The Impact of COVID-19 on Sepsis-Related Mortality in the United States

Background: Coronavirus disease 2019 (COVID-19)-related organ dysfunction is increasingly considered as sepsis of viral origin. In re-cent clinical and autopsy studies, sepsis has been present in the ma-jority of decedents with COVID-19. Given the high mortality toll of COVID-19, sepsis epidemiology would be expected to be substantial-ly transformed. However, the impact of COVID-19 on sepsis-related mortality at the national level has not been quantified. We aimed to estimate the contribution of COVID-19 to sepsis-related mortality in the USA during the first year of the pandemic. Methods: We used the Centers for Disease Control Wide-Ranging Online Data for Epidemiological Research (CDC WONDER) Mul-tiple Cause of Death dataset to identify decedents with sepsis during 2015 -2019, and those with a diagnosis of sepsis, COVID-19, or both in 2020. Negative binomial regression was used on the 2015 -2019 data to forecast the number of sepsis-related deaths in 2020. We then compared the observed vs. predicted number of sepsis-related deaths in 2020. In addition, we examined the frequency of a diagnosis of COVID-19 among decedents with sepsis and the proportion of a diag-nosis of sepsis among decedents with COVID-19. The latter analysis was repeated within each of the Department of Health and Human Services (HHS) regions. Results: In 2020, there were 242,630 sepsis-related deaths, 384,536 COVID-19-related deaths, and 35,807 deaths with both in the USA. The predicted number of sepsis-related deaths for 2020 was 206,549 (95% confidence interval (CI): 201,550 -211,671). COVID-19 was reported in 14.7% of decedents with sepsis, while a diagnosis of sep-sis was reported in 9.3% of all COVID-19-related deaths, ranging from 6.7% to 12.8% across HHS regions.Conclusions: A diagnosis of COVID-19 was reported in less than one in six of decedents with sepsis in 2020, with corresponding less than one in 10 diagnoses of sepsis among decedents with COVID-19. These findings suggest that death certificate-based data may have substantially underestimated the toll of sepsis-related deaths in the USA during the first year of the pandemic.