Quantitative multiorgan proteomics of fatal COVID‐19 uncovers tissue‐specific effects beyond inflammation
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 hu...
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| Format: | Article |
| Language: | English |
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Springer Nature
2023-07-01
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| Series: | EMBO Molecular Medicine |
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| Online Access: | https://doi.org/10.15252/emmm.202317459 |
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| author | Lisa Schweizer Tina Schaller Maximilian Zwiebel Özge Karayel Johannes Bruno Müller‐Reif Wen‐Feng Zeng Sebastian Dintner Thierry M Nordmann Klaus Hirschbühl Bruno Märkl Rainer Claus Matthias Mann |
| author_facet | Lisa Schweizer Tina Schaller Maximilian Zwiebel Özge Karayel Johannes Bruno Müller‐Reif Wen‐Feng Zeng Sebastian Dintner Thierry M Nordmann Klaus Hirschbühl Bruno Märkl Rainer Claus Matthias Mann |
| author_sort | Lisa Schweizer |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-901eda2487d34885bb7571aa2ad46f4e |
| institution | Kabale University |
| issn | 1757-4676 1757-4684 |
| language | English |
| publishDate | 2023-07-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj-art-901eda2487d34885bb7571aa2ad46f4e2025-08-20T03:46:25ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842023-07-0115912110.15252/emmm.202317459Quantitative multiorgan proteomics of fatal COVID‐19 uncovers tissue‐specific effects beyond inflammationLisa Schweizer0Tina Schaller1Maximilian Zwiebel2Özge Karayel3Johannes Bruno Müller‐Reif4Wen‐Feng Zeng5Sebastian Dintner6Thierry M Nordmann7Klaus Hirschbühl8Bruno Märkl9Rainer Claus10Matthias Mann11Department of Proteomics and Signal Transduction, Max Planck Institute of BiochemistryPathology, Medical Faculty, University of AugsburgDepartment of Proteomics and Signal Transduction, Max Planck Institute of BiochemistryDepartment of Proteomics and Signal Transduction, Max Planck Institute of BiochemistryDepartment of Proteomics and Signal Transduction, Max Planck Institute of BiochemistryDepartment of Proteomics and Signal Transduction, Max Planck Institute of BiochemistryPathology, Medical Faculty, University of AugsburgDepartment of Proteomics and Signal Transduction, Max Planck Institute of BiochemistryHematology and Oncology, Medical Faculty, University of AugsburgPathology, Medical Faculty, University of AugsburgPathology, Medical Faculty, University of AugsburgDepartment of Proteomics and Signal Transduction, Max Planck Institute of BiochemistryAbstract 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.https://doi.org/10.15252/emmm.202317459COVID‐19mass spectrometrypathologyproteomicsvirus |
| spellingShingle | Lisa Schweizer Tina Schaller Maximilian Zwiebel Özge Karayel Johannes Bruno Müller‐Reif Wen‐Feng Zeng Sebastian Dintner Thierry M Nordmann Klaus Hirschbühl Bruno Märkl Rainer Claus Matthias Mann Quantitative multiorgan proteomics of fatal COVID‐19 uncovers tissue‐specific effects beyond inflammation EMBO Molecular Medicine COVID‐19 mass spectrometry pathology proteomics virus |
| title | Quantitative multiorgan proteomics of fatal COVID‐19 uncovers tissue‐specific effects beyond inflammation |
| title_full | Quantitative multiorgan proteomics of fatal COVID‐19 uncovers tissue‐specific effects beyond inflammation |
| title_fullStr | Quantitative multiorgan proteomics of fatal COVID‐19 uncovers tissue‐specific effects beyond inflammation |
| title_full_unstemmed | Quantitative multiorgan proteomics of fatal COVID‐19 uncovers tissue‐specific effects beyond inflammation |
| title_short | Quantitative multiorgan proteomics of fatal COVID‐19 uncovers tissue‐specific effects beyond inflammation |
| title_sort | quantitative multiorgan proteomics of fatal covid 19 uncovers tissue specific effects beyond inflammation |
| topic | COVID‐19 mass spectrometry pathology proteomics virus |
| url | https://doi.org/10.15252/emmm.202317459 |
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