that SSRI users had a significantly lower risk of Long COVID compared to nonusers (adjusted causal relative risk 0.90, 95% CI (0.86, 0.94)).

Conclusion These findings suggest that SSRI use during COVID-19 infection may be protective against Long COVID, supporting the hypothesis that serotonin may be a key mechanistic biomarker of Long COVID.

Source: Zachary Butzin-Dozier, Yunwen Ji, Sarang Deshpande, Eric Hurwitz, Jeremy Coyle, Junming (Seraphina) Shi, Andrew Mertens, Mark J. van der Laan, John M. Colford Jr., Rena C. Patel, Alan E. Hubbard, the National COVID Cohort Collaborative (N3C) Consortium. SSRI Use During Acute COVID-19 Infection Associated with Lower Risk of Long COVID Among Patients with Depression. medRxiv 2024.02.05.24302352; doi: https://doi.org/10.1101/2024.02.05.24302352 https://www.medrxiv.org/content/10.1101/2024.02.05.24302352v1.full-text (Full text)