I note some of you via the Q&A session are having problems seeing your MS team or getting hold of them via email or telephone. The reason for this may be because they are off ill or self-isolating or they have been redeployed. I am aware that most MS Centres have moved to remote telemedicine clinics, mainly using a phone.
I discovered that the platform that NHSX (formerly NHS Digital) has been pushing AccuRx Fleming for video consultations. It is particularly common for GPs to use this platform. I set it up for myself in literally 5 minutes yesterday and will be doing as many of my remote clinics via the platform, which runs in a web browser or if you want you can use the App.
The following YouTube video shows you how quick and easy it is to get going.
#MSCOVID19: update on the outcome of cases with MS & COVID-19
We keep getting asked about if there is any data on whether or not people with MS are more likely to get COVID-19 if they do get are they more likely to get the severe disease and die from the infection?
Last week I logged into a very useful webinar organised by the iWiMS. They have now put the webinar online for you to watch.
The Italian registry reported 143 patients with MS and COVID-19 with five deaths. As you can from the table below the five patients who died from COVID-19 had more advanced or progressive MS and were all over the age of 50. Only two were on DMTs; one on rituximab and the other on dimethyl fumarate. Importantly the observation that to date only a 143 patients with MS had developed COVID-19 suggests that pwMS are not at increased risk of COVID-19. Please be aware that these figures may be biased in terms of reporting. On the webinar the Spanish, French, Australians, Germans and Americans discussed their cases as well.
The messages I took away from the webinar were reassuring and in line with my expectations. People with MS don’t seem to more susceptible to COVID-19 than the general population, nor are they more likely to get severe COVID-19 and die from complications than the general population. Similar to the general population age is an important risk factor when it comes to COVID-19 mortality in pwMS.
CoI: multiple
A #MSCOVID19 reality check
Are you aware of how the COVID-19 pandemic is going to play out?
People are being lulled into a sense of security that over the next 2-3 months the pandemic and mini-epidemics in each country and region will be over and things will start to return to normal. This is not correct.
The current strategy is to flatten the curve and extend the tail of the epidemic. What this means is that the COVID-19 epidemic will last many more months and is likely to extend into next year. The purpose of flattening the curve is simply to manage limited NHS resources, i.e. ventilators, CPAP (continuous positive airway pressure) machines, ITU and hospital beds, supplies of PPE (personal protective equipment) and staff. At present, it is estimated that 25% of NHS staff are off ill and/or self-isolating because another family member is ill.
By flattening the curve it will keep the stream of patients with severe COVID-19 infection to a manageable level. Instead of them arriving at NHS hospital in a 3 month window they will now arrive over a 6 to 9 month window.
If the lockdown is very extensive and prolonged as it has been in China you can stop the spread of infection in the community, but there will still be flares of infection and hence further lockdowns will be required. These flares will be triggered by asymptomatic viral shedders or people returning to China from outside its borders who are infected. I am almost certain that China is not telling us their whole story. We are not hearing about the COVID-19 flares, which according to basic epidemiological principles has to be happening.
I think it is highly unlikely that the UK will take the Chinese approach to our epidemic. This means that COVID-19 will move from being an epidemic, i.e. an increasing number of cases, to becoming endemic. The latter means the number of new cases becomes stable and at a level, the NHS can cope with. Eventually, herd immunity will occur that will slow down the spread of infection to very low levels. For herd immunity to occur it is estimated that at least 80% of the population, and possibly more, will have to get infected with SARS-CoV-2 so that it will ring-fence people who are susceptible to infection and stop the person-to-person spread, which has driven the epidemic.
How quickly herd immunity occurs depends on how soon the government relaxes or stops the lockdown and start letting people socialise and to start spreading the virus again. If the government removes the lockdown at the end of June as some commentators have suggested then I would estimate it would take about 18 months for the British population to acquire herd immunity.
