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Quantitative multiorgan proteomics of fatal COVID-19 uncovers tissue-specific effects beyond inflammation
Lisa Schweizer1, Tina Schaller2, Maximilian Zwiebel1
1Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany.
Abstract:
SARS-CoV-2 may directly and indirectly damage lung tissue and other host organs, but there are few system-wide, untargeted studies of these effects on the human body. Here, we developed a parallelized mass spectrometry (MS) proteomics workflow enabling the rapid, quantitative analysis of hundreds of virus-infected FFPE tissues. The first layer of response to SARS-CoV-2 in all tissues was dominated by circulating inflammatory molecules. Beyond systemic inflammation, we differentiated between systemic and true tissue-specific effects to reflect distinct COVID-19-associated damage patterns. Proteomic changes in the lungs resembled those of diffuse alveolar damage (DAD) in non-COVID-19 patients. Extensive organ-specific changes were also evident in the kidneys, liver, and lymphatic and vascular systems. Secondary inflammatory effects in the brain were related to rearrangements in neurotransmitter receptors and myelin degradation. These MS-proteomics-derived results contribute substantially to our understanding of COVID-19 pathomechanisms and suggest strategies for organ-specific therapeutic interventions.
Insights
This study reveals widespread organ damage from SARS-CoV-2 infection, impacting lungs, kidneys, liver, and brain. Proteomics identified distinct COVID-19 damage patterns and inflammation, suggesting targeted therapies.
Area of Science:
- Biochemistry
- Pathology
- Immunology
Background:
- SARS-CoV-2 infection causes significant morbidity and mortality.
- Systemic and organ-specific damage mechanisms remain incompletely understood.
- Few untargeted, system-wide proteomic studies exist for COVID-19 organ damage.
Purpose of the Study:
- To comprehensively analyze the systemic and organ-specific proteomic changes induced by SARS-CoV-2 infection.
- To differentiate between general inflammation and true tissue-specific damage patterns.
- To identify potential therapeutic targets for COVID-19 organ damage.
Main Methods:
- Development of a parallelized mass spectrometry (MS) proteomics workflow.
- Quantitative proteomic analysis of hundreds of virus-infected Formalin-Fixed Paraffin-Embedded (FFPE) tissues.
- System-wide, untargeted analysis to capture a broad range of molecular changes.
Main Results:
- Initial response across all tissues dominated by systemic inflammatory molecules.
- Lung proteomic changes mimicked diffuse alveolar damage (DAD) seen in non-COVID-19 patients.
- Significant organ-specific proteomic alterations observed in kidneys, liver, lymphatic, and vascular systems.
- Brain exhibited secondary inflammatory effects, including neurotransmitter receptor alterations and myelin degradation.
Conclusions:
- SARS-CoV-2 infection induces complex, multi-organ damage beyond systemic inflammation.
- Proteomic profiling reveals distinct COVID-19-associated organ damage patterns.
- Findings support the development of organ-specific therapeutic strategies for COVID-19.
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