RESUMO
Patients with antibody deficiency disorders, such as primary immunodeficiency (PID) or secondary immunodeficiency (SID) to B-cell lymphoproliferative disorder (B-CLPD), are two groups vulnerable to developing the severe or chronic form of coronavirus disease caused by SARS-CoV-2 (COVID-19). The data on adaptive immune responses against SARS-CoV-2 are well described in healthy donors, but still limited in patients with antibody deficiency of a different cause. Herein, we analyzed spike-specific IFN-γ and anti-spike IgG antibody responses at 3 to 6 months after exposure to SARS-CoV-2 derived from vaccination and/or infection in two cohorts of immunodeficient patients (PID vs. SID) compared to healthy controls (HCs). Pre-vaccine anti-SARS-CoV-2 cellular responses before vaccine administration were measured in 10 PID patients. Baseline cellular responses were detectable in 4 out of 10 PID patients who had COVID-19 prior to vaccination, perceiving an increase in cellular responses after two-dose vaccination (p < 0.001). Adequate specific cellular responses were observed in 18 out of 20 (90%) PID patients, in 14 out of 20 (70%) SID patients and in 74 out of 81 (96%) HCs after vaccination (and natural infection in some cases). Specific IFN-γ response was significantly higher in HC with respect to PID (1908.5 mUI/mL vs. 1694.1 mUI/mL; p = 0.005). Whereas all SID and HC patients mounted a specific humoral immune response, only 80% of PID patients showed positive anti-SARS-CoV-2 IgG. The titer of anti-SARS-CoV-2 IgG was significantly lower in SID compared with HC patients (p = 0.040), without significant differences between PID and HC patients (p = 0.123) and between PID and SID patients (p =0.683). High proportions of PID and SID patients showed adequate specific cellular responses to receptor binding domain (RBD) neoantigen, with a divergence between the two arms of the adaptive immune response in PID and SID patients. We also focused on the correlation of protection of positive SARS-CoV-2 cellular response to omicron exposure: 27 out of 81 (33.3%) HCs referred COVID-19 detected by PCR or antigen test, 24 with a mild course, 1 with moderate symptoms and the remaining 2 with bilateral pneumonia that were treated in an outpatient basis. Our results might support the relevance of these immunological studies to determine the correlation of protection with severe disease and for deciding the need for additional boosters on a personalized basis. Follow-up studies are required to evaluate the duration and variability in the immune response to COVID-19 vaccination or infection.
RESUMO
BACKGROUND: Prophylactic vaccination has proven to be the most effective strategy to fight the COVID-19 pandemic. METHODS: This was a prospective observational cohort study involving 30 predominantly antibody deficiency disorders (ADD)-afflicted adult patients on immunoglobulin replacement therapy vaccinated with three doses of the mRNA-1273 COVID-19 vaccine, and 10 healthy controls. Anti-RBD IgG antibodies were determined in plasma samples collected just before the first dose of mRNA-based COVID-19 vaccine and on weeks 4, 8, 24, and 28 following the first vaccination. Patients were categorized based on the levels of anti-RBD antibodies determined on w8 as non-, low-, and responders. Chi-square and Kruskal-Wallis tests were used to see if any variables correlated with humoral response levels. Any adverse effects of the mRNA-based vaccine were also noted. RESULTS: The COVID-19 vaccine was safe and well-tolerated. The humoral response elicited at w8 after vaccination depended on the type of ADD, the type of immunoglobulin deficiency, the presence of granulomatous lymphocytic interstitial lung disease, recent use of immunosuppressive drugs, and the switched memory B cells counts. The third vaccine dose boosted humoral response in previous responders to second dose but seldom in non-responders. CONCLUSIONS: The humoral response of patients with predominant ADD depends mostly on the type of immunodeficiency and on the frequency of B and T cell populations.