One strategy that is likely to be employed is for high-risk people to be screened for immunity to SARS-CoV-2 by testing for the presence of antibodies in their blood and only letting them out of self-isolation if they are immune. This strategy is in anticipation that there will be an effective vaccine for SARS-CoV-2. I personally think this is a high-risk strategy. Vaccines for respiratory infections are notoriously difficult to make. Immunity from a vaccine may not be lifelong and the virus will mutate and drift, which will make the vaccine less effective. Importantly, the logistics of getting a vaccine tested and deployed globally makes it highly unlikely that we will see a vaccine deployed at a population level before 18 months. Just maybe a vaccine may be ready for very high-risk patients towards the end of 2021.
What does this mean for people with MS and the general population? It means that you really need to prepare yourself to be infected with SARS-CoV-2 and to possibly get COVID-19. I predict at 80% of us, yes 4 out of 5 of us, will be infected with SARS-CoV-2. The good news is that it looks like at a population level the proportion of people who get asymptomatic infections may be higher than previous estimates. The CDC (Centre for Disease Control) estimates asymptomatic infection rates as being 25% and higher. This means that when we get the real denominator of people infected with SARS-CoV-2 we will find that the proportion who get severe COVID-19 will be much less than 5% and the mortality or death rate from the infection will be much lower than the 2-5% that is currently being quoted.
Another possibility that I think is more likely than a vaccine is the emergence of effective antivirals and immunotherapies for treating COVID-19 and severe COVID-19. There are a lot of ongoing trials with repurposed drugs. I predict that when one or more of these trials are positive the registration of the drug, and adoption of the drug, into clinical practice will be very rapid. This means COVID-19 will be treatable and the proportion of people needing ITU and ventilation will drop and the mortality rate will improve. I predict that such a drug discovery is only months away.
You also have to realise that the ‘suits’ (yes, they tend to be men in grey suits) or the ‘Whitehall economists are frantically working away at their various economic models and will be weighing up the economic costs of the COVID-19 epidemic versus the health of the population. At some point in the near future, they will decide that GB Inc. has to to get back to work and the consequences of doing that will be the loss of lives due to severe COVID-19. The decision will be based on four competing factors (1) is the NHS now in a position to cope vs. (2) the mental health of the population (will they continue to adhere) vs. (3) the cost of a continued lockdown to the British economy vs. (4) the number of lives that will be lost. This is the harsh reality of being in charge of a country.
So, in conclusion, please don’t be lulled into a sense of false security; the COVID-19 pandemic is far from over, you are likely at some point to get COVID-19, don’t hold your breath expecting a vaccine to save you, but be optimistic and expect an anti-viral and/or anti-inflammatory to change the prognosis of COVID-19 soon. Please don’t believe China’s figures and take our politicians comments for what they are; political spin to manage expectations (unrealistic expectations).
CoI: I am about to leave the trenches to start fighting the war and I am very anxious.
#MSCOVID19 – natalizumab extended interval dosing
More questions around managing MS during the COVID-19 pandemic; this time in relation to natalizumab (Tysabri) dosing.
The COVID-19 NHS crisis is a double-whammy for pwMS. First, it is redeploying staff away from MS services to work on the frontline. Secondly, the message has gone out to stop pwMS coming to NHS hospitals, or even connecting with other healthcare facilities such as GP practices, in an attempt to prevent them from being exposed to SARS-CoV-2. Most MS centres, including ours, have converted all of our clinics to telemedicine. Saying that I saw a very anxious patient with recently diagnosed highly-active MS in our urgent face-2-face neurology clinic yesterday. She needed to be seen as she was in the middle of an attack and in my opinion, should start on a high-efficacy DMT as soon as possible (possibly natalizumab). I am not prepared to make her wait 3, 6, 9, 12 or 18 months to access a high-efficacy therapy and bridging her on a low efficacy DMT would not be in her best interests. If time is brain why should we be compromising on her treatment because of COVID-19? Do you agree?
Seeing this patient face-2-face yesterday helped. She was very anxious and being face-2-face allowed me to counsel her properly. The consultation felt right and is a possible example of why you can’t necessarily do everything using a telemedicine portal.
One of the consequences of COVID-19 is that some pwMS are finding it difficult getting hold of NHS staff and getting their questions answered, which is one the reasons I started the MS-Selfie COVID-19 & MS microsite. Some centres such as ours have converted all our patients on natalizumab onto 6-weekly infusions, others have pushed this out to 8 weeks and some patients from other centres are reporting that their natalizumab infusions have been suspended indefinitely. The mixed messages around dosing and/or suspending dosing is causing a lot of anxiety (see my daily Q&A sessions on MS-Selfie).
