The SARS-CoV-2 infection (COVID-19) era impact on incidence of sudden deaths due to Myocardial Infarction (Heart Attack) in States and Union Territories of India- A cross-sectional comparative study (2018-2022) (preprint)

Despite modern cardiovascular drugs, latest advanced treatment protocols, several decades of research like longitudinal cohort study of Framingham (ongoing cardiovascular study of residents of the city of Framingham, Massachusetts), as well as various strategies to prevent and control mortality due to myocardial infarction (popularly known as Heart Attack), global improvement against cardiovascular disease (CVD) is flat-lining. COVID-19 affects the cardiovascular system leading to myocardial damage and dysfunction mainly via (ACE-2) the Angiotensin-converting enzyme 2 receptor. The cardiovascular complications of acute COVID-19 are well described in several research studies, but the post- COVID-19 cardiovascular manifestations particularly mortality due to myocardial infarction have not yet been comprehensively evaluated or characterized in research studies. This study aimed to assess the impact of COVID-19 on annual incidence (new cases number only) of mortality due to MI in different states and union territories (UT) of India. This study is cross-sectional, quantitative, and retrospective in nature. There is an overall increase of 11.02 percent in new MI cases related mortality during the COVID-19 period. This study revealed that there is 25.80 percent increase in total number of new MI cases related mortality in 2022 in comparison to pre-COVID-19 year of 2018. The Male-Sudden death due to Myocardial Infarction increased during COVID-19 year 2022 by 26.71 percent in comparison to 2018 pre- COVID-19 year. Percent wise top 3 states reporting sudden death due to MI in males include Maharashtra, Kerala and Gujarat. This study revealed that there is 26.71 percent increase in total number of new MI cases related mortality in males in 2022 in comparison to pre-COVID-19 year of 2018. There is an overall increase of 11.24 percent in new MI cases related mortality in males during the COVID-19 period of this study. The Sudden death due to Myocardial Infarction in female increased by 20.17 percent during COVID-19 year 2022 in comparison to 2018 pre- COVID-19 year.

A case of fatal multi-organ inflammation following COVID-19 vaccination.

A 14-year-old Japanese girl died unexpectedly 2 days after receiving the third dose of the BNT1262b2 mRNA COVID-19 vaccine. Autopsy findings showed congestive edema of the lungs, T-cell lymphocytic and macrophage infiltration in the lungs, pericardium, and myocardium of the left atria and left ventricle, liver, kidneys, stomach, duodenum, bladder, and diaphragm. Since there was no preceding infection, allergy, or drug toxicity exposure, the patient was diagnosed with post-vaccination pneumonia, myopericarditis, hepatitis, nephritis, gastroenteritis, cystitis, and myositis. Although neither type of inflammation is fatal by itself, arrhythmia is reported to be the most common cause of death in patients with atrial myopericarditis. In the present case, arrhythmia of atrial origin was assumed as the cause of cardiac failure and death. In sudden post-vaccination deaths, aggressive autopsy systemic search and histological examination involving extensive sectioning of the heart, including the atrium, are indispensable.

Sudden Death Associated With Possible Flare-Ups of Multiple Sclerosis After COVID-19 Vaccination and Infection: A Case Report and Literature Review.

We present an autopsy case of a 19-year-old man with a history of epilepsy whose unwitnessed sudden death occurred unexpectedly in the night. About 4 years before death, he was diagnosed with unilateral optic neuritis (ON). Demyelinating disease was suspected, but he was lost to follow up after the recovery. Six months before death, he received a second dose of mRNA coronavirus disease 2019 (COVID-19) vaccine. Three months before death, he experienced epileptic seizures for the first time. Seventeen days before death, he was infected with COVID-19, which showed self-limited course under home isolation. Several days before death, he complained of seizures again at night. Autopsy revealed multifocal gray-tan discoloration in the cerebrum. Histologically, the lesions consisted of active and inactive demyelinated plaques in the perivenous area of the white matter. Perivascular lymphocytic infiltration and microglial cell proliferation were observed in both white matter and cortex. The other major organs including heart and lung were unremarkable. Based on the antemortem history and postmortem findings, the cause of death was determined to be multiple sclerosis with suspected exacerbation. The direct or indirect involvement of cortex and deep gray matter by exacerbated multiple sclerosis may explain the occurrence of seizures. Considering the absence of other structural abnormalities except the inflammatory demyelination of the cerebrum, fatal arrhythmia or laryngospasm in the terminal epileptic seizure may explain his sudden unexpected death in the benign circumstances. In this case, the onset of seizure was preceded by COVID-19 vaccination, and the exacerbation of seizure was preceded by COVID-19 infection, respectively. Literature reporting first manifestation or relapse of multiple sclerosis temporally associated with COVID-19 vaccination or infection are reviewed.

