Interferon gamma immunotherapy in five critically ill COVID-19 patients with impaired cellular immunity: a case series

van Laarhoven, Arjan; Kurver, Lisa; Overheul, Gijs J.; Kooistra, Emma J.; Abdo, Wilson F.; van Crevel, Reinout; Duivenvoorden, Raphaël; Kox, Matthijs; ten Oever, Jaap; Schouten, Jeroen; van de Veerdonk, Frank L.; van der Hoeven, Hans; Rahamat-Langendoen, Janette; van Rij, Ronald P.; Pickkers, Peter; Netea, Mihai G.

Background Prolonged SARS-CoV-2 shedding has been described in immunocompromised COVID-19 patients, resulting in protracted disease and poor outcome. Specific therapy to improve viral clearance and outcome for this group of patients is currently unavailable. Methods Five critically ill COVID-19 patients with severe defects in cellular immune responses, high SARS-CoV-2 viral RNA loads, and no respiratory improvement were treated with interferon gamma, 100 μg subcutaneously, thrice weekly. Bronchial secretion was collected every 48 hours for routine diagnostic SARS-CoV-2 RT-PCR and viral culture. Findings Interferon gamma administration was followed by a rapid decline in SARS-CoV-2 load and a positive to negative viral culture conversion. Four patients recovered and no signs of hyperinflammation were observed. Conclusions Interferon gamma may be considered as adjuvant immunotherapy in a subset of immunocompromised COVID-19 patients. Funding AvL and RvC are supported by National Institute of Health [R01AI145781]. GJO and RPvR are supported by a VICI grant [016.VICI.170.090] from the Dutch Research Council (NWO). WFA is supported by Clinical Fellowship grant [#9071561]) of Netherlands Organization for Health Research and Development. MGN is supported by an ERC Advanced Grant [#833247] and a Spinoza Grant of the Netherlands Organization for Scientific Research.