Mass SARS-Cov-2 vaccination campaign represents the only strategy to defeat the global pandemic we are facing. Immunocompromised patients represent a vulnerable population at high risk of developing severe COVID-19 and thus should be prioritized in the vaccination programs and in the study of the vaccine efficacy. Nevertheless, most data on efficacy and safety of the available vaccines derive from trials conducted on healthy individuals; hence, studies on immunogenicity of SARS-CoV2 vaccines in such populations are deeply needed. Here, we perform an observational longitudinal study analyzing the humoral and cellular response following the BNT162b2 mRNA COVID-19 vaccine in a cohort of patients affected by inborn errors of immunity (IEI) compared to healthy controls (HC). We show that both IEI and HC groups experienced a significant increase in anti-SARS-CoV-2 Abs 1 week after the second scheduled dose as well as an overall statistically significant expansion of the Ag-specific CD4+CD40L+ T cells in both HC and IEI. Five IEI patients did not develop any specific CD4+CD40L+ T cellular response, with one of these patients unable to also mount any humoral response. These data raise immunologic concerns about using Ab response as a sole metric of protective immunity following vaccination for SARS-CoV-2. Taken together, these findings suggest that evaluation of vaccine-induced immunity in this subpopulation should also include quantification of Ag-specific T cells.

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To the Editor, Many authors recently reported the effect of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic on patients affected by Inborn Errors of Immunity (IEI). 1,2 Although mostly experiencing a mild disease and the course of the infection is comparable or even less symptomatic than the general population, young male IEIs patients were more severely affected and more frequently admitted to intensive care unit compared with the age-matched healthy peers. 3 Most viral variants were actually first described in immunocompromised patients. 4,5 Indeed, impaired B and/or T cell function can be responsible for persisting viral shedding often observed in IEI patients with subsequent higher risk of persistent viral replication and mutation within the host. 6 Noteworthily, in the last 2 years Inborn Errors of type I IFN immunity and autoantibodymediated phenocopies of IEIs were identified as responsible for life-threatening COVID-19. These conditions were not considered in the studies about IEIs and SARS-CoV-2 infection. 7,8 Predisposition to increased risk and most severe infection in IEI, despite a lack of clear data in favor of a high risk for progression to severe COVID-19, led the scientific community to recommend the use of early SARS-CoV2-directed treatments to potentially reduce the incidence of long-lasting infection, as well as morbidity and mortality risk. 9Casirivimab-imdevimab, also known as REGEN-COV, is an antispike mAb that has been authorized for the treatment of high-risk patients (>12 years of age, >40 kg) with mild-to-moderate COVID-19. 10 Bamlanivimab, named LY-CoV555, then combined with etesevimab, showed a beneficial effect for accelerating the natural decline of the viral load over time. In December 2021, it was approved by FDA for patients<12 years. 10 Sotrovimab, formerly known as VIR-7831, is an engineered human mAb that neutralizes SARS-CoV-2. 10 There are several data confirming the safety and efficacy in both adults and pediatric population. 11 We describe a cohort of 63 SARS-CoV-2-infected IEI patients, providing the first case series report on the early employment of anti-SARS-CoV-2 treatments with antiviral drugs and MAbs in these patients (Table S1). Thirty-nine patients were younger than 18 years (median age 9.5 years), whereas 24 were adults (median age 33 years). Male-to-female ratio was 1:1. Seven individuals have been