LAUSR

We read with great interest the article by Ane F Salinas et al. [1] concerning early immune responses after BNT162b2 immunization in a cohort of 41 SARS-CoV-2 infectionnaïve or previously infected patients with common variable immune deficiencies (CVID) and 6 X-linked agammaglobulinemia (XLA) patients, as it adds valuable information about the humoral and cellular immunogenicity of the vaccine in patients with inborn errors of immunity (IEI). They evaluated the serum levels of SARS-CoV-2-specific antibodies and Spike-specific Band T-cells before immunization and 1 week after the second dose of BNT162b2, and found antibody responses in eight of the 34 CVID patients (23.5%) and in none of the 6 XLA patients [1]. In a similar study of a cohort of 60 CVID patients (49 previously uninfected and 11 previously infected by SARSCoV-2) and six XLA patients (only one previously infected) vaccinated with BNT162b2 or mRNA-1273, we measured the serum concentration of anti-Spike Receptor Binding Domain antibodies (total Ig; Roche Elecsys Anti-SARSCoV-2 S reagent) before (T0) and 4 weeks after vaccination (T2). All the patients were receiving replacement therapy and tests of the infused immunoglobulin products showed no detectable levels of anti-Spike Ig. Our CVID patients were similar to those of Salinas et al. and were vaccinated at approximately the same time of the year (see Patients and Methods as Supplemental data). We found that 35/49 patients previously uninfected by SARSCoV-2 (71.4%) responded to the vaccine and produced antiSpike Ig, a percentage that is three times higher than that found by Salinas et al. [1]. The difference in response rates may have been due to a difference in antibody production between the two cohorts: Salinas et al. evaluated early immune responses 1 week after the second dose of BNT162b2, whereas our patients were tested 4 weeks after two-dose immunization, thus giving them a longer time to produce antibodies. Thirty-seven of our previously uninfected CVID patients (76%) received mRNA-1273 vaccine, and 29 of these (78.4%) had detectable serum anti-Spike Ig concentrations with a median T2 level of 311 U/mL (range 0.4 to > 7500), whereas six of the 12 receiving BNT162b2 (50%) produced antibodies with a median T2 level of 114 U/mL (range 0.4 to > 7500). Therefore, although both studies showed that median serum Ig levels increased between T0 to T2, our findings show that the increase was greater in the patients receiving mRNA1273 (see Fig. 1). Moreover, comparison of antibody production between the previously infected (N = 9) and previously uninfected CVID patients (N = 37) receiving mRNA-1273 vaccine showed that total anti-Spike Ig production at T2 was higher among the former (4302 U/mL vs 311 U/mL, respectively; p = 0.026). This data was also observed in the two previously infected CVID patients who received BNT162b2 (median T2 titer 3783.5 U/mL vs 114 U/mL of the previously 12 uninfected patients) (see Fig. 1). Significantly higher antibody production after mRNA1273 vaccination has been demonstrated in a recent study that directly compared humoral responses to BNT162b2 and mRNA-1273 in a cohort of healthcare workers in Belgium [2]. Greater responses to mRNA-1273 were observed in previously infected and previously uninfected workers of all * Maria Carrabba [email protected]