(B) Scatter plot of SFCs/106 PBMC and time since last anti\CD20 treatment dose, with linear regression line including a 95% CI. cell responses against the SARS\CoV\2 Wuhan strain and the Delta variant. Results SARS\CoV\2\specific antibodies were found less frequently in patients (70% [57/82]) compared with controls (82/82 [100%], value of <0.05 was set as statistically significant. Results Patient Characteristics Eighty\two patients (median age 40?years [IQR?=?22], 72% women) and 82 age\ and sex\matched healthy controls were included (Table?S1). Patients were diagnosed with multiple sclerosis (n?=?64), followed by neuromyelitis optica spectrum disorders (n?=?7), myasthenic syndromes (n?=?7), autoimmune encephalitis (n?=?2), or chronic inflammatory demyelinating polyneuropathy (n?=?2). Among the patients, 82 were treated with rituximab (RTX; n?=?76) or ocrelizumab (OCR; n?=?6). Ten patients received comedication (azathioprine n?=?3, tocilizumab n?=?3, oral prednisone n?=?2, subcutaneous or intravenous immunoglobulins n?=?2, eculizumab n?=?1, or mycophenolate mofetil n?=?1). Timing and dosing of anti\CD20 treatment were performed according to the discretion of the treating physician. The median time between the last anti\CD20 infusion and the first vaccine dose was 6?months (IQR?=?5). The time between the last infusion and baseline was 0 to 6?months in 43 patients (52%), >6 to 12?months in 27 patients (33%), and >12?months in 12 patients (15%), respectively. Seventy one of 82 (87%) patients and all healthy controls received the BNT162b2 (Pfizer/BioNTech) vaccine, whereas 11 of 82 (13%) patients were vaccinated with the mRNA\1,273 (Moderna) vaccine. Humoral Response to SARS\CoV\2 Vaccination At baseline (V1), 3 patients and 1 healthy participant had detectable antibodies against the SARS\CoV\2 spike (S) RBD. After the first vaccination (V2), fewer patients on anti\CD20 therapy (28 of 82, 33%) generated an antibody response compared TPCA-1 with healthy controls (80 of 82, 98%, < 0.001). Furthermore, an inverse correlation was observed between SARS\CoV\2 T cell levels and the time interval from last anti\CD20 treatment to vaccination (=\0.28, Kendall's tau, < 0.05; see Fig ?Fig4B4B). Open in a separate windows Physique 4 Correlation between the time since last anti\CD20 treatment and vaccine responses. (A) Scatter plot of antibody levels to the RBD of the spike Mouse monoclonal to CD53.COC53 monoclonal reacts CD53, a 32-42 kDa molecule, which is expressed on thymocytes, T cells, B cells, NK cells, monocytes and granulocytes, but is not present on red blood cells, platelets and non-hematopoietic cells. CD53 cross-linking promotes activation of human B cells and rat macrophages, as well as signal transduction protein and time since last anti\CD20 treatment with linear regression line including a 95% CI. (B) Scatter plot of SFCs/106 PBMC and time since last anti\CD20 treatment dose, with linear regression line including a 95% CI. Participants are marked as follows: Rituximab, green; Ocrelizumab, blue; BNT162b2 vaccine, circle; mRNA\1,273 vaccine; triangle. CI = confidence TPCA-1 interval; SARS\CoV\2 = severe acute respiratory syndrome\coronavirus 2; PBMC = peripheral blood mononuclear cell; RBD = receptor\binding domain name; SFC = spot forming cell. [Color physique can be viewed at www.annalsofneurology.org] Adverse Events In patients, data on adverse events were systematically recorded until visit 3. Local and systemic reactions after the first and after the second vaccine dose included fever (7/79 [9%] and 21/78 [27%]), local reaction (60/79 [76%] and 64/78 [82%]), nausea (8/79 [10%] and 8/78 [10%]), shivering (6/79 [8%] and 13/78 [17%]), fatigue (27/79 [34%] and 34/78 [44%]), headache (13/79 [16%] and 32/78 TPCA-1 [41%]), sweating (5/79 [6%] and 13/78 [16%]), and myalgia (7/79 [9%] and 15/78 [19%]), respectively. Transient worsening of pre\existing neurologic symptoms was reported in 6 of 79 (8%) patients after the first vaccination and in 8 of 78 (10%) patients after the second vaccination. Two infections (bacterial respiratory tract infection and urinary tract contamination) and one serious adverse event (herpes zoster) occurred. Relapses requiring steroid therapy were reported in one patient after the first vaccination and in 2 patients after the second vaccination (Table?2). TABLE 2 Univariate Logistic Regression Model Assessing Seroconversion in Anti\CD20 Treated Patients
Age0.97 (0.94C1.00)0.0810.031Sex, female0.54 (0.16C1.59)0.2870.012Disease, multiple sclerosis0.85 (0.24C2.59)0.7780.001Disease duration, years0.99 (0.92C1.07)0.8030.001Months since anti\CD20 onset0.99 (0.97C1.00)0.1210.024Months since last anti\CD201.46 (1.20C1.86)0.0010.228Lymphocytes/mcl1.00 (1.00C1.00)0.5690.003 Open in a separate window CI?=?confidential interval; OR?=?odds ratio; R2?=?McFadden’s R squared. There were no significant differences of anti\SARS\CoV\2 antibody levels or T cell levels between patients with or without side effects (Table?3). Accordingly, univariate and multivariate logistic regression after adjusting for age, sex, and vaccine type did not show increased odds of side effects depending on antibody or T cell levels (Table?4). TABLE 3 Antibody and T Cell Levels in Patients TPCA-1 With or Without Side Effects After the Second Vaccine Dose (Wilcoxon Rank Sum.