Antibody and T-cell responses to coronavirus disease 2019 vaccination in common variable immunodeficiency and specific antibody deficiency.

BACKGROUND: Clinical trials of the mRNA coronavirus disease 2019 (COVID-19) vaccines excluded individuals with primary antibody deficiencies. OBJECTIVE: To evaluate whether antibody and T-cell responses to mRNA COVID-19 vaccination in patients with common variable immunodeficiency (CVID) and specific antibody deficiency (SAD) were comparable to those in healthy controls. METHODS: We measured antibody responses against the spike glycoprotein and the receptor-binding domain (RBD) in addition to severe acute respiratory syndrome coronavirus 2 specific T-cell responses using peripheral blood mononuclear cells 2 to 8 weeks after the subjects completed the primary 2-dose vaccine series. RESULTS: The study comprised 12 patients with CVID, 7 patients with SAD, and 10 controls. Individuals with CVID had lower immunoglobulin (Ig) G and Ig A levels against spike glycoprotein than did both individuals with SAD (P = .27 and P = .01, respectively) and controls (P = .01 and P = .004, respectively). The CVID group developed lower IgG titers against the RBD epitope than did the control group (P = .01). Participants with CVID had lower neutralizing titers than did the control group (P = .002). All participants with SAD developed neutralizing titers. All 3 groups (SAD, CVID, and control) developed antigen-specific CD4+ and CD8+ T-cell responses after vaccination. CONCLUSION: Our results suggest that patients with CVID may have impaired antibody responses to COVID-19 vaccination but intact T-cell responses, whereas patients with SAD would be expected to have both intact antibody and T-cell responses to vaccination.

Antibody and T-cell responses to COVID-19 Vaccination in Common Variable Immunodeficiency and Specific Antibody Deficiency

Background Clinical trials of the mRNA COVID-19 vaccines excluded individuals with primary antibody deficiencies. Objective The aim of this study was to evaluate whether antibody and T-cell responses to mRNA COVID-19 vaccination in patients with Common Variable Immunodeficiency (CVID) and Specific Antibody Deficiency (SAD) were comparable to healthy controls. Methods We measured antibody responses against the S protein and the receptor binding domain (RBD) as well as SARS-CoV2 specific T-cell responses using peripheral blood mononuclear cells (PBMCs) 2-8 weeks after subjects completed the primary 2-dose vaccine series. Results 12 patients with CVID, 7 patients with SAD, and 10 controls were included in the study. Individuals with CVID had lower IgG and IgA levels against S protein compared to both individuals with SAD (p= 0.27 and p=0.01, respectively) and as well as to controls (p=0.012 and p=0.004, respectively). The CVID group developed lower IgG titers against the RBD epitope compared to the control group (p=0.014). CVID participants had lower neutralizing titers compared to the control group (p=0.002). All SAD participants developed neutralizing titers. All three of our groups (SAD, CVID, and control) developed antigen-specific CD4+ and CD8+ T-cell responses after vaccination. Conclusion Our results suggest that patients with CVID may have impaired antibody responses to COVID-19 vaccination but intact T-cell responses, while patients with SAD would be expected to have both intact antibody and T-cell responses to vaccination.

Robust Antibody and T Cell Responses to SARS-CoV-2 in Patients with Antibody Deficiency.

Immunocompromised patients, including those with inborn errors of immunity (IEI), may be at increased risk for severe or prolonged infections with SARS-CoV-2 (Zhu et al. N Engl J Med. 382:727-33, 2020; Guan et al. 2020; Minotti et al. J Infect. 81:e61-6, 2020). While antibody and T cell responses to SARS-CoV-2 structural proteins are well described in healthy convalescent donors, adaptive humoral and cellular immunity has not yet been characterized in patients with antibody deficiency (Grifoni et al. Cell. 181:1489-1501 e1415, 2020; Burbelo et al. 2020; Long et al. Nat Med. 26:845-8, 2020; Braun et al. 2020). Herein, we describe the clinical course, antibody, and T cell responses to SARS-CoV-2 structural proteins in a cohort of adult and pediatric patients with antibody deficiencies (n = 5) and controls (related and unrelated) infected with SARS-CoV-2. Five patients within the same family (3 with antibody deficiency, 2 immunocompetent controls) showed antibody responses to nucleocapsid and spike proteins, as well as SARS-CoV-2 specific T cell immunity at days 65-84 from onset of symptoms. No significant difference was identified between immunocompromised patients and controls. Two additional unrelated, adult patients with common variable immune deficiency were assessed. One did not show antibody response, but both demonstrated SARS-CoV-2-specific T cell immunity when evaluated 33 and 76 days, respectively, following SARS-CoV-2 diagnosis. This report is the first to show robust T cell activity and humoral immunity against SARS-CoV-2 structural proteins in some patients with antibody deficiency. Given the reliance on spike protein in most candidate vaccines (Folegatti et al. Lancet. 396:467-78, 2020; Jackson et al. N Engl J Med. 383:1920-31, 2020), the responses are encouraging. Additional studies will be needed to further define the timing of onset of immunity, longevity of the immune response, and variability of response in immunocompromised patients.

The Future of Telehealth in Allergy and Immunology Training

With emerging interest in the use of telemedicine, allergy-immunology should be at the forefront of adoption and implementation of these services. Patients report a greater desire for telemedicine services as well as satisfaction with video-based visits with their providers. Interim virtual visits can accommodate overscheduled clinics, reduce burdens of travel to distant sites, improve access to subspecialty care, and increase adherence during monitoring of chronic allergic conditions. The outpatient nature of allergy-immunology coupled with the ease of conducting many aspects of a routine visit via telemedicine makes the incorporation of telehealth training into fellowship programs highly desirable. The short-term closure of hospital-affiliated clinics, in particular, for vulnerable or immunodeficient patients, in the setting of a global pandemic demonstrates the timeliness of this topic.A framework for implementing telemedicine into the allergy-immunology curriculum, training faculty on appropriate supervision, providing elective clinical experience in the form of continuity clinics, and simulating telemedicine delivery is discussed. Proposed telemedicine competencies desired for the independent practice of telemedicine are suggested.