SARS-CoV-2 has an overall lower case fatality rate (0.0–29%), although variable by country, than that of Severe Acute Respiratory Syndrome coronavirus (SARS, 9.5%) and Middle East Respiratory Syndrome coronavirus (MERS, 34.4%), but more efficient and aggressive viral transmission. The ACE2 receptor is localized on several human tissues, including pulmonary, renal, cardiovascular, and gastrointestinal epithelia, and is expressed by arterial and venous endothelial cells and arterial smooth muscle cells, making them potential targets for SARS-CoV-2 infection. SARS-CoV-2 infects the host by binding to the angiotensin-converting enzyme 2 (ACE2) receptor with its structural spike glycoprotein (S protein). Coronavirus disease-2019 (COVID-19) caused by human-to-human transmission occurs by virus contact with oral, nasal, or ocular mucosa, commonly by inhalation of small droplets exhaled by an infected person. SARS-CoV-2 is a new member in the betacoronavirus genus of the family of Coronaviridae. The severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) infection has affected most countries worldwide, with 34,026,003 confirmed cases and 1,015,107 deaths estimated by the World Health Organization as of October 1st, 2020. This study supports the notion that autopsy studies are of utmost importance to our understanding of disease features and treatment effect to increase our knowledge of COVID-19 pathophysiology and contribute to more effective treatment strategies. The pathologic findings emerging from autopsy and biopsy studies reviewed herein suggest that in addition to a direct viral effect in some organs, a unifying pathogenic mechanism for COVID-19 is ARDS with its known and characteristic inflammatory response, cytokine release, fever, inflammation, and generalized endothelial disturbance. Diffuse alveolar damage, thromboembolism, and nonspecific shock injury in multiple organs were the main findings in this review. Demographic data, comorbidities at presentation, histopathologic findings, and virus detection strategies by organ system were collected. A total of 58 studies reporting 662 patients were included. PubMed and Medline (EBSCO and Ovid) were queried from Jto Septemand histopathologic data from autopsy and biopsy studies were collected based on 2009 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. This review summarizes the histopathologic findings and clinicopathologic correlations from autopsies and biopsies performed in patients with COVID-19. Despite an initial reluctance to perform autopsies due to concerns for aerosolization of viral particles, a large number of autopsy studies published since May 2020 have shed light on the pathophysiology of Coronavirus disease 2019 (COVID-19). The severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) pandemic has had devastating effects on global health and worldwide economy.
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