Immune, inflammatory and prothrombotic parameters in COVID-19 patients treated with an anti EGFR antibody.

ABSTRACT

SARS-CoV-2 infection causes a range of clinical presentations and induces changes in both innate and adaptive branches of the immune system. Furthermore, direct viral action to the cells of the lung promotes over-expression of the epidermal growth factor receptor (EGFR) which triggers pro-inflammatory response, contributes to coagulopathy and intravascular thrombi as well as lung fibrosis. Based on the role of this signaling pathway in the pathophysiology of the disease, nimotuzumab, an anti-EGFR monoclonal antibody, was used to treat patients with COVID-19. The aim of this study was to determine IL-6 and PAI-1 concentrations and lymphocyte subpopulations profiles in moderately and severely ill COVID-19 patients diagnosed during the B.1.617.2 variant wave in Cuba and included in a phase I/II trial to evaluate the safety and preliminary effect of nimotuzumab in COVID-19 disease. We observed high serum levels of IL-6, elevated plasma concentration of PAI-1, mean values of neutrophils to lymphocytes ratio (NLR) above three and CD4+ lymphopenia in both groups of patients. PAI-1 and IL-6 circulating levels decreased in patients treated with nimotuzumab. More than 95% of patients in which IL-6 decreased or increased slightly, were alive within 14 days after the monoclonal antibody administration. Patients with moderate and severe disease, were no different regarding the studied parameters, addressing the idea that several immune alterations could be present before the infection becomes clinically relevant. These findings suggest that nimotuzumab could be an attractive therapeutic option to interfere with the negative relationship between cytokines and procoagulant mediators in the inflammatory and prothrombotic phases of the disease.