Covid-19 Guidance for Professionals

GUIDANCE FOR HEALTH PROFESSIONALS MANAGING NEUROMYELITIS OPTICA SPECTRUM DISORDER (NMOSD) IN RESPONSE TO THE THREAT OF WIDESPREAD COVID-19 INFECTION

Version 2 Date: 20/03/2020 Author: Katy Murray Disseminated for comments to: – Prof Jacqueline Palace and Dr. Maria Leite on behalf of UK NMOSD service – Dr Saif Huda on behalf of UK NMOSD service – ABN MS advisory group

Background There is considerable uncertainty about the impact of the coronavirus COVID-19 on the UK, and the situation is evolving on a daily basis. As of 13th March 2020, the UK has moved from the ‘containment’ to the ‘delay’ phase of the pandemic response. The Chief Medical Officer has estimated that the likely duration of an epidemic in the UK is 6 months. People with compromised immune systems, the elderly, and those with other comorbidities such as respiratory illnesses may be at risk of more severe symptoms with COVID-19. Most people with NMOSD are on immunosuppression. The additional absolute risk that these treatments pose is not known but the risks of stopping therapy, particularly for those with Aquaporin-4 (AQP4) antibodies is high.

Advice related to immunosuppression in NMOSD in individuals without symptoms of COVID-19 infection 1. People with NMOSD should not stop or alter their medication without discussion with their neurology team.

2. We recognise that aquaporin 4 positive NMOSD are particularly prone to relapses which may be severe. The prognosis of anti-MOG cases and seronegative cases is less clear.

3. Individuals taking azathioprine, mycophenolate mofetil, methotrexate +/- regular prednisolone [and a very small number of people taking anti-IL6 therapies] should continue to take their treatment as normal. Evidence is limited but these medications might increase the risk of COVID-19 infection and its complications.
However, in almost all cases this risk is outweighed by the benefits of the medication in reducing the chance of an NMOSD relapse.

4. Rituximab infusions moderately increase the risk of viral infections, so individuals may be more prone to COVID-19 and its complications. In most NMOSD patients this risk is outweighed by the effectiveness of rituximab in supressing relapses, and the treatment should continue as normal. If your centre has an established pathway for optimizing timing of rituximab infusions based on CD19+ [or CD19+ CD27+] monitoring, then this should be utilized. CD19 counts should be checked monthly from 6 months after previous rituximab infusion, delaying the next infusion until CD19 count is no longer supressed. In centres where CD19 monitoring is not readily available it may not be practical to burden the health service trying to set this up now. Instead, timing of rituximab infusions should be guided by individual patient’s risk factors for severe COVID-19 infection (age, comorbidities) versus risk of NMO relapse (previous relapse history, aquaporin 4 status) and also considering the capacity and infection risk associated with hospital attendance. Clinicians should be alert to the risk of hypogammaglobulinemia following rituximab therapy. Individuals with low immunoglobulins should be considered high risk for infection generally and we advise deferring further rituximab and involving clinical immunology colleagues, particularly related to supplementary iv immunoglobulin (although this will not be helpful for COVID-19 infection due to lack of herd immunity and hence lack of specific antibodies in current ivIg supplies).

5. Newly diagnosed NMOSD patients should be started on oral immunosuppression such as mycophenolate mofetil or azathioprine, and prednisolone, and maintained on this, ideally, until the COVID-19 epidemic is over.

6. NMOSD relapses are frequently severe and should be managed with high dose methyl prednisolone in the first instance. Those failing to respond to steroids should be considered for either plasma exchange or intravenous immunoglobulin treatment. Plasma exchange may transiently increase susceptibility to severe infection. Intravenous immunoglobulin is probably a safe option in those with concurrent COVID-19 infection.

Advice for people with NMOSD on immunosuppression who have COVID-19 1. In cases of NMOSD with severe COVID-19 infection [for instance requiring admission] we recommend considering pausing immunosuppression and covering with steroids or increasing their maintenance steroid dose [for instance prednisolone 20mg daily], to reduce NMOSD relapse risk. 2. Stopping immunosuppression is not generally necessary for individuals with NMOSD who are mildly affected by COVID-19.

Specialised advice for clinicians For advice on the more challenging situations, such as management of antibody-negative NMOSD, clinicians are encouraged to seek the advice of the two highly specialised NMO services: Oxford: NMO.Advice@ouh.nhs.uk Liverpool: nmo.advice@thewaltoncentre.nhs.uk For advice on Scottish NMOSD patients please contact nmo.advice@thewaltoncentre.nhs.uk and it will be dealt with or forwarded to the Scottish NMOSD neurology team.