The severe-acute respiratory syndrome coronavirus type 2 enters via the angiotensin converting enzyme (ACE2), a crucial part of the kallikrein-kinin system. Though studies have reported the effect of cytokine storm on COVID-19 severity, the role of bradykinin and kallikrein has received less attention. In this study, we assessed the levels of plasma bradykinin and kallikrein during the early phase of COVID-19.The study involved 42 COVID-19 patients (22 severe and 20 moderate cases) along with 10 controls. Sandwich ELISA was used to estimate the soluble levels of bradykinin and kallikrein at the time of admission and on day 7 post-admission. Correlation analysis was used to examine the relationship between D-dimer and bradykinin as well as kallikrein.

Result: Compared to healthy controls, a significant (p?0.01) increase in bradykinin and kallikrein was noted in severe cases at the time of admission. Within the group, we observed elevated levels (p?0.001) of soluble bradykinin at day 7 in moderate as well as severe cases when compared to the time of admission. However, no such alteration was found in kallikrein levels. During the course of infection, we found significant (p?0.001) increase in both protein levels in severe cases compared to moderate cases. Interestingly, a strong positive correlation (p?0.001) was obtained between bradykinin and D-dimer. Conclusion: Increased shedding of bradykinin during the early phase of infection, particularly in the severe form of SARS-CoV-2. Along with D-dimer, the plasma bradykinin levels could serve as clinical prognostic biomarker for the early prediction of COVID-19 disease severity. However, further studies are needed to ascertain its role in host-virus interplay.