A randomized, double-blind, placebo controlled trial of IL-7 in critically ill COVID-19 patients.

Abstract

Background: Lymphopenia and failure of lymphocytes to mount an early IFN-γ response correlate with increased mortality in COVID-19. Given the essential role of CD4 helper and CD8 cytotoxic cells in eliminating viral pathogens, this profound loss in lymphocytes may impair patients' ability to eliminate the virus. IL-7 is a pleiotropic cytokine that is obligatory for lymphocyte survival and optimal function.

Methods: We conducted a prospective, double-blind, randomized, placebo-controlled trial of CYT107, recombinant human IL-7, in 109 critically-ill lymphopenic COVID-19 patients. The primary endpoint was to assess CYT107's effect on lymphocyte recovery with secondary clinical endpoints including safety, ICU and hospital length-of-stay, incidence of secondary infections, and mortality.

Results: CYT107 was well-tolerated without precipitating a cytokine storm or worsening pulmonary function. Absolute lymphocyte counts increased in both groups without significant difference between CYT107 and placebo. COVID-19 patients receiving CYT107 but not concomitant antiviral medications, known inducers of lymphopenia, had a final lymphocyte count that was 43% greater than placebo (p=0.067). There were significantly fewer treatment-emergent adverse events in CYT107 versus placebo-treated patients (p<0.001), consistent with a beneficial drug effect. Importantly, CYT107 treated patients had 44% fewer hospital-acquired infections versus placebo-treated patients (p=0.014).

Conclusions: Given that hospital-acquired infections are responsible for a large percentage of COVID-19 deaths, this effect of CYT107 to decrease nosocomial infections could substantially reduce late morbidity and mortality in this highly lethal disease. The strong safety profile of CYT107 and its excellent tolerability provide support for trials of CYT107 in other potential pandemic respiratory viral infections.

Trial registration: NCT04379076, NCT04426201, NCT04442178, NCT04407689; NCT04927169.