Lethality of SARS-CoV-2 infection-a comparative autopsy study focusing on COVID-19 development and virus variants

Aims: Different SARS-CoV-2 variants are driving various waves of infection of the corona pandemic. Official statistics provide no information on who died due to coronavirus disease 2019 (COVID-19) or an alternative disease during which SARS-CoV-2 infection was detected. The current study aims at addressing the effect of the different variants evolving during the pandemic on fatal outcomes. Methods and results: Standardised autopsies were performed on 117 people who died of a SARS-CoV-2 infection and the findings were interpreted in clinical and pathophysiological contexts. The typical histological sequence of COVID-19-related lung injury was detected independently of the disease-causing virus variant, but was significantly less common (50 versus 80-100%) and less severe in cases infected by omicron variants compared to precedent variants (P < 0.05). COVID-19 was less often the leading cause of death following omicron infection. Extrapulmonary manifestations of COVID-19 did not contribute to death in this cohort. Lethal COVID-19 may occur after complete SARS-CoV-2 vaccination. Reinfection was not the cause of death in any of the autopsies of this cohort. Conclusion: Autopsies represent the gold standard in determining the cause of death after SARS-CoV-2 infection and autopsy registers are currently the only available data source allowing for evaluation of which patients died of COVID-19 or with SARS-CoV-2 infection. Compared to previous variants, infection with an omicron variant affected the lungs less frequently and resulted in less severe lung disease.