Is it safe to suspend natalizumab infusions?
No, it is not safe. I am particularly concerned that some patients are having their natalizumab infusions stopped without a definite date for recommencing their infusions or at least transitioning them onto another DMT to prevent rebound disease activity, which can on rare occasions be life-threatening.
How does extended interval dosing work?
Yes, EID looks safe. Real-life data suggest from a clinical perspective it is not associated with an obvious increase in disease activity (relapses). However, the data on this is preliminary and Biogen is currently doing a study to address whether or not EID is associated with any loss of disease activity. This is called the NOVA trial and will include MRI monitoring as part of the outcome. One thing that is clear is that EID reduces the risk of PML in JCV positive patients substantially.
The theory behind EID is that some cells are less sensitive to the effects of natalizumab and that if you delay the next natalizumab infusion by 1 or 2 weeks the saturation of their surface receptors drops below a threshold and allows these cells to traffic into the central nervous system. If these less natalizumab-sensitive cells are the antiviral CD8+ T-cells and/or the natural-killer cells that fight viruses then this could allow immune surveillance of the CNS to occur that will prevent PML from occurring. If you get the EID right the desaturation of the immune cells causing MS, possibly the memory B cells, is insufficient not to allow these cells to traffic and to reactivate MS. It is clear that not all cells are made equal when it comes to the effect of natalizumab. Importantly, there are several other adhesion molecules on cells that impact on their adhesion (stickiness) to the blood vessels in the CNS. It could also be a delicate balance between the availability of different accessory adhesion molecules that makes the difference.
How safe is extended interval dosing and does it matter if it is every 6 or 8 weeks?
Everyone gets a standard natalizumab dose of 300mg every 4 weeks. This means a 50kg person gets double the relative dose compared to a 100kg person. The half-life of antibody therapies, such as natalizumab, is linked to how much drug or antibody is given. Therefore for the 50kg smaller person, 8 weeks may be fine, but for the larger 100kg person 8 weeks is too long a gap. Based on the real-life data 6 weeks seems to be a good compromise. Therefore I personally would not be comfortable recommending an 8-week interval for all patients. Slide 38 in the deck below demonstrates that as the dosing interval increases so does the impact of body weight on natalizumab’s efficacy.
In reality every person with MS on natalizumab should probably have personalised dosing based on actual saturation of the VLA-4 molecule or equivalent biomarker (e.g. sVCAM-1). This would get us away from guessing and optimising the effectiveness of natalizumab at the same time as decreasing the risk of PML or other CNS complication linked to reduced immunosurveillance.
Zhovtis Ryerson et al. Extended interval dosing of natalizumab in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2016 Aug;87(8):885-9.
BACKGROUND: Natalizumab (NTZ), a monoclonal antibody to human α4β1/β7 integrin, is an effective therapy for multiple sclerosis (MS), albeit associated with progressive multifocal leukoencephalopathy (PML). Clinicians have been extending the dose of infusions with a hypothesis of reducing PML risk. The aim of the study is to evaluate the clinical consequences of reducing NTZ frequency of infusion up to 8 weeks 5 days.
METHODS: A retrospective chart review in 9 MS centres was performed in order to identify patients treated with extended interval dosing (EID) regimens of NTZ. Patients were stratified into 3 groups based on EID NTZ treatment schedule in individual centres: early extended dosing (EED; n=249) every 4 weeks 3 days to 6 weeks 6 days; late extended dosing (LED; n=274) every 7 weeks to 8 weeks 5 days; variable extended dosing (n=382) alternating between EED and LED. These groups were compared with patients on standard interval dosing (SID; n=1093) every 4 weeks.
RESULTS: 17% of patients on SID had new T2 lesions compared with 14% in EID (p=0.02); 7% of patients had enhancing T1 lesions in SID compared with 9% in EID (p=0.08); annualised relapse rate was 0.14 in the SID group, and 0.09 in the EID group. No evidence of clinical or radiographic disease activity was observed in 62% of SID and 61% of EID patients (p=0.83). No cases of PML were observed in EID group compared with 4 cases in SID cohort.
