Characterization of the anti-spike IgG immune response to COVID-19 vaccines in people with a wide variety of immunodeficiencies

Research on COVID-19 vaccination in immune-deficient/disordered people (IDP) has primarily focused on cancer and organ transplantation populations. In a prospective cohort of 195 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.