Characterization of post-acute multi-organ sequelae following SARS-CoV-2 Infection in the Delta and Omicron Eras in a...

Multi-organ post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) is extensively documented. Recent studies in predominantly Caucasian populations suggest that the evolution of SARS-CoV-2 variants can influence risk (as measured by hazard ratios) and rates (as measured by incidence rate ratios) of PASC, and they also highlight the protective effects of COVID-19 vaccination. However, it is unclear whether risks or rates of PASC have changed over different Omicron subvariants in an Asian population with high uptake of COVID-19 vaccine booster doses.

We constructed a national cohort of individuals infected with SARS-CoV-2 and estimated the 31-300-day risks and rates of pre-specified new-incident diagnoses across the cardiovascular, neuropsychiatric, auto-immune, renal, and gastrointestinal domains between 1,427,985 and 3,284,081 unique individuals who tested positive or negative for SARS-CoV-2 infection respectively, across Delta, Omicron BA.1/2, BA.4/5, and XBB predominance. We compared risks/rates of new-incident diagnoses between test positives and test negatives in each era.

Compared to test-negatives, asides from increased risk of renal outcomes in BA.1/2 (aHR, 1.17; 95% CI, 1.09-1.26), there were no increased risks of composite diagnoses in other organ systems across all 4 variants of concern. In terms of individual outcomes, there were increased risks or rates of diagnosis of individual neuropsychiatric outcomes, such as memory problems, Alzheimer's disease across all eras, and loss of smell or taste only in Delta. There were also increased risks of diagnosis of individual renal outcomes, such as end stage renal failure in BA.1/2 (aHR, 1.52; 95% CI, 1.27-1.81). In COVID-19 survivors who were hospitalised, risks and rates of cardiovascular, neuropsychiatric, and renal diagnoses in the post-acute period were increased in most eras. COVID-19 vaccinations reduced the risks of composite diagnoses.

The risks/rates of pre-specified new-incident multi-organ PASC were modest over all studied COVID-19 eras. The risk was further attenuated with booster vaccination during the Omicron BA.4/5 and XBB periods compared with the Omicron BA.1/2 period.