Professor Charlie Knowles, a close colleague and friend, has just penned this ballad to the NHS in remembrance for all the NHS staff who have died fighting coronavirus on the frontline.
He is using the anthem to fundraise for the families of NHS workers who have lost their lives in the call of duty. So if you feel like giving please do (JustGiving).
So if you are someone with MS who is shielding or being very careful about social distancing and want to avoid getting COVID-19 you may be considering what your own exit strategy is. How do you de-risk yourself and prevent yourself from becoming infected with SARS-CoV-2?
At present, it looks as if the UK government’s strategy is to ring-fence you with people who are immune to SARS-CoV-2, the so-called herd immunity paradigm, and hope an effective vaccine emerges in the next 12-18 months to secure the safety of the high-risk or vulnerable population. This strategy is high-risk because there is no guarantee that sufficient numbers of healthy people in the general population will get COVID-19 to ring-fence the vulnerable. To be honest there are too many vulnerable people. In addition, there will always be holes in the science behind the herd-immunity paradigm; who says immunity to SARS-CoV-2 will be long-term and why wouldn’t new strains of virus emerge to fool the immune system. This means that vulnerable people will have to live in fear that they may acquire COVID-19 unless they get an asymptomatic/mild infection and/or vaccinated and have proof they have neutralising anti-viral protective immunity against SARS-CoV-2.
So the next questions are if and when an effective SARS-CoV-2 vaccine emerges (1) how good will the vaccine be and (2) if I am on a disease-modifying therapy will I respond to the vaccine?
In general, vaccines can be hit and miss. Politicians, particularly Donald Trump, and the general public seem to think that an effective vaccine is imminent. Yes, it may be but it is more likely, based on industry timelines, that an effective vaccine for SARS-CoV-2 is years away. Developing a vaccine for respiratory viruses is not easy, particularly for viruses that mutate rapidly and have mechanisms built into their nucleic acid which results in antigenic drift, i.e. the proteins they express on their surface rapidly mutate to escape immune detection. The latter is a particular problem with for example the influenza virus; antigenic drift happens annually. We also know this is a problem with coronaviruses because immunity is not life long and wanes within years. This is why we get recurrent common colds.
The other problem with viruses and vaccines is the so-called original antigenic sin. This is when you make an immune response to a virus or vaccine antigen. The virus then mutates and when you get infected with the new strain the antibodies you make to the original strain or vaccine don’t neutralise the new strain and may even enhance infection with the new strain. In addition, your immune system doesn’t treat the new strain as a new infection and thinks it is the original strain and hence doesn’t make new antibodies against the new strain. This why it is referred to as antigenic sin. Vaccine development has a long history of failing because of these sorts of issues and is why we haven’t got highly effective vaccines against major viruses such as dengue fever.
Another issue with SARS-CoV-2 is that it looks like some of the important binding sites on the spike protein of the virus are heavily modified with sugar molecules. This means that neutralizing antibodies against SARS-CoV-2 may need to be against so-called glycoprotein segments of the spike protein. Glycoprotein vaccines are much more difficult to make and in themselves are less effective in inducing antibodies than pure protein vaccines. The reason for this is that the immune system processes sugar (glyco) antigens differently to protein antigens.
I am telling you all this to make you aware that vaccine development is difficult, very difficult, and there are a lot of issues that will need to be considered to make sure a vaccine against SARS-CoV-2 is effective and safe.
The other issue is having an immune system that is capable of mounting an immune response to a vaccine. I think in general a live-attenuated SARS-CoV-2 vaccine is unlikely to be developed. Live vaccines tend to be legacy vaccines from an era before we had the tools to make recombinant proteins. Therefore it is highly likely that all the vaccines that will be developed will either be nucleic acid, protein or glycoprotein component vaccines. In general immune responses to vaccines are blunted by immunosuppressive therapies. This has relevance to pwMS because the DMT you are on may block the required immune response to the vaccine. So your careful and patient waiting for an effective vaccine may be futile.
In general, interferon-beta, glatiramer acetate, teriflunomide, dimethyl fumarate and natalizumab are unlikely to block or attenuate immune responses to a component SARS-CoV-2 vaccine. Similarly, once immune system reconstitution has occurred post alemtuzumab, cladribine, mitoxantrone or HSCT vaccine responses should be restored to normal or near normal. In the depletion phase of IRTs (immune reconstitution therapies) it is likely that vaccine responses will be blunted. In the case of S1P modulators, such as fingolimod and siponimod, and the anti-CD20 therapies (ocrelizumab and rituximab), which are continuous immunosuppressive therapies, vaccine responses are likely to be blunted. I use the term blunted rather than inhibited responses because pwMS on these therapies may still make antibodies to the vaccine components but not to the required level to create protective immunity.
