Potential role of anti‐ interleukin‐17 in COVID ‐19 treatment

Dear Editor, COVID-19 is a new type of coronavirus disease that occurs as a pandemic disease. Most of the treatments available for COVID-19 are symptomatic. Taking precautions and developing effective treatment are urgent needs, especially for serious, life-threatening cases. COVID-19 occurs through severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 causes lung edema and lung failure in patients, this infection may develop liver, heart, and kidney damage, and acute respiratory distress syndrome. These symptoms occur as a result of cytokine storm associated with elevated interleukin (IL)-1α, IL-2, IL-7, IL-8, IL-9, IL-10, IL-17, Granulocyte Macrophage ColonyStimulating Factor, and Granulocyte-Colony Stimulating Factor serum levels. The most important function of IL-17 is the initiation of neutrophilic infiltration into infected tissues and the activation of tissue response to extracellular pathogens. The second function is carried out through the indirect mechanism, such as the induction of IL-6 and chemokines. There are now several antibody-based biological agents that block IL-17 (ixekizumab, secukinumab, and brodalumab). It was found that IL-17 elevation worsened the clinic both in pandemic respiratory diseases such as COVID and in nonrespiratory diseases caused by some viruses. Xu et al reported that a patient with severe COVID-19 had numerous CCR4+ CCR6+ TH-17 cells in their peripheral blood that supported TH-17-type cytokine storm. Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) and SARS-CoV patients also have high TH-17 responses or increased IL17-related pathways. In patients with MERS-CoV, lower interferon (IFN)-γ and IFN-α with higher IL-17 have worse results than the reverse phenotype. The H1N1 virus increases strong TH17 (and TH1) responses. H1N1 caused acute lung injury due to IL-17 in a mice model. Rogo et al observed an increased risk of infection in those who showed IL-17 gene polymorphism in a case-control study conducted in people infected with seasonal influenza A/H3N2 virus. In a study evaluating children with influenza A viral pneumonia, it was observed that IL-17 levels were observed to be significantly higher in the patient group. In the study of mice infected with novel swine-origin influenza A (H1N1) virus that started in 2009 and became pandemic, it was observed that acute lung injury improved in mice with IL-17 deficiency or treated with monoclonal antibodies against IL-17. In this study, anti-IL-17 monoclonal antibodies have been proposed as potential treatment against this disease. After we submitted this publication, Pacha et al have published that anti-IL-17 may be useful in the treatment of COVID-19. IL-17 increases in some respiratory diseases and can lead to worsening of the clinic. IL-17 has been shown to increase and cause fibrosis in the airways in mice models with chronic obstructive pulmonary disease (COPD). IL-17 expression in bronchial submucosa was found to be increased in COPD patients, and cigarette-induced alveolar type 2 and inflammation in mice decreased with genetic deletion of IL-17. Similarly, severe asthma is associated with increased levels of IL-17, IL-17F, and neutrophils in the lung. Consequently, an increase in IL-17 contributes to cytokine storm in pulmonary viral infections, including COVID-19, which causes tissue damage and possibly triggers lung edema. Targeting IL-17 can benefit patients in this regard. IL-17 increases in many respiratory infections caused by viruses such as COVID-19, lung diseases such as COPD-asthma, and some nonrespiratory viral diseases and may contribute to worsening the clinic. Anti-IL-17 treatments have been found to contribute to clinic healing in pandemic influenza infections and virus-infected tissues in mice or humans. However, anti-IL-17 therapy seems to be useful in comorbid conditions such as COPD and asthma, which may be accompanied by infections. Therefore, we believe that anti-IL-17 therapy can be successful especially in people infected with COVID-19, severe lung injury, and/or comorbid conditions accompanied by diseases such as COPD and asthma.