Abstract
The complement system, a network of highly-regulated proteins, represents a vital part of the innate immune response. Over-activation of the complement system plays an important role in inflammation, tissue damage, and infectious disease severity. The prevalence of MERS-CoV in Saudi Arabia remains significant and cases are still being reported. The role of complement in Middle East Respiratory Syndrome coronavirus (MERS-CoV) pathogenesis and complement-modulating treatment strategies has received limited attention, and studies involving MERS-CoV-infected patients have not been reported. This study offers the first insight into the pulmonary expression profile including seven complement proteins, complement regulatory factors, IL-8, and RANTES in MERS-CoV infected patients without underlying chronic medical conditions. Our results significantly indicate high expression levels of complement anaphylatoxins (C3a and C5a), IL-8, and RANTES in the lungs of MERS-CoV-infected patients. The upregulation of lung complement anaphylatoxins, C5a, and C3a was positively correlated with IL-8, RANTES, and the fatality rate. Our results also showed upregulation of the positive regulatory complement factor P, suggesting positive regulation of the complement during MERS-CoV infection. High levels of lung C5a, C3a, factor P, IL-8, and RANTES may contribute to the immunopathology, disease severity, ARDS development, and a higher fatality rate in MERS-CoV-infected patients. These findings highlight the potential prognostic utility of C5a, C3a, IL-8, and RANTES as biomarkers for MERS-CoV disease severity and mortality. To further explore the prediction of functional partners (proteins) of highly expressed proteins (C5a, C3a, factor P, IL-8, and RANTES), the computational protein–protein interaction (PPI) network was constructed, and six proteins (hub nodes) were identified.Graphical abstract Supplementary InformationThe online version contains supplementary material available at 10.1007/s10875-021-01061-z.
Highlights
The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has gained significant attention in the medical and scientific communities
The results indicated that lung complement C5a was positively correlated with factor P, IL-8, and RANTES, whereas complement C3a was positively correlated with IL-8 and RANTES (Table 2)
Several inflammatory cytokines/ chemokines and over-activation of complement proteins are significantly associated with severe MERS-CoV infections and a higher fatality rate [5, 6, 8]
Summary
The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has gained significant attention in the medical and scientific communities. Elevated inflammatory cytokine and chemokine levels during SARS‐CoV-1, MERS‐CoV, and SARS‐CoV‐2 infections are significantly associated with massive infiltration of immune cells into the lungs and poor disease outcome [5, 8,9,10]. Over-activation of pulmonary and systemic complement plays a key role in inflammation, endothelial cell damage, thrombus formation, and intravascular coagulation, which results in multiple organ failure and eventually death [12, 15, 17]. This over-stimulation leads to the formation of the complement anaphylatoxins, C3a and C5a. C5a is a chemoattractant for neutrophils, monocytes, eosinophils, and T cells [15, 18]
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