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1.
Int J Legal Med ; 135(6): 2335-2345, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1442101

ABSTRACT

Thorough postmortem investigations of fatalities following vaccination with coronavirus disease 2019 (COVID-19) vaccines are of great social significance. From 11.03.2021 to 09.06.2021, postmortem investigations of 18 deceased persons who recently received a vaccination against COVID-19 were performed. Vaxzevria was vaccinated in nine, Comirnaty in five, Spikevax in three, and Janssen in one person. In all cases, full autopsies, histopathological examinations, and virological analyses for the severe acute respiratory syndrome coronavirus 2 were carried out. Depending on the case, additional laboratory tests (anaphylaxis diagnostics, VITT [vaccine-induced immune thrombotic thrombocytopenia] diagnostics, glucose metabolism diagnostics) and neuropathological examinations were conducted. In 13 deceased, the cause of death was attributed to preexisting diseases while postmortem investigations did not indicate a causal relationship to the vaccination. In one case after vaccination with Comirnaty, myocarditis was found to be the cause of death. A causal relationship to vaccination was considered possible, but could not be proven beyond doubt. VITT was found in three deceased persons following vaccination with Vaxzevria and one deceased following vaccination with Janssen. Of those four cases with VITT, only one was diagnosed before death. The synopsis of the anamnestic data, the autopsy results, laboratory diagnostic examinations, and histopathological and neuropathological examinations revealed that VITT was the very likely cause of death in only two of the four cases. In the other two cases, no neuropathological correlate of VITT explaining death was found, while possible causes of death emerged that were not necessarily attributable to VITT. The results of our study demonstrate the necessity of postmortem investigations on all fatalities following vaccination with COVID-19 vaccines. In order to identify a possible causal relationship between vaccination and death, in most cases an autopsy and histopathological examinations have to be combined with additional investigations, such as laboratory tests and neuropathological examinations.


Subject(s)
COVID-19 Vaccines , Forensic Medicine , Vaccination/adverse effects , Adult , Aged , Aged, 80 and over , Anaphylaxis/mortality , Autopsy , Causality , Cause of Death , Female , Germany/epidemiology , Humans , Male , Middle Aged , Myocarditis/mortality , Purpura, Thrombocytopenic, Idiopathic/mortality
2.
Cardiovasc Pathol ; 54: 107361, 2021.
Article in English | MEDLINE | ID: covidwho-1281392

ABSTRACT

COVID-19 has a significant effect upon the cardiovascular system. While a number of different cardiovascular histopathologies have been described at post-mortem examination, the incidence of typical viral myocarditis in COVID-19 positive patients appears very low [1-3]. In this study, we further characterize and quantify the inflammatory cell infiltrate in a COVID-19 study cohort and compare the findings to both an age and disease matched control cohort and a cohort of patients diagnosed with typical inflammatory myocarditis. All study and control cohorts had 1 or more of the comorbidities most commonly associated with severe disease (hypertension, type II diabetes, obesity, or known cardiovascular disease). The results demonstrate a skewed distribution of the number of CD68+ cells in COVID-19 hearts, with upper quantiles showing a significant increase as compared to both matched control hearts, and those with myocarditis. In contrast, hearts from typical inflammatory myocarditis contained increased numbers of CD4+, and CD8+ cells compared to both COVID-19 and control cohorts. In conclusion, the presence of an increased number of CD68+ cells suggests that COVID-19 may incite a form of myocarditis different from typical viral myocarditis, and associated with diffusely infiltrative cells of monocytes/macrophage lineage.


Subject(s)
Antigens, CD/analysis , Antigens, Differentiation, Myelomonocytic/analysis , COVID-19/immunology , Macrophages/immunology , Myocarditis/immunology , Myocardium/immunology , Adult , Aged , Autopsy , Biomarkers/analysis , COVID-19/mortality , COVID-19/pathology , COVID-19/virology , Case-Control Studies , Female , Host-Pathogen Interactions , Humans , Immunohistochemistry , Macrophages/virology , Male , Middle Aged , Myocarditis/mortality , Myocarditis/pathology , Myocarditis/virology , Myocardium/pathology , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity
4.
Crit Pathw Cardiol ; 20(1): 44-52, 2021 03 01.
Article in English | MEDLINE | ID: covidwho-1135914

