Background: MS patients treated with monoclonal antibodies have an increased risk of infections. Natalizumab (NTZ) is a monoclonal antibody indicated in highly active Relapsing-Remitting MS. Management of MS patients treated with NTZ during the pandemic is a challenge to neurologist. Objectives: We aim to study the safety and management of MS patients on NTZ during the pandemic. Methods: Prospective study of MS patients on NTZ during COVID-19 pandemic considering risk of COVID19 infection, coming to the day hospital for the infusion, disease risk and risk of delaying or stopping treatment. We evaluate demographic features, time on NTZ and dose interval and COVID-19 infection and symptoms. RT-PCR COVID-19 tests from nasopharyngeal sample was performed before NTZ treatment. Results: We analyzed 68 patients treated with NTZ, 70% women and a mean age of 43 years, treated with NTZ for 67 months (range: 2 to 139). In 33% of patients NTZ treatment was changed from every 4 weeks to every 6w to decrease visits to the hospital. 41% of patients continued receiving NTZ every 4 weeks and 59% every 6w. From May 2020 to January 2021, 451 nasal swab PCR COVID-test were carried out 24-72 hours before NTZ infusion. Twelve patients showed a positive result and NTZ was not administered; test was repeated 1-2 weeks later with a negative result and NTZ was restarted. Overall, 17 patients had COVID19. During first wave (March-June 2020), 5 patients suffered from COVID19, 4 showed mild symptoms including fever, asthenia, cough and myalgias, and a 44 years old woman with persistent fever and multilobar pneumonia on CT solved with treatment. After implementing PCR COVID-test before NTZ we detected 9 asymptomatic patients with COVID19 infection and 3 symptomatic patients, a 32y woman with anosmia and ageusia, a 31y woman with cough and sore throat and a 48y man with fever, cough and dyspnea, that required hospitalization due to multilobar pneumonia and need of oxygen. The patient was treated with tocilizumab and was discharge in a week. There were no statistically significant differences in age, dose interval or treatment duration between patients with COVID19 and non-COVID19. Conclusions: No increased risk for severe illness from COVID-19 were detected in MS patients on natalizumab. In some cases NTZ was delayed 1-2 weeks due to COVID19 infection but was restarted with no complications or reactivation of COVID19. Most patients were asymptomatic, therefore PCR COVID-test before NTZ infusion could be useful in order to prevent widespread virus outbreak at infusion center.