586. Immunogenicity of COVID-19 mRNA Vaccines in Patients with Lymphoid Malignancies

Abstract Background Patients with lymphoid malignancies are at high risk of severe COVID-19 disease and were not included in the phase 3 mRNA vaccine trials. Many patients with lymphoid malignancies receive immunosuppressive therapies, including B-cell depleting agents, that may negatively impact humoral response to vaccination. Methods We recruited patients with lymphoid malignancies and healthy participants who planned to receive two doses of SARS-CoV-2 mRNA vaccine (BNT162b2 or mRNA-1273). Blood was drawn at baseline, prior to second dose of vaccine, and 28 days after last vaccination. Disease characteristics and therapies were extracted from patients’ electronic medical record. An ultrasensitive, single molecule array (Simoa) assay detected anti-Spike (S), anti-S1, anti-receptor binding domain (RBD), and anti-Nucleocapsid (N) IgG from plasma at each timepoint. Results 23 healthy participants and 37 patients with lymphoid malignancies were enrolled (Table 1). Low titers of anti-N (Fig 1A) demonstrate no prior exposure or acquisition of COVID-19 before vaccination or during the study. 37.8% of the lymphoid malignancy cohort responded to the vaccine, using an internally validated AEB cutoff of 1.07. A significantly higher magnitude of anti-S (p< 0.0001), anti-S1 (p< 0.0001) and anti-RBD (p< 0.0001) are present in the healthy as compared to lymphoid malignancy cohort at the second dose and day 28 post-series (Fig 1B, Fig 1C and Fig 1D). Anti-S IgG titers were compared between the healthy cohort, treatment naïve, and treatment experienced groups (Fig 2). The treatment naïve cohort had high titers by series completion which were not significantly different from the healthy cohort (p=0.2259), although the treatment experienced group had significantly decreased titers (p< 0.0001). Of the 20 patients who had received CD20 therapy, there was no clear correlation of anti-S IgG response with time from CD20 therapy, although most patients who received CD20 therapies within 12 months from the vaccine had no response (Figure 3). Table 1. Demographics Figure 1. Anti-N, Anti-S, Anti-S1, Anti-RBD and Anti-N Ig G for healthy v. lymphoid malignancy cohort The dotted line at 1.07 marks in an internally validated threshold to mark anti-S IgG response. The black bars denote median with 95% CI. Figure 2: Anti-S IgG for healthy v. treatment naïve v. treatment experienced The dotted line at 1.07 marks in an internally validated threshold to mark antibody response. The black bars denote median with 95% CI. Conclusion The vaccine-induced immune response was poor among treatment-experienced patients with lymphoid malignancies, especially among those who received CD20 therapies within 12 months. Figure 3. Months from CD20 therapy v. anti-S IgG titers The dotted line at 1.07 marks in an internally validated threshold to mark antibody response. Disclosures Jennifer Crombie, MD, AbbVie (Grant/Research Support)Bauer (Grant/Research Support)Karyopharm (Consultant)MorphoSys (Consultant) Philippe Armand, MD PhD, ADCT, Celgene, Morphosys, Daiichi, Miltenyi, Tessa, C4, Genmab, Enterome, Regeneron, Genentech, Epizyme, Astra Zeneca (Consultant, Sorry to put them all in, hope you can deconvolute for me)Affimed, Adaptive, BMS, Merck, Kite, IGM, Genentech (Research Grant or Support, Institutional research funding) David Walt, PhD, Quanterix Corporation (Board Member, Shareholder) Nicolas C. Issa, MD, AiCuris (Scientific Research Study Investigator)Astellas (Scientific Research Study Investigator)GSK (Scientific Research Study Investigator)Merck (Scientific Research Study Investigator)