The story with anti-CD20 therapies is potentially more complex. Surprisingly, antibody response to common vaccines occur on anti-CD20 therapies, but antibody response to glycoprotein vaccines, for example, the pneumococcal vaccine are blunted or inhibited the most. This may be particularly relevant to a SARS-CoV-2 vaccine that is likely to require antibodies to glycoprotein antigens to generate neutralizing antibodies, i.e. antibodies that neutralise the virus and prevent infection.
Is this information important for pwMS? Yes, I think it is and may affect whether or not pwMS start or continue treatment with S1P modulators or anti-CD20 therapies. In other words, if you want to make yourself ‘vaccine ready’ you need to consider your DMT choice.
As a research group, we are very interested in the antibody responses to SARS-CoV-2 in pwMS who have had COVID-19. We are in the process of trying to rapidly develop an antibody assay for IgG and IgM antibodies that can differentiate between binding and neutralizing anti-SARS-CoV-2 antibodies. This will allow us to study whether or not the immune response to SARS-CoV-2 is different in patients on S1P-modulators and anti-CD20 therapies and to compare these responses to patients on other DMTs and to patients who are not on DMTs. This will potentially allow us to give patients detailed information in the future about their risk of getting delayed COVID-19 and whether or not they respond to emerging vaccines once they arrive.
In conclusion, as we start to think about exit strategies for pwMS post-COVID-19 being able to respond to a future SARS-CoV-2 vaccine is a major factor HCPs and pwMS need to consider when deciding on what DMT to start or continue with for the long-term.
Now some questions for you. For those of you who consider yourself, ‘COVID-19 vulnerable’ is being able to respond to a future SARS-CoV-2 vaccine relevant to you? Does it affect your thinking about which DMT you want to be treated with? Please let’s start a discussion on this important topic.
I think the vaccine issues is important enough for me to have added a new column to my DMT COVID-19 table (version 4.0) and to change the colouring scheme to a patchwork.
CoI: multiple
Is there anything you can do to prepare for when you get COVID-19?
If you live in the UK you will have realised by now that the government plans to extend the tail of the SARS-CoV-2 epidemic to allow herd immunity to develop and at the same time protecting the most vulnerable people from getting COVID-19 by shielding. I have already said this strategy is dangerous and likely to be very leaky and will result in a lot of excess deaths.
What this means is that most of us (~80%) will become infected with SARS-CoV-2 at some point in the next 6-18 months and a significant proportion of us who are infected with the virus will get symptomatic disease or COVID-19. Therefore you should prepare yourself for getting COVID-19 and potentially severe COVID-19.
If you did get severe COVID-19 is there anything you can do to maximise your chances of surviving the infection and its immune complications? Preparing for a physiological stressor like COVID-19 is called prehabilitation. Prehabilitation is usually used for patients about to have major elective surgery with the objective of reducing the chances of operative and post-operative complications.
So if you have multiple sclerosis a COVID-19 prehabilitation programme makes sense. The following is a list of things I recommend you do:
Are there things I have left off this list? If you have MS and have already had COVID-19 is there anything you can advise your fellow patients about what they should be doing to prepare for when they get COVID-19? I am particularly interested in hearing about your personal hospital experiences.
I will also load this post on the COVID-19 section of MS-Selfie.
The new normal is the not laying on of hands.
Social distancing applies to inpatient care as well. The diktat from infection control is to limit the amount of direct contact we have with patients, especially vulnerable patients, to reduce the inadvertent spread of SARS-CoV-2 between HCPs and patients. I am finding this very difficult. I was trained and practised medicine were the clinical examination was revered; it was the one skill that differentiated us from other HCPs. Interestingly, what has become clear to me is that you can largely manage patients with metrics that are not dependent on the clinical examination. Just maybe, Professor Chris Hawkes, a colleague of ours, was right when he said he doesn’t have to examine his patients anymore (see below). I was so outraged by the article that my mentor (Prof, Vivian Fritz) and I wrote a rebuttal (see below). It is interesting to read our words 10 years later in the middle of the COVID-19 pandemic where we have been advised to try and avoid the physical examination.
The remarkable thing is that I have been able to get away with not examining about 90% of the patients I have seen in the last two weeks. Even my outpatient work has moved onto a telemedicine platform and is being done via an online video link. Will this become the new normal? In the future, I envisage you all being asked to sign-up to completing a self-monitoring protocol, for example, the web-EDSS, 9HPT, T25W, daily activity monitoring, BP, pulse, body weight, cognition (online or smartphone app assessment) and a set of PROMs (patient-related outcome measures) every 3-6 months. You will have your regular bloods and annual MRI monitoring done close to where you live and the results and images will be analysed by an AI-bot and the metrics automatically loaded into your electronic patient record. All this information will be collated and summarized in a dashboard that is shared between you and your neurologist so that when the video consultation happens it can be done as efficiently as possible in a standardised format.
