This week saw several bits of information appear that has led me to change my position on several DMTs in terms of their risk for pwMS during the COVID-19 pandemic.
Firstly, the verbal update by Maria Pia-Sormani on the Italian cohort of patients with MS who had COVID-19. These figures were given during the iWiMS weekly COVID-19 &MS webinar. There are now 380 cases of pwMS and COVID-19 reported in the Italian register with only 5 deaths. The mortality rates are well below that of the general population and suggest that pwMS are not at increased risk of severe COVID-19. This is good news. This data also supports the hypothesis that mild-to-moderate immunosuppression may be good and in fact, reduce the chances of pwMS getting severe COVID-19. This is not surprising as severe COVID-19 is almost certainly immune-mediated disorder. The five patients that died (see table below) tended to be older, have more advanced disease and comorbidities.
It is now clear that SARS-CoV-2 is neurotropic with the second, but first published, case of meningoencephalitis with virus detectable in the spinal fluid. This now increases the risk of natalizumab for pwMS. You don’t want to be on natalizumab if SARS-CoV-2 disseminates to the CNS. It is very important that if you are on natalizumab and get COVID-19 that you look-out for CNS symptoms. The fact that most MS centres have shifted their patients onto EID (extended interval dosing) will reduce this risk but it remains concerning. For more information on how EID reduces this risk please see my explanation on MS-Selfie.
At a personal level I have now 6 patients with MS on various DMTs who have all come through having had COVID-19 without any problems. I have asked them to register themselves on the MS register study and I will be reporting them next week.
I would urge you to watch the weekly iWiMS webinar which will keep the MS community up-to-date with what is happening in relation to COVID-19 and MS.
I therefore updated my table and have added a ranking to reflect the changing advice. Please note I have downgraded the risk associated with anti-CD20 therapies based on the emerging evidence as well. More on this later.
Moriguchi et al. A First Case of Meningitis/Encephalitis Associated With SARS-Coronavirus-2. Int J Infect Dis 2020 Apr 3 PMID: 32251791
Novel coronavirus (SARS-Coronavirus-2:SARS-CoV-2) which emerged in Wuhan, China, has spread to multiple countries rapidly. We report the first case of meningitis associated with SARS-CoV-2 who was brought in by ambulance due to a convulsion accompanied by unconsciousness. He had never been to any foreign countries. He felt generalized fatigue and fever (day 1). He saw doctors nearby twice (day2 and 5) and was prescribed Laninamivir and antipyretic agents, His family visited his home and found that he was unconsciousness and lying on the floor in his vomit. He was immediately transported to this hospital by ambulance (day 9). Under emergency transport, he had transient generalized seizures that lasted about a minute. He had obvious neck stiffness. The specific SARS-CoV-2 RNA was not detected in the nasopharyngeal swab but was detected in a CSF. Anti- HSV 1 and varicella-zoster IgM antibodies were not detected in serum samples. A brain MRI showed hyperintensity along the wall of right lateral ventricle and hyperintense signal changes in the right mesial temporal lobe and hippocampus, suggesting the possibility of SARS-CoV-2 meningitis. This case warns the physicians of patients who have CNS symptoms.
CoI: multiple
You say you have 6 patients with MS who have had Covid 19. Did they manage to get a test? If not, are they self reporting that they had Covid 19? If the latter, how can you be sure it is Covid 19 and not a bad cold? I only ask because I suspect I may have had mild Covid 19 ( very mild cough for 4 days in the evening with a strange feeling that someone was sitting on my chest. No fever.). However, unless I get an antibody test I will never know.
If they are hospitalised people get tests, if they are not they probably won’t. I guess we have to wait. Yes antibody testing is the problem with not having an antibody test and this is why it is terribly frustrating to be sat at home, doing nothing when we have a quantitative test designed, and planned but we are being shut out because of “Health and safety” and a view that only big pharma can do this….I wouldn’t really care, but we maybe could have an option in 2 weeks and test outselves for version 1 all being well or 4-6 weeks for the prototype….Aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaargh!!!!!!
Thank you for the update. What do you suggest those of us on Natalizumab do when the matter remains ‘concerning’ despite EID, which as you say, most of us have been moved to? Do we try and get a change of therapy? What are we looking out for as regards concerning symptoms? Most of us are not being monitored at the moment in the usual way at the moment. Thank you.
I have separated natalizumab into SID (intermediate-risk) and EID (low-risk); I would recommend all pwMS on natalizumab switch to EID.
We know that EID reduces the risk of PML, by over 90% and I suspect this will be the same for clearing SARS-CoV2 from the CNS.
Does the SID risk drop in the f6-weeks after changing to EID (i.e. week 5) or does the it take longer?
F6 = first 6 weeks after shifting from SID to EID
Can you link to the MS register you mention?
Yes. I will report my cases via the register.
I have had relatively stable spms for over 10 years and am on no disease modifying therapies, nor have I been for circa 20 years (55yo male). Is the immune system of PWMS like me likely to affect the course of CoVid-19 any differently from the general population? Thanks
What’s your secret for retaining stability?
I honestly don’t have one. I am progressing but very slowly.
All things in moderation and enjoy the good things in life!
“What’s your secret for retaining stability?”
In my case..5 years of steady worsening spms and still getting lesions so I had hsct after 30 years of ms ..edss improved..enough said.
