Quantitative multiorgan proteomics of fatal COVID‐19 uncovers tissue‐specific effects beyond inflammation

• Published in: EMBO molecular medicine Vol. 15; no. 9; p. e17459
• Main Authors: Schweizer, Lisa, Schaller, Tina, Zwiebel, Maximilian, Karayel, Özge, Müller‐Reif, Johannes Bruno, Zeng, Wen‐Feng, Dintner, Sebastian, Nordmann, Thierry M, Hirschbühl, Klaus, Märkl, Bruno, Claus, Rainer, Mann, Matthias
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 11.09.2023; EMBO Press; John Wiley and Sons Inc; Springer Nature
• Subjects: Adrenal glands; Alveoli; Biomedicine; Blood vessels; Brain research; COVID-19; EMBO23; EMBO35; EMBO56; Infections; Inflammation; Influenza; Kidneys; Liver; Lung diseases; Lungs; Lymphatic system; Mass spectrometry; Mass spectroscopy; Molecular Medicine; Myelin; Neurotransmitter receptors; Pandemics; Pathology; Patients; Pneumonia; Proteins; Proteomics; Scientific imaging; Severe acute respiratory syndrome coronavirus 2; Therapeutic applications; Tissues; Vascular system; Viral infections; virus; mass spectrometry; pathology; COVID‐19; proteomics; virus; COVID-19
• ISSN: 1757-4676; 1757-4684
• DOI: 10.15252/emmm.202317459

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. Synopsis This study reports a proteomic investigation of fatal COVID‐19 across organs using mass spectrometry, highlighting the central role of circulating inflammatory molecules and uncovering tissue‐specific alterations beyond inflammation. Parallelized sonification and streamlined MS‐based proteomics for FFPE tissue. Circulating inflammatory effectors dominate tissue responses to SARS‐CoV‐2. Deconvolution of the inflammatory response unmasks organ‐specific effects. Distinct remodeling of lung tissue compared to other destructive lung diseases. Graphical Abstract This study reports a proteomic investigation of fatal COVID‐19 across organs using mass spectrometry, highlighting the central role of circulating inflammatory molecules and uncovering tissue‐specific alterations beyond inflammation.