As a person with MS, the question is how do you feel about not being examined by your neurologist or having face-to-face visits? What about having a standardised and highly-automated follow-up appointment?
Already our managers are asking us what parts of the COVID-induced reconfigured NHS services do we want to keep? As the patients or clients, we should be asking what you want? For example, should I continue to run my online MS&COVID-19 Q&A service, but widen it to MS in general? In reality, this Q&A service is morphing into micro-consultation service. Could this be something we expand as a Barts-MS service?
Hawkes CH. I’ve stopped examining patients! Practical Neurology 2009;9:192-194.
Professor Gavin Giovannoni and Professor Vivian Fritz. A plea to neurologists, especially privileged British neurologists. Practical Neurology Published on 1 March 2010.
Sometimes it is necessary to make a point with overemphasis and we believe that was done in the letter by Chris Hawkes. We agree that it is essential to talk to a patient and to watch them and observe how they speak, what they are saying and what they are doing with their body as they walk in and out of a room. However, to exclude the examination is a form of conceit. The only reason that a very senior neurologist can observe so much is from a long period of diligently examining all patients and slowly learning shortcuts by pattern recognition. But you can’t teach neurology that way. Students must first be taught the discipline of a routine in order to learn which part of the routine can be discarded in individual patients. When a TIA is caused by atrial fibrillation a finger on the pulse will lead you to the ECG as the first test. A stethoscope on the neck will suggest that a Doppler should happen immediately. When resources are limited (which occurs in much more than half the world) it is important to direct your tests sensibly rather than blindly ordering a battery. If a student can’t distinguish between an upper and lower motor lesion then the differential of a paralysed limb trebles and an EMG, as well as an MRI, needs to be done routinely. We are not against spending more time talking to a patient, even if it means less time examining, but don’t eliminate the examination. It’s like throwing the baby out with the bathwater. When in doubt the most cost-effective investigation is to retake the history and to examine the patient. We mustn’t forget that an essential part of any consultation is to gain the trust and respect of the patient; if a patient doesn’t trust the consultant they are unlikely to accept the diagnosis and treatment plan. We have all seen patients for second and third opinions when on completing the examination they compliment you on how thorough you have been and inform you that their previous consultants hadn’t bothered to examine them. The “laying on of hands” is as essential to today’s consultation as it was in the past. In today’s litigious environment not examining a patient would be welcomed by the opposing legal team with glee. We doubt any expert witness would support the notion of not examining a patient as standard clinical practice. In the new era of revalidation admitting to your peers that you do not examine your patients would be inviting an early retirement or a change in career.
Are we in danger of dropping the ball?
I am enjoying doing general medicine again but the majority of the patients under my care on an acute medical ward have social problems. Social problems that either got them into the hospital in the first place and/or social problems that are now preventing them from being discharged.
My brief sojourn into general medicine highlights why the social determinants of health are by far the largest determinants of health-related outcomes at a population level. Interestingly, social determinants of health, or the health gap that Michael Marmot refers to, is also playing out in the COVID-19 patients. Social deprivation not only increases your chances of getting COVID-19 but the economic fall-out of the lockdown will be felt by the poorest more than those of us who are better off.
If you have a social conscience I would urge you to read the report ‘From pandemics to poverty Hotspots of vulnerability in times of crisis’, by Vidya Diwakar from the ODI.
Another thing that strikes me is the unnecessary complications several of our non-COVID-19 patients are experiencing because of delays in their treatment. I have one patient who was meant to be treated with cyclophosphamide in mid-March for a so-called CNS vasculitis (inflammation of the blood vessels of the walls of the brain) who has recently been admitted in crisis. Several delays have occurred because of the COVID-19 epidemic. The consequences of this delay are potentially catastrophic for this patient. COVID-19 is not a reason to delay urgent medical treatments. I suspect the same thing is happening to people with MS, with potentially catastrophic consequences.
If you have highly active MS and you need aggressive control of your disease you probably need it sooner rather than later. Time is brain whether or not there is a COVID-19 pandemic. The risks of COVID-19 to individual patients who are immunosuppressed can be managed with self-isolation and shielding. In addition, I am not convinced outside of possibly acute treatment with HSCT or alemtuzumab that our immunosuppressive therapies carry much of a risk to pwMS. In fact, the more real-life data I see the more I am reassured that pwMS on licensed immunomodulatory and immunosuppressive MS therapies seem to be weathering the storm of COVID-19 rather better than expected.
The problem we have is that MS services have been halted or are been run by a skeleton staff with no capacity to treat MS actively and aggressively. I think we have been complicit in the government’s shutdown of routine services that provide important time-dependent treatment and care for patients with chronic conditions such as MS.
