High viral loads: what drives fatal cases of COVID-19 in vaccinees? – an autopsy study

• DOI: 10.1038/s41379-022-01069-9
• Publication Date: 2022-04-04T07:33:32Z
• Authors: 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; Claudia Wylezich
• Keywords: 0301 basic medicine; ddc:610; 03 medical and health sciences; SARS-CoV-2; COVID-19; Humans; Autopsy; Viral Load; Real-Time Polymerase Chain Reaction; Article; Aged; 3. Good health

AbstractBackgroundThe rate of SARS-CoV-2 breakthrough infections in vaccinees is becoming an increasingly serious issue.ObjectiveTo determine the causes of death, histological organ alteration, and viral spread in relation to demographic, clinical-pathological, viral variants, and vaccine types.DesignComprehensive retrospective observational cohort study. Setting: Consecutive cases from four German academic medical centers.PatientsDeceased 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.ResultsAutopsies 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.LimitationsRestricted number of casesConclusionsFatal 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.Funding sourceThis work was supported by the German Registry of COVID-19 Autopsies (www.DeRegCOVID.ukaachen.de) and funded by the Federal Ministry of Health (ZMVI1-2520COR201), 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).