ABSTRACT

Due to the lack of prospective, randomized, controlled clinical studies on inflammation and cardiovascular involvement, the exact mechanism of cardiac injury among patients with Coronavirus Disease 2019 (COVID-19) still remains uncertain. It was demonstrated that there is a high and significantly positive linear correlation between troponin T and plasma high-sensitivity C-reactive protein levels, biomarkers of cardiac injury and systemic inflammation, respectively. Cardiac injury and inflammation is a relatively common association among patients hospitalized with COVID-19, and it is related to higher risk of in-hospital mortality. In our literature search, we identified several potential mechanisms of myocardial tissue damage, namely, coronavirus-associated acute myocarditis, angiotensin-converting enzyme 2 receptor binding affinity to the virus Spike protein, increased cytokine secretion, and hypoxia-induced cardiac myocyte apoptosis. Elucidation of the disease pathogenesis and prospective histopathological studies are crucial for future proper treatment in case of renewed outbreaks. Of interest is that with hundred of thousands of bodies available for autopsy studies, no prospective investigation has been reported so far. Strong efforts and continued research of the cardiovascular complications and identification of risk factors for poor prognosis in COVID-19 are steadily needed. The high morbidity and mortality of COVID-19, its monumental economic burden and social impact, the despair of a new pandemic outbreak, and the thread of potential utilization of novel severe acute respiratory syndrome coronavirus 2 as biologic weapons make it a preponderant necessity to better comprehend the therapeutic management of this lethal disease. Emerging as an acute infectious disease, COVID-19 may become a chronic epidemic because of genetic recombination. Therefore, we should be ready for the reemergence of COVID-19 or other coronaviruses.


Subject(s)
Arrhythmias, Cardiac/virology , COVID-19/complications , Myocarditis/blood , Myocarditis/virology , SARS-CoV-2/pathogenicity , Arrhythmias, Cardiac/diagnosis , Arrhythmias, Cardiac/mortality , Biomarkers/blood , C-Reactive Protein/metabolism , COVID-19/blood , COVID-19/mortality , Cytokines/blood , Hospitalization , Humans , Myocarditis/mortality , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Troponin T/blood
5.
ESC Heart Fail ; 8(1): 37-46, 2021 02.
Article in English | MEDLINE | ID: covidwho-1064350

ABSTRACT

AIMS: COVID-19, a respiratory viral disease causing severe pneumonia, also affects the heart and other organs. Whether its cardiac involvement is a specific feature consisting of myocarditis, or simply due to microvascular injury and systemic inflammation, is yet unclear and presently debated. Because myocardial injury is also common in other kinds of pneumonias, we investigated and compared such occurrence in severe pneumonias due to COVID-19 and other causes. METHODS AND RESULTS: We analysed data from 156 critically ill patients requiring mechanical ventilation in four European tertiary hospitals, including all n = 76 COVID-19 patients with severe disease course requiring at least ventilatory support, matched to n = 76 from a retrospective consecutive patient cohort of severe pneumonias of other origin (matched for age, gender, and type of ventilator therapy). When compared to the non-COVID-19, mortality (COVID-19 = 38.2% vs. non-COVID-19 = 51.3%, P = 0.142) and impairment of systolic function were not significantly different. Surprisingly, myocardial injury was even more frequent in non-COVID-19 (96.4% vs. 78.1% P = 0.004). Although inflammatory activity [C-reactive protein (CRP) and interleukin-6] was indifferent, d-dimer and thromboembolic incidence (COVID-19 = 23.7% vs. non-COVID-19 = 5.3%, P = 0.002) driven by pulmonary embolism rates (COVID-19 = 17.1% vs. non-COVID-19 = 2.6%, P = 0.005) were higher. CONCLUSIONS: Myocardial injury was frequent in severe COVID-19 requiring mechanical ventilation, but still less frequent than in similarly severe pneumonias of other origin, indicating that cardiac involvement may not be a specific feature of COVID-19. While mortality was also similar, COVID-19 is characterized with increased thrombogenicity and high pulmonary embolism rates.


Subject(s)
COVID-19/complications , Cardiomyopathies/etiology , Acute Disease , Aged , COVID-19/mortality , COVID-19/therapy , Cardiomyopathies/mortality , Case-Control Studies , Female , Humans , Intensive Care Units/statistics & numerical data , Length of Stay/statistics & numerical data , Male , Myocarditis/etiology , Myocarditis/mortality , Pneumonia/complications , Respiration, Artificial , Retrospective Studies , Tertiary Care Centers
6.
Medicina (Kaunas) ; 56(12)2020 Dec 09.
Article in English | MEDLINE | ID: covidwho-1024604

ABSTRACT

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) gained worldwide attention at the end of 2019 when it was identified to cause severe respiratory distress syndrome. While it primarily affects the respiratory system, we now have evidence that it affects multiple organ systems in the human body. Cardiac manifestations may include myocarditis, life threatening arrhythmias, acute coronary syndrome, systolic heart failure, and cardiogenic shock. Myocarditis is increasingly recognized as a complication of Coronavirus-19 (COVID-19) and may result from direct viral injury or from exaggerated host immune response. The diagnosis is established similar to other etiologies, and is based on detailed history, clinical exam, laboratory findings and non-invasive imaging studies. When available, cardiac MRI is the preferred imaging modality. Endomyocardial biopsy may be performed if the diagnosis remains uncertain. Current management is mainly supportive with the potential addition of interventions recommended for severe COVID-19 disease, such as remdesivir, steroids, and convalescent plasma. In the setting of cardiogenic shock and refractory, life-threatening arrhythmias that persist despite medical therapy, advanced mechanical circulatory support devices should be considered. Ultimately, early recognition and aggressive intervention are key factors in reducing morbidity and mortality. Our management strategy is expected to evolve further as we learn more about COVID-19 disease and the associated cardiac complications.