"Untold Distress" - How did the COVID-19 pandemic affect those who had previously experienced an epilepsy-related bereavement?

PURPOSE: This study explores the impact of the COVID-19 pandemic and lockdown on people with lived experience of sudden bereavement as a consequence of an epilepsy-related death. METHOD: We developed an online survey with fixed choice and open-ended response formats to collect data on grief symptoms and well-being during the pandemic. A total of 275 people bereaved by epilepsy-related deaths between 1980-2020 participated in this study: with 79 participants providing free-text responses for inductive thematic analysis. RESULTS: In total, 84% of participants reported a bereavement following a sudden death of a person aged under 40, with 22% aged 19 and under. The majority (77% of participants) reported they had been thinking more about the person who died compared to before the COVID-19 outbreak and 54% had experienced more distressing flashbacks to the time of death. Additionally, 61% reported more difficulties falling asleep and staying asleep and 88% of participants reported that the outbreak and response measures had negatively impacted upon their mental health. Medication was being taken for a diagnosed mental health condition by 33% of participants at the time of the study. We categorized these negative experiences during COVID in to four main-themes - 'Family', 'Lifestyle', 'Personal Well-being' and 'Health Services and Shielding Populations'. The 'Personal Well-being' theme was inextricably linked to grief symptoms including 'reflection on the death', 're-exposure to feeling', 'grief', 'salience of sudden deaths in the media' and 'inability to commemorate anniversaries and rituals'. These findings were consistent for bereaved people irrespective of the recency of the death. CONCLUSION: This study highlights the impact of the disruption caused by the pandemic on the grief-management of those bereaved by epilepsy-related death. Grief is not static and its management is connected to the psychosocial and formal support structures that were disrupted during the pandemic. The removal of these supports had an adverse effect upon the mental health and well-being of many bereaved. There is an urgent need for a system-wide transformation of epilepsy and mental health services to be inclusive of the needs and experiences of people impacted by sudden deaths in epilepsy and the contribution of the specialist service developed by families and clinicians to meet this gap.

Autopsy in the era of advanced cardiovascular imaging.

Historically, autopsy contributed to our current knowledge of cardiovascular anatomy, physiology, and pathology. Major advances in the understanding of cardiovascular diseases, including atherosclerosis and coronary artery disease, congenital heart diseases, and cardiomyopathies, were possible through autopsy investigations and clinicopathological correlations. In this review, the importance of performing clinical autopsies in people dying from cardiovascular disease, even in the era of advanced cardiovascular imaging is addressed. Autopsies are most helpful in the setting of sudden unexpected deaths, particularly when advanced cardiovascular imaging has not been performed. In this setting, the autopsy is often the only chance to make the correct diagnosis. In previously symptomatic patients who had undergone advanced cardiovascular imaging, autopsies still play many roles. Post-mortem examinations are important for furthering the understanding of key issues related to the underlying diseases. Autopsy can help to increase the knowledge of the sensitivity and specificity of advanced cardiovascular imaging modalities. Autopsies are particularly important to gain insights into both the natural history of cardiovascular diseases as well as less common presentations and therapeutic complications. Finally, autopsies are a key tool to quickly understand the cardiac pathology of new disorders, as emphasized during the recent coronavirus disease 2019 pandemic.

An autopsy case of COVID-19 with a sudden death : Clinico-pathological comparison. (preprint)

Autopsy was performed on a COVID-19 patient, who suddenly died despite the extensive anti-viral and anti-inflammatory therapies. Although moderate subpleural fibrosis was seen, pathology of DAD, a well-known cause for pulmonary failure, was minimum. Instead, severe hemorrhage was observed. Therapeutic effects were indicated, however why severe hemorrhage occurred was unclear.

