Breakthrough COVID-19 infection after vaccination in people with multiple sclerosis on disease modifying therapies in Latin America: data from RELACOEM registry

Introduction: In this study we aimed to monitor the risk of breakthrough COVID-19 infection in pwMS on different Disease Modifying Therapies (DMT) included in RELACOEM, a LATAM registry of MS and NMOSD patients infected with and vaccinated against COVID-19. Method(s): retrospective cohort study conducted between May 2021 and December 2021. The primary outcome was the appearance of infection during the follow-up time (at least three months after complete vaccination (second dose)). Specific information was requested (vaccine received, dose, date, symptoms, COVID- 19 infection, need for hospitalization, ventilatory assistance, treatment, and evolution). The primary objective of the analysis was to compare the incidence of breakthrough SARS-CoV-2 infections among the vaccinated pwMS in each DMT group. These conditions entail a PCR-confirmed test, and a time lag of at least 14 days from a full vaccination cycle (after the second vaccination dose). Cumulative incidence was reported by Kaplan Meier survival curves as well as incidence density. Result(s): A total of 857 pwMS patients from eight countries in LATAM were included. Mean age was 44.3 +/-12 years. The most frequent treatment used was fingolimod in 171 (19.9%). Most frequent first and second dose received was Astra-Zeneca (33%). During follow-up, a total of 28 COVID-19 cases were observed for a total exposure time of 150.965 days. The overall cumulative incidence was 3.2% (SE 0.22%) with an overall incidence density (ID) of 1.8 x 10.000 patients/day (95%CI 0.2-3.2). Compared to other DMTs, the incidence rate of breakthrough infections was significantly higher on ocrelizumab (6.02 (95%CI=5.65-7.16, RR=5.17 95%CI 3.27-7.12) and rituximab (6.94 (95%CI=6.15-9.12, RR= 5.93 95%CI 3.55-7.32) compared with other DMTs. No significant differences in the risk of breakthrough were observed for vaccine subtypes. Conclusion(s): An increased risk of breakthrough COVID-19 infections was observed in patients treated with ocrelizumab and rituximab.

Longitudinal humoral immune response against COVID-19 adenovirus-based vaccines in patients with multiple sclerosis from Argentina undergoing immunosuppressive treatment

Introduction: Most reports related to humoral immune response to COVID 19 vaccines in people with Multiple Sclerosis (pwMS) were performed on mRNA-based vaccines. Objective(s): to analyze the longitudinal humoral immune responses to adenovirus-based vaccines (Sputnik V and AZD1222) in pwMS under different diseases modifying therapies (DMTs) Methods: IgG anti- SARS-COV-2 spike titers in a cohort of 101 pwMS and 28 healthy controls (HC) were measured 6 weeks after vaccination using the COVID-AR kit according to the manufacture instructions. Both patients and controls received two or three doses of Sputnik, AZD1222 or a mixed schedule (MS) of both vaccines. The neutralizing capacity was evaluated by measuring antibody neutralizing titers using SARS COV-2 pseudotyped particles. Result(s): 60.5% of pwMS were female, mean EDSS: 2.49 +/-1.5, age: 36.6 +/-10.7, disease duration 7.6 +/- 5.1 years. DMTs: 45 pwMS were under fingolimod, 23 under dimethyl fumarate, 14 under cladribine and 19 under antiCD20 monoclonal antibodies. Vaccines: 35.7% Sputnik V, 51.9% AZD1222 and 12.4 % MS. No antibody response to a 2nd dose was found in 41.3% of pwMS under fingolimod and 73.6% under antiCD20. We found a correlation between lower lymphocyte count and lower antibody titers in pwMS under fingolimod (r: 0.67, 95% CI: 0.46-0.81, p=<=0.0001). A correlation was also found between the antibody titer and the last dose of antiCD20 (r: 0.49, 95% CI: 0.03-0.7, p=0.03). In March 2022, 57 pwMS received their 3nddose, 6 patients under fingolimod and 7 under antiCD20 remained without any antibody response. We did not find differences in the neutralization capacity with different DMT and or vaccines. Multivariate regression analysis showed antiCD20 (beta= -,349, 95% CI: -3655.6-369.01, p=0.017) and fingolimod (beta=-,399, 95% CI: -3363.8-250.9, p=0.023) treatments as independent factor associated with low antibody response (r2 adjusted=0.157). Conclusion(s): This is the first report of longitudinal humoral immune response of patients under adenovirus-based vaccines, specially Sputnik V, that demonstrate that these vaccines have similar results to those obtained with mRNA-based vaccines.

