Case Study of Autopsy Findings in a Population of Post-COVID-19 Vaccination in Thailand.

This retrospective cohort study included 34 forensic autopsies of deceased individuals. The collected cases were all those died within 30 days of immunization against COVID-19 between February 2021 and December 2021 in the service area of Bhumibol Adulyadej Hospital. The hospital has postmortem inquest service areas covering the Bang Khen, Don Mueang, Sai Mai, and Thung Song Hong counties of Bangkok and the Khu Khot districts of Pathum Thani. The death of a patient within 1 month was considered a potential event from vaccination. A protocol developed by the Adverse Events of Special Interest (AESI) expert committee, Department of Disease Control, Ministry of Public Health, was used to investigate individuals and whether the side effects were due to the vaccine (Fig. 1 ). Information about the deceased was collected from documents, including medical records, death certificates, and autopsy reports. Age, sex, comorbidities, dose and type of vaccine, duration between vaccination and death, and cause of death were also recorded. The autopsy included external and internal examinations. Gross morphology and histopathological findings were recorded and reported during internal examination. Laboratory data were also obtained. Evidence of COVID-19 vaccine-related adverse events, including anaphylaxis, myocarditis, pericarditis, and thrombosis with thrombocytopenia syndrome, has been thoroughly investigated for its possible association with death. This study was approved by the institutional review board (no. 30/66), including permission to display individual case information. AESI surveillance for COVID-19.

Of the 34 deceased cases in this study, the majority (70.59%) were male. Their ages ranged from 19 to 84 to years (mean = 52.76 years), and the most frequent age group was more than 60 years, with 41.18% of cases followed by 41 to 60 years (35.29% cases) and <40 years (23.53% cases). Approximately 50.0% of the cases had no comorbidities, but hypertension was prevalent in approximately 23.52% of cases, followed by diabetes mellitus (11.76%). Most of the deceased individuals (82.36%) had received the AstraZeneca vaccine, whereas the others were vaccinated with Sinovac (11.76%) and Sinopharm (5.88%). Regarding the number of COVID-19 vaccine doses received by the individuals, approximately 58.82% had their first, 35.30% had received the second, and the remaining 5.88% had the third (Table 1 ). Demographic and Clinical Characteristics of the Deceased Individuals (N = 34) None of the individual died of COVID-19. Table 2 lists the causes of death, which were found to be natural during the autopsy. Approximately 73.53% of the deaths were due to cardiovascular diseases, and ischemic heart disease was the main cause of death (n = 17). Likewise, central nervous system disease and gastrointestinal disease each caused 20.58% of the deaths. Mortality due to respiratory diseases was the lowest (2.94%). Laboratory results were missing in 70.58% of the cases to further assess the cause of death. Cause of Deaths and Laboratory Results The study also estimated the descriptive statistics for survival time. Among the 34 deceased subjects with 360 person-days, the estimated incidence was 9/100 days. Fifty percent of the patients survived 9 days or longer (median survival time), whereas 75% survived 16 days or longer. The Kaplan–Meier survival curve of individuals over 30 days is shown in Figure 2 . A Kaplan–Meier survival curve of the individuals in 30 days. The autopsy findings and other details of the deceased are listed in Table 3 . Two individuals (cases 1 and 4), younger than 65 years, died on the same day as the first AstraZeneca vaccination. Cardiovascular disease was a common cause of death in both the cases. One individual (case 22) died on the first day after the third dose of the AstraZeneca vaccine, after 2 earlier doses of the Sinovac vaccine. This was the only case in this study that received vaccines from 2 different companies. The youngest case aged 19 years (case 32) without any comorbidities died on the fourth day of the first Sinopharm vaccination, and autopsy revealed cardiomegaly (heart weight, 450 g), severe pulmonary edema and congestion, and renal atrophy. The dating of thrombus formation revealed it to be old; therefore, the cause of death from the vaccine was ruled out. Likewise, case 7 had a pulmonary embolism, and the underlying cause of death was concluded to be deep vein thrombosis based on histology. The thrombus was old and, therefore, unlikely to occur after vaccination in a single day. After reviewing our findings, the causal relationship between vaccination and death was not established by the AESI Expert Committee, Department of Disease Control, Ministry of Public Health, Thailand. Autopsy Findings and Other Details of the Cases DM indicates diabetes mellitus; HT, hypertension; CVA: cerebrovascular disease; ESRD: end-stage renal disease.

