Immunosuppression and immunomodulation are valuable therapeutic approaches for managing neuroimmunological diseases. In times of the Coronavirus disease 2019 (COVID-19) pandemic, clinicians must deal with the question of whether immunotherapy should currently be initiated or discontinued in neurological patients. Uncertainty exists especially because different national medical associations publish different recommendations on the extent to which immunotherapies must be continued, monitored, or possibly switched during the current pandemic.
Based on the most recently available data both about the novel coronavirus and the approved immunotherapies for neurological diseases, we provide an updated overview that includes current treatment strategies and the associated COVID-19 risk, but also the potential of immunotherapies to treat COVID-19.
Outstanding questions and concluding remarks
In general, immunotherapies are a mainstay in the management of neuroimmunological diseases, while it is still unclear whether and how they increase the risk of COVID-19 and its complications. The risks of treatment cessation can be higher than the risk of a worsened COVID-19 disease course under ongoing immunotherapy. In this context, factors such as the local prevalence rate for COVID-19 might also play a role regarding future therapeutic decisions.
Moreover, the current lockdown in various countries around the world has led to limited availability of healthcare services. Future studies should therefore also investigate the relationship between such treatment delay and disease activity. In general, the potential long-term risk of infection must be considered in future treatment decisions. Hence, approved selective immunotherapies from other indications should also be investigated for their use in rare neuroinflammatory diseases. It is, therefore, appropriate to amend the off-label use regulations and, in particular, to consider immunological investigations. In this review, we have outlined several beneficial aspects of immunotherapies in COVID-19 cases: antiviral effects of IFN-ß, CsA, and teriflunomide; leukocyte sequestration by natalizumab or S1PR modulators; complement inhibition by eculizumab; as well as potential immunoregulatory effects in terms of a cytokine storm by IVIG or GCS. So far, however, the experience is limited to therapies that target IL-6. This is mainly explained by previous successful observations with tocilizumab in CRS, which seems to be a hallmark in severe COVID-19 cases [87,88]. The major challenge of the current and future COVID-19 studies investigating the above-mentioned therapies could be to determine the right time for starting and discontinuing treatment. Several biomarkers are available to identify the beginning of the host response phase and should be considered as regular inclusion criteria in clinical trials . The use of immunotherapies other than tocilizumab beyond clinical trials or without using a standardized definition for the inflammatory host phase should be avoided, as neither success nor failure will allow conclusions to be drawn.
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