#MSCOVID19: it’s over, but it is not

Barts-MS rose-tinted-odometer: ★★★★★

I have just completed the Virtual New York City Marathon in London and have clearly survived to tell the tale. Not only did I prove many doubters wrong, I even managed to surprise myself by dipping under the 3:20 mark (3:19:07 when I clocked 42.2km on my Garmin). It was only 3 years ago, due to chronic right hip pain, that I decided my running career was over. I interpreted the pain as being due to early osteoarthritis. Despite still having some hip pain it is so much better than it was. I suspect losing weight and exercising, or using the hip, has given it a new lease of life. This for me is one of the positives of COVID-19.; it has allowed many people like me to reassess their lives and to do different things. If COVID-19 hadn’t happened I would not have just completed a virtual marathon. My experience gives credence to the saying ‘use it or lose it’.

My motivation for doing the marathon was to raise money for Dr Ruth’s and Dr Kang’s COVID-19 antibody study. The reason ‘it is not over yet’ is that we have many miles to go before we reach our target of £25,000. The good news is that we very close to raising £10,000, which is the first funding milestone, which will allow us to actually start the process of recruiting pwMS and collecting their bloodspots on Guthrie cards for our antibody assay. 

Prof G after completing his NYC virtual marathon

I, therefore, want to take a moment and thank those of you who have been so generous and donated money to our study. Your support and encouragement are much appreciated. For those of you who have not donated yet please consider making a small contribution; every little bit helps and also demonstrates that this is not just our project, but a community project. 

The next phase of our fundraising will involve a series of topical webinars, but more on that later. At the moment we are discussing the logistics of how we can make this happen in a way that allows everyone to have a chance of attending the webinars. 

If you have other ideas for us to raise the money please let us know.  

CoI: multiple

Twitter: @gavinGiovannoni  Medium: @gavin_24211

#MSCOVID19: one microdonation at a time

Thank you for being such kind and generous supporters for our Barts-MS COVID-19 antibody study. It is clear that Prof G running the virtual NYC marathon this weekend, or next, depending on the weather, is not going to get us to the finish line. Therefore, we are going to take your advice and launch Barts-MS webinars. The webinar idea was suggested by one of you in the comments when we launched our fund-raising campaign.

There will be a limited number of places to watch these webinars, but to be allocated a ticket we are expecting viewer’s to make a microdonation towards our fundraising efforts so that Drs Ruth & Kang can start and complete our COVID-19 or coronavirus seroprevalence study.

At the end of the antibody study we should be able to answer some of the following questions:

  1. How many pwMS in the UK have antibodies to the SARS-CoV-2?
  2. What type of antibodies are they, i.e. IgM, IgG or IgA, what is the titre or level of these antibodies and are they neutralising? Neutralising means they inhibit coronavirus infection of cells in culture.
  3. How many pwMS seroconverted who had documented COVID-19, possible COVID-19 or no history of COVID-19?
  4. What is the seroconversion rate on different DMTs?
  5. We also hope to follow a group of pwMS longterm with repeat testing to see how long these antibodies last and to see how many seronegative pwMS convert to becoming seropositive with time.
  6. When a coronavirus vaccine or vaccines emerges we able to use the assay to see who makes an antibody response or not and hence we plan to compare different response rates on different DMTs.

The following are some suggestions for topics for the webinars:

  1. What are arguments for and against HSCT as a first-line treatment for MS?
  2. What is on the horizon for treatment of advanced MS?
  3. What will the management of MS look like in 2030?
  4. How can we make MS prevention a reality?
  5. What is smouldering MS and is it treatable?
  6. How are we managing MS during the COVID-19 pandemic?
  7. Will I be able to have a coronavirus vaccine when one arrives?
  8. Etc …..

These topics are not fixed in stone. If you have any suggestions let us know. Do you have any problems with us running these webinars? Would you be interested in attending? How do you feel about having to donate to attend the webinars?

For those of you interested the following is Prof G’s planned marathon route and if you want to make a micro-donation towards the study please click on the link below.

26.32 miles of bliss or hell

CoI: multiple

#MSCOVID19 running the talk

Barts-MS rose-tinted-odometer: ★★★★★

In anticipation of a second-lockdown at a meeting with colleagues last night I was asked the question about what positive experiences I could reflect on from the first lockdown. Firstly, no international travel and a focus on family, home life and the realisation that we can live more sustainably. Secondly, walking or running the talk. I decided to take my own prehabilitation advice seriously and I have managed to rehabilitate my physical and mental self and get my right hip working again. This is quite remarkable. Three years ago I had written off any future prospect of running long distance never mind a marathon. Six months into the pandemic and I am getting ready to try and complete a marathon in a months time.  Why? Funding and important time-sensitive research for people with multiple sclerosis. 

