160. Cellular/humoral Response to SAR-CoV-2 Infection and Vaccination in B cell Depleted Patients with Rituximab (RituxiVac)

Background: The immune response to viral infections normally involves both humoral and cellular immunity. Patients on rituximab have prolonged B cell depletion and the humoral immune response is blocked. When the COVID 19 epidemic started in early 2020, virtually the entire population of the world had no detectable adaptive immunity. Thus, the immune responses of individuals infected with COVID 19, or vaccinated to COVID 19, or both, could be assessed starting with a clear slate. Among patients on rituximab with COVID 19, the immune response is without B cells. Methods: We reviewed the available data on 630 patients who achieved B cell depletion during the COVID era (1/1/2020 to 7/26/2021) for the impact of SARS-CoV-2 infection and vaccination on their clinical and serologic course. T cell responses are being assessed in a subset of patients. Results: After the last dose of rituximab, the median time to B cell recovery was 280 days (IQR, 272 – 363) (Figure 1A). Forty-seven patients contracted symptomatic COVID 19 while B cell depleted. Of these 47 patients, the infection occurred in 36 patients prior to vaccination (of which 33 patients (91.7%) survived), in 3 patients during vaccination (of which 1 patient (33.3%) survived), and in 6 patients after vaccination (of which 5 patients (83.3%) survived). Two patients developed COVID 19 twice, once each before and after vaccination. Among the 6 total patients who died from COVID 19, additional risk factors were present in all, including advanced age (mean 74; range 57-92), CKD (n = 4), severe obesity (n = 2), cardiac disease (n = 2), and interstitial lung disease (n=1) (Figure 1C.) Antibodies to SARS-CoV-2 remained absent in all 41 surviving patients. Thirty-five COVID 19-naïve patients were identified who were vaccinated during B cell depletion and tested for SARS-CoV-2 spike antibodies. 33 of 35 had no detectable antibodies and 2 had very low levels of antibodies. Among 12 patients vaccinated during documented or imputed early B cell recovery, 6 had SARS-CoV-2 antibodies. Among 9 patients vaccinated after B cell recovery, 8 had SARS-CoV-2 antibodies (Figure 1D). T cell responses to SARS-CoV-2 peptides are being tested from an available subset of B cell depleted COVID survivors and from an available subset of B cell depleted vaccinated patients. Conclusions: Rituximab treatment for autoimmune disease leads to prolonged B cell depletion. B cell depletion completely prevents a detectable antibody response to COVID 19. Nevertheless, among unvaccinated patients who contract SARS-CoV-2 infection, survival appears comparable to that of broader non-B-cell depleted populations with a similar degree of other risk factors. Recovery from COVID 19 without antibodies appears dependent on other aspects of the immune system and is presumably T cell driven. However, it remains to be seen if the current vaccines can provide protection from COVID 19 among B cell depleted patients. Studies of the T cell responses to SARS-CoV-2 infection and vaccination may lead to additional strategies for new vaccine creations. Disclosures: In collaboration with Ragon Institute of MGH, MIT and Harvard. Funded by the Vasculitis and Glomerulonephritis Center, Ragon Insitute of MGH, MIT and Harvard, and Center for Disease Control and Prevention (DHHS)