Incidence and mortality of COVID-19 in Iranian multiple sclerosis patients treated with disease-modifying therapies

Abstract Background: Impaired immunity, in most cases, may render patients more vulnerable to infections and neutralize the effects of vaccines, raising great concerns regarding multiple sclerosis (MS) patients during the coronavirus disease 2019 (COVID-19) pandemic, considering that they are treated with immunosuppressive/immunomodulatory disease-modifying therapies (DMTs). Some studies, however, have suggested a beneficial protective role for these therapies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We aimed to investigate the incidence and mortality of COVID-19 in more than 25,000 MS patients in Iran, who were treated with different DMTs. Material and methods: We gathered relevant data pertaining to registered Iranian MS patients from major Iranian pharmaceutical companies, as well as MS societies from all provinces of Iran, who were treated with different DMTs. They were interviewed by nurses via telephone calls, and suspected/confirmed cases of COVID-19 were identified. Furthermore, regarding the deceased patients, it was determined whether or not their death was attributable to COVD-19, or whether they had any other comorbidities. Results: 25,436 treated MS patients (7,621 males; 30%, 17,815 females; 70%) were identified, with 144 of whom (0.57%) reported as confirmed cases of COVID-19 (45 males; 31.2%, 99 females; 68.8%). A total of 28 deaths (9 males; 32.1%, 19 females; 67.9%), among fingolimod- (one female), dimethyl fumarate- (one female), and rituximab-treated (8 males; 30.8%, 18 females; 69.2%) groups were identified. 21 (80.7%) out of 26 deceased rituximab-treated patients had progressive forms of MS, and 5 (19.2%) patients had other comorbidities. The lowest risk of COVID-19 was observed in the glatiramer acetate-treated patients. Furthermore, incidence of COVID-19 in dimethyl fumarate-treated patients was similar to that in the general population; thus, it was considered as the reference to calculate the relative risks for other DMTs. The relative risk was highest in rituximab-treated patients (5.56; 95% CI: 2.45-12.65), followed by natalizumab- (1.88; 95% CI: 0.42-8.39) and fingolimod-treated patients (1.87; 95% CI: 0.61-5.70). Conclusion: We observed that the risk of COVID-19 infection was higher among rituximab-, natalizumab-, and fingolimod-treated patients, with the highest risk among rituximab-treated patients. Although not all potential predisposing factors for severe COVID-19 were investigated, we advise clinicians to assess the risk profiles of each patient individually before initiating or continuing the application of the DMTs with higher potencies, during the COVID-19 pandemic. On the other hand, some DMTs (e.g., interferon-βs) may have protective effects. More controlled studies are needed to further evaluate the positive/negative effects of different DMTs in MS patients during the COVID-19 era.