Patients with autoimmune neurologic diseases: how is COVID-19 changing ongoing immunotherapies and the role of complement
Patients with autoimmune neuropathies, especially chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy, but also with other autoimmunities like myasthenia gravis, MS, and inflammatory myopathies, have been justifiably concerned as to whether their disease status adds an additional risk placing them into an immunosuppressed or immunocompromised category. There is no current evidence that any of the aforementioned autoimmune disorder itself makes them more susceptible to COVID-19, but some immunosuppressive or even immunomodulating therapies they are receiving may have this potential, although there are no validated data. Most autoimmune neuromuscular patients are maintained on steroids, mycophenolate, or azathioprine while most chronic inflammatory demyelinating polyneuropathy receive monthly IVIg. The same applies to patients with MS where it seems safe to start or continue treatment with the standard disease-modifying drugs. If clinically stable and not lymphopenic, there are no compelling or data-driven reasons to change anything in these patients and disturb clinical stability. For patients on monthly IVIg, there may be even a theoretical advantage that IVIg offers additional protection due to natural autoantibodies; if IVIg is not infused as home infusion, switching to self-administered subcutaneous IgG might be an option to diminish exposure, as has been proven effective.37 For patients on rituximab, the infusion intervals can be prolonged to more than 6 months because both B-cell reduction and clinical benefit can persist longer.38 New emerging data provide credence and reassurance regarding these issues, especially on immunomodulating drugs. In a large number of patients from Wuhan, published in this issue of the Journal,39 it was shown that altered immunity induced by disease-modifying drugs in patients with MS or neuromyelitis optica spectrum disorder appears insufficient to enhance susceptibility to COVID-19 infection. The results are important but not unexpected considering that most of these therapies target the adaptive immune response with little, if any, effect on suppressing the innate immunity that facilitates infection of macrophages and viral spread. Similar data from New York City area show that the incidence of hospitalization among patients with immune-mediated inflammatory diseases on therapy with steroids and biologic agents was consistent with that among patients with COVID-19 in the general population, concluding that ongoing use of biologics is not associated with worse COVID-19 outcomes.40 There is also new evidence suggesting possible beneficial effect of anticomplement therapies.41 Complement is an integral component of the innate immune response to viruses and an instigator of proinflammatory responses with evidence that activation of C3 exacerbates SARS-CoV–associated acute respiratory distress syndrome and C3-C5 complement deposits are abundant in the lung biopsies from patients with COVID-19.41 It was proposed that complement inhibition may alleviate the inflammatory complications of COVID-19 infection leading to ongoing trials with anti-C3 and anti-C5 agents.41,42 On this basis, eculizumab, an anti-C5 monoclonal antibody approved for neuromyelitis optica spectrum disorder and myasthenia gravis with some benefits in patients with GBS, may not be withheld, if indicated, as, like IVIg, may theoretically have added benefit.