THE FIRST REPORT FROM THE NATIONAL COVID-19 AUTOPSY REGISTRY IN GERMANY

BACKGROUND AND AIMS: Autopsies are an invaluable tool in medicine for studying the pathophysiology of diseases, including kidney diseases and causes of death. To facilitate multicenter autopsy-based studies and to provide a single point of contact for data analysis and reporting, the German COVID-19 Autopsy Registry (DeRegCOVID) was launched in April 2020 to uncover effects on pulmonary (micro)vasculature, systemic viral spread including the kidneys or interaction with the immune system. METHOD: The electronic registry uses a web-based electronic data collection system. Participation is voluntary and biomaterial remains at each site (decentralized biobanking). As of October 2021, the registry included N = 1129 autopsy cases with 69 271 individual data points containing information on 18 674 available biospecimens, including kidneys as part of the standard sampling protocol, collected at 29 German sites. RESULTS: In the N = 1095 eligible records, the male-to-female ratio was 1-8:1, with peaks at 65-69 and 80-84 years in men and >85 years in women. Analysis of the chain of events leading directly to death showed that in 86% of autopsy cases, COVID-19 was the actual cause of death, whereas in 14% of cases, COVID- 19 was a concomitant disease. The most common immediate cause of death was diffuse alveolar injury/acute respiratory distress syndrome, followed by multiorgan failure, including the kidneys. The registry supports several scientific projects, informs the public and provides reports to federal health authorities, which led to a change in the German Infection Protection Act and facilitated autopsies during pandemics. CONCLUSION: A national autopsy registry can provide multicenter quantitative information on COVID-19 deaths at the national level to support medical research, policy decisions and public discussions. Previous and ongoing studies also showed the potential of autopsies for nephrology research.

Complement activation induces excessive T cell cytotoxicity in severe COVID-19

Severe COVID-19 is linked to both dysfunctional immune response and unrestrained immunopathology, and it remains unclear whether T cells contribute to disease pathology. Here, we combined single-cell transcriptomics and single-cell proteomics with mechanistic studies to assess pathogenic T cell functions and inducing signals. We identified highly activated CD16(+) T cells with increased cytotoxic functions in severe COVID-19. CD16 expression enabled immune-complex-mediated, T cell receptor-independent degranulation and cytotoxicity not found in other diseases. CD16(+) T cells from COVID-19 patients promoted microvascular endothelial cell injury and release of neutrophil and monocyte chemoattractants. CD16(+) T cell clones persisted beyond acute disease maintaining their cytotoxic phenotype. Increased generation of C3a in severe COVID-19 induced activated CD16(+) cytotoxic T cells. Proportions of activated CD16(+) T cells and plasma levels of complement proteins upstream of C3a were associated with fatal outcome of COVID-19, supporting a pathological role of exacerbated cytotoxicity and complement activation in COVID-19.