Prospective Evaluation of Coronavirus Disease 2019 (COVID-19) Vaccine Responses Across a Broad Spectrum of Immunocompromising Conditions: the COVID-19 Vaccination in the Immunocompromised Study (COVICS)

Abstract

Background: We studied humoral responses after coronavirus disease 2019 (COVID-19) vaccination across varying causes of immunodeficiency.

Methods: Prospective study of fully vaccinated immunocompromised adults (solid organ transplant [SOT], hematologic malignancy, solid cancers, autoimmune conditions, human immunodeficiency virus [HIV]) versus nonimmunocompromised healthcare workers (HCWs). The primary outcome was the proportion with a reactive test (seropositive) for immunoglobulin G to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor-binding domain. Secondary outcomes were comparisons of antibody levels and their correlation with pseudovirus neutralization titers. Stepwise logistic regression was used to identify factors associated with seropositivity.

Results: A total of 1271 participants enrolled: 1099 immunocompromised and 172 HCW. Compared with HCW (92.4% seropositive), seropositivity was lower among participants with SOT (30.7%), hematological malignancies (50.0%), autoimmune conditions (79.1%), solid tumors (78.7%), and HIV (79.8%) (P < .01). Factors associated with poor seropositivity included age, greater immunosuppression, time since vaccination, anti-CD20 monoclonal antibodies, and vaccination with BNT162b2 (Pfizer) or adenovirus vector vaccines versus messenger RNA (mRNA)-1273 (Moderna). mRNA-1273 was associated with higher antibody levels than BNT162b2 or adenovirus vector vaccines after adjusting for time since vaccination, age, and underlying condition. Antibody levels were strongly correlated with pseudovirus neutralization titers (Spearman r = 0.89, P < .0001), but in seropositive participants with intermediate antibody levels, neutralization titers were significantly lower in immunocompromised individuals versus HCW.

Conclusions: Antibody responses to COVID-19 vaccines were lowest among SOT and anti-CD20 monoclonal recipients, and recipients of vaccines other than mRNA-1273. Among those with intermediate antibody levels, pseudovirus neutralization titers were lower in immunocompromised patients than HCWs. Additional SARS-CoV-2 preventive approaches are needed for immunocompromised persons, which may need to be tailored to the cause of immunodeficiency.

Keywords: COVID-19 vaccines; SARS-COV-2 antibody; SARS-CoV-2 neutralization; immunocompromised.

Figure 1.

Seropositivity and antibody levels. Results reflect anti-RBD antibody levels (signal to cut-off [S/CO] ratio) measured by the Beckman assay, unless otherwise indicated. A, Seropositivity in healthcare workers (HCWs) and immunocompromised participants. P values refer to comparisons between HCWs and immunocompromised participants (χ² test). Whiskers denote 95% confidence intervals. B, All antibody levels (seropositive and seronegative) in nonimmunocompromised HCWs and immunocompromised participants. C, Comparisons of antibody levels among only participants with positive results. P value determined by Wilcoxon rank-sum test. D, Decline in antibody levels per month following vaccination; whiskers denote 95% confidence intervals. E, Antibody levels stratified by vaccine type among all participants, after adjustment of age, time from vaccination, and underlying immunocompromising condition; whiskers denote 95% confidence intervals. F, Correlation of antibody levels measured by the Beckman (anti-RBD) and Bio-Rad Bio-Plex (anti-RBD) assays. Abbreviations: HIV, human immunodeficiency virus; RBD, receptor-binding domain; SOT, solid organ transplant.

Figure 2.

A, Scatter plot of 50% neutralization titer (NT50) for D614G pseudovirus (x-axis) by anti-RBD antibody levels (signal to cut-off [S/CO] ratio) measured by Beckman assay (y-axis). NT50 was defined as the highest serum dilution that neutralizes >50% of the D614G pseudovirus. Black filled circles are data from nonimmunocompromised healthcare workers; red filled circles are data from immunocompromised participants. B, Comparisons of antibody levels and NT50 across 100 study participants. Black, blue, and red boxes represent participants with antibody levels <1, 1–10, and >10, respectively. Among participants with antibody S/CO levels 1–10, NT50 were significantly lower among IC participants compared with HCWs. Abbreviations: HCWs, healthcare workers; IC, immunocompromised; RBD, receptor-binding domain.