Post-infection sequelae of COVID-19 and other infectious diseases—a nationwide Danish study with 40-month follow-up

Nationwide follow-up studies of long-term post-acute COVID-19 sequelae compared with sequelae of other infections have been lacking. Using nationwide registers, we analyzed all SARS-CoV-2 PCR test results, prescriptions for anti-infective agents, and hospitalizations with COVID-19 or other infections in Denmark from March 2020 to June 2023, including up to 40-month follow-up. We used Cox proportional hazards models with time-varying exposures to estimate the rates of first-time mental disorders (n = 5,306,132) and general medical conditions (n = 3,517,630). Here we show that positive SARS-CoV-2 PCR tests alone were not associated with clinically relevant increased rates of mental disorders or general medical conditions when compared with negative SARS-CoV-2 PCR tests, nor when compared to individuals with anti-infective prescriptions. Rates of general medical conditions after a positive compared with a negative SARS-CoV-2 PCR test were only elevated for virus types preceding Omicron and for individuals with less than 3 vaccination doses. Compared with the general population, the rates of mental disorders or general medical conditions were elevated among hospitalized COVID-19 patients, and particularly when ICU treatment was required. However, when comparing patients hospitalized with COVID-19 to patients hospitalized with non-COVID-19 pulmonary infections or other infections, the rates of mental disorders or general medical conditions were increased to the same extent. In conclusion, severe COVID-19 post-infection sequelae are comparable to sequelae observed after other infections of similar severity.