High viral loads: what drives fatal cases of COVID-19 in vaccinees?

 Klaus Hirschbuehl, Tina Schaller,  

View ORCID ProfileBruno Maerkl, Rainer Claus, Eva Sipos, Lukas Rentschler, Andrea Maccagno, Bianca Grosser, Elisabeth Kling, Michael Neidig, Thomas Kroencke, Oliver Spring, Georg Braun, Hans Boesmueller, Maximilian Seidl, Irene Esposito, Jessica Pablik, Julia Hilsenbeck,  View ORCID ProfilePeter Boor, Martin Beer, Sebastian Dintner, Claudia Wylezich

doi: https://doi.org/10.1101/2021.12.03.21267155

This article is a preprint and has not been certified by peer review [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.

PDF: https://www.medrxiv.org/content/10.1101/2021.12.03.21267155v1.full.pdf

Abstract

Background: The rate of SARS-CoV-2 breakthrough infections in vaccinees is becoming an increasingly serious issue. Objective: To determine the causes of death, histological organ alteration, and viral spread in relation to demographic, clinical-pathological, viral variants, and vaccine types. Design: Comprehensive retrospective observational cohort study. Setting: Consecutive cases from four German academic medical centers. Patients: Deceased with proven SARS-CoV-2 infection after vaccination who died between January and November 2021. Collections of 29 vaccinees which were analyzed and compared to 141 nonvaccinated control cases. Results: 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 the organism in vaccinated cases versus nonvaccinated cases (45% vs. 16%, respectively; P = 0.008). Vaccinated cases also showed high viral loads, reaching Ct values below 10, especially in the upper airways and lungs. This was accompanied by high rates of pulmonal bacterial or mycotic superinfections and the occurrence of immunocompromising factors such as malignancies, immunosuppressive drug intake, or decreased immunoglobulin levels. All these findings were particularly accentuated in partially vaccinated patients compared to fully vaccinated individuals. A fatal course after vaccination occurred in only 14% of all COVID-19 deceased in Augsburg. Limitations: Restricted number of cases Conclusions: Fatal cases of COVID-19 in vaccinees were rare and often associated with severe comorbidities or other immunosuppressive conditions. Interestingly, we observed striking virus dissemination in our case study, which may indicate a decreased ability to eliminate the virus in patients with an impaired immune system. However, the potential role of antibody-dependent enhancement must also be ruled out in future studies.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

This work was supported by the German Registry of COVID-19 Autopsies (www.DeRegCOVID.ukaachen.de), funded by the Federal Ministry of Health (ZMVI1-2520COR201), by the Federal Ministry of Education and Research within the framework of the network of university medicine (DEFEAT PANDEMICs, 01KX2021) and the German Federal Ministry of Food and Agriculture through the Federal Office for Agriculture and Food, project ZooSeq, grant number 2819114019.

https://www.medrxiv.org/content/10.1101/2021.12.03.21267155v1