Observational studyBMC medicine2024
SSRI use during acute COVID-19 and risk of long COVID among patients with depression.
Observational study in BMC medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- COVID-19 vaccination timing, relative to acute COVID-19, and subsequent risk of long COVID.EBioMedicine · 2026Article
- SSRI prescription during acute COVID-19 and risk of Long COVID symptoms and conditions among patients with depression.medRxiv : the preprint server for health sciences · 2026Article
- IL-6 Receptor Antagonists and Severe Post-COVID-19 Outcomes: An Emulated Target Trial.medRxiv : the preprint server for health sciences · 2026Article
- Associations of selective serotonin reuptake inhibitors and long COVID risk in patients with depression: a retrospective cohort study.Infection · 2026Article
- Analysis of epidemiological characteristics and influencing factors of Long COVID syndrome among university students in the post-pandemic era.Frontiers in public health · 2026Article
- SSRI/SNRI and long COVID in children and adolescents with neuropsychiatric conditions: a cohort study from the RECOVER Initiative.Nature. Mental health · 2026Article
- Childhood trauma and mental health outcomes in Post-COVID Syndrome: Results from a cross-sectional study in Germany.Brain, behavior, & immunity - health · 2025Article
- Causal Inference via Electronic Health Records in the National Clinical Cohort Collaborative: Challenges and Solutions in Long COVID Research.medRxiv : the preprint server for health sciences · 2025Article
- Therapeutic options for the treatment of post-acute sequelae of COVID-19: a scoping review.BMC infectious diseases · 2025Article
- Neuropsychiatric Manifestations of Long COVID-19: A Narrative Review of Clinical Aspects and Therapeutic Approaches.Life (Basel, Switzerland) · 2025Review
- Exploring the psychological impact of long COVID: symptoms, mechanisms, and treatments.Frontiers in psychiatry · 2025Review
- Association between cardiovascular, psychotropic and anti-inflammatory/analgesic drug use and vascular dysfunction in individuals with long COVID. BioICOPER study.Frontiers in cardiovascular medicine · 2025Article
- Predicting Long COVID in the National COVID Cohort Collaborative Using Super Learner: Cohort Study.JMIR public health and surveillance · 2024Article
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
backgroundLong 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 particles 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 be used to 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.
methodsIn 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 a comorbid depressive disorder, the leading indication for SSRI use, we evaluated the relationship between SSRI use during acute COVID-19 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 acute COVID-19 and not ending before SARS-CoV-2 infection. To minimize bias, we estimated relationships using nonparametric targeted maximum likelihood estimation to aggressively adjust for high-dimensional covariates.
resultsWe analyzed a sample (n = 302,626) of patients with a diagnosis of a depressive condition before COVID-19 diagnosis, where 100,803 (33%) were using an SSRI. We found that SSRI users had a significantly lower risk of Long COVID compared to nonusers (adjusted causal relative risk 0.92, 95% CI (0.86, 0.99)) and we found a similar relationship comparing new SSRI users (first SSRI prescription 1 to 4 months before acute COVID-19 with no prior history of SSRI use) to nonusers (adjusted causal relative risk 0.89, 95% CI (0.80, 0.98)).
conclusionsThese findings suggest that SSRI use during acute COVID-19 may be protective against Long COVID, supporting the hypothesis that serotonin may be a key mechanistic biomarker of Long COVID.
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