The first postmortem study of patients vaccinated against SARS-CoV-2.
Available at: https://doi.org/10.1016/j.ijid.2021.04.053
Commentary
This case is that of an 86-year-old man who received the COVID-19 vaccine.
The man's medical history included systemic arterial hypertension, chronic venous insufficiency, dementia, and prostate cancer.
On January 9, 2021, he received a 30 µg dose of BNT162b2, a nucleoside-modified RNA vaccine formulated with lipid nanoparticles, and showed no clinical symptoms for two weeks from that day. However, on day 18 he was admitted to the hospital due to worsening diarrhea. Since no clinical features of COVID-19 were identified on admission, no isolation procedure was performed and clinical examination revealed hypochromic anemia and antigen test and polymerase chain reaction (PCR) for SARS-CoV-2 were negative.
Gastrointestinal and colonoscopy were performed to determine the cause of diarrhea, which showed ulcerative lesions in the left colon flexure and a diagnosis of ischemic colitis. Treatment consisted of mesalazine and intravenous iron replacement, but the patient's condition subsequently deteriorated due to the onset of renal failure.
On the 24th day, the patient sharing the ward with the man tested positive for SARS-CoV-2.
On day 25, the patient was tested positive for SARS-CoV-2 by real-time PCR (RT-PCR). Further analysis of the (RT-PCR) swab sample showed no evidence of the mutant SARS-CoV-2 variants B.1.1.7, B.1.351 or B.1.1.28.1, suggesting that the patient was infected in the hospital room. The patient presented with fever and respiratory discomfort; auscultation of the lungs showed crackles. Despite oxygen supplementation (2 liters per minute) and initiation of antibiotic therapy with ceftriaxone, the patient died the next day of acute renal and respiratory failure.
Immunogenicity assessment by measuring spike protein (S1) antigen-binding immunoglobulin (Ig)G in serum samples obtained on day 25 showed no antibody response (8.7 U/ml, reference value <0.8-1.2 U/ml; RocheECLIA™), and no (nucleocapsid) NCP-IgG/IgM was not elicited (<0.1 U/ml, reference value >1.0 U/ml; RocheECLIA™).
These results indicate that the patient has already developed relevant immunogenicity through vaccination. A postmortem study of the patient revealed acute bilateral bronchopneumonia with abscesses and surrounded by bacterial cocci; there were no findings of symptoms commonly described for COVID-19-associated pneumonia. The heart showed bilateral ventricular hypertrophy (580 g body weight), and a histological diagnosis of ischemic cardiomyopathy was made. Transthyretin-type amyloidosis was detected in the heart but to a lesser extent in the lungs. The kidneys revealed both chronic damage and acute renal failure with microarteriosclerosis and interstitial fibrosis accompanied by bullous tubular degeneration. Examination of the brain revealed pseudocystic tissue necrosis in the left parietal lobe, which was diagnosed as an old infarcted area.
Detailed autopsy studies including molecular viral mapping of patients with positive SARS-CoV-2 tests and vaccinated against SARS-CoV-2 after vaccination have not been reported. As reflected in the reported spike-protein-based neutralizing IgG serum levels, this suggests that a single treatment with BNT162b2RNA vaccine induced significant immunogenicity.
From several weeks prior to vaccination (day 1) to just prior to death (day 24), the patient was free of clinical symptoms usually attributed to COVID-19. Furthermore, blood tests did not show IgM titers, which are typically observed 7-14 days after the onset of symptoms. However, the patient was determined to be SARS-CoV-2 positive, and both the Ct values measured on nasopharyngeal swabs and those measured on formalin-fixed, paraffin-embedded autopsy specimens showed viral load, suggesting contagiousness.
Since our patient died about two days after the first positive SARS-CoV-2 result, the molecular mapping data may reflect the early stages of viral infection. This early stage of infection may also explain why various regions, such as the olfactory bulb and liver, were not (yet) affected by systemic viral spread.
To summarize this study, the results of an autopsy case study of patients vaccinated with mRNA vaccine support the view that immunogenicity is already induced by the first dose of vaccine against SARS-CoV-2, while sterile immunity is not fully developed.
