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

Abstract

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 ( β = 0.80, p = 0.025) and in studies with higher proportions of patients with comorbidity ( β = 0.17, p = 0.046), progressive disease course ( β = 0.15, p = 0.027), and current treatment with anti-CD20 agents ( β = 0.18, p < 0.001). Otherwise, higher proportions of patients treated with interferon beta ( β = – 0.16, p < 0.001) and teriflunomide ( β = – 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. Supplementary Information The online version contains supplementary material available at 10.1007/s00415-021-10951-6.

Antisense modulation of IL7R splicing to control sIL7R expression in human CD4+T cells

“…These biological drugs are more efficacious in preventing MS relapses than previous generation of MS drugs, but this improved efficacy comes at the cost of higher adverse side effects largely due to enhanced immunosuppression. These adverse side effects have been particularly damaging during the COVID-19 pandemic; for example, ocrelizumab largely reduces the effectiveness of COVID-19 vaccines (Achiron et al, 2021; Tallantyre et al, 2022), and correlates with higher COVID-19 mortality among MS patients (Prosperini et al, 2022). Accordingly, there exists a need for non-immunosuppressive drugs that are safer for the patients, and we propose this could be achieved by tailoring new drugs to correct specific MS etiologies.…”

Neuro-Ophthalmic Implications of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Related Infection and Vaccination

“…In a cohort of 211 individuals with MS, the third dose of the BNT162b2 mRNA vaccine was associated with a transient increase of MS symptoms in 3.8% and a relapse in 3.3% 29 . Increased mortality and reduced efficacy of vaccination in MS are related to anti-CD20 therapies that reduce the B -cell count and can cause hypogammaglobulinemia 26,29 . The IRR for an acute demyelinating event is higher in the 28 days following 2 …”

“…25 There is an increased risk of death from SARS-CoV-2 infection in MS. 26 The main contributing factors are higher age, more severely affected individuals with MS, and treatment with CD20 immunosuppressive drugs. 26 Adjusting for these risk factors gives a pooled statistical mortality of 1.97% (95% CI: 1.61-2.33). 26 In individuals with MS, a relapse can be triggered by SARS-CoV-2 infection and vaccination.…”

SARS-CoV-2 and neurodegenerative diseases: what we know and what we don’t

“…Data on the clinical outcome of SARS-CoV-2 infections on patients with other neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), or Huntington Disease (HD) are yet limited and will require further studies in the course of the pandemic (De Marchi et al 2021 ; Musson et al 2022 ). Also, chronic neurological diseases such as multiple sclerosis with increased disability and a progressive course of disease have been associated with higher mortality rates (Prosperini et al 2022 ; Barzegar et al 2021 ).…”

“…Interestingly, C9orf72 repeat expansions of intermediate length, a mutation often found in cases of familial ALS and frontotemporal dementia (FTD), have been associated with severe COVID-19 requiring mechanical ventilation (Zanella et al 2021 ). Multiple sclerosis itself has not been associated with a severe course of disease, whereas increased disability and a progressive course of the disease, which is mainly mediated by neurodegenerative processes, have (Prosperini et al 2022 ; Barzegar et al 2021 ). Future prospective studies including all healthcare services may shed light on the actual risk of patients with neurodegenerative disorders.…”