Clinical immunology : the official journal of the Clinical Immunology Society
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Growing clinical evidence has implicated complement as a pivotal driver of COVID-19 immunopathology. Deregulated complement activation may fuel cytokine-driven hyper-inflammation, thrombotic microangiopathy and NET-driven immunothrombosis, thereby leading to multi-organ failure. Complement therapeutics have gained traction as candidate drugs for countering the detrimental consequences of SARS-CoV-2 infection. ⋯ This broader inhibitory profile was associated with a more robust decline of neutrophil counts, attenuated neutrophil extracellular trap (NET) release, faster serum LDH decline, and more prominent lymphocyte recovery. These early clinical results offer important insights into the differential mechanistic basis and underlying biology of C3 and C5 inhibition in COVID-19 and point to a broader pathogenic involvement of C3-mediated pathways in thromboinflammation. They also support the evaluation of these complement-targeting agents as COVID-19 therapeutics in large prospective trials.
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Upper respiratory tract is the primary site of SARS-CoV-2 replication. Releasing of pro and anti-inflammatory mediators plays an important role in the immunopathogenesis of Coronavirus Disease 2019 (COVID-19). The aim of this study was to evaluate the early inflammatory response in upper airway by measuring of IFN-γ, TGF-β1 and RANTES at mRNA level. ⋯ TGF-β1 and RANTES expressions were lower in SARS-CoV-2 infected patients than controls (p < 0.0001; p = 0.0011, respectively). A significant correlation between IFN-γ and TGF-β1 was observed in SARS-CoV-2 asymptomatic patients (r = +0.61, p = 0.0014). The findings suggest that imbalance between IFN-γ and TGF-β1 expression could be an impact in clinical expression of SARS-CoV-2 infection.