Autopsy plays a vital role in describing the pathophysiology of the disease and causes of death. This study investigated autopsy findings in deceased individuals within 30 days of COVID-19 vaccination and estimated the median survival time. In Thailand, all unknown, unnatural, and custody deaths require autopsy. The studied cases were all natural deaths sent to Bhumibol Adulyadej Hospital postmortem. The results revealed that approximately 73.53% of deaths were due to cardiovascular diseases. The noncardiac causes of death revealed on autopsy were subarachnoid hemorrhage, intracerebral hemorrhage, ischemic stroke, and COVID-19 pneumonia. Males were predominant in the autopsied population. This finding was similar to that of a previous study by Liu et al , 18 which investigated post-COVID-19 vaccination deaths within 7 days. Two deaths occurred on the same day, and 3 deaths occurred on the day after vaccination. None of the patients had comorbidities such as hypertension, high blood cholesterol, or coronary artery disease. This is different from a previous study by Schneider et al , 10 reporting death after the COVID-19 vaccine due to preexisting diseases. It is to highlight that acute myocardial infarction and pulmonary embolism are reported in death after AstraZeneca vaccination but in rare occurrences. 19 The cause of death in all cases was well established, and the most common cause was ischemic heart disease (n = 17). However, deaths after COVID-19 vaccination have not been concluded from the postmortem in the reported study by Manu. 20 The literature suggests that coronary artery disease represents the most sudden cardiovascular death (SCD), accounting for up to 80%. 21 Autopsy findings showing greater than 75% narrowing of the coronary artery lumen confirm SCD such that the left anterior descending coronary artery (LAD), the right coronary artery (RCA), and the left circumflex artery (LCX) stenosis are critical findings. 22 LAD ≥75% was observed in the majority of deceased with SCD, followed by the RCA and LCX in this study. In other words, major deaths after vaccination in this study were confirmed as cardiovascular deaths, which could be due to preexisting conditions. None of the acute cardiac deaths had acute coronary thromboses that were otherwise associated with COVID-19 infection. Subarachnoid hemorrhage (SAH), intracerebral hemorrhage (ICH), and ischemic stroke are among the noncardiac causes of death reported in this study. These findings are likely due to the adenoviral vector vaccines due to deep vein thrombosis and manifest 5 to 30 days after vaccination. 23 Vaccine-triggered formation of antiplatelet factor 4 immunoglobulin G, which activates platelets, has been described as the major event underlying these findings. 24 , 25 SAH and ICH can be primary or secondary to venous thrombosis. 26 , 27 Supporting the findings of ischemic stroke in this study, inflammatory vascular thrombotic occlusions were previously revealed in the vessels of multiple body organs. 28 However, in this study, 1 case of subarachnoid hemorrhage and ICH was antiplatelet factor 4 negative and did not match the criteria for vaccine-induced thrombotic thrombocytopenia. 29 Additionally, there was no evidence of venous thrombosis in these patients. Death due to bowel perforation and gastrointestinal (GI) bleeding has been reported previously after COVID-19 vaccination, and there were 3 deaths due to GI diseases. 27 Sudden death due to GI causes is less common; however, acute liver failure, massive bleeding, and acute pancreatitis have been described in the literature. 30 , 31 Hepatomegaly, ruptured right liver abscesses, congested fatty liver, ruptured appendicitis, ruptured ileitis, and upper GI bleeding were observed during autopsy of the deceased. Interestingly, a few of them had underlying diseases such as hypertension and diabetes, but others did not. Pulmonary edema and congestion in several deceased patients may be due to cardiovascular disease. However, there is also the possibility of noncardiac pulmonary edema. 22 In sudden pulmonary edema, cardiac arrest occurs within a few hours of the onset of symptoms. All deaths in the study were matched with the definition of sudden and unexpected death or sudden cardiac death in terms of the WHO, the ICD-10, and the medical examiner's or death investigator's perspective. 32 , 33 Moreover, the cause of death was the same as that of instantaneous or sudden death, which may result from the pathology of the heart and its vessels, noncardiac vessels, pulmonary system, and central nervous system. 34 This means that all causes of death were coincident and unrelated to COVID-19 immunization. Therefore, the Thai government should distribute this information to the public to guarantee the safety of the COVID-19 vaccine and to ensure public confidence. The limitations of this study must be considered when interpreting these findings. Most importantly, this was a single-center study, with a small sample size. The author is aware that the power of the study might not been adequate to capture these rare deaths. Additionally, the mRNA vaccine phase was not included in this study. There is a possibility of missing cases; however, all natural deaths in the service area of the hospital were included in the study. In this study, no causal association was observed between COVID-19 vaccination and mortality. This was based on autopsy results and other details reviewed by the AESI Expert Committee of the Department of Disease Control, Ministry of Public Health, Thailand. These findings are vital for clarifying the COVID-19 vaccine-related deaths in Thailand. Autopsy discoveries, including gross morphology, histological microscopic studies, toxicological laboratory results, and molecular and clinical chemistry findings, are crucial in establishing a causal relationship for fatal adverse effects after COVID-19 vaccination. This aids in dealing with the disease by increasing the confidence of the public regarding vaccination and the safety evaluation of vaccines. The median death duration of 9 days (ranged 2–16 days) justifies similar studies with a shorter duration in the future.