Patterns of C1-Inhibitor Plasma Levels and Kinin–Kallikrein System Activation in Relation to COVID-19 Severity
Background: Although more than four years have passed since the pandemic began, SARS-CoV-2 continues to be of concern. Therefore, research into the underlying mechanisms that contribute to the development of the disease, especially in more severe forms, remains a priority. Sustained activation of th...
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2024-11-01
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| author | Silvia Berra Debora Parolin Chiara Suffritti Andrea Folcia Andrea Zanichelli Luca Gusso Chiara Cogliati Agostino Riva Antonio Gidaro Sonia Caccia |
| author_facet | Silvia Berra Debora Parolin Chiara Suffritti Andrea Folcia Andrea Zanichelli Luca Gusso Chiara Cogliati Agostino Riva Antonio Gidaro Sonia Caccia |
| author_sort | Silvia Berra |
| collection | DOAJ |
| description | Background: Although more than four years have passed since the pandemic began, SARS-CoV-2 continues to be of concern. Therefore, research into the underlying mechanisms that contribute to the development of the disease, especially in more severe forms, remains a priority. Sustained activation of the complement (CS), contact (CAS), and fibrinolytic and kinin–kallikrein systems (KKS) has been shown to play a central role in the pathogenesis of the disease. Since the C1 esterase inhibitor (C1-INH) is a potent inhibitor of all these systems, its role in the disease has been investigated, but some issues remained unresolved. Methods: We evaluated the impact of C1-INH and KKS on disease progression in a cohort of 45 COVID-19 patients divided into groups according to disease severity. We measured plasma levels of total and functional C1-INH and its complexes with kallikrein (PKa), reflecting KKS activation and kallikrein spontaneous activity. Results: We observed increased total and functional plasma concentrations of C1-INH in COVID-19 patients. A direct correlation (positive Spearman’s r) was observed between C1-INH levels, especially functional C1-INH, and the severity of the disease. Moreover, a significant reduction in the ratio of functional over total C1-INH was evident in patients exhibiting mild to intermediate clinical severity but not in critically ill patients. Accordingly, activation of the KKS, assessed as an increase in PKa:C1-INH complexes, was explicitly observed in the mild categories. Conclusions: Our study’s findings on the consumption of C1-INH and the activation of the KKS in the less severe stages of COVID-19 but not in the critical stage suggest a potential role for C1-INH in containing disease severity. These results underscore the importance of C1-INH in the early phases of the disease and its potential implications in COVID-19 progression and/or long-term effects. |
| format | Article |
| id | doaj-art-a6e1bbd73f474220b352387acb0ec8a1 |
| institution | Kabale University |
| issn | 2075-1729 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | MDPI AG |
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| series | Life |
| spelling | doaj-art-a6e1bbd73f474220b352387acb0ec8a12024-12-27T14:35:48ZengMDPI AGLife2075-17292024-11-011412152510.3390/life14121525Patterns of C1-Inhibitor Plasma Levels and Kinin–Kallikrein System Activation in Relation to COVID-19 SeveritySilvia Berra0Debora Parolin1Chiara Suffritti2Andrea Folcia3Andrea Zanichelli4Luca Gusso5Chiara Cogliati6Agostino Riva7Antonio Gidaro8Sonia Caccia9Department of Biomedical and Clinical Sciences, Università degli Studi di Milano, 20157 Milan, ItalyDepartment of Biomedical and Clinical Sciences, Università degli Studi di Milano, 20157 Milan, ItalyDepartment of Biomedical and Clinical Sciences, Università degli Studi di Milano, 20157 Milan, ItalyDepartment of Biomedical and Clinical Sciences, Università degli Studi di Milano, 20157 Milan, ItalyDepartment of Biomedical Sciences for Health, Università degli Studi di Milano, 20133 Milan, ItalyDepartment of Biomedical and Clinical Sciences, Università degli Studi di Milano, 20157 Milan, ItalyDepartment of Biomedical and Clinical Sciences, Università degli Studi di Milano, 20157 Milan, ItalyDepartment of Biomedical and Clinical Sciences, Università degli Studi di Milano, 20157 Milan, ItalyDepartment of Internal Medicine, Ospedale Luigi Sacco, 20157 Milan, ItalyDepartment of Biomedical and Clinical Sciences, Università degli Studi di Milano, 20157 Milan, ItalyBackground: Although more than four years have passed since the pandemic began, SARS-CoV-2 continues to be of concern. Therefore, research into the underlying mechanisms that contribute to the development of the disease, especially in more severe forms, remains a priority. Sustained activation of the complement (CS), contact (CAS), and fibrinolytic and kinin–kallikrein systems (KKS) has been shown to play a central role in the pathogenesis of the disease. Since the C1 esterase inhibitor (C1-INH) is a potent inhibitor of all these systems, its role in the disease has been investigated, but some issues remained unresolved. Methods: We evaluated the impact of C1-INH and KKS on disease progression in a cohort of 45 COVID-19 patients divided into groups according to disease severity. We measured plasma levels of total and functional C1-INH and its complexes with kallikrein (PKa), reflecting KKS activation and kallikrein spontaneous activity. Results: We observed increased total and functional plasma concentrations of C1-INH in COVID-19 patients. A direct correlation (positive Spearman’s r) was observed between C1-INH levels, especially functional C1-INH, and the severity of the disease. Moreover, a significant reduction in the ratio of functional over total C1-INH was evident in patients exhibiting mild to intermediate clinical severity but not in critically ill patients. Accordingly, activation of the KKS, assessed as an increase in PKa:C1-INH complexes, was explicitly observed in the mild categories. Conclusions: Our study’s findings on the consumption of C1-INH and the activation of the KKS in the less severe stages of COVID-19 but not in the critical stage suggest a potential role for C1-INH in containing disease severity. These results underscore the importance of C1-INH in the early phases of the disease and its potential implications in COVID-19 progression and/or long-term effects.https://www.mdpi.com/2075-1729/14/12/1525C1-INHC1-INH functionalkinin–kallikrein system (KKS)C1-INHIBITOR-kallikrein complexesCOVID-19 |
| spellingShingle | Silvia Berra Debora Parolin Chiara Suffritti Andrea Folcia Andrea Zanichelli Luca Gusso Chiara Cogliati Agostino Riva Antonio Gidaro Sonia Caccia Patterns of C1-Inhibitor Plasma Levels and Kinin–Kallikrein System Activation in Relation to COVID-19 Severity Life C1-INH C1-INH functional kinin–kallikrein system (KKS) C1-INHIBITOR-kallikrein complexes COVID-19 |
| title | Patterns of C1-Inhibitor Plasma Levels and Kinin–Kallikrein System Activation in Relation to COVID-19 Severity |
| title_full | Patterns of C1-Inhibitor Plasma Levels and Kinin–Kallikrein System Activation in Relation to COVID-19 Severity |
| title_fullStr | Patterns of C1-Inhibitor Plasma Levels and Kinin–Kallikrein System Activation in Relation to COVID-19 Severity |
| title_full_unstemmed | Patterns of C1-Inhibitor Plasma Levels and Kinin–Kallikrein System Activation in Relation to COVID-19 Severity |
| title_short | Patterns of C1-Inhibitor Plasma Levels and Kinin–Kallikrein System Activation in Relation to COVID-19 Severity |
| title_sort | patterns of c1 inhibitor plasma levels and kinin kallikrein system activation in relation to covid 19 severity |
| topic | C1-INH C1-INH functional kinin–kallikrein system (KKS) C1-INHIBITOR-kallikrein complexes COVID-19 |
| url | https://www.mdpi.com/2075-1729/14/12/1525 |
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