Myocarditis-induced Sudden Death after BNT162b2 mRNA COVID-19 Vaccination in Korea: Case Report Focusing on Histopathological Findings.

We present autopsy findings of a 22-year-old man who developed chest pain 5 days after the first dose of the BNT162b2 mRNA vaccine and died 7 hours later. Histological examination of the heart revealed isolated atrial myocarditis, with neutrophil and histiocyte predominance. Immunohistochemical C4d staining revealed scattered single-cell necrosis of myocytes which was not accompanied by inflammatory infiltrates. Extensive contraction band necrosis was observed in the atria and ventricles. There was no evidence of microthrombosis or infection in the heart and other organs. The primary cause of death was determined to be myocarditis, causally-associated with the BNT162b2 vaccine.

A case of persistent severe sequelae of COVID-19 infection: potential role in sudden death?

Depending on the stage of the disease, autopsy findings of COVID-19 may include a spectrum of cardiopulmonary pathologies including alveolar hyaline membrane formation, vascular thrombosis, and intracardiac thrombi. Identification of a COVID-19 positive decedent in the absence of clinical history relies primarily on post-mortem nasopharyngeal (NP) or oropharyngeal (OP) swabs for real time polymerase chain reaction (RT-PCR). In the absence of definitive microbiology testing, post-mortem computed tomography (PMCT) may be a powerful adjunct tool for screening. Persistence of pathological changes may prolong physiological alterations and increase the risk of cardiopulmonary compromise. This current case outlines the forensic presentation, utilization of screening tools including PMCT, and the autopsy findings of a recent toxicology related sudden death case in the context of severe sequelae of COVID-19 pneumonia. This case demonstrates the limitation of NP and OP swabs in the post-mortem setting, the value of PMCT as an adjunct screening tool, and raises the consideration of COVID-19 sequelae as a potential contributing risk factors in sudden death cases in the community.

SARS-CoV-2 spike protein induces abnormal inflammatory blood clots neutralized by fibrin immunotherapy (preprint)

Blood clots are a central feature of coronavirus disease-2019 (COVID-19) and can culminate in pulmonary embolism, stroke, and sudden death. However, it is not known how abnormal blood clots form in COVID-19 or why they occur even in asymptomatic and convalescent patients. Here we report that the Spike protein from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to the blood coagulation factor fibrinogen and induces structurally abnormal blood clots with heightened proinflammatory activity. SARS-CoV-2 Spike virions enhanced fibrin-mediated microglia activation and induced fibrinogen-dependent lung pathology. COVID-19 patients had fibrin autoantibodies that persisted long after acute infection. Monoclonal antibody 5B8, targeting the cryptic inflammatory fibrin epitope, inhibited thromboinflammation. Our results reveal a procoagulant role for the SARS-CoV-2 Spike and propose fibrin-targeting interventions as a treatment for thromboinflammation in COVID-19.

Autoimmunity and Antibody Dependent COVID-19 Enhancement of SARS CoV-2 Vaccination: A Global Human Right to Know then Decide. (preprint)

Nucleic acid based - mRNA based and adenovirus vectored - vaccines, were first ever or first commercially ever approved for the public, respectively. However, these newly emergency approved types possess a potential risk to induce auto-immune diseases e.g., thrombocytopenia, myocarditis and immune induced thrombosis and thromboembolism that might be fatal and could reason for some of the post vaccination sudden death reports. Moreover, all SARS CoV-2 types of vaccines, depending on the spike protein immunogenicity, especially the conventional inactivated ones might increase the likelihood of COVID-19 severity upon re-infection through antibody dependent enhancement which might reason for the recently described abundance of hospital admissions within seven days of vaccination and might also reason for some of the serious adverse effects encountered with administration of convalescent plasma to COVID-19 patients as well as they might share in development of some lethal SARS CoV-2 variants. Importantly, we suggest that SARS CoV-2 mass vaccination campaigns were the worst ever decision made and that making these COVID-19 vaccines compulsory or administering them to children or pregnant participants might be considered as a crime against humanity to the extent that no prior companies- governmental agreements would ever secure impunity. Finally, a full informed personalized risk benefit ratio especially for some described high-risk groups must be secured while suggesting that the subunit vaccines are the least hazardous ones.

