Association of Disease-Modifying Therapies with COVID-19 Susceptibility and Severity in Patients with Multiple Sclerosis: A Systematic Review and Network Meta-Analysis

  1. Mahdi Barzegar
  2. Shakiba Houshi
  3. Erfan Sadeghi
  4. Mozhgan Sadat Hashemi
  5. Ghasem Pishgahi
  6. Sara Bagherieh
  7. Alireza Afshari-Safavi
  8. Omid Mirmosayyeb
  9. Vahid Shaygannejad
  10. Aram Zabeti

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Abstract

Background. We conducted this study to assess the effect of disease-modifying therapies (DMTs) on coronavirus disease (COVID-19) susceptibility and severity in people with multiple sclerosis (MS). Methods. Available studies from PubMed, Scopus, EMBASE, Web of Science, and gray literature, including reference lists and conference abstracts, were searched from December 1, 2019, to July 26, 2021. We included cross-sectional, case-control, and cohort studies assessing the association of DMTs with risk of contracting COVID-19 or its outcomes in MS patients on univariate or multivariate regression analyses. We conducted a network meta-analysis (NMA) to compare the risk of COVID-19 and developing severe infection across DMTs. Results. Out of the initial 3893 records and 1883 conference abstracts, a total of 10 studies were included. Pairwise comparisons showed that none of the DMTs meaningfully affect the risk of acquiring infection. There was significant total heterogeneity and inconsistency across this NMA. In comparison with no DMT, dimethyl fumarate (0.62 (0.42, 0.93)), fingolimod (0.55 (0.32, 0.94)), natalizumab (0.50 (0.31, 0.81)), and interferon (0.42 (0.22, 0.79)) were associated with a decreased risk of severe COVID-19; but, rituximab was observed to increase the risk (1.94 (1.20, 3.12)). Compared to rituximab or ocrelizumab, all DMTs were associated with a decreased risk. Pairwise comparisons showed no differences across other DMTs. Interferon and rituximab were associated with the lowest and highest risks of severe COVID-19. Conclusion. Our study showed an increased risk of severe COVID-19 in patients on rituximab and ocrelizumab. No association with COVID-19 severity across other DMTs was observed.

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  1. Version published to 10.1155/2022/9388813
  2. ScreenIT

    SciScore for 10.1101/2021.06.11.21258765: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Information source and search strategy: We comprehensive searched electronic databases including PubMed, Scopus, EMBASE, and Web of Science from December 1, 2019, to April 12, 2021.
    PubMed
    suggested: (PubMed, RRID:SCR_004846)
    EMBASE
    suggested: (EMBASE, RRID:SCR_001650)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    More advanced disease-related functional limitations such as respiratory muscle weakness, impaired cough, and respiratory failure [39-41] can increase the risk of respiratory infections such as COVID-19 [42, 43]. It seems that disease duration and course of the disease are not independent risk factors for COVID-19 severity. The association of course and duration of MS could be related to age, MS severity, and presence of comorbidity. There is much less information about the effects of race and ethnicity on COVID-19 susceptibility and severity among MS patients. Previous studies have found disproportionality of COVID-19 cases among different races and ethnicity; however, the difference was not statistically significant [15, 16, 19, 24]. In the report from the North American registry, the Black or African American race was independently associated with adverse COVID-19 outcomes [7]. It has been proposed that the impact of race and ethnicity is relating to preexisting comorbidity, healthcare access, behavioral, and socioeconomic factors rather than genetic background [44-46]. Our findings suggest that obesity could be a driver of COVID-19 poor outcomes [5, 7, 27]. The results of COViMS and Covisep registries provided some evidence regarding the association of cardiovascular comorbid conditions and adverse disease prognosis [5, 7]. Moreover, COViMS results suggested that hypertension may be linked to an increased risk of death [7]. The possible mechanism underlying the associatio...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

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  3. Version published to 10.1101/2021.06.11.21258765v1 on medRxiv