Cellular response evaluation in immunosuppressed individuals to help guide monoclonal antibody COVID-19 prophylactic treatment administration

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Immunocompromised patients are highly susceptible to viral infections and often have suboptimal humoral responses to SARS-CoV-2 vaccination. SARS-CoV-2-specific cellular responses were assessed in candidates for tixagevimab/cilgavimab (Evusheld) prophylaxis to support clinical decision-making in addition to serology. Between June and September 2022, 146 immunocompromised individuals were classified according to their serology (negative < 260 vs. positive ≥ 260 BAU/mL). Peripheral blood mononuclear cells (PBMCs) were stimulated with a Spike peptide pool, and IFN-γ, IL-2, IL-21, and IL-5 responses were measured using a Fluorospot assay. Only 38.3% of negative serology patients showed a cellular response compared to 55.6% of those with positive serology. Negative serology was linked to lower polyfunctionality (38.8% vs. 72.2%) and decreased IFN-γ and IL-2 responses. Previous COVID-19 increased the probability of IFN-γ response (OR 2.33) and IL-2 (OR 3.15), while corticosteroid intake reduced the probability of IFN-γ response (OR 0.33). Multivariate analysis estimated that less than 15% of negative serology patients, with no previous COVID, and on corticosteroids, would mount an IFN-γ response, compared to 68–90% in positive serology individuals, with previous infection, and not receiving corticosteroids. Evaluating cellular responses can provide additional information to serology and can help identify patients most at risk of insufficient immune protection.