SARS CoV-2 adenovirus and RNA based vaccines potential autoimmune complications: could we lower the chances? (preprint)

Nucleic acid based - mRNA based and adenovirus vectored - vaccines, were first ever or first commercially ever approved for the public, respectively. However, these newly emergency approved types possess a potential risk to induce auto-immune diseases e.g., thrombocytopenia, myocarditis and immune induced thrombosis and thromboembolism that might be fatal and could reason for some of the post vaccination sudden death reports. Moreover, all SARS CoV-2 types of vaccines, depending on the spike protein immunogenicity, especially the conventional inactivated ones might increase the likelihood of COVID-19 severity upon re-infection through antibody dependent enhancement which might reason for the recently described abundance of hospital admissions within seven days of vaccination and might also reason for some of the serious adverse effects encountered with administration of convalescent plasma to COVID-19 patients as well as they might share in development of some lethal SARS CoV-2 variants. Importantly, we suggest that SARS CoV-2 mass vaccination campaigns were the worst ever decision made and that making these COVID-19 vaccines compulsory or administering them to children or pregnant participants might be considered as a crime against humanity to the extent that no prior companies- governmental agreements would ever secure impunity. Finally, a full informed personalized risk benefit ratio especially for some described high-risk groups must be secured while suggesting that the subunit vaccines are the least hazardous ones.

An outbreak of SARS-CoV-2 with high mortality in mink (Neovison vison) on multiple Utah farms (preprint)

The breadth of animal hosts that are susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and may serve as reservoirs for continued viral transmission are not known entirely. In August 2020, an outbreak of SARS-CoV-2 occurred in multiple mink farms in Utah and was associated with high mink mortality and rapid viral transmission between animals. The outbreak's epidemiology, pathology, molecular characterization, and tissue distribution of virus within infected mink is provided. Infection of mink was likely by reverse zoonosis. Once established, infection spread rapidly between independently housed animals and farms, and caused severe respiratory disease and death. Clinical signs were most notably sudden death, anorexia, and increased respiratory effort. Gross pathology examination revealed severe pulmonary congestion and edema. Microscopically there was pulmonary edema with moderate vasculitis, perivasculitis, and fibrinous interstitial pneumonia. Reverse transcriptase polymerase chain reaction (RT-PCR) of tissues collected at necropsy demonstrated the presence of SARS-CoV-2 viral RNA in multiple organs including nasal turbinates, lung, tracheobronchial lymph node, epithelial surfaces, and others. Whole genome sequencing from multiple mink was consistent with published SARS-CoV-2 genomes with few polymorphisms. The Utah mink SARS-CoV-2 strain fell into Clade GH, which is unique among mink and other animal strains sequenced to date and did not share other spike RBD mutations Y453F and F486L found in mink. Localization of viral RNA by in situ hybridization revealed a more localized infection, particularly of the upper respiratory tract. Mink in the outbreak reported herein had high levels of virus in the upper respiratory tract associated with mink-to-mink transmission in a confined housing environment and were particularly susceptible to disease and death due to SARS-CoV-2 infection.

[Clinical and anatomical analysis of mortality from COVID-19 in sudden death and in those who died in health care facilities]. / Kliniko-anatomicheskii analiz letal'nosti ot COVID-19 pri skoropostizhnoi smerti i u umershikh v lechebno-profilakticheskikh uchrezhdeniyakh.

OBJECTIVE: Assessment of pathological and morphological changes in those who died from COVID-19 including persons received therapy in medical and preventive institutions (LPI) and who died suddenly from this pathology at home. The analysis data of the pathological and anatomical changes in 57 deaths from COVID-19 in hospitals and 74 forensic medical examinations where infectious pathology was established as the main cause of death are presented. For microscopy the sections were stained with hemotoxylin and eosin, OCG, immunohistochemical study with markers for CD3, CD 4, CD 20, SK-7. The mixed viral and bacterial lesions of the lungs were detected more often than pure viral infection in those who died suddenly from COVID-19 compared with people whose death occurred in medical facilities. This allows speaking about the lack of adequate antibiotic therapy out-patiently. Features of mononuclear lung infiltration in COVID-19 with a predominance of a moderately pronounced reaction of T-lymphocytes and a mild B-lymphocytic reaction indicate a decrease in immunological reactivity. Conducting clinical and anatomical analysis allows determining the features of pathogenesis and morphogenesis in each specific fatal case and informing the clinicians of health facilities (clinics and hospitals) allows the autopsy doctor (pathologist, forensic physician) to provide significant assistance in improving the quality of diagnosis and treatment of patients with this highly contagious severe viral disease.

