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A randomized, double-blind, placebo-controlled trial of IL-7 in critically ill patients with COVID-19
Manu Shankar-Hari, … , Marcel van den Brink, Richard Hotchkiss
Manu Shankar-Hari, … , Marcel van den Brink, Richard Hotchkiss
Published February 4, 2025
Citation Information: JCI Insight. 2025;10(6):e189150. https://doi.org/10.1172/jci.insight.189150.
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Clinical Research and Public Health COVID-19 Clinical trials Infectious disease

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

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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, patients with lymphopenia who have COVID-19. 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 a significant difference between CYT107 and placebo. Patients with COVID-19 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). CONCLUSION. 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. FUNDING. Funding for the trial was provided by RevImmune and the Cancer Research Institute.

Authors

Manu Shankar-Hari, Bruno Francois, Kenneth E. Remy, Cristina Gutierrez, Stephen Pastores, Thomas Daix, Robin Jeannet, Jane Blood, Andrew H. Walton, Reinaldo Salomao, Georg Auzinger, David Striker, Robert S. Martin, Nitin J. Anand, James Bosanquet, Teresa Blood, Scott Brakenridge, Lyle L. Moldawer, Vidula Vachharajani, Cassian Yee, Felipe Dal-Pizzol, Michel Morre, Frederique Berbille, Marcel van den Brink, Richard Hotchkiss

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Figure 4

No difference in mortality in CYT107- versus placebo-treated patients.

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No difference in mortality in CYT107- versus placebo-treated patients.
T...
The mortality rate was calculated at day 30 or hospital discharge if patients left the hospital prior to day 30. (A) The overall mortality was 32.7% in CYT107-treated patients (n = 55) versus 38.9% in placebo-treated patients (n = 54) and was not statistically different (P = 0.59) (Table 3). (B) Because of potential effects of antiviral agents to inhibit the putative beneficial effects of CYT107, mortality rates were also determined separately for patients receiving CYT107 but no antiviral drugs and similarly for placebo-treated patients who were not receiving antiviral drugs. Mortality for CYT107-treated patients (n = 22) and placebo-treated patients (n = 23) was 22.7% and 47.8%, respectively (P = 0.17) (Table 3). Comparison of mortality was performed using the log-rank (Mantel-Cox) test.

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