CONCLUSIONS: Dosing intervals up to 8 weeks 5 days did not diminish effectiveness of NTZ therapy. Further monitoring is ongoing to evaluate if the risk of PML is reduced in patients on EID.
CoI: multiple
#MSCOVID19: so what is a safe lymphocyte count?
What is a safe lymphocyte count; 500, 800 or 1000/mm3?
In your peripheral blood, you have circulating leukocytes or white blood cells which help fight infections. When you get your blood results back you often get told your total white cell count or WCC. However, the WCC is a composite and includes different populations of cells. The white cells can be divided into the lymphocyte and non-lymphocyte populations. The non-lymphocyte population or the innate (hard-wired) immune cells are often referred to as polymorphs (neutrophils, eosinophils and basophils) and monocytes (circulating macrophage precursors).
When it comes to lymphocytes we divide them into so-called B-cells and T-cells. B-cells come from the bone marrow; yes B is for Bone. In contrast, T-cells from the thymus; T is for Thymus, which is sweetbread if you like eating offal.
B-cells are specialised cells that use antibodies to recognise infections or cancers. On the other hand, T-cells use T-cell receptors for identifying infections or cancers. There are two broad categories of T-cells. CD4+ T-cells that generally react to foreign protein (generally infections) and cancer proteins (onco-antigens) that circulate outside of cells (extracellular antigens). In contrast, the CD8 pathway is for recognising foreign proteins that are expressed inside cells such as viruses. The CD4 cells tend to orchestrate an immune response and help other cells clear the infection; for example, the stimulate B-cells to make antibodies and produce molecules that attract macrophages to the site of inflammation. A small population of CD4 cells cab cytotoxic and kill target cells directly by producing proteins that kill the target cell.
In comparison, CD8 cells are much more sensitive to being activated and typically do their own killing; this is why a subset of them are called cytotoxic T-lymphocytes (CTLs). CTLs are like military commandos; they survey the body and if they identify a cell that is infected with a virus they kill it there and then. This is why CD8 CTLs are so important in fighting viral infections such as COVID-19.
In a routine blood count, we don’t get back detailed numbers of the lymphocyte subpopulations we simply get the absolute lymphocyte count (ALC), which includes both the B-cells and T-cells.
So what is a normal lymphocyte count?
There are different ways of defining a normal laboratory range in medicine. The most popular way is to take thousands of healthy volunteers of all ages and sexes and measure their ALC and then work out the normal range using the 2.5th and 97.5th percentile on the assumption that 2.5% of the population has abnormally low counts and 2.5% have abnormally high counts. If you do this then you get a different normal range for different populations; for example in the large Danish study below the normal range for Danish people, using this method is defined as 1.1–3.7×109/L or 1100 – 3700/mm3.
To simplify and standardise things the WHO (World Health Organisation) has defined the lower limit of normal as 1.0×109/L or 1000/mm3. This is not necessarily correct because at a population level people with an ALC of 1000/mm3 are at a greater risk of having an infection and dying than someone with an ALC higher than this. What I am trying to say is that the so-called ‘normal’ cutoffs are not black and white boundaries and that the risk of infections is affected by many other factors, in particular age and comorbidities.
For example, the older you get the greater the proportion of your lymphocytes in your peripheral blood become dedicated to fighting latent or dormant viruses such as cytomegalovirus (CMV) and Epstein-Bar virus (EBV). This means older people have less naive lymphocytes to fight new infections. So a younger person with an ALC of 1000/mm3 may have 10-20% of the peripheral T-cells dedicated to controlling CMV and EBV and someone over the age of 70 may be using 60-70% of their T-cells to keep CMV and EBV controlled. When the latter happens we refer to the T-cell repertoire (variability of all the T-cell clones) as being restricted and is indicative of immunosenescence, i.e. the majority of peripheral T-cell clones can’t be used for anything else other than controlling CMV and EBV. This may explain why an older age is such an important risk factor for developing severe COVID-19.