Sudden Death After Electroconvulsive Therapy in the Context of Coronavirus Disease 2019.

CONCLUSIONS: Although ECT is a safe procedure, caution should be exercised in the context of COVID-19, as it is now clear that patients who recovered from COVID-19 might have an undetected venous thromboembolism that can cause untoward outcomes. ETHICAL CONSIDERATION: A written consent was obtained from the sister to the deceased patient.

Sudden death of COVID-19 patients in Wuhan, China: A retrospective cohort study.

BACKGROUND: In December 2019, coronavirus disease 2019 (COVID-19) emerged in Wuhan city and rapidly spread throughout China. So far, it has caused ~ 4000 deaths in this country. We aimed to systematically characterize clinical features and determine risk factors of sudden death for COVID-19 patients. METHODS: Deceased patients with COVID-19 in Tongji hospital from January 22 to March 23, 2020 were extracted. Patients who died within 24 hours after admission were identified as sudden deaths, and the others formed non-sudden deaths. The differences in clinical characteristics between the two groups were estimated. Risk factors associated with sudden deaths were explored by logistic regression. RESULTS: 281 deceased patients were enrolled in this study. Sudden death occurred in 28 (10.0%) patients, including 4 (14.3%) admitted to the intensive care unit. Fatigue was more common in sudden deaths (11, 47.8%) than in non-sudden deaths (40, 17.2%). Both the count and percentage of eosinophils were lower in sudden deaths than that in non-sudden deaths (P = 0.006 and P = 0.004). Compared with non-sudden deaths, sudden deaths had higher plasma levels of procalcitonin, C-reactive protein, D-dimer, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, lactate dehydrogenase, alkaline phosphatase and N-terminal pro-brain natriuretic peptide. There were not significant differences in gender, age, chest CT image features and comorbidities observed. CONCLUSIONS: The differences between the two groups suggested more severe systemic inflammation, multi-organ dysfunction, especially impaired liver and heart function in COVID-19 patients who died suddenly after admission. More researches are needed to verify these points.

Association between regional distributions of SARS-CoV-2 seroconversion and out-of-hospital sudden death during the first epidemic outbreak in New York.

BACKGROUND: Increased incidence of out-of-hospital sudden death (OHSD) has been reported during the coronavirus 2019 (COVID-19) pandemic. New York City (NYC) represents a unique opportunity to examine the epidemiologic association between the two given the variable regional distribution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in its highly diverse neighborhoods. OBJECTIVE: The purpose of this study was to examine the association between OHSD and SARS-CoV-2 epidemiologic burden during the first COVID-19 pandemic across the highly diverse neighborhoods of NYC. METHODS: The incidences of OHSD between March 20 and April 22, 2019, and between March 20 and April 22, 2020, as reported by the Fire Department of New York were obtained. As a surrogate for viral epidemiologic burden, we used percentage of positive SARS-CoV-2 antibody tests performed between March 3 and August 20, 2020. Data were reported separately for the 176 zip codes of NYC. Correlation analysis and regression analysis were performed between the 2 measures to examine association. RESULTS: Incidence of OHSD per 10,000 inhabitants and percentage of SARS-CoV-2 seroconversion were highly variable across NYC neighborhoods, varying from 0.0 to 22.9 and 12.4% to 50.9%, respectively. Correlation analysis showed a moderate positive correlation between neighborhood data on OHSD and percentage of positive antibody tests to SARS-CoV-2 (Spearman ρ 0.506; P <.001). Regression analysis showed that seroconversion to SARS-CoV-2 and OHSD in 2019 were independent predictors for OHSD during the first epidemic surge in NYC (R2 = 0.645). CONCLUSION: The association in geographic distribution between OHSD and SARS-CoV-2 epidemiologic burden suggests either a causality between the 2 syndromes or the presence of local determinants affecting both measures in a similar fashion.