Determinants of COVID-19-related lethality in multiple sclerosis: a meta-regression of observational studies

Objective To identify risk factors for an increased lethality of COVID-19 in patients with multiple sclerosis (MS). Methods We searched scientific databases to identify cohort studies with the number of deaths in patients with MS. We fitted inverse-variance weighted meta-regressions with random-effects models to identify potential moderators (determinants) of COVID-19-related lethality (outcome). Results After an independent screening, 18 articles satisfied the eligibility criteria; all data were collected before anti-SARS-COV-2 vaccination was available. Out of 5,634 patients, 111 died, yielding a pooled death rate of 1.97% (95% confidence intervals 1.61-2.33). There was a substantial heterogeneity between the included studies (Q(17) = 66.9, p < 0.001; I-2 = 77.5%), but no relevant publication bias (p = 0.085). Higher lethality was observed in studies including older patients (beta = 0.80, p = 0.025) and in studies with higher proportions of patients with comorbidity (beta = 0.17, p = 0.046), progressive disease course (beta = 0.15, p = 0.027), and current treatment with anti-CD20 agents (beta = 0.18, p < 0.001). Otherwise, higher proportions of patients treated with interferon beta (beta = - 0.16, p < 0.001) and teriflunomide (beta = - 0.11, p = 0.035) were associated with lower lethality. These estimates did not change even in both multivariable meta-regressions including adjustment variables and leave-one-out sensitivity analyses. Conclusion Except for age and comorbidities, risk factors in common with the general population, we identified MS-specific determinants influencing the lethality of COVID-19. Our findings suggest the implementation of a risk mitigation plan for patients with progressive MS and for those treated with anti-CD20 agents.

Automated summary

This study aimed to identify risk factors for increased lethality of COVID-19 in patients with multiple sclerosis (MS). The results showed that, in addition to age and comorbidities shared with the general population, there were MS-specific factors influencing the lethality of COVID-19, such as progressive disease course and current treatment with anti-CD20 agents. These findings suggest the need for a risk mitigation plan for patients with progressive MS and those treated with anti-CD20 agents.