TNF-α, iNOS Augmentation Due to Macrophages and Neutrophils Activity in Samples from Patients in Intensive Care Unit with COVID-19 Infection

Background and Aims: Cells and secreted molecules by the innate immune system are the essential factors in the pathogenesis and determining the severity of inflammation in COVID-19 patients. Severe inflammation results from increased activity of neutrophils, macrophages, and other cells with their products. Inflammatory cytokines such as tumor necrosis factor-a (TNF-a)  increases the severity and pathogenesis of the disease caused by the virus. Phagocytes are armed with inducible nitric oxide synthase (iNOS), that upon stimulation by proinflammatory cytokines augment an immune response against pathogens. Materials and Methods: Two groups of patients were included with COVID-19 infection from the intensive care unit (ICU, n=52) and (non-ICU-care, n=54). Blood samples were collected to measure cells and serum parameters, including lymphocytes, neutrophils, platelet counts, accompanied with C-reactive protein, lactate dehydrogenase, TNF-a and iNOS levels. Results: In the ICU group, increased white blood cells (p=0.048), decreased lymphocytes (p=0.0007), increased neutrophils (p=0.001), decreased platelets, increase serum levels for lactate dehydrogenase (p =0.0001), c-reactive protein (p=0.003), TNF-a (p=0.018), and iNOS (p=0.008) were statistically obtained. Positive correlations were calculated between TNF-a and iNOS (r=0.65, p=0.0002) and with c-reactive protein (r=0.52, p=0.003) and with lactate dehydrogenase (r=0.68, p=0.0001). Conclusion: Inflammation due to macrophages and neutrophils activity in COVID-19 patients and increased mediators correlate with disease progression. It seems that control of the cell activity and their inflammatory cytokines would be considered for therapeutic goals. Changing the polarization of inflammatory macrophages to anti-inflammatory macrophages with therapeutic applications could prevent the severity of the provocative course of the disease.