SARS-CoV-2 infection and long-term risk of cardiovascular and renal morbidity

Cardiovascular and renal consequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been studied intensively in high-risk groups, but the consequences of mild infection for the general population, particularly beyond the acute phase of infection, remain unclear. We examined long-term associations between SARS-CoV-2 infection and cardiovascular disease (CVD) and kidney disease (KD) in the general population, with emphasis on age and vaccination status at the time of infection, mild infection, and SARS-CoV-2 variant.

We conducted a register-based cohort study in Denmark that included all Danish residents with ≥1 PCR test for SARS-CoV-2 infection in the period March 2020-December 2022. We defined exposure as a positive PCR test for SARS-CoV-2 infection and used Cox regression to estimate hazard ratios for 15 CVD outcomes and six KD outcomes, comparing persons testing positive for SARS-CoV-2 infection and persons who only ever tested negative for infection. The cohort for CVD analyses included 4 508 489 persons without pre-existing CVD [median follow-up 25.2 months/person, interquartile range (IQR) 21.7-27.5 months]; 2 698 261 persons (59.8%) tested positive for SARS-CoV-2 infection during the study period. The cohort for the KD analyses included 5 150 480 persons without pre-existing KD (median follow-up 25.1 months, IQR 21.7-27.4 months), 2 983 233 (57.9%) of whom tested positive for infection. SARS-CoV-2 infection was associated with slight increases in the risks of pulmonary embolism, venous embolism/thrombosis, arrhythmias, chronic renal failure, unspecified renal failure, and other/unspecified KD up to a year after infection; infection was not associated with the other disease groups tested. The strongest associations between SARS-CoV-2 infection and CVD and KD were observed among unvaccinated persons and persons infected with earlier (pre-omicron) variants.

We found little evidence that infection with SARS-CoV-2 was associated with increased long-term risks of CVD or KD in the general population. Increased CVD risks associated with SARS-CoV-2 infection appeared limited to three outcomes (pulmonary embolism, venous embolism/thrombosis, arrhythmias), and the potential increases in risk were small. Our KD results also suggested that any persistent risks associated with SARS-CoV-2 infection were minimal; however, these findings need to be confirmed in other populations. Most importantly, in a largely vaccinated population, long-term CVD and KD risks differed little for omicron-infected and uninfected persons.