Index Entries

Klaus Hirschbühl, Tina Schaller, Bruno Märkl, Rainer Claus, Eva Sipos, Lukas Rentschler, Andrea Maccagno, Bianca Grosser, Elisabeth Kling, Michael Neidig, Thomas Kröncke, Oliver Spring, Georg Braun, Hans Bösmüller, Maximilian Seidl, Irene Esposito, Jessica Pablik, Julia Hilsenbeck, Peter Boor, Martin Beer, Sebastian Dintner, and Claudia Wylezich
April 1, 2022
Modern Pathology

"Abstract

The rate of SARS-CoV-2 infections in vaccinees has become a relevant serious issue. This study aimed to determine the causes of death, histological organ alteration, and viral spread in relation to demographic, clinical-pathological, viral variants, and vaccine types for deceased individuals with proven SARS-CoV-2 infection after vaccination who died between January and November 2021. Twenty-nine consecutively collected cases were analyzed and compared to 141 nonvaccinated control cases. Autopsies were performed on 16 partially and 13 fully vaccinated individuals. Most patients were elderly and suffered from several relevant comorbidities. Real-time RT-PCR (RT-qPCR) identified a significantly increased rate of generalized viral dissemination within organ systems in vaccinated cases versus nonvaccinated cases (45% vs. 16%, respectively; P = 0.008) mainly with Ct-values of higher than 25 in non-respiratory samples. However, vaccinated cases also showed high viral loads, reaching Ct-values below 10, especially in the upper airways and lungs... All these findings were particularly accentuated in partially vaccinated patients compared to fully vaccinated individuals...

Introduction

[R]eports on autopsies of SARS-CoV-2 breakthrough infections are widely lacking. Currently, only a single case report from Germany of a partially vaccinated case is available...

Discussion

... The aim of this study was to investigate a cohort of 29 fatal COVID-19 cases in vaccinees by collecting all available metadata including SARS-CoV-2 antibody testing and by using necropsy, in situ hybridization, RT-qPCR analysis, and whole-genome sequencing to analyze the course of infection, allowing a substantiated disease and strain characterization.

The focus was on the comparison between partially vaccinated... and fully vaccinated cases...

The macroscopic and histomorphological findings in the partially vaccinated deceased individuals were similar to the findings in the nonvaccinated cases. Most patients died due to COVID-19 pneumonia with typical DAD [diffuse alveolar damage]... [A] high rate of viral dissemination detected by RT-qPCR within the organ system was an unanticipated result in this study, which was especially accentuated in the partially vaccinated compared to fully vaccinated cases (11 of 16 vs. five of 13, respectively; P = 0.144). In several cases, RT-qPCR identified the RNA of SARS-CoV-2 in all investigated samples, including cerebrospinal fluid, CNS, and soft tissues...

Two major contrary theses could explain this viral spread: 1) the vaccination itself and 2) the constitution of the individual. The first is mediated by antibody-dependent enhancement (ADE), which is known from other viral infections, such as dengue, Ebola, and HIV. In ADE, antibodies do not eliminate the virus or do so only to a reduced extent; instead, they promote viral uptake into the host's cells...

Focusing on potential patient-related factors, the immune system is of major interest in the context of failing viral elimination. Both collections in this study are characterized by a high median age and a high rate of potentially immune compromising conditions...

A high viral infection, both in terms of the spread within the organ system and viral load in the respiratory system (detected by RT-qPCR), together with high rates of immunocompromising conditions, are the most striking findings of this study, which were accentuated in cases with an incomplete vaccination status."

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adverse events,antibody dependent enhancement (ADE),breakthrough cases,COVID-19,deaths,vaccines