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Objective: To compare humoral and cellular responses to COVID-19 vaccines in 400 consecutive MS patients who were on Ocrelizumab ('OCR') and other disease-modifying therapies ('nonOCR') at the time of vaccination. Background: Peripheral B-cell depletion with anti-CD20 therapies, attenuates humoral responses to vaccines, but less is known about cellular responses. Design/Methods: Consecutive MS patients from NYU MS Care Center were invited to participate if they completed COVID-19 vaccination ≥6 weeks previously. Immune testing included anti-spike RBD antibody (Elecsys Anti-SARS-CoV-2) (Roche Diagnostics);multiepitope bead-based immunoassays (MBI) of antibody-responses to SARS-COV-2 spike proteins (threshold of 'positivity'was chosen as 2 SD below non-OCR mean);T-cell responses to SARSCoV-2 Spike protein using IFNγ enzyme-linked immune-absorbent spot (Invitrogen) and TruCulture (Myriad RBM) assays;high dimensional immunophenotyping;live virus immunofluorescence-based microneutralization assay. Results: Antibody and T cell data was available on 145/355 patients enrolled to date (mean age: 40.0 years;75% female;48% non-white;39% on OCR;12% with prior COVID-19 infection;vaccines: 58% Pfizer/BioNTech, 36% Moderna and 6% Johnson&Johnson;median vaccine-tosample time: 93 (+/-32) days). In OCR, Elecsys Anti-SARS-CoV-2 Ab titers were detected in 30/63 (48%;mean antibody titer in log scale: 1.63) and in non-OCR - in 78/81 (96%, mean Ab titer in log scale: 2.83;p<0.0001). In OCR, antibody response by MBI were detected in 41/57 (72%, mean level in log scale: 3.09) and in non OCR - in 68/72 (94%, mean level in log scale: 4.08;p<0.001). Neutralizing antibodies were detected in 10/42 (38%) of OCR and 24/43 (56%) of non-OCR (p=0.1). T-cell activation based on induced IFNg secretion (TruCulture) was observed in 50/64 (78%) OCR and 43/81 (53%) non-OCR (p=0.002). Conclusions: Preliminary results suggest robust vaccine-specific T-cell immune response to SARS-CoV2 vaccines in B-cell depleted patients, but markedly attenuated antibody responses. Final results of pre-planned multivariable analyses stratified by DMT class and high-dimensional immunophenotyping will be presented.
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[Figure: see text].
ABSTRACT
Objective: To compare humoral and T-cell responses to COVID- 19 vaccines in 400 MS patients who were on Ocrelizumab ('OCR') v. other disease-modifying therapies ('non-OCR') at the time of vaccination. Introduction: Peripheral B-cell depletion with anti-CD20 therapies attenuates humoral responses to vaccines. Whether immune responses to COVID-19 vaccines differ between B-cell depleted and non-B cell depleted MS patients is not known. Methods: Consecutive MS patients from NYU MS Care Center were invited to participate if they completed COVID-19 vaccination ≥6 weeks previously. Immune testing included anti-spike RBD antibody (Elecsys Anti-SARS-CoV-2) (Roche Diagnostics);multiplex bead-based immunoassays of antibody-responses to SARS-COV-2 spike proteins;T-cell responses to SARS-CoV-2 Spike protein using IFNγ enzyme-linked immune-absorbent spot (Invitrogen) and TruCulture (Myriad RBM) assays;high dimensional immunophenotyping;and live virus immunofluorescencebased microneutralization assay. Results: As of 7/15/2021, 105 MS subjects were enrolled (mean age: 40.5 years;76% female;41% non-white;38% on OCR;12% with prior COVID-19 infection). 95% were fully vaccinated with mRNA vaccines (Pfizer/Moderna);5% - with adenovirus-based vaccine (Johnson&Johnson). Median time from sample collection to last vaccine was 79 days. Positive Elecsys Anti-SARS-CoV-2 Ab titers post-vaccine were detected in 11/37 (30%) in OCR (mean level: 702 U/mL among seropositives) and 54/54 (100%) patients in non-OCR (mean level: 2310 U/mL;p<0.0001). Positive response by multiplex assay (threshold of 'positive' defined as 2 SD below the mean for the non-OCR) were detected in 10/27 (37%) OCR and 29/31 (94%) non-OCR (p<0.00001). T-cell activation based on induced IFNγ secretion (TruCulture) was detected in 20/25 (80%) OCR and 16/19 (84%) non-OCR patients (p=0.71). Conclusions: Preliminary results suggest robust T-cell immune response to SARS-CoV2 vaccines in approximately 80% of both OCR and non-OCR MS patients. Antibody responses were markedly attenuated in OCR compared to non-OCR group. Updated results will be presented.
