Anti-IL-6 Receptor Antibody Treatment for Severe COVID-19 and the Potential Implication of IL-6 Gene Polymorphisms in Novel Coronavirus Pneumonia

Abstract

Although severe acute respiratory virus 2 (SARS-CoV-2)-infected patients tend to present with mild to moderate symptoms, some may develop severe or life-threatening disease. There remains an urgent need for efficacious management of COVID-19, because despite current ongoing clinical treatment trials, no effective treatments have been reported. Previously, our analysis demonstrated that excessive inflammatory responses, marked by an elevated level of interleukin-6 (IL-6) and C- reactive protein (CRP), are strongly associated with COVID-19 progression. Moreover, there is also a probable association between the disease progression observed in COVID-19 with IL-6 gene polymorphism. This article summarizes the cumulative evidence on the efficacy of anti-IL-6 receptor (anti-IL-6R) antibody among severe COVID-19-infected patients. Additionally, a meta-analysis was also performed to estimate the association between IL-6 gene polymorphism with predisposition as well as disease severity of pneumonia in general. Our analysis confirmed that anti-IL-6R antibody treatment could effectively treat severe COVID-19-infected patients, marked by suppression of CRP and improvement of clinical symptoms. The second analysis showed that although IL- 6 gene polymorphism did not predispose to pneumonia, carrier status of the IL-6–174C allele is associated with a higher level of IL-6 production and pneumonia severity. Altogether, our study strengthens the notion that IL-6 plays a pivotal role in COVID-19 progression, and suppression of IL-6 signalling cascade shows a promising therapy in severe forms of SARS-CoV-2 infection.