ABSTRACT
Introduction: Chronic immunosuppression with anti-CD20 therapy can increase the risk of serious infections including complicated COVID19. Objectives and Aims: To evaluate the rates and predictors of serious infections in MS and NMOSD patients treated with anti- CD20 agents. Method(s): MS and NMOSD patients treated with ocrelizumab or rituximab at University Hospitals Cleveland Medical Center were evaluated. Patients hospitalized for any infection during their anti- CD20 therapy were identified and compared to those without infection-related hospitalizations. Significant differences were evaluated in a multivariate logistic regression model to identify predictors of serious infection. Result(s): There were 184 patients treated with anti-CD20 therapy (average age 48+/-13 years, 67% females, 84% MS). Of those, 21 (11%) patients had one or more serious infection during therapy including 16 MS patients treated with ocrelizumab and 5 NMOSD patients treated with rituximab. The most common serious infections were complicated COVID19 (9), bacterial skin infections (5), bacterial pneumonia (3), urosepsis (3), ocular infection (1), and disseminated shingles (1). Compared to those without serious infections, patients with serious infections had a higher average time on anti-CD20 therapy (1087.57+/-5 days vs 796.28+/-35 t= -2.61, P=0.005) and were more likely to have total lymphopenia (80% vs 40%;P=.004). There was a trend towards higher rates of hypogammaglobulinemia in patients with serious infections (24% vs 10%;P=.07). Logistic regression identified total lymphopenia (<1.0 x109/L) as an independent predictor of serious infection in patients treated with anti-CD20 therapy. Conclusion(s): Serious infections are rare in MS and NMOSD patients treated with anti-CD20 therapies. Those with serious infections were exposed to treatment longer and more frequently had lymphopenia and hypogammaglobulinemia. Total lymphopenia during therapy is an independent risk factor for serious infections.
ABSTRACT
Objective: We aim to determine the prevalence and clinical characteristics of iatrogenic CNS inflammation associated with vaccinations at a tertiary neuroimmunology clinic and compare the frequency of these events before and after the COVID-19 pandemic. Background: Various vaccines are implicated in rare demyelinating events. Although influenza is the most commonly-implicated vaccine, an increasing number of CNS inflammatory events are linked to SARS-CoV-2 vaccines. Design/Methods: We analyzed consecutive patients seen over 4 years (2017-2021) at a tertiary neuroimmunology clinic who were screened for iatrogenic CNS inflammation secondary to vaccinations. In patients with suspected iatrogenic events, the Naranjo Adverse Drug Reaction Probability Scale was used to score the probability of vaccine-related events as doubtful, possible, probable, or definite. Results: In total, 419 patients were seen over 4 years and were screened. Eleven cases were identified, and the total prevalence was 2.6% (82% female, average age 56+/- 18 years). Most events (10, 91%) were scored as probable. The following disease phenotypes were identified: multiple sclerosis relapse (6, 55%), optic neuritis (1, 9%), monophasic MOGAD (1, 9%), transverse myelitis relapse (1, 9%), seropositive NMOSD (1, 9%), and autoimmune encephalitis (1, 9%). The vaccines included influenza (n=4), SARS-CoV-2 mRNA (n=3), swine flu (n=1), and HPV (n=1). Two patients were exposed simultaneously to multiple vaccines (tetanus, MMR, and VZV;tetanus, hepatitis A, and meningococcal vaccines). Spontaneous resolution occurred in 36% of events, complete response to corticosteroids/immunotherapy in 46%, partial response in 9%, and unresponsiveness in 9%. Finally, 8 patients (73%) had relapsing disease and 3 patients (27%) had monophasic disease. Conclusions: Post-vaccination iatrogenic CNS inflammation is a rare but distinct neuroimmunological disease spectrum mostly involving spontaneous recovery or responsiveness to corticosteroids. We did not identify an excess of SARS-CoV-2 vaccine-related events. The rare occurrence and predominantly favorable prognosis suggest the benefit of vaccination outweighs the neurological risks, especially during the COVID-19 pandemic.
ABSTRACT
Objective: to compare different variables in MS patients with positive versus negative spike protein antibody following SARS-COV-2 vaccination Background: Many MS-related clinical, demographic, and immunological variables can potentially impact vaccine response and those variables have not been fully explored. Design/Methods: patients with MS and related neuroimmunological disorders who requested verification of the immune response to the SARS-COV-2 vaccine were tested for the spike protein antibody between January and September of 2021. We compared patients with positive versus negative spike protein antibody. Results: Forty patients (mean age 53+/-11, 77% females) were included. Twenty-two patients had positive post-vaccination spike protein antibody (55%) and 18 were negative (45%). Negative patients were more likely to have been on B-cell therapy (83% vs 32%, P=.001) while positive patients were more likely to have been on a fumarate (36% vs 5.5%, P=.02). There was no difference between the two groups in the utilization of S1P1 modulators or non-selective immunosuppressants, gender, age, race, disease phenotype, vaccine brand, and lymphocyte counts. Half the positive patients on fumarates had lymphopenia at the time of vaccination but none below 0.8×109 /L. Among patients on B-cell therapy, 32% had a positive humoral response and were more likely to have detectable CD19 cells at the time of vaccination compared to negative patients (P=0.04). There was no difference between the two subgroups in terms of vaccine timing relative to B-cell therapy dose or the presence of hypogammaglobinemia. None of the patients with or without humoral response had post-vaccination COVID19 infection. Conclusions: B-cell therapy is associated with negative humoral responses to SARS-COV-2 vaccines but patients with detectable CD19 counts are more likely to have a positive antibody. The fumarates are associated with positive humoral response even in the presence of mild lymphopenia. Both positive and negative humoral responses were equally seen in S1P1 modulator patients.