RT Journal Article
SR Electronic
T1 Multiplexed proteomics and imaging of resolving and lethal SARS-CoV-2 infection in the lung
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.10.14.339952
DO 10.1101/2020.10.14.339952
A1 Marian Kalocsay
A1 Zoltan Maliga
A1 Ajit J. Nirmal
A1 Robyn J. Eisert
A1 Gary A. Bradshaw
A1 Isaac H Solomon
A1 Yu-An Chen
A1 Roxanne J. Pelletier
A1 Connor A. Jacobson
A1 Julian Mintseris
A1 Robert F. Padera
A1 Amanda J. Martinot
A1 Dan H. Barouch
A1 Sandro Santagata
A1 Peter K. Sorger
YR 2020
UL http://biorxiv.org/content/early/2020/10/15/2020.10.14.339952.abstract
AB Normal tissue physiology and repair depends on communication with the immune system. Understanding this communication at the molecular level in intact tissue requires new methods. The consequences of SARS-CoV-2 infection, which can result in acute respiratory distress, thrombosis and death, has been studied primarily in accessible liquid specimens such as blood, sputum and bronchoalveolar lavage, all of which are peripheral to the primary site of infection in the lung. Here, we describe the combined use of multiplexed deep proteomics with multiplexed imaging to profile infection and its sequelae directly in fixed lung tissue specimens obtained from necropsy of infected animals and autopsy of human decedents. We characterize multiple steps in disease response from cytokine accumulation and protein phosphorylation to activation of receptors, changes in signaling pathways, and crosslinking of fibrin to form clots. Our data reveal significant differences between naturally resolving SARS-CoV-2 infection in rhesus macaques and lethal COVID-19 in humans. The approach we describe is broadly applicable to other tissues and diseases.Summary Proteomics of infected tissue reveals differences in inflammatory and thrombotic responses between resolving and lethal COVID-19.Competing Interest StatementPKS is a member of the SAB or BOD member of Applied Biomath, RareCyte Inc., and Glencoe Software; PKS is also a member of the NanoString SAB. SS is a consultant for RareCyte Inc. The other authors declare no outside interests.