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

Abstract

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. Supplementary Information The online version contains supplementary material available at 10.1007/s10875-021-01046-y.

Covid-19 in patients with chronic lymphocytic leukemia: clinical outcome and B- and T-cell immunity during 13 months in consecutive patients

“…In addition, we show that SARS-CoV-2 specific T cell immunity occurs in the majority of CLL convalescents which was usually but not always paralleled by seroconversion. This is in line with a recent report on 5 patients with antibody deficiencies [ 20 ] and a group of 22 patients with mixed hematological malignancies [ 15 ]. Whether T cell responses may occur also following Covid-19 vaccination in CLL is under investigation.…”

Vaccination in PADs

“…The rationale, as for the flu vaccine, is that T cell responses can be generated even in the absence of a complete antibody response [33]. Recent evidence suggests that CVID patients may develop an antibody response and in vitro T-cell reactivity to SARS-CoV-2 antigens [34].…”

SARS-CoV-2 Neutralization in Convalescent Plasma and Commercial Lots of Plasma-derived Immunoglobulin

“…Active immunization of patients with primary immunodeficiencies (PID) as well as secondary immunodeficiencies (SID), which in part manifest as impeded or a complete lack of humoral response, has recently been reported with encouraging findings [18,19]. However, not all patients within this heterogeneous group are amenable to vaccination or vaccination might not lead to immune protection [20,21].…”

“…Therefore, the reactivity and neutralizing potency of these IgG pharmaceutical products are directly dependent on the epidemiologic experience of the donor population [19][20][21].…”