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Human Phenotype

Transmission

Seroprevalence
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    Pathophysiology of SARS-CoV-2: targeting of endothelial cells renders a complex disease MESHD with thrombotic microangiopathy MESHD and aberrant immune response. The Mount Sinai COVID-19 autopsy experience

    Authors: Clare Bryce; Zachary Grimes; Elisabet Pujadas; Sadhna Ahuja; Mary Beth Beasley; Randy Albrecht; Tahyna Hernandez; Aryeh Stock; Zhen Zhao; Mohamed Al Rasheed; Joyce Chen; Li Li; Diane Wang; Adriana Corben; Kenneth Haines; William Westra; Melissa Umphlett; Ronald E Gordon; Jason Reidy; Bruce Petersen; Fadi Salem; MariaIsabel Fiel; Siraj M El Jamal; Nadejda M Tsankova; Jane Houldsworth; Zarmeen Mussa; Wen-Chun Liu; Brandon Veremis; Emilia Sordillo; Melissa Gitman; Michael Nowak; Rachel Brody; Noam Harpaz; Miriam Merad; Sacha Gnjatic; Ryan Donnelly; Patricia Seigler; Calvin Keys; Jennifer Cameron; Isaiah Moultrie; Kae-Lynn Washington; Jacquelyn Treatman; Robert Sebra; Jeffrey Jhang; Adolfo Firpo; John Lednicky; Alberto Paniz-Mondolfi; Carlos Cordon-Cardo; Mary Fowkes

    doi:10.1101/2020.05.18.20099960 Date: 2020-05-22 Source: medRxiv

    BACKGROUND Severe Acute Respiratory Syndrome MESHD Coronavirus-2 (SARS-CoV-2) and its associated clinical syndrome MESHD COVID-19 are causing overwhelming morbidity and mortality around the globe, disproportionately affecting New York City. A comprehensive, integrative autopsy series that advances the mechanistic discussion surrounding this disease MESHD process is still lacking. METHODS Autopsies were performed at the Mount Sinai Hospital on 67 COVID-19 positive patients and data from the clinical records were obtained from the Mount Sinai Data Warehouse. The experimental design included a comprehensive microscopic examination carried out by a team of expert pathologists, along with transmission TRANS electron microscopy, immunohistochemistry, RNA in situ hybridization, as well as immunology and serology assays. RESULTS Laboratory results of our COVID-19 cohort show elevated inflammatory markers, abnormal coagulation values, and elevated cytokines IL-6, IL-8 and TNF. Autopsies revealed large pulmonary emboli in four cases. We report microthrombi in multiple organ systems including the brain, as well as conspicuous hemophagocytosis HP and a secondary hemophagocytic lymphohistiocytosis MESHD-like syndrome MESHD in many of our patients. We provide electron microscopic, immunofluorescent and immunohistochemical evidence of the presence of the virus and the ACE2 receptor in our samples. CONCLUSIONS We report a comprehensive autopsy series of 67 COVID-19 positive patients revealing that this disease MESHD, so far conceptualized as a primarily respiratory viral illness, also causes endothelial dysfunction, a hypercoagulable state, and an imbalance of both the innate and adaptive immune responses. Novel findings reported here include an endothelial phenotype of ACE2 in selected organs, which correlates with clotting abnormalities and thrombotic microangiopathy MESHD, addressing the prominent coagulopathy and neuropsychiatric symptoms. Another original observation is that of macrophage activation syndrome MESHD, with hemophagocytosis HP and a hemophagocytic lymphohistiocytosis MESHD-like disorder, underlying the microangiopathy and excessive cytokine release. We discuss the involvement of critical regulatory pathways.

    SARS-CoV-2 Infection MESHD Associated Hemophagocytic Lymphohistiocytosis MESHD: An autopsy series with clinical and laboratory correlation.

    Authors: Andrey Prilutskiy; Michael Kritselis; Artem Shevtsov; Ilyas Yambayev; Charitha Vadlamudi; Qing Zhao; Yachana Kataria; Shayna Sarosiek; Adam Lerner; John Mark Sloan; Karen Quillen; Eric Burks

    doi:10.1101/2020.05.07.20094888 Date: 2020-05-12 Source: medRxiv

    Background: A subset of COVID-19 patients exhibit clinical features of cytokine storm. However, clinicopathologic features diagnostic of hemophagocytic lymphohistiocytosis MESHD (HLH) have not been reported. Pathologic studies to date have largely focused on the pulmonary finding of diffuse alveolar damage (DAD). To this aim, we study the reticuloendothelial organs of four consecutive patients dying of COVID-19 and correlate with clinical and laboratory parameters to detect HLH. Methods: Autopsies restricted to chest and abdomen were performed on four patients who succumbed to COVID-19. Spleen, liver, and multiple pulmonary hilar/mediastinal lymph nodes were sampled in all cases. Bone marrow was obtained by rib squeeze in a subset of cases. Routine H&E staining as well as immunohistochemical staining for CD163 was performed to detect hemophagocytosis HP. Clinical and laboratory results from pre-mortem blood SERO samples were used to calculate H-scores. Findings: All four cases demonstrated DAD within the lungs. Three of the four cases had histologic evidence of hemophagocytosis HP within pulmonary hilar/mediastinal lymph nodes. One case showed hemophagocytosis HP in the spleen but none showed hemophagocytosis HP in liver or bone marrow. Lymphophagocytosis was the predominant form of hemophagocytosis HP observed. One patient showed diagnostic features of HLH with an H-score of 217 while a second patient was likely HLH with a partial H-score of 145 due to missing triglyceride level. Both patients exhibited high fever MESHD fever HP and early onset rise in serum SERO ferritin; however, neither bicytopenia, pancytopenia MESHD pancytopenia HP, nor hypofibrinogenemia HP were observed in either. The remaining two patients had H-scores of 131 and 96. Interpretation: This is the first report of SARS-CoV-2 associated HLH. Identification of HLH in a subset of patients with severe COVID-19 will inform clinical trials of therapeutic strategies.

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MeSH Disease
Human Phenotype
Transmission
Seroprevalence


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