Multi-systemic risk of post-acute sequelae associated with SARS-CoV-2 reinfection

Increased risk of post-acute sequelae was found to occur in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 reinfections). However, it is unclear whether these increases in post-acute risk are found in milder Omicron reinfections, or persist in a highly boosted population.

We utilised national COVID-19 databases and healthcare-claims records of Singapore to construct SARS-CoV-2 infected and uninfected cohorts over periods of Delta, Omicron BA.1/2, BA.4/5 and XBB predominance (1 July 2021-28 February 2023). The 300-day risk and excess burdens of pre-specified new-incident diagnoses across cardiovascular, neuropsychiatric, endocrine, auto-immune, renal, respiratory and gastrointestinal domains was compared across SARS-CoV-2 re-infected individuals (N = 57,222), SARS-CoV-2-infected individuals without documented re-infection (N = 1,239,119), and population-based un-infected controls (N = 3,409,170). Risk trajectories between groups were compared to examine whether differences in risk of post-acute sequelae persisted over follow-up time.

There was an estimated 21% (hazards ratios (HR) = 1.21; 95% Confidence interval (CI) [1.15-1.28]) increase in risk of any post-acute sequelae, and increased post-acute risk of cardiovascular (HR = 1.20; 95% CI [1.09-1.32]), gastrointestinal (HR 1.26; 95% CI [1.16-1.38]), neurological (HR 1.32; 95% CI [1.23-1.42]), endocrine (HR 1.26; 95% CI [1.18-1.35]), respiratory (HR 1.63; 95% CI [1.44-1.83]) and renal (HR 1.28; 95% CI [1.12-1.47]) sequelae associated with SARS-CoV-2 reinfections. Associated risks of post-acute sequelae were greater in reinfections compared to first infections. Excess burdens per 1000 of any post-acute sequelae were also higher in reinfected individuals, and reinfected individuals also had higher outcome probabilities of post-acute sequelae over follow-up time. Risks of post-acute sequelae persisted in fully vaccinated and boosted individuals.

Reinfection with SARS-CoV-2 is associated with increased risk of post-acute sequelae. Reducing burden of post-acute complications due to SARS-CoV-2 necessitates strategies for preventing reinfection, such as updated vaccines with better effectiveness against infection.