PT  - JOURNAL ARTICLE
AU  - Marian Kalocsay
AU  - Zoltan Maliga
AU  - Ajit J. Nirmal
AU  - Robyn J. Eisert
AU  - Gary A. Bradshaw
AU  - Isaac H Solomon
AU  - Yu-An Chen
AU  - Roxanne J. Pelletier
AU  - Connor A. Jacobson
AU  - Julian Mintseris
AU  - Robert F. Padera
AU  - Amanda J. Martinot
AU  - Dan H. Barouch
AU  - Sandro Santagata
AU  - Peter K. Sorger
TI  - Multiplexed proteomics and imaging of resolving and lethal SARS-CoV-2 infection in the lung
AID  - 10.1101/2020.10.14.339952
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.10.14.339952
4099  - http://biorxiv.org/content/early/2020/10/15/2020.10.14.339952.short
4100  - http://biorxiv.org/content/early/2020/10/15/2020.10.14.339952.full
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.