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

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.

Nimotuzumab Increases the Recovery Rate of Severe and Critical COVID-19 Patients: Evaluation in the Real-World Scenario

EGFR signaling is an important regulator of SARS-CoV induced lung damage, inflammation and fibrosis. Nimotuzumab is a humanized anti-EGFR antibody registered for several cancer indications. An expanded access study was conducted to evaluate the safety and recovery rate of severe and critical patients with confirmed SARS-CoV-2 infection, treated with nimotuzumab in combination with the standard of care in the real-world scenario. The antibody was administered as an intravenous infusions every 72 h, up to 5 doses. In order to assess the impact of nimotuzumab, the recovery rate was compared with a paired retrospective cohort. Control patients received standard treatment according the national protocol but not nimotuzumab. Overall, 1,151 severe or critical patients received nimotuzumab in 21 hospitals of Cuba. Median age was 65 and 773 patients had at least one comorbidity. Nimotuzumab was very well-tolerated and mild or moderate adverse events were detected in 19 patients. 1,009 controls matching with the nimotuzumab patients, were selected using a “propensity score” method. The 14-day recovery rate of the nimotuzumab cohort was 72 vs. 42% in the control group. Controls had a higher mortality risk (RR 2.08, 95% CI: 1.79, 2.38) than the nimotuzumab treated patients. The attributable fraction was 0.52 (95% CI: 0.44%;0.58), and indicates the proportion of deaths that were prevented with nimotuzumab. Our preliminary results suggest that nimotuzumab is a safe antibody that can reduce the mortality of severe and critical COVID-19 patients.