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

Clare Bryce; Zachary Grimes; Elisabet Pujadas; Sadhna Ahuja; Mary Beth Beasley; Randy Albrecht; Tahyna Hernandez; Aryeh Stock; Zhen Zhao; Mohamed Rizwan AlRasheed; Joyce Chen; Li Li; Diane Wang; Adriana Corben; G. Kenneth Haines; William H. Westra; Melissa Umphlett; Ronald E. Gordon; Jason Reidy; Bruce Petersen; Fadi Salem; Maria Isabel Fiel; Siraj M. El Jamal; Nadejda M. Tsankova; Jane Houldsworth; Zarmeen Mussa; Brandon Veremis; Emilia Sordillo; Melissa R. Gitman; Michael Nowak; Rachel Brody; Noam Harpaz; Miriam Merad; Sacha Gnjatic; Wen Chun Liu; Michael Schotsaert; Lisa Miorin; Teresa A. Aydillo Gomez; Irene Ramos-Lopez; Adolfo Garcia-Sastre; 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 E. Fowkes

doi:10.1038/s41379-021-00793-y

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

Clare Bryce, Zachary Grimes, Elisabet Pujadas, Sadhna Ahuja, Mary Beth Beasley, Randy Albrecht, Tahyna Hernandez, Aryeh Stock, Zhen Zhao, Mohamed Rizwan AlRasheed, Joyce Chen, Li Li, Diane Wang, Adriana Corben, G. Kenneth Haines, William H. Westra, Melissa Umphlett, Ronald E. Gordon, Jason Reidy, Bruce PetersenFadi Salem, Maria Isabel Fiel, Siraj M. El Jamal, Nadejda M. Tsankova, Jane Houldsworth, Zarmeen Mussa, Brandon Veremis, Emilia Sordillo, Melissa R. Gitman, Michael Nowak, Rachel Brody, Noam Harpaz, Miriam Merad, Sacha Gnjatic, Wen Chun Liu, Michael Schotsaert, Lisa Miorin, Teresa A. Aydillo Gomez, Irene Ramos-Lopez, Adolfo Garcia-Sastre, 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 E. Fowkes

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Pages (from-to)	1456-1467
Number of pages	12
Journal	Modern Pathology
Volume	34
Issue number	8
DOIs	https://doi.org/10.1038/s41379-021-00793-y
State	Published - Aug 2021
Externally published	Yes

ASJC Scopus subject areas

General Medicine

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Bryce, C., Grimes, Z., Pujadas, E., Ahuja, S., Beasley, M. B., Albrecht, R., Hernandez, T., Stock, A., Zhao, Z., AlRasheed, M. R., Chen, J., Li, L., Wang, D., Corben, A., Haines, G. K., Westra, W. H., Umphlett, M., Gordon, R. E., Reidy, J., ... Fowkes, M. E. (2021). Pathophysiology of SARS-CoV-2: the Mount Sinai COVID-19 autopsy experience. Modern Pathology, 34(8), 1456-1467. https://doi.org/10.1038/s41379-021-00793-y

Bryce, C, Grimes, Z, Pujadas, E, Ahuja, S, Beasley, MB, Albrecht, R, Hernandez, T, Stock, A, Zhao, Z, AlRasheed, MR, Chen, J, Li, L, Wang, D, Corben, A, Haines, GK, Westra, WH, Umphlett, M, Gordon, RE, Reidy, J, Petersen, B, Salem, F, Fiel, MI, El Jamal, SM, Tsankova, NM, Houldsworth, J, Mussa, Z, Veremis, B, Sordillo, E, Gitman, MR, Nowak, M, Brody, R, Harpaz, N, Merad, M, Gnjatic, S, Liu, WC, Schotsaert, M, Miorin, L, Aydillo Gomez, TA, Ramos-Lopez, I, Garcia-Sastre, A, Donnelly, R, Seigler, P, Keys, C, Cameron, J, Moultrie, I, Washington, KL, Treatman, J, Sebra, R, Jhang, J, Firpo, A, Lednicky, J, Paniz-Mondolfi, A, Cordon-Cardo, C & Fowkes, ME 2021, 'Pathophysiology of SARS-CoV-2: the Mount Sinai COVID-19 autopsy experience', Modern Pathology, vol. 34, no. 8, pp. 1456-1467. https://doi.org/10.1038/s41379-021-00793-y

