Immunogenicity of COVID-19 Vaccination in Immunocompromised Patients: An Observational, Prospective Cohort Study Interim Analysis

Abstract

Objectives: Immunocompromised patients were excluded from COVID-19 vaccine clinical trials. The objectives of the study were to measure antibody responses, levels, and neutralization capability after COVID-19 vaccination among immunocompromised patients and compare these variables to those of immunocompetent healthcare workers. Methods This is an interim analysis of an ongoing observational, prospective cohort study which launched on April 14, 2021 across Western Pennsylvania. Participants were healthy healthcare workers (HCW) and immunocompromised patients who had completed their COVID-19 vaccination series. Individuals with a history of COVID-19 were not eligible. Serum was collected to measure for the presence of IgG against the SARS-CoV-2 Spike protein using a semi-quantitative assay; antibody levels were available for comparisons. A quasi-random subset of patients was selected for pseudovirus neutralization assays. Seropositivity with 95% Clopper-Pearson exact confidence intervals and distribution of antibody levels were measured. To identify risk factors for seronegativity, clinical characteristics were univariately compared between antibody reactive and non-reactive individuals within the immunocompromised group. Results: 107 HCW and 489 immunocompromised patients were enrolled. Compared to HCWs, seropositivity was significantly lower (p<.001) among immunocompromised patients with Solid organ transplant (SOT), autoimmune, hematological malignancies, and solid tumors (HCW=98.1%; SOT=37.2%; autoimmune=83.8%; hematological malignancies=54.7%; and solid tumor=82.4%, p < 0.05). Over 94% of patients with Human Immunodeficiency Virus were seropositive. Among seropositive patients, antibody levels were much lower among SOT (4.5 [2.1,13.1], p=.020). Neutralization titers tightly correlated with antibody levels (Spearman r = 0.91, p < 0.0001). Conclusion: Our findings demonstrate the heterogeneity of the humoral immune response to COVID-19 vaccines based on underlying immunosuppressive condition and highlight an urgent need to optimize and individualize COVID-19 prevention in these patients. These findings also have implications on public health guidance, particularly given revised Centers for Disease Control and Prevention recommendations permitting vaccinated individuals to abandon masking and social distancing in most settings. Future studies are warranted to determine assessment of cellular immunity, longitudinal measurement of immune responses, and the safety and efficacy of revaccination.

Rheumatoid arthritis patients treated with Janus kinase inhibitors show reduced humoral immune responses following BNT162b2 vaccination

“…Immunocompromised patients, children under the age of 16 and pregnant women were excluded from the COVID-19 vaccine clinical trials [ 9 ]. Soon after the completion of these clinical trials, several groups have tested the efficacy of the mRNA-based COVID-19 vaccines in individuals with impaired immune responses or in immunocompromised individuals [ 12 , 24 , 25 ]. A recent study has tested the efficacy of mRNA-based vaccines in various immunocompromised conditions, including solid-organ transplant, haematological malignancies, solid tumours being treated with systemic or radiation therapy over the past 12 months, autoimmune or chronic inflammatory conditions being treated over the past 12 months, and HIV infection [ 25 ].…”

The biological and clinical significance of emerging SARS-CoV-2 variants

“…Nonetheless, in vitro neutralization studies and epidemiological vaccine efficacy studies indicate weaker protection against emerging variants for most of the non-mRNA vaccines. Moreover, regardless of the vaccine received, reductions in vaccine-elicited humoral immunity is likely to be clinically significant for persons with impaired immunity as a result of underlying disease, immunosuppressive drugs or older age [241][242][243][244] .…”

Immune Evasive Effects of SARS-CoV-2 Variants to COVID-19 Emergency Used Vaccines

“…Besides, the immune status of the body also affected vaccine efficacy. A study of immunocompromised populations showed seropositivity rates of 98.1% for healthcare workers, 37.2% for solid organ transplants, 83.8% for autoimmune diseases, 54.7% for hematologic malignancies and 82.4% for solid tumors ( 100 ). In addition to the above, Moderna developed another vaccine against the B.1.351 and other variants, called mRNA-1273.351, based on cross-neutralizing activity ( 101 ).…”