A Phase I Clinical Trial to Evaluate the Safety of NK cells in COVID-19 (RELEASE)

The severity of COVID 19 symptoms has a direct correlation with lymphopenia, affecting natural killer (NK) cells. SARS-CoV-2 specific “memory” NK cells obtained from convalescent donors can be used as cell immunotherapy. In 2022 a phase I, dose-escalation, single center clinical trial was conducted to evaluate the safety and feasibility of the infusion of CD3-/CD56+ NK cells against moderate/severe cases of COVID-19 (NCT04578210). Six participants with pneumonia and/or lymphopenia were infused. Four patients received a single-dose infusion of NK cells of 1×106/kg, and the following two patients a dose of 2×106/kg of NK cells. All participants’ clinical status and inflammation markers were monitored. No serious adverse events were reported after infusion. Exploratory outcomes included the donor chimerism, NK-cell immunophenotype evolution, and immune lymphocyte reconstitution. This study provides preliminary evidence supporting the idea that treatment of COVID-19 patients with moderate/severe symptoms using NK from COVID-19 convalescent donors is feasible and safe. [Display omitted] •NK “memory” from convalescent donors as an adoptive therapy for COVID-19 patients (RELEASE).•Clinical trial assessed NK cell infusion safety, immune recovery, and patient outcomes.•No serious adverse events reported.•Clinical trial found no dose-limiting toxicities after NK cell infusion.