We have a problem with the current antibody tests for detecting past infection with coronavirus. The current assays are not sensitive enough and are not detecting antibodies in a large number of people with asymptomatic or mild infection and possibly in pwMS who are on certain immunosuppressive disease-modifying therapies, in particular the anti-CD20 treatments rituximab, ocrelizumab and ofatumumab. Detecting antibodies in these people is really important in that it would indicate that they have been exposed to the virus and therefore likely to have cellular immunity. 

In response to this challenge and  thanks to a grant from the Barts Charity, our group (Dr Kang and his team) have developed an ultrasensitive assay (GloBody) that will work on blood spots. Preliminary results show  that the assay is detecting antibodies in samples that have been called negative with commercial antibody assays. This is not unexpected because the assay was designed to have amplification steps to detect very low levels of antibodies. We did this because we want to study low-level antibody responses in pwMS on and off different DMTs.

This assay will now allow us to test a large number of pwMS using self-collected blood spots to see if they have been infected with coronavirus and are now immune. The tragedy is we have been promised a grant to do the initial part of this study by a charity. However, as donations have dried up this charity can’t afford to give us the money to cover the initial costs of the study. This is when I took up your suggestion to crowdfund. To show how serious I am about the crowdfunding I have decided to run the virtual New York City Marathon. All I have to do is record a single 42.2km run using the GPS-tracking application STRAVA sometime between the 18th October and 1st November. 

one run at a time.

In reality, I started my training very late and don’t really have the time to get truly marathon ready. However, as it is so important for us to raise the money so we can get this critical time-sensitive research done I am going to give it a go anyway. 

I would like to thank those of you who have already sponsored me. I would also like to urge you to donate to our cause. Even a small donation or £2-£5 would help. Microdonations all add-up. 

Thank you. 

CoI: multiple

Twitter: @gavinGiovannoni 

Medium: @gavin_24211

#MSCOVID19: Fundraising

Two months ago we floated the concept of doing a UK-wide seroprevalence study in UK residents with MS to see how many had seroconverted to become anti-SARS-CoV-2 antibody positive and to see if there are differences in seroconversion rates between people on different DMTs. 

The motivation was based on a prediction that people with MS on ocrelizumab would have lower titres of anti-SARS-CoV-2 antibody titres, be more likely to be seronegative despite a history of COVID-19 and less likely to have neutralizing anti-spike protein RBD (receptor binding domain) antibodies compared to patients on other DMTs.

It looks like we may be correct; some early case reports suggest pwMS on ocrelizumab may not seroconvert. 

In addition to the cross-sectional analysis, we proposed following the seronegative pwMS over time to study how the COVID-19 pandemic evolves and monitor the development of herd immunity. 

We have designed the study and in parallel, to applying for funding we got the study approved by our University and Ethics committee. We thought we had the funding approved, but at the last minute due to a funding crisis, our funder said no. We are now sitting with a dilemma; an approved study with no funding. So we are having to revert to plan B; crowdfunding

Forms response chart. Question title: Do you think it is worth doing a national COVID-19/coronavrius seroprevalence study?. Number of responses: 88 responses.

When we did our survey you all agreed that crowdfunding would be one potential solution to our funding crisis. However, we can’t simply ask you to donate money. We have to put our money where our mouths are. So I have decided to come out of marathon running retirement to raise money for this study that will be managed by Dr Ruth Dobson and Dr Angray Kang. 

I have signed up for the virtual New York City Marathon in the medal-winning category. My aim is to complete a 26.2-mile run in London between October 17 and November 1. I will be joining runners from around the globe to make this the world’s largest virtual marathon. The question is does my right hip have enough cartilage left in it for me to complete the run? 

In addition, to me attempting to complete a marathon with a failing hip I am gently prodding other members of Bart-MS to do something as well. I may have one taker already, but more on this later. 

Our objective is to raise £25,000 to cover the costs of posting out blood spots to study participants. As this study is time sensitive we need to raise the money ASAP.

If you want to help us raise the funds please do not hesitate to contact us. 