The WHO has also created grades of lymphopaenia based on the ALC:
- Grade 0 >= 1000/mm3
- Grade 1 = 800-999/mm3
- Grade 2 = 500-799/mm3
- Grade 3 = 200-499/mm3
- Grade 4 < 200/mm3
I know that a lot of you are confused because some neurologists are saying that you are at high risk of severe COVID-19 if your ALC is less than 1000/mm3, others like me are saying that you are only at increased risk if your counts are less than 800/mm3 and still others who are saying that you should only worry if your ALC is less than 500/mm3.
Apologies, about the confusion, but as with most things in medicine nothing is certain or definitive; it is a soft call and advice also needs to be pragmatic and generalisable to the wider MS population.
For example, if you are treated with alemtuzumab your counts may never get above 1000/mm3 before the next course. It is clear that the infection risk post-alemtuzumab drops quite precipitously after 3-6 months when most patients have ALC above 500/mm3. So should we use 500/mm3 then as the safe limit? I say no because most of the patients in the alemtuzumab trials were young and had no comorbidities. Therefore, this advice does not take into account immunosenescence and other factors. So then why not recommend 1000/mm3? I personally think this is too conservative and means people will be hyper-cautious when they don’t necessarily have to be.
To try and explain the subtleties to you I have hacked the data from the large Danish study below to show that infection risk increases linearly below an ALC of ~1700/mm3. Even at a WHO grade zero or ‘normal’, there is a 26% higher risk of infection, at Grade 2 (800/mm3 cut-off) there is a 44% increase in risk and with Grade 3 (500/mm3) it starts to increase rapidly (+76%).
I hope you now understand the complexities about setting a normal lymphocyte range and advice about what is safe. Since I was taught how to use azathioprine, one of the original immunosuppressants, I have always used 800/mm3 as my target cut-off for pragmatic reasons. I think the evidence supports this position, but I am sure many of my critics will have other opinions.
What COVID-19 is teaching me is that the MS community is not comfortable with uncertainty, but as we live in an uncertain world you are going to have to adapt to conflicting advice. Until data emerges we have only opinions, this is just one opinion, which may differ from the opinion you were given last week.
Warny et al. Lymphopenia and Risk of Infection and Infection-Related Death in 98,344 Individuals From a Prospective Danish Population-Based Study. PLoS Med, 15 (11), e1002685 2018 Nov 1 eCollection Nov 2018.
Background: Neutropenia increases the risk of infection, but it is unknown if this also applies to lymphopenia. We, therefore, tested the hypotheses that lymphopenia is associated with increased risk of infection and infection-related death in the general population.
Methods and findings: Of the invited 220,424 individuals, 99,191 attended examination. We analyzed 98,344 individuals from the Copenhagen General Population Study (Denmark), examined from November 25, 2003, to July 9, 2013, and with available blood lymphocyte count at date of examination. During a median of 6 years of follow-up, they developed 8,401 infections and experienced 1,045 infection-related deaths. Due to the completeness of the Danish civil and health registries, none of the 98,344 individuals were lost to follow-up, and those emigrating (n = 385) or dying (n = 5,636) had their follow-up truncated at the day of emigration or death. At date of examination, mean age was 58 years, and 44,181 (44.9%) were men. Individuals with lymphopenia (lymphocyte count < 1.1 × 109/l, n = 2,352) compared to those with lymphocytes in the reference range (1.1-3.7 × 109/l, n = 93,538) had multivariable-adjusted hazard ratios of 1.41 (95% CI 1.28-1.56) for any infection, 1.31 (1.14-1.52) for pneumonia, 1.44 (1.15-1.79) for skin infection, 1.26 (1.02-1.56) for urinary tract infection, 1.51 (1.21-1.89) for sepsis, 1.38 (1.01-1.88) for diarrheal disease, 2.15 (1.16-3.98) for endocarditis, and 2.26 (1.21-4.24) for other infections. The corresponding hazard ratio for infection-related death was 1.70 (95% CI 1.37-2.10). Analyses were adjusted for age, sex, smoking status, cumulative smoking, alcohol intake, body mass index, plasma C-reactive protein, blood neutrophil count, recent infection, Charlson comorbidity index, autoimmune diseases, medication use, and immunodeficiency/hematologic disease. The findings were robust in all stratified analyses and also when including only events later than 2 years after first examination. However, due to the observational design, the study cannot address questions of causality, and our analyses might theoretically have been affected by residual confounding and reverse causation. In principle, fluctuating lymphocyte counts over time might also have influenced analyses, but lymphocyte counts in 5,181 individuals measured 10 years after first examination showed a regression dilution ratio of 0.68.