Impact of the coronavirus SARS COV-2 (COVID19) pandemic on the quality of life and mood of patients with multiple sclerosis

Introduction: Multiple Sclerosis (MS) is a disabling chronic disease with clinical heterogeneity and uncertain prognosis. Evaluating the health-related quality of life (HRQoL) of patients is important for the multidisciplinary therapeutic approach including physical, psychic and social aspects that influence the wellbeing of people with consequences in the course of the disease. As of March 2020 due to the Coronavirus 2019 (COVID-19) pandemic and quarantine measures, habits and access to the health system have been substantially modified. Objective(s): Our aim was to evaluate depression level and HRQoL of MS patients and compare this results with pre-pandemic assessment (2019). Patients and Methods: A cross-sectional study was conducted between March and July 2021. Measuring instruments: Clinical, HRQoL: Multiple Sclerosis International Quality of Life questionnaire (MusiQol), Depression: Beck Depression Inventory II (BDI-II), and pandemic-related aspects using a ad-hoc questionnaire. The results of MusiQol and BDI-II were compared with those obtained from the 2019 evaluations. Parametric and nonparametric statistics were used, to define significance a value of p <0.05 was accepted. Result(s): We evaluated 62 patients. In the comparative analysis with 2019, a significant decrease in HRQoL was observed (z=- 2.21, p=0.03). The affected domains were activities of daily living, psychological well-being, and sexual and sentimental life. In contrast, no significant changes were observed in the assessment of depression using BDI-II (z=-0.39, p=0.69). Conclusion(s): HrQoL of MS patients is decreased compared to 2019. The pandemic itself, health and quarantine measures have negatively impacted on HRQoL, substantially impairing patients' performance in activities of daily living, psychological wellbeing, and sexual and sentimental life.

Breakthrough COVID-19 infection after vaccination in patients with NMOSD in Latin America: data from RELACOEM registry

Objective: The objective of the study was to evaluate the incidence of COVID-19 infections after vaccination in NMOSD patients included in RELACOEM, a LATAM registry of MS and NMOSD patients infected and vaccinated for COVID-19. Method(s): Retrospective cohort study developed between May 2021 to December 2021. The primary outcome was the appearance of infection during the follow up time (at least three months after complete vaccination (second dose)). Data was collected through the contact between the treating physician and the patient. Specific information was requested (vaccine received, dose, date, symptoms, COVID-19 infection, need for hospitalization, ventilatory assistance, treatment, and evolution). The primary objective of the analysis was to compare the incidence of breakthrough SARS-CoV-2 19 infections among the vaccinated pwMS in each DMT group. These conditions entail a PCR-confirmed test, and a time lag of at least 14 days from a full vaccination cycle (after the second vaccination dose). Cumulative incidence was reported by Kaplan Meier survival curves as well as incidence density. Result(s): A total of 49 NMOSD patients from eight countries in LATAM were included. Mean age was 43.8 +/-13 years. The most frequent treatment use was rituximab in 29 (59.2%). The mean follow up after the second dose was 149 +/- 32 days. Most frequent first and second dose received was Pfizer (28.6%), followed by Sinopharm (24.5%). During follow up a total of 2 COVID-19 cases were observed for a total exposure time of 8627 days. Cumulative incidence was 4.1% (SE 0.87%) with an overall incidence density of 2.31 x 10.000 patients/day (95%CI 1.13-3.71). Both cases occurred in patients under rituximab (2/29, exposure time 4208, IR 4.7 x 10,000 patients/day 95%CI 3.5-5.1). No hospitalizations were reported for both cases. Conclusion(s): We observed an ID of COVID-19 infection after vaccination of 2.31 x 10.000 patients/day in NMOSD patients.

Impact of the coronavirus SARS COV-2 (COVID19) pandemic on the quality of life and mood of patients with multiple sclerosis

