ABSTRACT
Cancer patients have an increased risk of severe COVID-19 infection due to the suppression of the immune systemand the development of cytokine release syndrome (CRS) that favor respiratory syndromes and interstitialpneumonia. However, substantial differences exist between patients treated with chemotherapy and patients treated with immune checkpoint inhibitors (ICIs), for which the risk of COVID-19 infection and the immunologic and cytokineprofile in case of infection have not yet been well characterized. The administration of ICIs for the treatment ofsevere COVID-19 infection has been recently suggested. However, no conclusive data have been generated on thismatter. To recognize the therapeutic potential of ICIs administration in COVID-19 patients with or without cancer, theUniversal Immune System Simulator (UISS) prediction model was used to simulate the immunologic response ofCOVID-19 patients after ICIs administration. Briefly, UISS represents an appropriate computational modelinginfrastructure able to simulate the dynamics of every single entity of the immune system after a stimulus or atherapeutic intervention by using an agent-based methodology. Therefore, the UISS platform, already used for theprediction of the efficacy of specific SARS-CoV-2 candidate vaccines, was here adopted to characterize theimmunologic behavior in both COVID-19 and cancer patients and to predict the effects of ICIs in these patients. Thecomputational results allowed us to identify key inflammatory and immune-related factors responsible for severerespiratory syndromes in COVID-19 infected patients with and without cancer. UISS results suggest that theadministration of ICIs modulates the immune system and the inflammatory status in both groups of patients withCOVID-19 infection, reducing the risk of severe symptoms. Although the results of the present study are still undervalidation in peripheral blood samples obtained from COVID-19 patients and from cancer patients after two cycles oftreatment with ICIs, we can speculate that ICIs may be a good therapeutic approach for the treatment of COVID-19severe respiratory syndrome even with a concomitant cancer diagnosis. If this is the case, the lower expressionlevels of inflammatory biomarkers can result in the drop-down of the viral load, assessed by droplet digital PCR inCOVID-19 patients.