Functional mass spectrometry indicates anti-protease and complement activity increase with COVID-19 severity
Investigations on some innate immunity proteins can yield misleading information, as investigators often rely on static measurements and assume a direct correlation to function. As protein function is often not directly proportional to protein abundance, and mechanistic pathways are interconnected a...
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| Format: | Article |
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Frontiers Media S.A.
2025-01-01
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| Series: | Experimental Biology and Medicine |
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| Online Access: | https://www.ebm-journal.org/articles/10.3389/ebm.2025.10308/full |
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| author | Douglas D. Fraser Douglas D. Fraser Swapan Roy Matt Kuruc Maritza Quintero Logan R. Van Nynatten Gediminas Cepinskas Gediminas Cepinskas Haiyan Zheng Amenah Soherwardy Devjit Roy |
| author_facet | Douglas D. Fraser Douglas D. Fraser Swapan Roy Matt Kuruc Maritza Quintero Logan R. Van Nynatten Gediminas Cepinskas Gediminas Cepinskas Haiyan Zheng Amenah Soherwardy Devjit Roy |
| author_sort | Douglas D. Fraser |
| collection | DOAJ |
| description | Investigations on some innate immunity proteins can yield misleading information, as investigators often rely on static measurements and assume a direct correlation to function. As protein function is often not directly proportional to protein abundance, and mechanistic pathways are interconnected and under constant feedback regulatory control, functional analysis is required. In this study, we used functional mass spectrometry to measure anti-protease and complement activity in plasma obtained from coronavirus disease 2019 (COVID-19) patients. Our data suggests that within 48 h of hospital admission, COVID-19 patients undergo a protease storm with significantly elevated neutrophil elastase (p < 0.001) and lymphocyte granzyme B (p < 0.01), while, anti-protease activity is significantly increased, including alpha-1 antitrypsin (AAT; p < 0.001) and alpha-1-antichymotrypsin (ACT; p < 0.001). Concurrently, the ratio of C3a to C3beta activity significantly decreased with increasing COVID-19 severity, suggesting more complement activation (Mild COVID-19 p < 0.05; Severe COVID-19 p < 0.001). Activity levels of AAT, ACT and C3a/C3beta remained unchanged over 10 hospital days. Our data suggests that COVID-19 is associated with both a protease storm and complement activation, with the former somewhat balanced with increased anti-protease activity. Evaluation of the AAT/ACT ratio and C3a/C3beta ratio indicated that COVID-19 severity is associated with both neutrophil elastase neutralization and complement activation. |
| format | Article |
| id | doaj-art-e04e514713514d75afc614e2507669c4 |
| institution | Kabale University |
| issn | 1535-3699 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Experimental Biology and Medicine |
| spelling | doaj-art-e04e514713514d75afc614e2507669c42025-01-29T04:11:20ZengFrontiers Media S.A.Experimental Biology and Medicine1535-36992025-01-0125010.3389/ebm.2025.1030810308Functional mass spectrometry indicates anti-protease and complement activity increase with COVID-19 severityDouglas D. Fraser0Douglas D. Fraser1Swapan Roy2Matt Kuruc3Maritza Quintero4Logan R. Van Nynatten5Gediminas Cepinskas6Gediminas Cepinskas7Haiyan Zheng8Amenah Soherwardy9Devjit Roy10London Health Sciences Centre Research Institute, London, ON, CanadaPediatrics, Western University, London, ON, CanadaBiotech Support Group LLC, Monmouth Junction, NJ, United StatesBiotech Support Group LLC, Monmouth Junction, NJ, United StatesPediatrics, Western University, London, ON, CanadaMedicine, Western University, London, ON, CanadaLondon Health Sciences Centre Research Institute, London, ON, CanadaMedical Biophysics, Western University, London, ON, CanadaRutgers Center for Integrative Proteomics, Rutgers University, Piscataway, NJ, United StatesRutgers Center for Integrative Proteomics, Rutgers University, Piscataway, NJ, United StatesNathan Littauer Hospital, Gloversville, NY, United StatesInvestigations on some innate immunity proteins can yield misleading information, as investigators often rely on static measurements and assume a direct correlation to function. As protein function is often not directly proportional to protein abundance, and mechanistic pathways are interconnected and under constant feedback regulatory control, functional analysis is required. In this study, we used functional mass spectrometry to measure anti-protease and complement activity in plasma obtained from coronavirus disease 2019 (COVID-19) patients. Our data suggests that within 48 h of hospital admission, COVID-19 patients undergo a protease storm with significantly elevated neutrophil elastase (p < 0.001) and lymphocyte granzyme B (p < 0.01), while, anti-protease activity is significantly increased, including alpha-1 antitrypsin (AAT; p < 0.001) and alpha-1-antichymotrypsin (ACT; p < 0.001). Concurrently, the ratio of C3a to C3beta activity significantly decreased with increasing COVID-19 severity, suggesting more complement activation (Mild COVID-19 p < 0.05; Severe COVID-19 p < 0.001). Activity levels of AAT, ACT and C3a/C3beta remained unchanged over 10 hospital days. Our data suggests that COVID-19 is associated with both a protease storm and complement activation, with the former somewhat balanced with increased anti-protease activity. Evaluation of the AAT/ACT ratio and C3a/C3beta ratio indicated that COVID-19 severity is associated with both neutrophil elastase neutralization and complement activation.https://www.ebm-journal.org/articles/10.3389/ebm.2025.10308/fullCOVID-19functional mass spectrometryneutrophil elastaselymphocyte granzyme Bcomplement |
| spellingShingle | Douglas D. Fraser Douglas D. Fraser Swapan Roy Matt Kuruc Maritza Quintero Logan R. Van Nynatten Gediminas Cepinskas Gediminas Cepinskas Haiyan Zheng Amenah Soherwardy Devjit Roy Functional mass spectrometry indicates anti-protease and complement activity increase with COVID-19 severity Experimental Biology and Medicine COVID-19 functional mass spectrometry neutrophil elastase lymphocyte granzyme B complement |
| title | Functional mass spectrometry indicates anti-protease and complement activity increase with COVID-19 severity |
| title_full | Functional mass spectrometry indicates anti-protease and complement activity increase with COVID-19 severity |
| title_fullStr | Functional mass spectrometry indicates anti-protease and complement activity increase with COVID-19 severity |
| title_full_unstemmed | Functional mass spectrometry indicates anti-protease and complement activity increase with COVID-19 severity |
| title_short | Functional mass spectrometry indicates anti-protease and complement activity increase with COVID-19 severity |
| title_sort | functional mass spectrometry indicates anti protease and complement activity increase with covid 19 severity |
| topic | COVID-19 functional mass spectrometry neutrophil elastase lymphocyte granzyme B complement |
| url | https://www.ebm-journal.org/articles/10.3389/ebm.2025.10308/full |
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