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Quantitative multi-organ proteomics of fatal COVID-19 uncovers tissue-specific effects beyond inflammation
- Publication Year :
- 2022
- Publisher :
- Cold Spring Harbor Laboratory, 2022.
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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 discriminated 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.
Details
- Database :
- OpenAIRE
- Accession number :
- edsair.doi...........f521c00e6a8bdafb09ce7e8a3c60eb4d