The Effect of SARS-CoV-2 Reinfection on Long-Term Symptoms in the Innovative Support for Patients With SARS-CoV-2 Infections Registry (INSPIRE)

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.