Session: P-25. COVID-19 Vaccines
Background. Patients with lymphoid malignancies are at high risk of severe COVID-19 disease and were not included in the phase 3 mRNA vaccine trials. Many patients with lymphoid malignancies receive immunosuppressive therapies, including B-cell depleting agents, that may negatively impact humoral response to vaccination.
Methods. We recruited patients with lymphoid malignancies and healthy participants who planned to receive two doses of SARS-CoV-2 mRNA vaccine (BNT162b2 or mRNA-1273). Blood was drawn at baseline, prior to second dose of vaccine, and 28 days after last vaccination. Disease characteristics and therapies were extracted from patients' electronic medical record. An ultrasensitive, single molecule array (Simoa) assay detected anti-Spike (S), anti-S1, anti-receptor binding domain (RBD), and anti-Nucleocapsid (N) IgG from plasma at each timepoint.
Results. 23 healthy participants and 37 patients with lymphoid malignancies were enrolled (Table 1). Low titers of anti-N ( Fig 1A) demonstrate no prior exposure or acquisition of COVID-19 before vaccination or during the study. 37.8% of the lymphoid malignancy cohort responded to the vaccine, using an internally validated AEB cutoff of 1.07. A significantly higher magnitude of anti-S (p< 0.0001), anti-S1 (p< 0.0001) and anti-RBD (p< 0.0001) are present in the healthy as compared to lymphoid malignancy cohort at the second dose and day 28 post-series ( Fig 1B, Fig 1C and Fig 1D). Anti-S IgG titers were compared between the healthy cohort, treatment naïve, and treatment experienced groups (Fig 2). The treatment naïve cohort had high titers by series completion which were not significantly different from the healthy cohort (p=0.2259), although the treatment experienced group had significantly decreased titers (p< 0.0001). Of the 20 patients who had received CD20 therapy, there was no clear correlation of anti-S IgG response with time from CD20 therapy, although most patients who received CD20 therapies within 12 months from the vaccine had no response ( Figure 3).  Figure 1. Anti-N, Anti-S, Anti-S1, Anti-RBD and Anti-N Ig G for healthy v. lymphoid malignancy cohort The dotted line at 1.07 marks in an internally validated threshold to mark anti-S IgG response. The black bars denote median with 95% CI. The dotted line at 1.07 marks in an internally validated threshold to mark antibody response. The black bars denote median with 95% CI.
Conclusion. The vaccine-induced immune response was poor among treatment-experienced patients with lymphoid malignancies, especially among those who received CD20 therapies within 12 months. S396 • OFID 2021:8 (Suppl 1) • Abstracts  Background. Hospitalizations are an opportunity to increase vaccine uptake and hospital-based strategies have been effective at increasing influenza and pneumococcal vaccination. Offering COVID-19 vaccination at discharge can reduce barriers to vaccination and target patients at high risk for severe illness and death. We evaluated a COVID-19 vaccine intervention implemented as part of routine discharge planning.

An Intervention to Improve COVID-19 Vaccination Rates Among Inpatients at a Veterans Affairs Hospital
Methods. We trained healthcare personnel during April 2021 to review and document vaccine eligibility and interest for adult inpatients on medical, surgical, or psychiatric wards at the Atlanta VA Medical Center during discharge planning using a templated note in the electronic medical record (EMR). Outpatient vaccination center personnel were deployed to the participating wards daily (except Sundays) to facilitate vaccine administration at discharge. We measured the percentage of discharged patients with vaccine eligibility documented using the template and compared the number of patients vaccinated at discharge in the 4 weeks pre-and post-training. All Georgia adults became eligible for COVID-19 vaccines on March 25, 2021, prior to our intervention.
Results. Of the 769 patients discharged from one of the participating wards during the 4-week post-training, 474 (62%) had vaccine eligibility documented (Table 1). Of the 474 patients with documentation, 88 (19%) were eligible. Reasons for ineligibility included prior vaccination (n=266, 69%), patient refusal (n=103, 27%), and acute COVID infection (n=12, 3%). Of the 88 eligible patients, 61 (69%) received vaccination before discharge. In total, 16 of 793 inpatients in the pre-training period and 61 of 769 in the post-training period (2% vs 8%; p< 0.05) were vaccinated prior to discharge. Table 1. COVID-19 vaccine eligibility and vaccination before discharge during the post-training period, reported by week Conclusion. We found relatively high and sustained uptake of an intervention to screen hospitalized patients for COVID-19 vaccination eligibility. Creating a templated note in the EMR resulted in vaccination of nearly 70% of eligible patients prior to hospital discharge. Background. Well-regulated clinical trials have shown authorized COVID-19 vaccines to be immunogenic and highly efficacious. Information about antibody responses after vaccination in real-world settings is needed.

Disclosures. All Authors
Methods. We evaluated seroconversion rates in adults reporting ≥ 1 dose of an authorized COVID-19 vaccine in a U.S. multistate longitudinal cohort study, the COVID-19 Community Research Partnership. Participants were recruited through 12 participating healthcare systems and community outreach. Participants had periodic home-based serologic testing using either a SARS-CoV-2 nucleocapsid and spike IgM/IgG lateral flow assay (63% of participants) or a SARS-CoV-2 spike IgG enzyme-linked immunosorbent assay (37% of participants). The timing and number of tests before and after vaccination varied based on participant time in study. Participants were included if they were seronegative on the last test before and had >1 test result after vaccination (some had previously been seropositive, but seroreverted). A weighted Cox regression model with right censoring was used to obtain adjusted hazard ratios for sex, age, race/ethnicity, and prior seropositivity. Time-to-event (seroconversion) was defined as time to first positive test > 4 days after vaccination; participants were censored at the date of their last available test result.
Results. 13,459 participants were included and 11,722 seroconverted (Table). Median time in study was 272 days (range 31-395). Median follow-up time from vaccine to last available test was 56 days (range 1-147). Participants had a median of 3 tests (range 1-12) before and 2 tests (range 1-8) after vaccination. Based on the Kaplan-Meier method, median time to seroconversion after first COVID-19 vaccination was 35 days (interquartile range: 25-45). Likelihood of seroconversion decreased with older age (Table). Female participants, non-Hispanic Black participants, and participants who were previously seropositive were more likely to seroconvert (Table).