Chances are that antibody response would have been generated after the 1st?and the 2nd?vaccine doses, 5?months after the prior infusion, despite re-treatment with ocrelizumab on day 9 post-vaccination (Fig.?1). dose 21?days later. There was a moderate post-vaccination systemic reaction with myalgias and fatigue. He received another ocrelizumab infusion 9?days after the second dose of the vaccine (Fig.?1). The decision to receive treatment on schedule was made considering his excellent therapeutic response to date with on-label use of ocrelizumab. On the day of infusion, he had complete depletion of CD19?+?and CD20?+?but Immunoglobulin G (IgG) level and Absolute Lymphocyte Count (ANC) were normal (Fig.?1). At the time of infusion he tested negative for antibodies to the SARS-CoV-2 nucleoplasmid antigen (Roche Elecsys Anti-SARS-CoV-2), an assay that interrogates for a humoral immune response to SARS-CoV-2 indicating prior infection [6]. This assay does 6-Quinoxalinecarboxylic acid, 2,3-bis(bromomethyl)- not reflect an immune response from the mRNA vaccines, directed against virus spike but not nucleocapsid protein. Open in a Rabbit Polyclonal to ZDHHC2 separate window Fig. 1 Timeline of patients ocrelizumab infusions, vaccination, SARS-CoV-2 test and laboratory results. Patient had serial SARS-CoV-2 PCR tests (negative) through the institutional research program. The red stars indicate negative SARS-CoV-2 PCR tests. Reference range for Anti-SARS-CoV-2 assay (nucleoplasmid)? ?1.00 COI, Anti-SARS-CoV-2 spike (S)? ?0.8 U/mL, WBC 4.00C10.00?K/uL, Lymphocytes 18.0C41.0%, ALC 0.72C4.10?K/uL, IgG 700C1,600?mg/dL, IgA 70C400?mg/dL, IgM 40C230?mg/dL, CD19 7.0C27.0% lymphocytes, CD20 3.0C20.0% lymphocytes 27?days after the second vaccine dose and 18?days after ocrelizumab infusion, the patient was tested using the Roche Elecsys Anti-SARS-CoV-2 S assay (Fig.?1). This assay is intended for qualitative and semiquantitative detection of antibodies to the SARS-CoV-2 spike (S) protein receptor-binding domain. It is designed to detect adaptive immune response indicating prior infection, and 6-Quinoxalinecarboxylic acid, 2,3-bis(bromomethyl)- to uniquely detect SARS-Cov-2 anti-S antibodies post mRNA vaccination [7]. Based on the manufacturers internal studies in healthy subjects and patients infected with SARS-CoV-2 (positive RT-PCR), the assay is highly specific with a negative predictive value (NPV) of 99.98, while its sensitivity increases from 90.6% 0C7?days after confirmed infection to 96.6%? ??=?15?days after positive RT-PCR [8]. The result of this spike antibody assay was negative in our patient indicating no measurable post-vaccination immunity (negative results? ?0.40 U/mL). Discussion To our knowledge, this is the first report of SARS-COV-2 vaccine response in a patient with multiple sclerosis on intravenous anti-CD20 therapy. There are cases of negative SARS-CoV-2 IgG assays in MS patients with PCR-confirmed COVID-19 infection on ocrelizumab [2C4]. A recent publication 6-Quinoxalinecarboxylic acid, 2,3-bis(bromomethyl)- of persistent anti-SARS-CoV-2 IgG antibodies following COVID19 infection in patient on ofatumumab, suggests a detectable humoral response to SARS-CoV-2 [9]. Another investigation indicates that binding titers to spike receptor-binding domain (RBD) protein as assessed on enzyme-linked immunosorbent assay (ELISA) are significantly increased on day 15 post initial 100-g dose of mRNA-1273 vaccination [10]. Further, unpublished internal validation studies in 24 healthy volunteers for Anti-SARS-CoV-2 S assay at our institution (Dr. Petr Jarolim) suggest positive anti-spike?serology?after the first dose of mRNA vaccine in all subjects, with some showing titers greater than 250 U/mL (analytical measurement range). The VELOCE trial in RRMS patients showed attenuated but present humoral responses following pneumococcal, influenza and tetanus toxoid vaccinations upon initiation of ocrelizumab [5]. Blunted immunity to hepatitis B vaccine has been observed in patients on rituximab [11, 12]. Ocrelizumab does not affect plasma cells directly and na? ve B-cells generally recover significantly faster than memory B-cells [12]. Our patient did not seroconvert when tested 27?days after the second dose of the Pfizer mRNA vaccine. It is likely that antibody response would have been generated after the 1st?and the 2nd?vaccine doses, 5?months after the.