Association of Immune Semaphorins with COVID-19 Severity and Outcomes

Abstract

Semaphorins have recently been recognized as crucial modulators of immune responses. In the pathogenesis of COVID-19, the activation of immune responses is the key factor in the development of severe disease. This study aimed to determine the association of serum semaphorin concentrations with COVID-19 severity and outcomes. Serum semaphorin concentrations (SEMA3A, -3C, -3F, -4D, -7A) were measured in 80 hospitalized adult patients with COVID-19 (moderate (n = 24), severe (n = 32), critical, (n = 24)) and 40 healthy controls. While SEMA3C, SEMA3F and SEMA7A serum concentrations were significantly higher in patients with COVID-19, SEMA3A was significantly lower. Furthermore, SEMA3A and SEMA3C decreased with COVID-19 severity, while SEMA3F and SEMA7A increased. SEMA4D showed no correlation with disease severity. Serum semaphorin levels show better predictive values than CRP, IL-6 and LDH for differentiating critical from moderate/severe COVID-19. SEMA3F and SEMA7A serum concentrations were associated with the time to recovery, requirement of invasive mechanical ventilation, development of pulmonary thrombosis and nosocomial infections, as well as with in-hospital mortality. In conclusion, we provide the first evidence that SEMA3A, SEMA3C, SEMA3F and SEMA7A can be considered as new biomarkers of COVID-19 severity.

SARS‐CoV‐2, periodontal pathogens, and host factors: The trinity of oral post‐acute sequelae of COVID‐19

“…143 The activities of plexin, a protein that serves as a receptor for semaphorin family signalling proteins, mediate neuropilin functions and aid axonal guidance and neural development. In turn, Nrp1 and Nrp2 act as co-receptors for the ligand semaphorins, 144,145 which may cause inappropriate immune checkpoint control of T memory cells function, B lymphocyte activities, and T regulatory cell (CD4þ/Foxp3þ/CD25) differentiation. The shift towards Treg stimulates the release of immunosuppressive cytokines, IL-10 and TGF-β, depleting mucosal resistance to SARS-CoV-2.…”