Incidence and Potential Risk Factors of Human Cytomegalovirus Infection in Patients with Severe and Critical COVID-19: A retrospective cohort study

Background Human cytomegalovirus (HCMV) reactivation occurs in immunosuppressed individuals and is known to increase mortality. Although patients with coronavirus disease 2019 (COVID-19) are often associated with steroid use and intensive care unit (ICU) treatment and may be at risk for comorbid HCMV reactivation, there are still insufficient studies. This study aimed to examine the incidence and potential risk factors of HCMV infection in patients with severe COVID-19 and evaluate the relationship between HCMV infection and mortality. Methods We used administrative claims data from advanced treatment hospitals in Japan to identify and analyze patients with severe or critical COVID-19. We explored potential risk factors for HCMV infection using multivariable regression models and its contribution to mortality in patients with COVID-19. Results Overall, 33,151 patients who progressed to severe or critical COVID-19 illness were identified. The incidence of HCMV infection was 0.3–1.7%. Steroids, immunosuppressants, ICU admission, and blood transfusion were strongly associated with HCMV reactivation. Furthermore, HCMV reactivation was associated with patient mortality independent of the observed risk factors for death. Conclusions HCMV infection is a notable complication in patients with COVID-19 receiving steroids, immunosuppressants, ICU admission, and blood transfusion, and it can significantly increase mortality risk.