Subject(s)
COVID-19/complications , COVID-19/drug therapy , COVID-19/therapy , Myocarditis/virology , SARS-CoV-2 , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Alanine/analogs & derivatives , Alanine/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/virology , Humans , Immunization, Passive , Myocarditis/mortality , Myocarditis/therapy , Steroids/therapeutic use
7.
Cardiovasc Pathol ; 50: 107300, 2021.
Article in English | MEDLINE | ID: covidwho-1023486

ABSTRACT

The COVID-19 pandemic, the result of severe acute respiratory syndrome (SARS)-CoV-2, is a major cause of worldwide mortality with a significant cardiovascular component. While a number of different cardiovascular histopathologies have been reported at postmortem examination, their incidence is unknown, due to limited numbers of cases in any given study. A literature review was performed identifying 277 autopsied hearts across 22 separate publications of COVID-19 positive patients. The median age of the autopsy cohort was 75 and 97.6% had one or more comorbidities. Initial review of the data indicate that myocarditis was present in 20 hearts (7.2%); however, closer examination of additional reported information revealed that most cases were likely not functionally significant and the true prevalence of myocarditis is likely much lower (<2%). At least one acute, potentially COVID-19-related cardiovascular histopathologic finding, such as macro or microvascular thrombi, inflammation, or intraluminal megakaryocytes, was reported in 47.8% of cases. Significant differences in reporting of histopathologic findings occurred between studies indicating strong biases in observations and the need for more consistency in reporting. In conclusion, across 277 cases, COVID-19-related cardiac histopathological findings, are common, while myocarditis is rare.


Subject(s)
COVID-19/complications , Myocarditis/pathology , Myocardium/pathology , Adult , Aged , Aged, 80 and over , Autopsy , COVID-19/mortality , COVID-19/virology , Cause of Death , Comorbidity , Female , Humans , Male , Middle Aged , Myocarditis/mortality , Myocarditis/virology , Risk Factors , Young Adult
8.
Cardiovasc Pathol ; 50: 107300, 2021.
Article in English | MEDLINE | ID: covidwho-893655

ABSTRACT

The COVID-19 pandemic, the result of severe acute respiratory syndrome (SARS)-CoV-2, is a major cause of worldwide mortality with a significant cardiovascular component. While a number of different cardiovascular histopathologies have been reported at postmortem examination, their incidence is unknown, due to limited numbers of cases in any given study. A literature review was performed identifying 277 autopsied hearts across 22 separate publications of COVID-19 positive patients. The median age of the autopsy cohort was 75 and 97.6% had one or more comorbidities. Initial review of the data indicate that myocarditis was present in 20 hearts (7.2%); however, closer examination of additional reported information revealed that most cases were likely not functionally significant and the true prevalence of myocarditis is likely much lower (<2%). At least one acute, potentially COVID-19-related cardiovascular histopathologic finding, such as macro or microvascular thrombi, inflammation, or intraluminal megakaryocytes, was reported in 47.8% of cases. Significant differences in reporting of histopathologic findings occurred between studies indicating strong biases in observations and the need for more consistency in reporting. In conclusion, across 277 cases, COVID-19-related cardiac histopathological findings, are common, while myocarditis is rare.


Subject(s)
COVID-19/complications , Myocarditis/pathology , Myocardium/pathology , Adult , Aged , Aged, 80 and over , Autopsy , COVID-19/mortality , COVID-19/virology , Cause of Death , Comorbidity , Female , Humans , Male , Middle Aged , Myocarditis/mortality , Myocarditis/virology , Risk Factors , Young Adult
10.
Fetal Pediatr Pathol ; 39(3): 263-268, 2020 Jun.
Article in English | MEDLINE | ID: covidwho-245661

ABSTRACT

Background: Cardiac damage is frequently referred to in patients with SARS-CoV-2, is usually diagnosed by enzyme elevations, and is generally thought to be due to underlying coronary artery disease. There are references to cardiomyopathies accompanying coronavirus, but there has been no histologic confirmation.Case report: A previously healthy 17 year male old presented in full cardiac arrest to the emergency department after a 2 day history of headache, dizziness, nausea and vomiting. Autopsy demonstrated an enlarged flabby heart with eosinophilic myocarditis. There was no interstitial pneumonia or diffuse alveolar damage. Postmortem nasopharyngeal swabs detected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) known to cause coronavirus disease 2019 (COVID-19). No other cause for the eosinophilic myocarditis was elucidated.Conclusion: Like other viruses, SARS-CoV-2 may be associated with fulminant myocarditis.


Subject(s)
Coronavirus Infections/mortality , Eosinophilia/mortality , Myocarditis/mortality , Myocarditis/virology , Pneumonia, Viral/mortality , Adolescent , Betacoronavirus , COVID-19 , Coronavirus Infections/complications , Eosinophilia/complications , Fatal Outcome , Heart Arrest/complications , Heart Arrest/virology , Humans , Male , Myocarditis/complications , Pandemics , Pneumonia, Viral/complications , SARS-CoV-2
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