Document Type
Article
Publication Date
6-18-2025
Abstract
BACKGROUND: The clinical consequences of repeated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are not clear, especially as they relate to long-term symptoms after infection. We analyzed data collected for the Innovative Support for Patients with SARS-CoV-2 Infections Registry (INSPIRE) to determine whether reinfection changes the likelihood of symptoms 3-6 months after reinfection compared with the likelihood in individuals experiencing a single infection.
METHODS: Individuals reporting a single SARS-CoV-2 infection or a single reinfection were included in this analysis. A positive SARS-CoV-2 test occurring ≥90 days after a first infection was considered a reinfection. Outcomes included severe fatigue (fatigue severity score ≥25) and the presence of organ system symptoms 3-6 months after the last infection.
RESULTS: The analysis included 886 individuals, 415 (46.8%) of whom experienced reinfection. For individuals who experienced their first infections in either the pre-Delta or Delta periods, the odds of having ≥3 symptoms 3-6 months after their most recent infection was lower in those reinfected than those with a single infection (weighted adjusted odds ratio, 0.45 [95% confidence interval, .21-.95] and 0.51 [.32-.79], respectively). However, in individuals reporting their first infection during the Omicron wave, the odds of reporting ≥3 symptoms after the most recent infection was higher in those reinfected than in those with a single infection (weighted adjusted odds ratio, 1.54 [95% confidence interval, 1.02-2.34]).
CONCLUSIONS: The timing of initial infection, reinfection, and the variants involved may play important roles in longer-term clinical outcomes. Repeated infection with Omicron variants may increase the risk of long-term symptoms.
Recommended Citation
Openshaw, John J.; Chen, Ji; Rodriguez, Robert; Gottlieb, Michael; McCullough, Kalyani; Santangelo, Michelle; Hill, Mandy J.; Gatling, Kristyn; Idris, Ahamed H.; McDonald, Samuel; Wisk, Lauren E.; Dyal, Jonathan; Wang, Ralph C.; Rising, Kristin L.; Kean, Efrat; O'Laughlin, Kelli N.; Stephens, Kari A.; Malicki, Caitlin; Lin, Zhenqiu; Spatz, Erica S.; Yu, Huihui; Weinstein, Robert A.; and Elmore, Joann, "The Effect of SARS-CoV-2 Reinfection on Long-Term Symptoms in the Innovative Support for Patients with SARS-CoV-2 Infections Registry (INSPIRE)" (2025). Department of Emergency Medicine Faculty Papers. Paper 272.
https://jdc.jefferson.edu/emfp/272
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Supplementary Data
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PubMed ID
40576557
Language
English
Comments
This article is the author's final published version in Clinical Infectious Diseases, Volume 81, Issue 3, September 15, 2025, Pages 416–426.
The published version is available at https://doi.org/10.1093/cid/ciaf225.. Copyright © The Author(s) 2025.