Journal Article

Patterns of C1-Inhibitor Plasma Levels and Kinin–Kallikrein System Activation in Relation to COVID-19 Severity

Suffritti, Chiara, Zanichelli, Andrea, Cogliati, Chiara, Riva, Agostino, Berra, Silvia, Gidaro, Antonio, Caccia, Sonia, Parolin, Debora, Folcia, Andrea, Gusso, Luca

2024

Overview

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.

• Publisher: MDPI AG
• Subject: C1-INH / C1-INH functional / C1-INHIBITOR-kallikrein complexes / Complement activation / COVID-19 / Ethylenediaminetetraacetic acid / Fibrin / Health aspects / Icatibant / Infections / Inflammation / Inhibitors / Kallikrein / Kallikreins / kinin–kallikrein system (KKS) / Laboratories / Long-term effects / Medical research / Medicine, Experimental / Molecular weight / Pandemics / Pathogenesis / Patients / Peptides / Plasma / Plasma levels / Severe acute respiratory syndrome coronavirus 2 / Viral diseases