According to research published in Cellular and Molecular Life Sciences, an antimicrobial peptide of catelicidin, LL-37, appears to be elevated during SARS-CoV-2 infection and may contribute to hypercoagulation in patients with COVID-19.
The researchers evaluated the role of LL-37 in patients with confirmed COVID-19 at Chongqing Public Health Medical Center and the Department of Infectious Diseases, Southwest Hospital, China’s Third Military Medical University.
They analyzed coagulation function, including prothrombin and thrombin time (PT and TT), activated partial thromboplastin time (APTT), and fibrinogen level, as well as plasma LL-37 levels in patients with COVID- 19 and control participants without COVID-19. 19 (HC). The team also evaluated the mechanism of action of LL-37 in human alveolar basal epithelial cells and a murine model.
Keep reading
A total of 62 patients with COVID-19 and 21 matched controls by age and sex without COVID-19 were included in the study. Patients with COVID-19 were divided into mild to moderate (MM; n = 40) and severe / critical (SC; n = 22) groups.
Compared with HCs, patients with COVID-19 showed shortened TT (HC, 17.96 ± 0.98 s; MM, 14.60 ± 0.79 s; SC, 15.43 ± 1.37 s; P <0.001 for HC vs MM and HC vs SC) and increased fibrinogen levels (HC, 2.81 ± 0.48 g / L; MM, 4.21 ± 0.83 g / L; SC, 4.81 ± 0.98 g / L; P <.001 for HC vs MM and HC vs SC). PT was not significantly different between groups (HC, 11.53 ± 0.52 s; MM, 12.00 ± 0.80 s; SC, 12.06 ± 1.29 s), but APTT was be significantly longer in patients with COVID-19 compared with HC (HC, 29.44). ± 3.52 s; MM, 41.35 ± 4.48 s; SC, 38.70 ± 9.63 s; P <.001 for HC vs MM and HC vs SC).
Patients with COVID-19 had elevated plasma LL-37 levels compared to HC (MM, 140 ± 46.47 ng / ml; SC, 147.6 ± 64.24 ng / ml; HC, 93.62 ± 48.14 ng / ml, P <0.01 for HC vs MM and HC vs SC).
The researchers showed that incubation of the SARS-CoV-2 ear protein at different concentrations (0.4, 2, and 10 μg / ml) with human alveolar basal epithelial cells significantly increased its hCAP18 expression (the precursor of LL-37) (control vs. 2 μg / ml; P <.05 and control vs. 10 μg / ml; P <.01).
They also showed that incubation of SARS-CoV-2 at different rates of infection (0.01, 0.05, and 0.25) with human alveolar basal epithelial cells significantly increased their LL-37 levels ( control vs. 0.05 and control vs. 0.25; P <.001 for both).
In a mouse model of FeCl3-induced carotid artery thrombosis, the team showed that LL-37 injection promoted thrombosis formation and shortened arterial occlusion time. They also found that LL-37 administration directly induced pulmonary thrombosis, whereas deletion of the mouse LL-37 gene inhibited thrombosis in the mouse model.
“These results suggest that the antimicrobial peptide of catelicidin LL-37 is elevated during SARS-CoV-2 infection, which may induce hypercoagulation in patients with COVID-19 by activating coagulation factors,” the authors concluded.
Reference
Duan Z, Zhang J, Chen X, et al. Role of LL-37 in thrombotic complications in patients with COVID-19. Cell Mol Life Sci. Published online May 21, 2022. doi: 10.1007 / s00018-022-04309-y