Barts-MS JustGiving Fund Raising Site

Prof G with his virtual New York City Marathon bib on. Does he have what it takes to complete 26.2 miles?

CoI: multiple

Exercise, exercise, exercise ….

If you live in London it is impossible not to have gotten caught up in London-Marathon fever over the weekend.

Eliud Kipchoge won the London marathon in the second fastest recorded time  (two hours two minutes 38 seconds). Interestingly, Kipchoge wears an electric blue band on his wrist, where four simple words are written: “No human is limited”. He has obviously not met someone with advanced MS who is disabled.

In the study below people with progressive MS used up to 2.81x times more energy on average, for simple mobility tasks, compared to control subjects. The progressive MSers in this study accumulated an oxygen deficit and experienced fatigue and exertion when repeating simple motor tasks such as rolling over in bed, moving from a lying to a sitting or a sitting to standing position, walking and climbing steps. Reasons for why MSers use more energy is complex but part of it is due to deconditioning, i.e. simply being unfit.

We don’t know how the brain perceives fatigue but a higher oxygen cost during physical activity is measured by the body and results in a greater perception of fatigue. The reason why Eliud Kipchoge can run mile after mile at a pace no man or woman has done before is that he is conditioned to do so and has trained his brain to not feel fatigue.

“The mind is what drives a human being, If you have that belief – pure belief in your heart – that you want to be successful then you can talk to your mind and your mind will control you to be successful. My mind is always free. My mind is flexible. That is why I wear this band on my wrist. I want to show the world that you can go beyond your thoughts, you can break more than you think you can break.” Eliud Kipchoge.

Lessons from elite marathon runners and the findings from this study suggest that rehabilitation interventions that increase endurance during physical tasks will help reduce fatigue in people with progressive MS. The question now is to get NHS resources allocated to setting-up a National exercise and training programme for MS-related fatigue and to get MSers to buy into the benefits of regular exercise no matter how disabled they are. I know this is easier said than done, but that is no excuse not to get it done; it needs to be done.

Please note, it is also not only about exercise, but how you live your life.

Kipchoge’s believes that “living simply sets you free”. For nearly 300 days a year, he lives and trains at a simple training centre in Kaptagat, a tiny village in the Kenyan highlands. He is known as the “boss man” by his training partners but that doesn’t stop him cleaning the toilets or doing his share of the daily chores. If you are interested in being inspired please watch ‘Breaking2’ a Nike sponsored project to see if the 2-hour barrier for the marathon could be broken. It is not that Kipchoge came so close to breaking the two-hour barrier, missing it by a mere 25 seconds, but his philosophy on how to live that is so inspiring. I am in awe!

Devasahayam et al. Oxygen cost during mobility tasks and its relationship to fatigue in progressive Multiple Sclerosis. Arch Phys Med Rehabil. 2019 Apr 23. pii: S0003-9993(19)30257-6.

OBJECTIVE: To compare the oxygen costs of mobility tasks between individuals with progressive MS using walking aids and matched controls and to determine whether oxygen cost predicted fatigue.

DESIGN: Cross-sectional descriptive.

SETTING: A rehabilitation research laboratory.

PARTICIPANTS: 14 adults with progressive MS (54.07+8.46 years of mean age) using walking aids and 8 age/sex-matched controls without MS.

INTERVENTIONS: Participants performed five mobility tasks (rolling in bed, lying to sitting, sitting to standing, walking and climbing steps) wearing a portable metabolic cart.

OUTCOME MEASURE(S): Oxygen consumption (V̇O2) during mobility tasks, maximal V̇O2 during graded maximal exercise test, perceived exertion and task-induced fatigue measured on a visual analogue scale before and after mobility tasks.

RESULTS: People with progressive MS had significantly higher oxygen cost in all tasks compared to controls (p<0.05): climbing steps (3.60 times more in MS), rolling in bed (3.53), walking (3.10), lying to sitting (2.50), and sitting to standing (1.82). There was a strong, positive correlation between task-induced fatigue and oxygen cost of walking, (rs(13)=0.626, p=0.022).

CONCLUSIONS: People with progressive MS used 2.81 times more energy on average for mobility tasks compared to controls. People with progressive MS experienced accumulation of oxygen cost, fatigue and exertion when repeating tasks and higher oxygen cost during walking was related to greater perception of fatigue. Our findings suggest that rehabilitation interventions that increase endurance during functional tasks could help reduce fatigue in people with progressive MS who use walking aids.