The following is a summary of “Target Trial Emulation of Severe Acute Respiratory Syndrome Coronavirus 2 Infection Versus No Infection and Risk of Post–Coronavirus Disease 2019 Conditions in the Omicron Variant Versus Prior Eras,” published in the April 2025 issue of Clinical Infectious Diseases by Ioannou et al. 

Coronavirus disease 2019 (COVID-19) has been related to the development of post–COVID–19 conditions (PCCs).   

Researchers conducted a retrospective study to specify if severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection increased the risk of selected PCCs or death up to 1 year after infection, across different viral strains and vaccination statuses.   

They utilized health records from the Veterans Health Administration to simulate a target trial comparing SARS-CoV-2 infection to no infection. Veterans who were positive for SARS-CoV-2 between March 2020 and April 2022 (n = 4,30,160) were matched 1:1 with veterans who had not tested positive. All-cause mortality and the cumulative incidence of 32 potential PCCs were assessed at 31–180 and 181–365 days post-infection or matched index date.   

The results showed that from 31 to 180 days, the cumulative incidence of death and all organ-level PCCs was higher in infected (n = 4,30,160) than uninfected participants, with smaller differences in the Omicron era compared to the wild-type (WT) era. The cumulative incidence was also lower in vaccinated individuals compared to unvaccinated. In the Omicron era, from days 181–365, the incidence of death and most PCCs was higher in infected vs uninfected participants, but only among unvaccinated individuals, not vaccinated ones.   

Investigators concluded that an excess burden of PCCs and mortality persisted 31–180 days after Omicron infection, though lower than in earlier eras, while beyond 180 days, a much lower excess burden was mainly observed among unvaccinated individuals in the Omicron era, suggesting vaccine protection. 

Source: academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaf087/8110189