RESUMO
Compared with previously prevalent variants of SARS-CoV-2, the Omicron lineages BA.1 and BA.2 are known to be associated with mild clinical courses. In addition, well-established animal models do not develop severe diseases. To address whether the supposedly fatal cases after Omicron-BA.1/2 infection show the known COVID-19 organ alterations, especially in the lungs, 23 full and 3 partial autopsies in the deceased with known Omicron BA.1/2 infections have been consecutively performed. Viral RNA was determined by RT-qPCR and RNA-in situ hybridization. The lineages were analyzed by whole genome sequencing or S-gene analysis. Despite high viral loads in almost all nasopharyngeal swabs and in 13 lung tissue samples, death caused by COVID-19-associated diffuse alveolar damage (DAD) in the acute and organizing stages was found in only eight cases (31%). This rate is significantly lower compared to previous studies, including non-Omicron variants, where rates of 92% and 69% for non-vaccinated and fully vaccinated vaccines were observed. It is of special interest that neither vaccination status nor known risk factors (i.e., age, comorbidities, obesity, immuno-suppression) were significantly associated with a direct cause of death by COVID-19. Only the reason for the hospital admission of the patients due to COVID-19-related symptoms showed a significant correlation with directly COVID-19-caused deaths (P < 0.001). DAD still occurred in the Omicron BA.1/BA.2 era of the SARS-CoV-2 pandemic but at a considerably lower frequency than seen with previous variants of concern. In our study, none of the known risk factors discriminated the cases with COVID-19-caused death from those that had COVID-19 infections but died due to a different disease. Therefore, the hosts genomics might play a key role in this regard. Further studies are urgently needed to elucidate the existence of a genomic mechanism as a risk factor for a fatal course.
RESUMO
BackgroundThe 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 cases ConclusionsFatal 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).