Conclusions: Lymphopenia was associated with increased risk of hospitalization with infection and increased risk of infection-related death in the general population. Notably, causality cannot be deduced from our data.
CoI: multiple
Live or let die – #MSCOVID19 decision-making
Although the following story is fiction a variation of it is playing out in many hospitals across the world right now.
Can you help Dubs make a decision? COVID-19 is pushing us to places we don’t want to go, but we have to prepare for the inevitable.
Dr Claire Dubois or Dubs as her friends preferred to call her was exhausted. She had been working for 14 hours with only short breaks to feed her caffeine addiction and to have a drink of water. Hunger was not a problem needed to worry about. She had just completed three death certifications in the palliative ward; cause of death ‘respiratory failure secondary COVID-19’.
Dubs had just been called to say an ITU bed had become available; fortunately, one patient had pulled through and was being stepped-down to the general ward. She was asked to go to ward 13e to do triage, that is she had to decide who was the most worthy patient to be stepped-up from the ‘COVID HOT’ ward to ITU. Two nights ago she had to perform this task twice. Dubs hated this part of her job. She had only been a consultant pulmonologist for just over two years and she had never had to make these kinds of life-and-death decisions before. To Dubs triage was a word that was meant to be used on the battlefield. Then again the prime minister had used the analogy of war to describe our fight against coronavirus; little did he know how appropriate the war analogy would become.
Sarah, the charge nurse on ward 13e, said there were three patients who had dropped their oxygen saturations in the last few hours and would almost certainly need a ventilator. Sarah had already checked for ITU beds availability in the other London COVID centres and none had a spare ventilator bed.
Patient 1: Louise was a 22-year old final year law student. She had been admitted to the hospital yesterday afternoon from a drug rehabilitation unit in Southeast London. She had been in her final year of University when her drug habit had escalated. She has started off using drugs recreationally on weekends, but over the last year, her drug habit had spiralled out of control. Her boyfriend had been the problem and had become her dealer and had gotten her hooked on oxycodone. Her parents had taken her out of University and booked her into a private drug rehabilitation centre ten weeks ago. She had been doing well. She was off all drugs, had broken up with her boyfriend and was just starting to complete some of her University assignments remotely. She was however still quite frail. Over the last two years, she had lost a lot of weight and had only weighed 43 kg when she was admitted to the rehabilitation unit. She had almost certainly picked up the coronavirus from someone in the rehab unit; she was the third inpatient to be diagnosed with COVID-19. She had become very short of breath yesterday and when she was admitted to the hospital her CT scan of the chest confirmed COVID pneumonia with greater than 50% white-out of her lungs. Louise had been coping with oxygen, but over the last 4 hours her oxygen saturations had dropped below 90% and her respiratory rate had increased to 36 breaths per minute. Without ventilation, Louise would not survive; even with ventilation, her chances of pulling through were maybe fifty-fifty.
Patient 2: Michael is a 46-year medically retired civil servant. Michael has secondary progressive multiple sclerosis and needs a walker or wheelchair to mobilise. In the last year, Michael had been admitted to hospital twice with severe urinary tract infections. During his last admission, he had had to have a suprapubic catheter inserted. Michael was not on any disease-modifying therapy but was on baclofen and clonazepam to control his spasticity and duloxetine for depression and chronic back pain. Michael had stopped working three years ago and had recently separated from his wife. Michael had a care package in place and carers came in twice a day to help him wash and get dressed in the morning and to help him in the evening. Michael could not cope with domestic chores and needed someone to come in once a week to clean his bungalow. Michael has two children a daughter of 17 studying for her A-levels and a 19-year old son studying engineering at the University of Bristol. Michael has a large friend group and would get out at least twice a week. He was an avid reader and spent a lot of time online as an active member of several Facebook groups. Michael had no idea where he picked up the virus but had been admitted to hospital two days ago by his GP who was concerned he was not coping at home. Michael had been doing very well but over the last 12 hours he had developed COVID-19 ARDS (acute respiratory distress syndrome) and his oxygen saturations had plummeted precipitously over the last two hours. It was clear that without assisted ventilation he would not survive the night.
