ABSTRACT
Background: Data collected from several international platforms provided important information about risk factors, including treatment exposure, impacting COVID-19 severity in people with multiple sclerosis (PwMS). However, up to now, factors increasing the risk of getting SARS-CoV2 infection in PwMS are not known. MS registers represent a suitable tool to provide denominators for risks assessment. Objectives: To assess risk factors for SARS-CoV2 infection in PwMS by using data collected in the Italian MS Register (IMSR). Methods: A case-control (1-2) study was set-up. PwMS with (cases) and without (controls) COVID-19 were identified within the IMRS and propensity-score matched by the date of COVID-19 diagnosis (cases) and the date of last visit (controls) and for the region of residence. COVID-19 risk was estimated by multivariable logistic regression models including demographic and clinical covariates. The role of DMTs exposure was assessed in 3 different models including: last recorded DMT or DMT sequences (induction strategy/escalation strategy/only first line DMT exposure/ never treated) or last DMTs grouped according to the place of administration (at hospital or self-administered at home). A minimal treatment exposure for each DMT was defined on the basis of the recognized minimal time required to be potentially effective. Results: A total of 779 [median (IQR) age: 42.40 years (33.00- 50.80);30.17% male] confirmed COVID-19 cases were matched to 1558 controls [46.90 years (37.50-55.70);35.82% male]. In all models, comorbidities, female sex and age were significantly associated (p<0.02) to a higher risk of getting COVID-19. Patients receiving Natalizumab as last DMT (OR (95% CI): 2.38(1.66-3.42), p<0.0001) and those who underwent an escalation treatment strategy (1.57 (1.16-2.13), p=0.003) were at significant higher COVID-19 risk. Moreover, the group of PwMS receiving last DMTs requiring hospital access (1.65(1.34-2.04), p<0.0001) showed a significant higher risk than those taking selfadministered DMTs at home. Conclusions: This case-control study embedded in the IMSR showed that PwMS at higher COVID-19 risk are younger, more frequently female and with comorbidities. Long-lasting escalation approach and last therapies that expose patients to the hospital environment seem to increase significantly the risk SARS-CoV2 infection in PwMS.