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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated clinical syndrome COVID-19 are causing overwhelming morbidity and mortality around the globe and disproportionately affected New York City between March and May 2020. Here, we report on the first 100 COVID-19-positive autopsies performed at the Mount Sinai Hospital in New York City. Autopsies revealed large pulmonary emboli in six cases. Diffuse alveolar damage was present in over 90% of cases. We also report microthrombi in multiple organ systems including the brain, as well as hemophagocytosis. We additionally provide electron microscopic evidence of the presence of the virus in our samples. Laboratory results of our COVID-19 cohort disclose elevated inflammatory markers, abnormal coagulation values, and elevated cytokines IL-6, IL-8, and TNFα. Our autopsy series of COVID-19-positive patients reveals that this disease, often conceptualized as a primarily respiratory viral illness, has widespread effects in the body including hypercoagulability, a hyperinflammatory state, and endothelial dysfunction. Targeting of these multisystemic pathways could lead to new treatment avenues as well as combination therapies against SARS-CoV-2 infection., (© 2021. The Author(s), under exclusive licence to United States & Canadian Academy of Pathology.)

Background & Aims: Given that gastrointestinal (GI) symptoms are a prominent extrapulmonary manifestation of COVID-19, we investigated intestinal infection with SARS-CoV-2, its effect on pathogenesis, and clinical significance., Methods: Human intestinal biopsy tissues were obtained from patients with COVID-19 (n = 19) and uninfected control individuals (n = 10) for microscopic examination, cytometry by time of flight analyses, and RNA sequencing. Additionally, disease severity and mortality were examined in patients with and without GI symptoms in 2 large, independent cohorts of hospitalized patients in the United States (N = 634) and Europe (N = 287) using multivariate logistic regressions., Results: COVID-19 case patients and control individuals in the biopsy cohort were comparable for age, sex, rates of hospitalization, and relevant comorbid conditions. SARS-CoV-2 was detected in small intestinal epithelial cells by immunofluorescence staining or electron microscopy in 15 of 17 patients studied. High-dimensional analyses of GI tissues showed low levels of inflammation, including down-regulation of key inflammatory genes including IFNG, CXCL8, CXCL2, and IL1B and reduced frequencies of proinflammatory dendritic cells compared with control individuals. Consistent with these findings, we found a significant reduction in disease severity and mortality in patients presenting with GI symptoms that was independent of sex, age, and comorbid illnesses and despite similar nasopharyngeal SARS-CoV-2 viral loads. Furthermore, there was reduced levels of key inflammatory proteins in circulation in patients with GI symptoms., Conclusions: These data highlight the absence of a proinflammatory response in the GI tract despite detection of SARS-CoV-2. In parallel, reduced mortality in patients with COVID-19 presenting with GI symptoms was observed. A potential role of the GI tract in attenuating SARS-CoV-2-associated inflammation needs to be further examined., (Copyright © 2021 AGA Institute. All rights reserved.)

Background: Thromboembolic disease is common in coronavirus disease-2019 (COVID-19). There is limited evidence on the association of in-hospital anticoagulation (AC) with outcomes and postmortem findings., Objectives: The purpose of this study was to examine association of AC with in-hospital outcomes and describe thromboembolic findings on autopsies., Methods: This retrospective analysis examined the association of AC with mortality, intubation, and major bleeding. Subanalyses were also conducted on the association of therapeutic versus prophylactic AC initiated ≤48 h from admission. Thromboembolic disease was contextualized by premortem AC among consecutive autopsies., Results: Among 4,389 patients, median age was 65 years with 44% women. Compared with no AC (n = 1,530; 34.9%), therapeutic AC (n = 900; 20.5%) and prophylactic AC (n = 1,959; 44.6%) were associated with lower in-hospital mortality (adjusted hazard ratio [aHR]: 0.53; 95% confidence interval [CI]: 0.45 to 0.62 and aHR: 0.50; 95% CI: 0.45 to 0.57, respectively), and intubation (aHR: 0.69; 95% CI: 0.51 to 0.94 and aHR: 0.72; 95% CI: 0.58 to 0.89, respectively). When initiated ≤48 h from admission, there was no statistically significant difference between therapeutic (n = 766) versus prophylactic AC (n = 1,860) (aHR: 0.86; 95% CI: 0.73 to 1.02; p = 0.08). Overall, 89 patients (2%) had major bleeding adjudicated by clinician review, with 27 of 900 (3.0%) on therapeutic, 33 of 1,959 (1.7%) on prophylactic, and 29 of 1,530 (1.9%) on no AC. Of 26 autopsies, 11 (42%) had thromboembolic disease not clinically suspected and 3 of 11 (27%) were on therapeutic AC., Conclusions: AC was associated with lower mortality and intubation among hospitalized COVID-19 patients. Compared with prophylactic AC, therapeutic AC was associated with lower mortality, although not statistically significant. Autopsies revealed frequent thromboembolic disease. These data may inform trials to determine optimal AC regimens., (Copyright © 2020. Published by Elsevier Inc.)