IL-7 safe for critically ill patients with COVID-19
Interleukin-7 can be safely given to critically ill patients with COVID-19 without fear of worsening inflammation or pulmonary injury, according to findings published in JAMA Network Open.
“IL-7 is currently in multiple randomized clinical trials for oncologic and infectious disorders, and a trial in the United Kingdom is evaluating its use among patients with severe COVID-19,” Pierre Francois Laterre, MD, of Saint-Luc University Hospital, at the Catholic University of Louvain, in Brussels, and colleagues wrote in a research letter. “Importantly, IL-7 has documented efficacy as an antiviral agent. IL-7 therapy has been shown to restore lymphocyte counts and functional activity, leading to decreased viral load and clinical improvement in several life-threatening viral infections.”
“It has been shown to increase CD4 and CD8 T-cells 3-fold, to improve T-cell activation, to not increase proinflammatory cytokines, and to be well tolerated in patients with bacterial sepsis,” they added. “Thus, a compelling scientific rationale exists for examining whether IL-7 is associated with restored host protective immunity in patients with COVID-19 and immunosuppression and improve outcomes.”
According to the authors, the ethics committee at Saint-Luc University Hospital approved IL-7 for compassionate use in 12 patients who were critically ill with COVID-19 and severe lymphopenia, who had 2 consecutive absolute lymphocyte counts of less than 700/L. These patients received an initial safety dose of 3 g/kg, followed by a dose of 10 g/kg, via intramuscular injection, twice per week for 2 weeks. A control group of 13 patients with COVID-19, who received standard care, were matched to the IL-7 group based on illness severity, comorbidities and other factors.
The authors analyzed the resulting data using a mixed-effects model with repeated measures and the autoregression 1 covariance structure. In addition, they used the logs of the absolute lymphocyte scores, as they provided a better fit to the model, they wrote. The associations of group, study day, and the group by study day interaction were all significant. Statistical significance was defined as P<.05, and all tests were 2-tailed.
According to the authors, there were no treatment-associated adverse effects, with IL-7 well tolerated without inducing changes in temperature, blood pressure, or Pao2:Fio2 ratio. IL-7 was not associated with any changes in tumor necrosis factor alpha, IL-1-beta and IL-12p70 concentrations, which were all below the level of detection at all time points in all patients. In addition, there was no consistent association of IL-7 treatment with IL-6 concentration.
Overall, 25% of patients in the IL-7 group demonstrated decreases in IL-6 concentrations, while 17% had increases in IL-6 concentration of approximately 1,000-1,500 pg/mL at 7 hours after administration. According to the authors, these changes in IL-6 concentration “may have been because of changes in the underlying patient physiologic state rather than because of IL-7.”
At day 30, secondary infections occurred in 58% who received IL-7, compared with 85% of those in the control group. In addition, 30-day mortality was 42% in the IL-7 group and 46% in the control group. IL-7 was associated with a restored lymphocyte count, with patients in that group demonstrating levels that were more than 2-fold greater than those in the control group (P=.02).
“IL-7 was associated with lymphocytes returning to a reference level, appearing to reverse a pathologic hallmark of COVID-19,” Laterre and colleagues wrote. “Importantly, previous studies have reported that IL-7–associated restoration of lymphocyte numbers enhanced the activity of antiviral agents. A limitation of the current study is that no phenotypic or functional studies of immune cells were conducted. Administration of IL-7 alone or in combination with other therapies warrants serious consideration for patients with COVID-19 and evidence of immunosuppression.”