Cellular and Humoral Immunity to SARS-CoV-2 Infection in Multiple Sclerosis Patients on Ocrelizumab and Other Disease-Modifying Therapies: A Multi-Ethnic Observational Study.

OBJECTIVE: The objective of this study was to determine the impact of multiple sclerosis (MS) disease-modifying therapies (DMTs) on the development of cellular and humoral immunity to severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection. METHODS: Patients with MS aged 18 to 60 years were evaluated for anti-nucleocapsid and anti-Spike receptor-binding domain (RBD) antibody with electro-chemiluminescence immunoassay; antibody responses to Spike protein, RBD, N-terminal domain with multiepitope bead-based immunoassays (MBI); live virus immunofluorescence-based microneutralization assay; T-cell responses to SARS-CoV-2 Spike using TruCulture enzyme-linked immunosorbent assay (ELISA); and IL-2 and IFNγ ELISpot assays. Assay results were compared by DMT class. Spearman correlation and multivariate analyses were performed to examine associations between immunologic responses and infection severity. RESULTS: Between January 6, 2021, and July 21, 2021, 389 patients with MS were recruited (mean age 40.3 years; 74% women; 62% non-White). Most common DMTs were ocrelizumab (OCR)-40%; natalizumab -17%, Sphingosine 1-phosphate receptor (S1P) modulators -12%; and 15% untreated. One hundred seventy-seven patients (46%) had laboratory evidence of SARS-CoV-2 infection; 130 had symptomatic infection, and 47 were asymptomatic. Antibody responses were markedly attenuated in OCR compared with other groups (p ≤0.0001). T-cell responses (IFNγ) were decreased in S1P (p = 0.03), increased in natalizumab (p <0.001), and similar in other DMTs, including OCR. Cellular and humoral responses were moderately correlated in both OCR (r = 0.45, p = 0.0002) and non-OCR (r = 0.64, p <0.0001). Immune responses did not differ by race/ethnicity. Coronavirus disease 2019 (COVID-19) clinical course was mostly non-severe and similar across DMTs; 7% (9/130) were hospitalized. INTERPRETATION: DMTs had differential effects on humoral and cellular immune responses to SARS-CoV-2 infection. Immune responses did not correlate with COVID-19 clinical severity in this relatively young and nondisabled group of patients with MS. ANN NEUROL 2022;91:782-795.

Hybrid and vaccine-induced immunity against SAR-CoV-2 in MS patients on different disease-modifying therapies.

OBJECTIVE: To compare "hybrid immunity" (prior COVID-19 infection plus vaccination) and post-vaccination immunity to SARS CoV-2 in MS patients on different disease-modifying therapies (DMTs) and to assess the impact of vaccine product and race/ethnicity on post-vaccination immune responses. METHODS: Consecutive MS patients from NYU MS Care Center (New York, NY), aged 18-60, who completed primary COVID-19 vaccination series ≥6 weeks previously were evaluated for SARS CoV-2-specific antibody responses with electro-chemiluminescence and multiepitope bead-based immunoassays and, in a subset, live virus immunofluorescence-based microneutralization assay. SARS CoV-2-specific cellular responses were assessed with cellular stimulation TruCulture IFNγ and IL-2 assay and, in a subset, with IFNγ and IL-2 ELISpot assays. Multivariate analyses examined associations between immunologic responses and prior COVID-19 infection while controlling for age, sex, DMT at vaccination, time-to-vaccine, and vaccine product. RESULTS: Between 6/01/2021 and 11/11/2021, 370 MS patients were recruited (mean age 40.6 years; 76% female; 53% non-White; 22% with prior infection; common DMT classes: ocrelizumab 40%; natalizumab 15%, sphingosine-1-phosphate receptor modulators 13%; and no DMT 8%). Vaccine-to-collection time was 18.7 (±7.7) weeks and 95% of patients received mRNA vaccines. In multivariate analyses, patients with laboratory-confirmed prior COVID-19 infection had significantly increased antibody and cellular post-vaccination responses compared to those without prior infection. Vaccine product and DMT class were independent predictors of antibody and cellular responses, while race/ethnicity was not. INTERPRETATION: Prior COVID-19 infection is associated with enhanced antibody and cellular post-vaccine responses independent of DMT class and vaccine type. There were no differences in immune responses across race/ethnic groups.

Challenges of conducting a remote behavioral weight loss study: Lessons learned and a practical guide.

OBJECTIVES: To describe challenges and lessons learned in conducting a remote behavioral weight loss trial. METHODS: The Personal Diet Study is an ongoing randomized clinical trial which aims to compare two mobile health (mHealth) weight loss approaches, standardized diet vs. personalized feedback, on glycemic response. Over a six-month period, participants attended dietitian-led group meetings via remote videoconferencing and were encouraged to self-monitor dietary intake using a smartphone app. Descriptive statistics were used to report adherence to counseling sessions and self-monitoring. Challenges were tracked during weekly project meetings. RESULTS: Challenges in connecting to and engaging in the videoconferencing sessions were noted. To address these issues, we provided a step-by-step user manual and video tutorials regarding use of WebEx, encouraged alternative means to join sessions, and sent reminder emails/texts about the WebEx sessions and asking participants to join sessions early. Self-monitoring app-related issue included inability to find specific foods in the app database. To overcome this, the study team incorporated commonly consumed foods as "favorites" in the app database, provided a manual and video tutorials regarding use of the app and checked the self-monitoring app dashboard weekly to identify nonadherent participants and intervened as appropriate. Among 135 participants included in the analysis, the median attendance rate for the 14 remote sessions was 85.7% (IQR: 64.3%-92.9%). CONCLUSIONS: Experience and lessons shared in this report may provide critical and timely guidance to other behavioral researchers and interventionists seeking to adapt behavioral counseling programs for remote delivery in the age of COVID-19.

Temporal Eating Patterns and Eating Windows among Adults with Overweight or Obesity.

We aim to describe temporal eating patterns in a population of adults with overweight or obesity. In this cross-sectional analysis, data were combined from two separate pilot studies during which participants entered the timing of all eating occasions (>0 kcals) for 10-14 days. Data were aggregated to determine total eating occasions, local time of the first and last eating occasions, eating window, eating midpoint, and within-person variability of eating patterns. Eating patterns were compared between sexes, as well as between weekday and weekends. Participants (n = 85) had a median age of 56 ± 19 years, were mostly female (>70%), white (56.5%), and had a BMI of 31.8 ± 8.0 kg/m2. The median eating window was 14 h 04 min [12 h 57 min-15 h 21 min], which was significantly shorter on the weekend compared to weekdays (p < 0.0001). Only 13.1% of participants had an eating window <12 h/d. Additionally, there was greater irregularity with the first eating occasion during the week when compared to the weekend (p = 0.0002). In conclusion, adults with overweight or obesity have prolonged eating windows (>14 h/d). Future trials should examine the contribution of a prolonged eating window on adiposity independent of energy intake.