Evaluation of Humoral and Cellular Responses in SARS-CoV-2 mRNA Vaccinated Immunocompromised Patients

Abstract

Background: Immunocompromised patients are at increased risk of severe COVID-19 and impaired vaccine response. In this observational prospective study, we evaluated immunogenicity of the BNT162b2 mRNA vaccine in cohorts of primary or secondary immunocompromised patients.

Methods: Five clinical groups of immunocompromised patients [primary immunodeficiency (PID) (n=57), people living with HIV (PLWH) (n=27), secondary immunocompromised patients with a broad variety of underlying rheumatologic (n=23) and homogeneous (multiple sclerosis) neurologic (n=53) conditions and chronic kidney disease (CKD) (n=39)] as well as a healthy control group (n=54) were included. Systemic humoral and cellular immune responses were evaluated by determination of anti-SARS-CoV-2 Spike antibodies using a TrimericS IgG assay (Diasorin) and through quantification of interferon gamma release in response to SARS-CoV-2 antigen with QuantiFERON SARS-CoV-2 assay (Qiagen), respectively. Responses were measured at pre-defined time-points after complete vaccination.

Results: All healthy controls, PLWH and CKD-patients had detectable antibodies 10 to 14 days (T2) and 3 months (T3) after administration of the second vaccination. In contrast, only 94.5% of the PID, 50.0% of the rheumatologic and 48.0% of neurologic patients developed antibodies at T2 and only 89.1% of the PID, 52.4% of the rheumatologic and 50.0% of neurologic patients developed antibodies at T3. At T3 no significant differences in cellular response between the healthy control group and the PLWH and CKD groups were found, while proportions of reactive subjects were lower in PID and rheumatologic patients and higher in neurologic patients. Humoral and cellular immune responses significantly correlated in the healthy control, PID, PLWH groups for all 3 antigens.

Conclusion: Patients with acquired or inherited immune disorders may show variable immune responses to vaccination with the BNT162b2 mRNA vaccine against SARS-CoV-2. Whether humoral, cellular or both immune responses are delayed depends on the patient group, therapy and individual risk factors. These data may guide the counselling of patients with immune disorders regarding vaccination of SARS-CoV-2.

Keywords: SARS-CoV-2; antibodies; humoral response; immunocompromised; vaccination.

Figure 1

Violin plots of anti-SARS-CoV-2 IgG antibodies at T0, T1, T2 and T3 time points between the healthy control group (●) and patient groups (▼): primary immunodeficiency patient group (A), PLWH (B), neurologic (C), rheumatologic (D) and CKD (E) patient groups. Patients with a documented Sars-CoV-2 infection are indicated with red symbols. Each plot represent the median, 25th and 75th percentiles. Outliers were determined by 1.5 time IQR. Statistical significance was calculated by Mann-Whitney U test. Significance was defined as a p-value < 0.05. Each plot represent the median, 25th and 75th percentiles. Outliers were determined by 1.5 time IQR. Statistical significance was calculated by Mann-Whitney U test. Significance was defined as a p-value < 0.05.

Figure 2

Line graphs presenting the difference in IFN gamma concentration for Ag1 (1) and Ag2 (2) between T0 and T3 for the healthy control group (A), primary immunodeficiency patients (B), PLWH (C), neurology (D), rheumatology (E) and CKD (F) patient groups. P-values indicating significant differences between the median concentrations are reported.

Figure 3

IFN gamma concentrations after stimulation of T-cells with the different antigen pools (Ag1, Ag2 and Ag3) between the healthy control group (●) and patient groups (▼): primary immune deficiency patient group (A), PLWH (B), neurology (C) rheumatology (D) and CKD (E) patient groups at T3. Patients with a documented Sars-CoV-2 infection are indicated with red symbols. Cellular responses were assessed by measuring interferon (IFN) gamma (IU/mL) by the QuantiFERON SARS-CoV-2 test on the Liaison XL analyser. Plots represent the median, 25th and 75th percentiles. Outliers were determined by 1.5 time IQR. Statistical significance was calculated by Mann-Whitney U test. Significance was defined as a p-value < 0.05.

Figure 4

Relationship between cellular and humoral immune response after vaccination with Pfizer BNY162b2 for the healthy control (A) and different patient groups: primary immune deficiency patient group (B) PLWH (C), neurology (D) rheumatology (E) and CKD (F) patient groups at T3. The relationship is presented for antigen 1 (blue), antigen 2 (orange) and antigen 3 (green). Cellular responses were assessed by measuring interferon (IFN) gamma (IU/mL) by the QuantiFERON SARS-CoV-2 test on the Liaison XL analyser and Humoral responses assessed by the Liaison^® SARS-CoV-2 TrimericS IgG chemiluminescent immunoassay on the Liaison XL. Correlation was calculated by using Spearman’s correlation coefficients.