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)
Authors: Haidar Ghady , Agha Mounzer , Bilderback Andrew , Lukanski Amy , Linstrum Kelsey , Troyan Rachel , Rothenberger Scott , McMahon Deborah K , Crandall Melissa D , Sobolewksi Michele D , Nathan Enick P , Jacobs Jana L , Collins Kevin , Klamar-Blain Cynthia , Macatangay Bernard J C , Parikh Urvi M , Heaps Amy , Coughenour Lindsay , Schwartz Marc B , Dueker Jeffrey M , Silveira Fernanda P , Keebler Mary E , Humar Abhinav , Luketich James D , Morrell Matthew R , Pilewski Joseph M , McDyer John F , Pappu Bhanu , Ferris Robert L , Marks Stanley M , Mahon John , Mulvey Katie , Hariharan Sundaram , Updike Glenn M , Brock Lorraine , Edwards Robert , Beigi Richard H , Kip Paula L , Wells Alan , Minnier Tami , Angus Derek C , Mellors John W 
Published: February 2022

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 &lt; .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 &lt; .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.