A clinical trial of IL-15 and IL-21 combination therapy for COVID-19 is warranted.

Previous studies of SARS-CoV-2 viral infection suggest that both the humoral and cytotoxic arms of the immune system are weak in patients with severe COVID-19 disease when compared to mild disease. A cytokine storm is also induced in severe disease. IL-15 has been shown to support the cytotoxic arm of the immune response. IL-21 has been shown to support both the cytotoxic and humoral arms of the immune response. In addition, in some settings, Il-21 has been shown to actually decrease IL-6 and TNF-alpha production, reducing the inflammatory proteins involved in the cytokine storm. Furthermore, in other settings, the combination of IL-15 and IL-21 has been shown to be more effective than either interleukin alone in promoting an effective immune response. Therefore, a clinical trial that examines the use of the combination of IL-15 and IL-21 for COVID-19 patients is warranted.