Loading...
Thumbnail Image
Publication

SSRI use during acute COVID-19 and risk of long COVID among patients with depression

Butzin-Dozier, Zachary
Ji, Yunwen
Deshpande, Sarang
Hurwitz, Eric
Anzalone, A Jerrod
Coyle, Jeremy
Shi, Junming
Mertens, Andrew
van der Laan, Mark J
Colford, John M
... show 2 more
Embargo Expiration Date
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 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.

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 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.

Results: We 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)).

Conclusions: These 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.

Source

Butzin-Dozier Z, Ji Y, Deshpande S, Hurwitz E, Anzalone AJ, Coyle J, Shi J, Mertens A, van der Laan MJ, Colford JM Jr, Patel RC, Hubbard AE; National COVID Cohort Collaborative (N3C) Consortium. SSRI use during acute COVID-19 and risk of long COVID among patients with depression. BMC Med. 2024 Oct 8;22(1):445. doi: 10.1186/s12916-024-03655-x. PMID: 39380062; PMCID: PMC11462648.

Year of Medical School at Time of Visit
Sponsors
Dates of Travel
DOI
10.1186/s12916-024-03655-x
PubMed ID
39380062
Other Identifiers
Notes
Funding and Acknowledgements
The UMass Center for Clinical and Translational Science (UMCCTS), UL1TR001453, provided data for this study.
Corresponding Author
Related Resources
Related Resources
Repository Citation
Rights
© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.Attribution 4.0 International