Patient 3: Reverend Charles Ryan is 78 and semi-retired. Reverend Ryan is married to Josephine his partner of 52 years. They have three children and six grandchildren. Reverend Ryan is still an active member of his congregation and in semi-retirement has taken on a lot of charitable work. He is a governor of the local school, a trustee on a charity that supports church schools in Malawi and he teaches theology at the local college. He writes a weekly column on religious matters for the local newspaper. Reverend Ryan is still physically active walking their dog twice a day. Apart from well-controlled hypertension and mild osteoarthritis of the left hip he has no other medical problems. He almost certainly picked-up the virus from one of his congregation a week or so ago. Initially, he thought he had a common cold and on the advice of his GP was self-isolating. He had been improving but two days ago he became short of breath and had to be admitted to hospital urgently yesterday. He was diagnosed as having COVID-related pneumonia. Over the last 24 hours, his breathing had become more laboured and his blood oxygenation levels had plummeted despite oxygen therapy. It was clear that he was tiring rapidly and would need to be ventilated very soon if he was going to survive.
Dr Dubois has to make a decision on which of these three patients gets the one ITU bed. Who do you think deserves the bed? Who deserves the chance to survive?
Skilling-up for the eye of the #MSCOVID19 storm
I want to apologise to my students and colleagues for not delivering on certain teaching and academic tasks; I will get there. I have had to spend the last 48+ hours starting the process of reskilling and learning new skills for when I am redeployed onto the front-line of the NHS. Our hospital is being reconfigured as if we are preparing for war. There are red or hot floors that are for managing the COVID-19 positive patients and green floors for the COVID-19 negative patients. There are new systems being put in place to triage and manage patients depending on their predicted outcome. Several wards are being converted into ITUs or ventilator units. The Royal London Hospital is being transformed.
If you are a neurologist the following slides from Dr Ali Jawad, from the Royal College of Physicians (RCP), is a good starting point to learn about COVID-19.
In the last 48 hours, I have ploughed through a new Chinese textbook on how to diagnose and manage COVID-19 and I am reading as much as I can in relation to what needs to be done on the frontline. I am also having to reskill myself in relation to my general medical skills. I spent yesterday shadowing a college on the general medical wards at the Royal London Hospital. The experience was uplifting; I have always loved general medicine and my experience made me recall my days as a medical student and as a medical registrar. I am particularly grateful to Professor Tom Bothwell (see my obituary ‘Emulating your mentor‘) who taught and influenced me most in my early years as a medical trainee.
We are anticipating that neurologists will be redeployed to work in A&E (accident and emergency), the general medical ward or even in the new makeshift ITUs (intensive care units) that are being established in London. One thing I still don’t feel competent to do, which I used to be able to do when I was a general medical registrar 30+ years ago, are awake intubations and to manage patients on a ventilator. I recall it not being that complicated. I worked for four months on an eight-bed respiratory ICU and was responsible for managing the unit when on-call. I am sure I could relearn these skills if and when the need arises.
I am doing this post to make you aware of the seriousness of the storm or tsunami that is about to hit us and what is expected of all HCPs working in the NHS. This is underlined by the fact the NHS is constructing temporary morgues across the country and converting conference venues into mass hospitals.
The following is an excerpt of an email I was sent yesterday:
…. We have been asked to support the resourcing process for the new Nightingale Hospital based at the Excel in East London due to open this weekend. The resources we are seeking to identify are varied but include expertise in the following areas:
Staff:
Clinical care especially ICU and rehabilitation post-ICU
Educators for Teaching and training of clinical staff
I appreciate these are broad categories but the plan will be to train up around 1000 or more clinicians to run a unit for ventilated patients with around a week to move from where we are now to a functioning unit…..
