Sars-Cov-2 Infection and Long-Term Risk of Cardiovascular and Renal Morbidity

ABSTRACT Importance 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. Objective To examine long-term associations between SARS-CoV-2 infection and cardiovascular and kidney disease (CVD, KD) in the general population, with emphasis on age and vaccination status at the time of infection, mild infection, and SARS-CoV-2 variant. Design Register-based cohort study. Setting Denmark Participants All Danish residents with ≥1 PCR test for SARS-CoV-2 infection, March 2020-December 2022. Exposure Positive PCR test for SARS-CoV-2 infection. Main Outcomes 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. Results 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. Conclusions and Relevance 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. KEY POINTS Question Does SARS-CoV-2 infection increase the long-term risks of cardiovascular disease (CVD) or kidney disease (KD) in a general population cohort with predominantly mild infection? Findings In a cohort study of >4.5 million persons that compared SARS-CoV-2 test-positive and test-negative persons, relative risks were slightly increased for 6 of 21 CVD and KD outcomes up to 1 year after infection. Among vaccinated individuals and omicron-infected persons, existing associations diminished dramatically. Meaning In the general population, long-term increases in CKD and KD risks associated with infection were small, limited to a few outcomes, and attenuated with vaccination and the omicron variant.