Immune response to COVID-19 vaccination in individuals with immune disorders

COVID-19 is caused by the novel SARS-CoV-2 and is associated with a hyper-inflammatory immune response which leads to severe and potentially life-threatening symptoms. Little is known about how and the extent to which COVID-19 presents in people with immunodeficiencies, but because of the known severity of the illness in the general population, vaccination against SARS-CoV-2 is critical. Understanding whether immunodeficient individuals produce an adequate immune response to the COVID-19 vaccine, as well as the number and type of AEs experienced in these people is necessary. Since the initiation of the study in April 2021, 308 study participants have been enrolled: 235 people with immune disorders, 73 healthy volunteers. Participant enrollment ended in January 2023 and sample collection ended July 2023 due to the ending of the COVID-19 emergency declaration and subsequent re-obligation of COVID-19 funds. We have collected samples from 1166 timepoints ranging from baseline through post-vaccination 5. Samples include microsamplers (dried whole blood), serum, plasma, PBMCs, and DNA extracted from buffy coat, although not all samples are available for every timepoint. We also collected 3173 saliva samples, RNA is available on 67 of 84 positives that were identified in the Department of Laboratory Medicine (11 pending RNA extraction). Analysis for the study is ongoing. From the first-round analytic cohort of 195 immune deficient people (IDP) and 35 healthy volunteers, anti-spike IgG was detected in 88% of IDP post-dose 2, increasing to 93% by six months post-dose 3. Despite high seroconversion, median IgG levels for IDP never surpassed 1/3 that of healthy volunteers. IgG binding to Omicron BA.1 was lower than all other variants. Angiotensin-converting enzyme 2 pseudo-neutralization (% inhibition) was only modestly correlated with anti-spike IgG concentration. IgG levels were not significantly altered by participants use of different mRNA-based vaccines, immunomodulating treatments, and prior SARS-CoV-2 infections. While our data show that three doses of COVID-19 vaccinations induce anti-spike IgG in most IDP, additional doses are needed to achieve the levels of protection in healthy volunteers. Due to the strikingly reduced IgG response to Omicron BA.1, the efficacy of additional vaccinations, including bivalent vaccines, should be studied in this population. Continued analysis will focus on T and B cell receptor repertoire of the post-vaccine samples, as well as a detailed analysis of breakthrough COVID-19 infections, including individuals with repeat and persistent infection. We will also be doing a second-round update to report on IgG response through the remainder of the sampling timepoints.