These are just a few of the reasons why pwMS in the UK need to understand that the management of MS and many other chronic diseases are being put on the backburner. In these extraordinary times, you will also need to upskill yourselves in the self-management of MS; you may have to take responsibility for some of your own care.
I am so impressed with the professionalism and the ‘can-do’ attitude of my NHS colleagues. Prior to this crisis morale in the NHS seemed to be very low, but yesterday’s experience showed me what a remarkable organisation the NHS really is. The call to arms has given the NHS a new sense of purpose. The willingness of the people who work in the NHS to make a difference makes me very proud. I predict that we are going to get through this crisis better than we expect and hopefully this will convince our politicians and politicians the world over that healthcare has to socialised.
I will try to continue running my #MSCOVID19 microsite to give you advice at a distance. The idea behind the site is simple; to provide you with information on COVID-19 and MS and to collate all the answers to the questions you have in one place, which makes it easier for others to find. You are also welcome to ask me non-COVID-19 questions? As I am not meant to be giving personal opinions online I will anonymise the question and provide generic advice that can then be used by the wider MS community.
Please take care of yourselves and we will hopefully see each other in a few months time.
CoI: multiple
#MSCOVID19 Webinars
Calling all HCPs who want to learn about managing MS during the COVID-19 epidemic. Please register for the following webinars via the MS Academy website. We plan to run a series of these over the coming weeks and months. The next one is on managing highly active and rapidly evolving severe MS in the current environment.
CoI: multiple
COVID-19 & MS Microsite
We have created a specific COVID19 & MS Microsite to curate relevant information for people with MS and their families. The site is being updated on a daily basis. Please use this site to ask clinical questions related to COVID-19 or use the form below. Please note the answers to questions will then appear on the COVID-19 & MS site. Thanks.
CoI: multiple
New UK guidelines for #MSCOVID19
If you live in the UK and have MS you may receive a letter from the NHS stating that you are potentially in the ‘extremely vulnerable group’ in relation to COVID-19. The reason for that is they are using GP databases and other sources of information to identify patients who may be on immunosuppressive therapy. If you receive one of these letters don’t be alarmed and please contact your MS Team for specific advice.
In my opinion, the only pwMS who should be classified as ‘extremely vulnerable group’ are those who have had HSCT and alemtuzumab in the last 3-6 months and are still immunodepleted or patients with severe disability who have swallowing problems and/or a history of recurrent chest infections.
You will have seen the UK Government have updated its guidance and is now “classifying people on immunosuppression as being extremely vulnerable, which probably includes pwMS on immunosuppressive DMTs. There are three reasons for this. (1) To protect you from potentially getting infected with SARS-CoV2 and (2) potentially getting more severe COVID-19 that needs hospitalisation and a potential ITU bed and ventilation. (3) There is also a potential risk of creating a population of super spreaders, which increases the risks to the general population. Immunosuppressed people may not be able to clear the virus quickly and hence shed more virus and for longer.
The current list of what is an immunosuppressive therapy is incomplete and was not drafted from an MS perspective. This is despite being a member of the subcommittee that was meant to help draft this guidance. I think it important to liaise with your own MS team about your own situation.
What about if you have MS and are an essential worker? If you can work from home, please work from home. If your job involves no contact with people then you may be able to continue working; however, please clear this with your organisation. If your job entails coming into contact with people and particularly people infected with SARS-CoV2 then you are going to have to self-isolate. This advice may seem harsh, but this is a war, a war against a virus, and it demands extraordinary sacrifices at an individual level for the good of society. This is not only about looking after your own health, but the health of the country.
The above may be relevant today and may change by tomorrow. If we don’t adhere to the Government’s advice, it will become a diktat tomorrow.
I have put together some slides to show how we think immunosuppression may affect the disease severity curve of COVID-19. Please note it is a may and not a definite as we don’t have evidence to back up these claims. I hope this is self-explanatory.
I predict that NHS letters will create a lot of anxiety so this is a warning not to panic. I am still collating this information on my COVID-19 & MS microsite.
CoI: multiple