Objective: Our objective was to assess the level of depression and HRQoL of MS patients and compare it with the 2019 pre-pandemic assessment. Background: Multiple Sclerosis (MS) is a disabling chronic disease with clinical heterogeneity and uncertain prognosis. Evaluating the health-related quality of life (HRQoL) of patients is important for the multidisciplinary therapeutic approach including physical, psychic and social aspects that influence the well-being of people with consequences in the course of the disease. As of March 2020 due to the Coronavirus 2019 (COVID-19) pandemic and quarantine measures, habits and access to the health system have been substantially modified. Design/Methods: A cross-sectional study was conducted. A virtual survey assessed HRQoL with the “Multiple Sclerosis International Quality of Life questionnaire” (MusiQol), depression with the Beck Depression Inventory II (BDI-II), and pandemic-related aspects using a questionnaire designed for this study. The results of MusiQol and BDI-II were compared with those obtained from the 2019 evaluations. Results: We evaluated 62 patients. In the comparative analysis with 2019, a significant decrease in HRQoL was observed (z=-2.21, p=0.03). The affected domains were activities of daily living, psychological well-being, and sexual and sentimental life. In contrast, no significant changes were observed in the assessment of depression using BDI-II (z=-0.39, p=0.69). Conclusions: HrQoL of MS patients is decreased compared to 2019. The pandemic itself, health and quarantine measures have negatively impacted HRQoL, substantially impairing patients' performance in activities of daily living, psychological well-being, and sexual and sentimental life.

Puede el COVID-19 exacerbar los síntomas de la esclerosis múltiple? análisis de una serie de casos

Introduction: Las inflamaciones periféricas pueden exacerbar lesiones pre-existentes en el Sistema Nervioso Central en contexto de enfermedades neurodegenerativas, incluyendo la Esclerosis Múltiple (EM). Objetives: Analizar el efecto de la infección por COVID-19 como generador de inflamación periférica en un grupo de pacientes con EM. Methods: Análisis retrospectivo de 400 historias clínicas de pacientes con EM de un centro de referencia. A los pacientes que presentaron COVID-19 se les realizó una encuesta sobre la presencia o ausencia de exacerbación de síntomas previos de EM durante la infección y hasta tres meses posterior a ella. Se incluyó: tipo de síntoma, duración y comienzo de la exacerbación, vacunación previa contra COVID-19 y severidad de la enfermedad. Además, se incluyó información clínica y demográfica de las historias clínicas. Se realizó un análisis descriptivo e inferencial utilizando el GraphPad Prism V6. Results: 41 pacientes fueron incluidos, 58,5% fueron mujeres y la edad promedio fue de 42.9 ± 11.3. 90,2% presentaban la forma remitente-recurrente (EMRR), el promedio de años de evolución de EM fue de 9.6 ± 6.60 y el EDSS promedio fue de 2.4 ± 2.1. 25 pacientes (61%) tuvieron exacerbaciones de EM, 9,7% (n=4) presentaron síntomas compatibles con recaídas y 7,3% (n=3) requirieron corticoides. Encontramos diferencias significativas en el EDSS entre los pacientes que exacerbaron sus síntomas de EM y los que no (p=0,03). Al efectuar un análisis de regresión multivariada encontramos que el EDSS se asoció de forma independiente a la presencia de exacerbaciones de la EM en contexto de infección por SARS CoV2 (OR= 2.44, p =0.022). Conclusions: Este estudio preliminar sugiere que la infección por COVID-19 podría desencadenar exacerbaciones de síntomas de la EM. Se necesitan nuevos estudios que diluciden la relación entre COVID-19 y EM.

Safety of COVID-19 vaccines in patients with multiple sclerosis from Latin America

Introduction: Patients with MS (pwMS) are currently receiving different COVID-19 vaccines in several Latin American countries. However, questions arise around the safety of these vaccines and whether vaccination might increase the risk of relapse activity. Therefore, we aimed to assess the safety and occurrence of relapses following COVID-19 vaccination in Latin American pwMS. Methods: A web-based survey was completed by 207 pwMS from Latin America to assess for adverse events associated with COVID-19 vaccination between February 1 and April 30, 2021. Results: All participants received the first dose and 84 the second. The different vaccines administered were: inactivated virus vaccines [(IVV);CoronaVac, BBIBP-CorV) ] in 117 (56.5%) patients, adenovirus vector vaccines [(AdV);Gam-COVID-Vac, AZD1222] in 53 (25.6%) and mRNA vaccines (BNT162b2) in 37 (17.9%). The mean follow-up after vaccination was 24 ± 16 days. Three (1.4%) patients reported having COVID-19 infection after vaccination (all occurring after the first dose). Any adverse events were reported in 61 (29.5%) and 23 (27.4%) individuals after the first and second doses respectively. These included pain at the injection site, headache, fever, flu-like symptoms, fatigue, and muscle or joint pain. A lower frequency of adverse events was found with IVV (x?=7.2, p=0.03). Four (1.9%) patients reported an MS relapse, all occurring after an IVV first dose. Mean time to relapse: 18 ± 13 days. None of these patients had stopped or postponed their MS treatment before vaccination. Conclusion: COVID-19 vaccines seem to be safe for pwMS from Latin America. No major safety signals appeared in this patientreported study.