T cell responses were largely independent of time from the last OCR infusion prior to infection, unlike humoral responses that tended to be weaker with shorter infusion\to\infection time. characteristics of patients with MS with laboratory confirmed COVID receiving OCR versus non\OCR by race/ethnicity. COVID?=?coronavirus disease; MS?=?multiple sclerosis; OCR?=?ocrelizumab. ANA-91-782-s004.docx (16K) GUID:?501A5ADE-A5E1-4932-BBE9-F834467C9092 Abstract 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); Oroxin B 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 IFN 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 (values <0.05 are shown in bold. Ab?=?antibody; COVID\19?=?coronavirus disease 2019; DMT?=?disease\modifying therapy; GA?=?glatiramer acetate; ID50?=?half\maximal inhibitory dilution; IgG?=?immunoglobulin; MBI?=?multiepitope bead\based immunoassay; Nabs?=?neutralizing antibodies; OCR?=?ocrelizumab; S1P?=?sphingosine 1\phosphate receptor modulators. Samples were available to measure functional neutralizing antibody (Nabs) titers in 77 patients with prior SARS\CoV\2 infection. Nab levels showed a strong correlation with anti\RBD antibody levels detected by MBI assay (values <0.05 are shown in bold. COVID\19?=?coronavirus disease 2019; DMT?=?disease\modifying therapy; GA?=?glatiramer acetate; MS?=?multiple sclerosis; NAT?=?natalizumab; OCR?=?ocrelizumab; S1P?=?sphingosine 1\phosphate receptor modulators. In patients with prior SARS\CoV\2 infection, there was Rabbit polyclonal to VDAC1 no trend for decreasing cellular responses (TruCulture IFN) with increasing time from infection neither in the entire cohort nor in OCR subset (data not shown). The multivariate analyses did not identify any predictors of TruCulture responses. In SARS\CoV\2 infected patients, the anti\Spike antibody by MBI and cellular IFN responses by TruCulture showed a moderate degree of correlation overall (r?=?0.53, p?<0.0001), and in both OCR (r?=?0.45, p?=?0.0002; Fig?S3A) and non\OCR (r?=?0.64, p?<0.0001; Fig?S3B) subsets. Relationship Between COVID\19 Infection Symptoms and Immune Responses to SARS\CoV\2 in Patients on OCR and Other DMTs In a multivariate model to predict MBI Spike levels based on DMT status and COVID\19 clinical variables (symptom duration, symptom number, and presence/absence of respiratory symptoms), only OCR treatment was a predictor for lower MBI Spike values. In a multivariate model to predict T\cell responses with TruCulture assay, longer COVID\19 symptom duration was associated with lower T\cell responses, but this relationship was driven by few outliers with long COVID and was not present if patients with symptoms that persisted for >1?month were excluded. In the 9 hospitalized patients, the mean anti\SARS\CoV\2 antibody values and T\cell responses were similar to the non\hospitalized group, except for TruCulture IFN responses that were higher in the hospitalized patients (data not shown). Discussion In an ethnically diverse group of 389 patients with MS from the New York Oroxin B University Multiple Sclerosis Care Center in New York City, 46% had laboratory evidence of prior SARS\CoV\2 infection. This prevalence is higher than what would be expected for our area based on the NYC Department of Health seroprevalence study from July 2021 (the end of our study period), 29 possibly due to over\representation in our Center of patients from Brooklyn, Queens, and Bronx neighborhoods with a very high incidence of prior SARS\CoV\2 infections (40C50%); use of highly sensitive multiplex bead\based immunoassays to measure seroprevalence; and the presumed greater motivation to participate in the study on the part of patients with suspected or known prior COVID\19. We confirmed COVID\19 diagnosis in 38% Oroxin B of patients with a history of COVID\19\like illness, but no commercial laboratory confirmation prior to enrollment, which is almost identical to the rate of SARS CoV\2 seropositivity among undocumented cases in a population\based study from New York City. 38 The rate of asymptomatic infection in our patients27%is lower than 33% rate in 2 large European studies, but higher than the 16% among World Trade Center responders in the New York City area. 39 Our results suggest that asymptomatic SARS CoV\2 infections are not uncommon among patients with MS and occur at a rate comparable to the general population. The high prevalence of SARS\CoV\2 infection in our patients with MS allowed us to investigate how the immune memory to SARS\CoV\2 varies depending on DMT status at the time of infection. Patients who developed.