Publication date: Jun 18, 2025
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. 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. 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]). 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.
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| Concepts | Keywords |
|---|---|
| Clear | COVID-19 |
| Coronavirus | long COVID |
| Months | post-COVID-19 syndrome |
| Organ | reinfection |
| Reinfection | SARS-CoV-2 |
Semantics
| Type | Source | Name |
|---|---|---|
| disease | MESH | Reinfection |
| disease | MESH | SARS-CoV-2 Infections |
| disease | MESH | infection |
| pathway | REACTOME | SARS-CoV-2 Infection |
| disease | MESH | Infectious Diseases |
| disease | MESH | Emergency |
| disease | MESH | long COVID |
| disease | MESH | syndrome |
| pathway | REACTOME | Reproduction |
| drug | DRUGBANK | Coenzyme M |
| pathway | REACTOME | Translation |
| disease | IDO | site |
| disease | IDO | assay |
| disease | IDO | symptom |
| disease | MESH | viral shedding |