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Autopsy study reveals what drives fatal cases of COVID-19 in fully vaccinated

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Given the limits of health systems around the world, achieving herd immunity against SARS-Coronavirus-2 (SARS-CoV-2) by recovering from an illness is not feasible.

Therefore, vaccination remains, at the moment, the only option for coping with the pandemic. Vaccines against SARS- CoV-2 targeting the viral spike protein have been available since the end of 2020.

In the United States, three vaccines (Pfizer-BioNTech COVID-19 Vaccine (BNT162b2), Moderna (mRNA-1273), and Johnson & Johnson vaccine (Ad26.COV2.S)), which have demonstrated the efficacy of up to 95% against COVID-19, have been approved by the Centers for Disease Control and Prevention (CDC) and put into use.

Apart from infection prevention, the primary purpose of vaccines against SARS-CoV-2 is to avoid severe COVID infection. It is expected that infection and sickness caused by SARS-CoV-2 will occur despite vaccination also known as Breakthrough infection, even after receiving the booster shots.

The primary objective of the study was to ascertain the causes of death, histological organ changes, and viral transmission in connection to demographic, clinical-pathological, viral variant, and vaccine type factors. 

Vaccination failure is typically characterized as the immune system’s inability to develop effective protection against a virus through antibody- and T-cell-mediated responses. By contrast, even when antibody titers are adequate, breakthrough infections occur.

During the COVID-19 outbreak, autopsies became extremely important for understanding the disease’s pathophysiology. In particular, the viral impacts on various organs in severe and deadly infections can, in most cases, only be examined through thorough autopsies in conjunction with advanced, cutting-edge diagnostic technologies.

Based on autoptic data, the most important COVID-19-associated organ abnormalities, such as diffuse alveolar damage, endotheliitis, and the role of thromboembolic events, have been characterized.

Despite this significant autoptic activity, especially in Europe and the United States, reports from autopsy of SARS-CoV-2 breakthrough infections are limited. Currently, just one case report of a partly vaccinated case from Germany is known.

The goal of this multicenter retrospective study was to present data from a series of fatal COVID-19 cases after partial and full vaccination. Special emphasis was placed on identifying risk factors, direct causes of death, and viral spread.

To study this, the team performed autopsy on 16 partially and 13 fully vaccinated people. The majority of patients were elderly and had a number of significant comorbidities.

The information was gathered from four German academic medical institutes who died between January and November 2021.

Eleven individuals in the partially immunized group received the BNT162b2 vaccine (BioNTech), and four received the AZD1222 vaccine (AstraZeneca). In one case, no information about the vaccine was provided.

The viral variants included six cases of non-VOCs (B.1.221, B.1.9.4) and ten VOCs (nine alpha, one delta).

The direct cause of death in three of the 16 cases was cerebral ischemia, cardiac failure, and bleeding, while 12 patients died directly due to severe COVID-19 pneumonia with diffuse alveolar damage (DAD).

And one patient died due to traumatic cerebral bleeding and COVID was not the cause of the death.

In partially vaccinated breakthrough infection patients, the lungs were the most affected organs.

Another remarkable observation in this collection was the high rate of malignancies in their medical history, at 56%.

In the fully vaccinated group, this study comprised 13 fully vaccinated cases. The median time from the last vaccination to a positive test of SARS-CoV-2 was 140 days (range: 28–283). The vaccines applied in the study groups were BNT162b2 (BioNTech) in 11 cases and AZD1222 (AstraZeneca) and CoronaVac (Sinovac) in one case each.

SARS-CoV-2 VOCs alpha and delta were the only viral variants present.


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.

According to known risk factors for a severe course of COVID-19 (e.g., cardiovascular diseases, diabetes, lung diseases, obesity, cancer, older age, immunosuppression), all but one of 16 partially vaccinated and all 13 fully vaccinated cases had at least one of the relevant comorbidities.


The study found that fatal cases of COVID-19 in fully vaccinated were rare and often associated with severe comorbidities or other immunosuppressive conditions.

Interestingly, they observed striking virus dissemination in their 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.

Important Note: Since medRxiv publishes preliminary scientific studies that have not been peer-reviewed, they should not be regarded as conclusive, should not be used to direct clinical practice/health-related behavior, and should not be seen as established information.

Source: medrxiv

Image Credit: Getty

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