SARS-CoV-2 Vaccination Responses in Vulnerable Populations

Abstract

Immunosuppressive medications are commonly prescribed to minimize the aberrant inflammatory responses in the autoimmune disorders rheumatoid arthritis (RA) and systemic sclerosis (SSc). It has been previously shown that immunosuppressive drugs can negatively impact responses to vaccination, though the impact differs by vaccine type. With the advent of the SARS-CoV-2 pandemic, and the development of new mRNA vaccines, it was unclear how well participants with RA and SSc, on immunosuppressive drugs, would response to these vaccinations. We hypothesized that people with RA or SSc, on immunomodulatory drugs, would have weaker humoral and cellular responses to SARS-CoV-2 vaccination, even following subsequent vaccinations, compared with healthy controls. To explore this, we collected blood and serum from participants with RA, SSc, and controls at various timepoints after multiple SARS-CoV-2 vaccinations. In Chapter 2, we determined that participants with RA on immunosuppressive drugs had weaker humoral and spike-specific CD4+ T cell responses, but not weaker spike-specific CD8+ T cell responses, than controls around the second, third, and fourth SARS-CoV-2 vaccinations. While costimulation inhibitors negatively impacted the humoral responses, the inclusion of JAK inhibitors in the immunosuppressive drug regimen was associated with weaker spike-specific CD4+ T cell responses, demonstrating that different immunosuppressive drugs impact unique arms of the memory response. In Chapter 3, we discovered that participants with SSc did not have lower humoral or spike-specific T cell responses to SARS-CoV-2 vaccination than controls. In Chapter 5, we determined that repeated SARS-CoV-2 vaccination did not cause T cell exhaustion in multiple vulnerable populations, including immunosuppressed participants with RA and older adults in long-term care, or healthy younger adults. Overall, our research has provided insight into SARS-CoV-2 vaccination responses in participants with RA and SSc, allowing patients and their doctors to make informed decisions regarding vaccination timelines and medication-specific concerns.