MassIVE MSV000090983

Partial Public PXD039157

Quantitative multi-organ proteomics of fatal COVID-19 uncovers tissue-specific effects beyond inflammation

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Description

SARS-CoV-2 directly damages lung tissue via its infection and replication process and indirectly due to systemic effects of the host immune system. There are few systems-wide, untargeted studies of these effects on the different tissues of the human body and nearly all of them base their conclusions on the transcriptome. Here we developed a parallelized mass spectrometry (MS)-based proteomics workflow allowing the rapid, quantitative analysis of hundreds of virus-infected and FFPE preserved tissues. The first layer of response in all tissues was dominated by circulating inflammatory molecules. To discriminate between these systemic and true tissue-specific effects, we developed an analysis pipeline revealing that proteome alterations reflect extensive tissue damage, mostly similar to non-COVID diffuse alveolar damage. The next most affected organs were kidney and liver, while the lymph-vessel system was also strongly affected. Finally, secondary inflammatory effects of the brain correlated with receptor rearrangements and the degradation of neuronal myelin. Our results establish MS-based tissue proteomics as a promising strategy to inform organ-specific therapeutic interventions following COVID-19 infections. [doi:10.25345/C5Z31NZ4Z] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: COVID-19 ; mass spectrometry ; tissue ; pathology ; proteomics ; clinic ; disease ; inflammation ; virus ; human

Contact

Principal Investigators:
(in alphabetical order) 		Matthias Mann, Max Planck Institute of Biochemistry, Germany
Rainer Claus, University of Augsburg, Germany
Submitting User: oroshi
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