Pathophysiology of SARS-CoV-2: the Mount Sinai COVID-19 autopsy experience

Abstract

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.

Nebulization of glutathione and N-Acetylcysteine as an adjuvant therapy for COVID-19 onset

“…The respiratory complications are attributed to a "cytokine storm syndrome" [ 4 , 5 ] an exaggerated systemic immune inflammatory response with oxidative stress ( figure 1 ) caused by increased levels of interleukin (IL)-6 and tumor necrosis factor α (TNF-α) along with decreased levels of interferon α and interferon β (IFN-α, IFN-β) [6] . The elevated levels of proinflammatory cytokines and chemokines such as tumour necrosis factor (TNF)-α, interleukin 1β (IL-1β), IL-6, IL-8 [ 2 , 7 ] and others indicate the cytokine storm plays a central role in the immunopathology of COVID-19, but the primary source or the exact virological mechanisms behind it have not been identified yet [8] . Dendritic cells (DCs) and alveolar macrophages phagocytose the virus-infected epithelial cells, followed by an immunosuppressive response characterized by lymphopenia, low CD4 and CD8 T cell counts and therefore an increased risk of bacterial infection 9 , 10 , 11 .…”

Comparison of Blood Counts and Markers of Inflammation and Coagulation in Patients With and Without COVID-19 Presenting to the Emergency Department in Seattle, WA

“…Much has been made of coagulopathy in association with COVID-19 due to the high rates of thrombotic complications in reports from Wuhan with focus shifting to a microthrombotic pathology as described in one of the first autopsy studies. 13 , 14 , 33 , 34 Our dataset was not specifically focused on investigating markers of coagulation and we did not collect information regarding rates of anticoagulation, thus limiting interpretations. However, our data fit the findings in the literature in which small to negligible increases in PT and significantly longer PTTs are noted in patients with COVID-19.…”

Longitudinal Assessment of Cytokine Expression and Plasminogen Activation in Hantavirus Cardiopulmonary Syndrome Reveals Immune Regulatory Dysfunction in End-Stage Disease

“…We suggest that the apparent etiology of the bacterial infection, highlighted by the excessive in-tandem levels of IL-12p40 and GM-CSF, was more significant than SNV-induced HCPS in light of the fact that the patient did not meet the criteria for ECMO. Thus, as with COVID-19 [ 82 , 83 ], other underlying conditions could significantly influence the pathophysiology and outcome. In a similar vein, Class II Patient 306 presented a temporally distinct co-infection of bacteria and SNV, which was apparent in two waves of immune activation involving different inflammatory mediators.…”