Quantitative multi-organ proteomics of fatal COVID-19 uncovers tissue-specific effects beyond inflammation
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ABSTRACT: 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.
INSTRUMENT(S): Orbitrap Exploris 480
ORGANISM(S): Homo Sapiens (ncbitaxon:9606)
SUBMITTER: Matthias Mann Rainer Claus
PROVIDER: MSV000090983 | MassIVE | Mon Jan 02 05:49:00 GMT 2023
SECONDARY ACCESSION(S): PXD039157
REPOSITORIES: MassIVE
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