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Importance Preventive interventions are needed to protect residents and staff of skilled nursing and assisted living facilities from COVID-19 during outbreaks in their facilities. Bamlanivimab, a neutralizing monoclonal antibody against SARS-CoV-2, may confer rapid protection from SARS-CoV-2 infection and COVID-19. Objective To determine the effect of bamlanivimab on the incidence of COVID-19 among residents and staff of skilled nursing and assisted living facilities. Design, Setting, and Participants Randomized, double-blind, single-dose, phase 3 trial that enrolled residents and staff of 74 skilled nursing and assisted living facilities in the United States with at least 1 confirmed SARS-CoV-2 index case. A total of 1175 participants enrolled in the study from August 2 to November 20, 2020. Database lock was triggered on January 13, 2021, when all participants reached study day 57. Interventions Participants were randomized to receive a single intravenous infusion of bamlanivimab, 4200 mg (n = 588), or placebo (n = 587). Main Outcomes and Measures The primary outcome was incidence of COVID-19, defined as the detection of SARS-CoV-2 by reverse transcriptase-polymerase chain reaction and mild or worse disease severity within 21 days of detection, within 8 weeks of randomization. Key secondary outcomes included incidence of moderate or worse COVID-19 severity and incidence of SARS-CoV-2 infection. Results The prevention population comprised a total of 966 participants (666 staff and 300 residents) who were negative at baseline for SARS-CoV-2 infection and serology (mean age, 53.0 [range, 18-104] years;722 [74.7%] women). Bamlanivimab significantly reduced the incidence of COVID-19 in the prevention population compared with placebo (8.5% vs 15.2%;odds ratio, 0.43 [95% CI, 0.28-0.68];P < .001;absolute risk difference, -6.6 [95% CI, -10.7 to -2.6] percentage points). Five deaths attributed to COVID-19 were reported by day 57;all occurred in the placebo group. Among 1175 participants who received study product (safety population), the rate of participants with adverse events was 20.1% in the bamlanivimab group and 18.9% in the placebo group. The most common adverse events were urinary tract infection (reported by 12 participants [2%] who received bamlanivimab and 14 [2.4%] who received placebo) and hypertension (reported by 7 participants [1.2%] who received bamlanivimab and 10 [1.7%] who received placebo). Conclusions and Relevance Among residents and staff in skilled nursing and assisted living facilities, treatment during August-November 2020 with bamlanivimab monotherapy reduced the incidence of COVID-19 infection. Further research is needed to assess preventive efficacy with current patterns of viral strains with combination monoclonal antibody therapy. This randomized clinical trial assesses the effect of a single intravenous infusion of bamlanivimab vs placebo on incidence of COVID-19 among residents and staff of skilled nursing and assisted living facilities. Question Among residents and staff of skilled nursing and assisted living facilities with high risk of SARS-CoV-2 exposure, what is the effect of bamlanivimab on the incidence of COVID-19? Findings This randomized phase 3 clinical trial included 966 participants who were residents and staff at US skilled nursing and assisted living facilities with at least 1 confirmed SARS-CoV-2 index case and who were negative at baseline for SARS-CoV-2 infection and serology, enrolled from August to November 2020. The incidence of COVID-19 infection among those treated with bamlanivimab vs placebo was 8.5% vs 15.2%, respectively, a difference that was statistically significant. Meaning Bamlanivimab monotherapy compared with placebo reduced the risk of COVID-19 in residents and staff of skilled nursing and assisted living facilities.