key: cord-0857472-us518bwp
authors: Hansen, Torsten; Titze, Ulf; Kulamadayil-Heidenreich, Nidhi Su Ann; Glombitza, Sabine; Tebbe, Johannes Josef; Röcken, Christoph; Schulz, Birte; Weise, Michael; Wilkens, Ludwig
title: First case of postmortem study in a patient vaccinated against SARS CoV2
date: 2021-04-16
journal: Int J Infect Dis
DOI: 10.1016/j.ijid.2021.04.053
sha: 2098ce588bdbc551aa90732664790b39c2d8dce6
doc_id: 857472
cord_uid: us518bwp

A previously symptomless 86-year-old man received single mRNA vaccine BNT162b2. Four weeks later, he succumbed to death due to acute renal and respiratory failure. Although he did not present with any symptoms specific for Coronavirus disease 19 (COVID19), he obtained positive testing for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), before he died. S1 antigen-binding notably showed significant levels for IgG, while nucleocapsid IgG/IgM was not elicited . By means of autopsy, acute bronchopneumonia and acute tubular failure were assigned as cause death of death. However, we did not observe any characteristic morphological features of COVID19. Postmortem molecular mapping by real time-polymerase chain reaction (RT-PCR) additionally revealed relevant SARS-CoV-2 Ct values in all organs examined (oropharynx, olfactory mucosa, trachea, lungs, heart, kidney, and cerebrum) except for liver and olfactory bulb. These results might contribute to the view that first vaccination induces immunogenicity, but not sterile immunity.

cerebrum) except for liver and olfactory bulb. These results might contribute to the view that first vaccination induces immunogenicity, but not sterile immunity.

Keywords: SARS-CoV-2, vaccine, autopsy, histology, RT-PCR We report on an 86-year-old male resident of a retirement home, who received vaccine against severe acute respiratory syndrome coronavirus-2 (SARS-CoV2). Past medical history included systemic arterial hypertension, chronic venous insufficiency, dementia, and prostate carcinoma. On January 9, 2021, the man received lipid nanoparticle-formulated, nucleoside-modified RNA vaccine BNT162b2 in a 30 µg dose. On that day as well as in the following two weeks, he presented with no clinical symptoms (Table 1) . On day 18, he was admitted to hospital for a history of worsening diarrhea. Since he did not present with any clinical signs of coronavirus disease 19 (COVID19), isolation in a specific setting did not occur. Laboratory testing revealed hypochromic anemia and increased creatinine serum levels.

Antigen test and polymerase chain reaction (PCR) for SARS-CoV2 were negative.

Gastroscopy and colonoscopy were performed in order to further investigate the cause of diarrhea.

Particularly, colonoscopy demonstrated an ulcerative lesion of the left colonic flexure, which was histologically diagnosed as ischemic colitis; PCR-analysis on biopsy specimens according to a previously reported method (Kaltschmidt et al., 2021) The patient now presented with fever and respiratory discomfort, and lung auscultation displayed crackles. In spite of starting supplemental oxygen (2 l per minute) and antibiotic therapy by ceftriaxone, the patient succumbed to death due to acute renal and respiratory failure on the following day.

J o u r n a l P r e -p r o o f Immunogenicity assessment by measuring (spike protein) S1 antigen-binding IgG in the serum

These results indicate that the patient had already developed relevant immunogenicity as cause of vaccination.

Postmortem study revealed bilateral acute bronchopneumonia with abscesses, sometimes being surrounded by bacterial cocci (Fig. 1 ). There were no findings of commonly described manifestations of COVID19-associated pneumonitis. In the heart, we found biventricular hypertrophy (weight 580 g) and histologically, we diagnosed ischemic cardiomyopathy. We detected amyloidosis of the transthyretin type in the heart and to a lesser extent in the lungs. The kidneys revealed both chronic damage with arteriolosclerosis and interstitial fibrosis, and acute renal failure with hydropic tubular degeneration. The examination of the brain revealed a left parietal pseudocystic tissue necrosis, which was diagnosed as old infarction area. (Fig. 1) 

examined with the exception of the liver and the olfactory bulb (Fig. 1) .

SARS CoV-2 with positive SARS CoV2-testing afterwards has not been reported yet. We suggest that single treatment with BNT162b2 RNA vaccine elicited a significant immunogenicity reflected by J o u r n a l P r e -p r o o f relevant S-protein based neutralizing IgG serum values. In the weeks before vaccination as well as the timespan between vaccination (day 1) and until shortly before death (day 24), the patient was free of any clinical symptoms typically ascribed to COVID19. Furthermore, the blood work did not show an IgM titer that generally is observed 7-14 days after symptom onset (Kim et al., 2020) . However, the patient was tested SARS CoV2 positive. Both the Ct value measured in nasopharyngeal swab as well as values measured in FFPE autopsy specimens indicate viral load and are suggestive for transmissibility.

We did not observe any characteristic morphological feature of COVID19 such as been reported in comprehensive morphological autopsy studies so far (Schaller et al., 2020; Edler et al., 2020 , Ackermann et al., 2020 . In the lungs we did not find any typical signs of diffuse alveolar damage, but an extensive acute bronchopneumonia, possibly of bacterial origin. We conclude that the patient died from bronchopneumonia and acute renal failure. Vogel et al., 2021) . Recently, Amit et al. (2021) published results on a clinical trial on health-care workers using vaccine BNT162b2 and could demonstrate substantial early reductions in SARS CoV2 infection and symptomatic COVID19 rates following first vaccine administration.

In summary, the results of our autopsy case study in a patient with mRNA vaccine confirm the view that by first vaccination against SARS CoV2 immunogenicity can already be induced, while sterile immunity obviously is not adequately developed.

Authors do not have any commercial or financial conflict of interest.

This case study was performed in the setting of the German national "Defeat Pandemics" project, approved by the Medical Association of Westphalia-Lippe, Münster, Germany (Ref. 2020-575-b-S) and carried out in accordance with the ethical principles of the Helsinki Declaration. Informed consent by the next-of-kin was additionally available.

There was no funding received from any individual or organization. The histomorphology is obtained by standard hematoxylin & eosin reaction, except for the myocardium on the right side (Congo red staining). The magnification is shown by bars. Note that in the lungs, we also observed colonies of cocci (arrow) in granulocytic areas. In addition, the results of molecular mapping are given as evaluated Ct value of the RT-PCR for SARS CoV2. Note that only in the olfactory bulb and the liver SARS CoV2 could not be detected.

J o u r n a l P r e -p r o o f 

Dying with SARS-CoV2 infection -an autopsy study of the first consecutive

Hepatic vasculopathy and regernative responses of the liver in fatal cases of COVID-19

Will SARS-CoV-2 infecion elicit long-lasting protective or sterilizing immunity? Implications for vaccine strategies (2020). Front Immunol

Covid-19: AstraZeneca vaccine is not linked to increased risk of blood clots

Postmortem examinations of patients with COVID19

ChAdOx1 nCoV-19 vaccine prevents SARS-CoV-2 pneumonia in rhesus macaques

Immunogenic BNT162b vaccines protect rhesus macaques from SARS-CoV-2

Safety, tolerability, and immunogenicity of COVID19 vaccines: a systematic review and meta-analysis

We are grateful for expert technical assistance of Ralf Bode and Nadine Weber (University hospital of OWL of the University of Bielefeld, Campus Lippe, Detmold). 

Not