@article{6527d6ef7f474365aa68aa4b22acb844,

title = "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.",

author = "Clare Bryce and Zachary Grimes and Elisabet Pujadas and Sadhna Ahuja and Beasley, {Mary Beth} and Randy Albrecht and Tahyna Hernandez and Aryeh Stock and Zhen Zhao and AlRasheed, {Mohamed Rizwan} and Joyce Chen and Li Li and Diane Wang and Adriana Corben and Haines, {G. Kenneth} and Westra, {William H.} and Melissa Umphlett and Gordon, {Ronald E.} and Jason Reidy and Bruce Petersen and Fadi Salem and Fiel, {Maria Isabel} and {El Jamal}, {Siraj M.} and Tsankova, {Nadejda M.} and Jane Houldsworth and Zarmeen Mussa and Brandon Veremis and Emilia Sordillo and Gitman, {Melissa R.} and Michael Nowak and Rachel Brody and Noam Harpaz and Miriam Merad and Sacha Gnjatic and Liu, {Wen Chun} and Michael Schotsaert and Lisa Miorin and {Aydillo Gomez}, {Teresa A.} and Irene Ramos-Lopez and Adolfo Garcia-Sastre and Ryan Donnelly and Patricia Seigler and Calvin Keys and Jennifer Cameron and Isaiah Moultrie and Washington, {Kae Lynn} and Jacquelyn Treatman and Robert Sebra and Jeffrey Jhang and Adolfo Firpo and John Lednicky and Alberto Paniz-Mondolfi and Carlos Cordon-Cardo and Fowkes, {Mary E.}",

note = "Funding Information: Ethics approval The Icahn School of Medicine Institution Review Board considers autopsies as nonhuman subjects (decedents). Approval for this study was provided by the Icahn School of Medicine Grants and Contracts Office. Publisher Copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to United States & Canadian Academy of Pathology.",

year = "2021",

month = aug,

doi = "10.1038/s41379-021-00793-y",

language = "English (US)",

volume = "34",

pages = "1456--1467",

journal = "Modern Pathology",

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T2 - the Mount Sinai COVID-19 autopsy experience

AU - Bryce, Clare

AU - Grimes, Zachary

AU - Pujadas, Elisabet

AU - Ahuja, Sadhna

AU - Beasley, Mary Beth

AU - Albrecht, Randy

AU - Hernandez, Tahyna

AU - Stock, Aryeh

AU - Zhao, Zhen

AU - AlRasheed, Mohamed Rizwan

AU - Chen, Joyce

AU - Li, Li

AU - Wang, Diane

AU - Corben, Adriana

AU - Haines, G. Kenneth

AU - Westra, William H.

AU - Umphlett, Melissa

AU - Gordon, Ronald E.

AU - Reidy, Jason

AU - Petersen, Bruce

AU - Salem, Fadi

AU - Fiel, Maria Isabel

AU - El Jamal, Siraj M.

AU - Tsankova, Nadejda M.

AU - Houldsworth, Jane

AU - Mussa, Zarmeen

AU - Veremis, Brandon

AU - Sordillo, Emilia

AU - Gitman, Melissa R.

AU - Nowak, Michael

AU - Brody, Rachel

AU - Harpaz, Noam

AU - Merad, Miriam

AU - Gnjatic, Sacha

AU - Liu, Wen Chun

AU - Schotsaert, Michael

AU - Miorin, Lisa

AU - Aydillo Gomez, Teresa A.

AU - Ramos-Lopez, Irene

AU - Garcia-Sastre, Adolfo

AU - Donnelly, Ryan

AU - Seigler, Patricia

AU - Keys, Calvin

AU - Cameron, Jennifer

AU - Moultrie, Isaiah

AU - Washington, Kae Lynn

AU - Treatman, Jacquelyn

AU - Sebra, Robert

AU - Jhang, Jeffrey

AU - Firpo, Adolfo

AU - Lednicky, John

AU - Paniz-Mondolfi, Alberto

AU - Cordon-Cardo, Carlos

AU - Fowkes, Mary E.

N1 - Funding Information: Ethics approval The Icahn School of Medicine Institution Review Board considers autopsies as nonhuman subjects (decedents). Approval for this study was provided by the Icahn School of Medicine Grants and Contracts Office. Publisher Copyright: © 2021, The Author(s), under exclusive licence to United States & Canadian Academy of Pathology.

PY - 2021/8

Y1 - 2021/8

N2 - 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.

AB - 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.

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

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