No not that we are aware of; this is another message that is implied by the Italian data that pwMS don’t appear to be more susceptible to COVID-19. Let’s wait for the data to be published. I suspect it will be out next week.
I am 6 years diagnosed woth HARRMS, 2.5 years post round two of alemtuzumab (which was my fourth DMD, previously i had been on on glatiramer acetate, then dimethyl fumarate, then natalizumab, they all failed to control my MS). My neurologist is recommending changing to ocrelizumab. I’ve to start this in the next couple of months, she definitely didn’t want to do a third round of lemtrada. I had been considering HSCT but that’s absolutely off the agenda now. Don’t know a huge amount about ocrelizumab, can it keep highly active MS under control? Alemtuzumab had slowed my galloping MS down but it cost me my thyroid. Always worried about having more disabling relapses!
“Don’t know a huge amount about ocrelizumab, can it keep highly active MS under control? ”
Ocrevus is a 23 year old drug..going back to rituximab origins in 1997..just given a new name 20 years later…What do you think..?..look at the chart..you tell us.?…
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5221476/
5-years after alemtuzumab with a lymphocyte count of 1.1 would I still be suppressed enough to potentially benefit were I to contract the virus?
Also have you been on the front line yet? I was surprised to see you posting again
Can you explain why certain therapies are listed more than once with different risk levels? I understand why natalizumab is listed, but it is unclear about the others.
Thank you so very much for your thoughtful, educational and perfectly transparent articles regarding COVID & MS. You’re helping my brain grow and understand all of ‘this’. You’re doing a fabulous job making the data fluent!
I am very interested in learning more about: “downgraded the risk associated with anti-CD20 therapies based on the emerging evidence as well”. I’m on Ocrevus, thus my interest in this (hopefully) upcoming topic.
Stay safe and well…..and thank you for your service….
I don’t understand. In that table it says At risk category. I am at Mavenclad week 4 year 2. So I am an intermediate risk of getting infected from covid19. Or is it my risk on severity of covid19 infection?
We don’t know if people on immunosuppression are at increased risk of COVID-19 or severe COVID-19. It looks like for severe COVID-19 the opposite may apply, i.e. immunosuppression helps reduce the risk of severe disease.
We do know that a large proportion of people who are infected with SARS-CoV-2, the virus that causes COVID-19, are asymptomatic. The question is does immunosuppression reduce the number of people who are asymptomatic? If it does then immunosuppression increases your chances of getting COVID-19.
In relation to being infected with SARS-CoV-2, pwMS are not at increased risk. What drives risks is your exposure to the virus, i.e. social contacts, travel, hygiene, etc. This is why the government is asking you to be sensible and to stay at home and self-isolate or shield if you are in the so-called vulnerable group.
Very interesting! It seems that the link to the table still goes to the version of 19 March?
Hello
What is the difference between standard and extended Tysabri treatments ? I go every 6 weeks for my shot.
6 weekly is EID
Yes thank you I just came across the article where it’s explained. My neurologist did this change of frequency a while ago so not covid related but to let people know : i personaly did not have any side effects from the frequency change. Hope its similar for other people, good luck to everyone and thank you for this great source of information!
good afternoon dear doctor, your comments are very interesting, you have any information on the use of glatiramer acetate in patients without MS but with Covid 19.
Why would you use it if you dont have MS….OK I forgot it is the aspirin of the twenty second centurary
I understand that glatiramer acetate is capable of stimulating the production of anti-inflammatory cytokines both peripherally and centrally, and as much has been said about the overproduction of pro-inflammatory cytokines in covid 19, that’s why I was asking .. . !! best regards
I understand that glatiramer acetate is capable of stimulating the production of anti-inflammatory cytokines both peripherally and centrally, and as much has been said about the overproduction of pro-inflammatory cytokines in covid 19, that’s why I was asking .. . !! best regards
yes it can do everything:-)
There is great anticipation for a COVID 19 vaccine. Should there be concern that if Ocrevus is started and a vaccine is developed, that person would not benefit from the vaccine. Is even a blunted response worth the risk with other options available?
by the time vaccine comes along ofatumumab will be approved
Would it not be a similar issue concerning a vaccine response. This is from their PI: “The safety of, and ability to generate a primary or anamnestic response to, immunisation with live attenuated or inactivated vaccines during treatment with ofatumumab has not been studied. The response to vaccination could be impaired when B-cells are depleted. Due to the risk of infection, administration of live attenuated vaccines should be avoided during and after treatment with ofatumumab, until B-cell counts are normalised. The risks and benefits of vaccinating patients during Arzerra therapy should be considered.”
They are too differnt issues surviving covid and making a vacine response for the fututre.
The response to a vaccine will be impaired if your B cells are depleted I have no doubt on that but can you make enough to be protected from re-infection.
My prediction is that once Arzerra comes around the reversibility will be appealing
With Fingolimod, would it be advisable to reduce the dose frequency (to alt day, or 5/week), if the absolute lymphocyte count is relatively low, 200-400?
I ask this in view of the possible risk of Covid-19 encephalitis with lymphocyte sequestration. I am nervous leaving people with an ALC of 200 on daily Fingolimod. Also, reducing the dose frequency will lessen the need for repeated testing. (Neurologist from SA)
Trying to find an updated version of your excel sheet (DMT + covid + vaccine), but the links on this page point to Error 404. Can you please help?
Not sure it has been updated…the ABN updated their view in November which coincides with ProfG getting run over