Dying at home during the SARS-CoV-2 endemic: The importance of defining the exact mechanism of death

Introduction: Coronavirus Disease 2019 (COVID-19) has become endemic in Europe thanks to the presence of less deadly and more infectious variants and to the existence of a significant portion of unvaccinated people among the general population. SARS-Cov-2 related deaths are probably going to fade in the next years, but Covid-19 should still be considered a potential cause of death in the out-of-hospital setting in the next future. Material and methods: Three (3) cases of unexpected death at home are here presented. Each case has been investigated with the same methodological approach: death scene investigation (DSI), complete autopsy with histology, immunohistochemistry, RNA in situ hybridization for SARS-CoV-2 spike protein in lung tissue, toxicology and microbiology. Results and Discussion: All three cases had a COVID + post-mortem nasopharyngeal swab. Histology and immunohistochemistry revealed a SARS-CoV-2 lung involvement in only two of the cases (Cases 2 and 3), while a septic bacterial pneumonia was found in Case 1, where RNA-in situ hybridization for viral spike protein showed no reactivity in pneumocytes. The integration of all postmortem evidence allowed to attribute a different role of SARS-Cov-2 in the determinism of the death. Conclusion: In the current post-pandemic context, SARS-CoV-2 remains a possible cause of death when investigating out-of-hospital unexpected deaths. Since a positive post-mortem swab does not automatically imply a COVID-19-related death, histology and immunohistochemistry are helpful for identifying SARS-CoV-2 lung involvement and, therefore, its potential active role in the determinism of death.