It is looking increasingly likely that we have over-resourced the management of COVID-19 patients at the expense of patients with other diseases. I predict that when the dust settles there will be many more deaths as a consequence of reconfiguring the NHS to deal with COVID-19 than there will be from severe COVID-19 itself. I am told that the London paramedics have seen a six-fold increase in calls for deaths at home during the lock-down compared to average. The question I ask is how many of these deaths could have been prevented if it wasn’t for the COVID-19 epidemic? Few people will die from MS, but how many pwMS will end up being more disabled because of COVID-19?
It is interesting how COVID-19 lock-down exit strategies are now dominating the news cycle. China who is relaxing its lockdown has just reported a flare-up of new cases, which is what happened in Singapore. This is the problem that now faces the UK and other countries.
We have quarantined a large number of vulnerable people including pwMS for several weeks and we now want to relax the lockdown with the risk of more infections and the potential exposure of high-risk people to the virus. Without widespread testing, contact tracing and repeated local lockdowns, relaxing the rules on social distancing is a risky exit strategy. I assume allowing the gradual spread of the virus through the general healthy population, whilst shielding the vulnerable is the covert or not so covert plan of the UK government. Eventually, this strategy will lead to sufficient herd immunity to allow the vulnerable back into society. The problem with this strategy is that it will be leaky and there will be an excess number of deaths. This shows you why governments are so edgy when asked what strategy they are pursuing. I am not sure that most have decided yet, which is why they are keeping both options open at present. What we really need is some certainty or an effective antiviral agent or a vaccine that works. The only way we are going to deliver on these is to invest in science and trust that as always scientist will innovate and get ourselves out of the mess we now find ourselves in.
I am interested to hear from you whether or not you feel the treatment of your MS is being compromised and whether or not you consider yourself vulnerable and, finally, what strategy you would like the government to adopt.
CoI: multiple
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
Can we assess MS relapses remotely?
Yes, I think we can. Most neurological assessments are based on history and examination. You definitely can take a history of new-onset neurological symptoms by telephone, or preferably using video consultation. I am currently using accuRx the most widely adopted NHS platform for remote consultations. It is remarkably easy to use and satisfaction levels are very high for both clinicians and patients. In addition, you can also do a brief or truncated neurological examination using a video link. I am beginning to ask some of my patients to complete a battery of online assessments (webEDSS, 9PHPT, T25W) and PROMS (MSIS-29) to document the impact of the relapse on their physical functioning.
Once you have documented a relapse the question arises should you treat the relapse with steroids?
At the moment I am trying to avoid steroids for relapses. Why? In general, the benefits of steroids in the treatment of relapses are quite small. They essentially speed-up the recovery by about 2 weeks. At 6-months the level of recovery from a relapse, as assessed by EDSS, is the same whether or not you have steroids. When you tell patients this they often agree not to be treated, particularly when you mention the potential side effects of high-dose steroids, i.e. avascular necrosis of the hip, steroid psychosis, diabetes, hypertension, insomnia and infections.
Despite this, some patients still prefer to be treated. This raises the question of IV (intravenous) versus oral. There have been several studies showing that there is no difference between high-dose IV or oral steroids in terms of relapse outcome. Therefore, in the current COVID-19 environment, when we are trying to avoid patients having to travel and come to the hospital, oral steroids are the prefered route. The steroids can be dispensed via your general practitioner or through our pharmacy with courier delivery if you live locally (within London or in the home counties).
Before starting steroids it is good to get some basic things done to try and de-risk the adverse events. This includes a recent blood pressure; we don’t want to prescribe high-dose steroids to someone with uncontrolled hypertension. Nowadays most people have access to some form of home BP measurement device.
If you have a history of recurrent urinary tract infections it is always advisable to have a urine dipstick done to make sure you don’t have an asymptomatic infection. Five days of steroids are sufficient to blunt your innate immune response, which has the potential to allow a bacterial urinary tract infection to become a systemic infection and to cause septicaemia. I learned a hard lesson early my MS career when I agreed for a patient to have his relapse treated by his GP without considering a UTI. The patient was admitted to ITU on day 4 of his course of oral steroids in septic shock and nearly died. A lesson to take UTIs seriously.
It is also important to make sure the relapse is not a pseudo-relapse, which are often triggered by a UTIs in patients with more advanced MS.
Not all patients have urine dipsticks at home, which is why you may have to attend your local GP practice or come to the hospital to get this done. Another solution is to purchase urine dipsticks online and do the test yourself. The latter is an example of taking control and self-managing your MS or UTI.
Please be aware in the context of a UTI the dipsticks assess two main things; (1) urine nitrite levels and (2) the presence of esterase and enzyme that is produced by white blood cells or leukocytes. Please be aware that about a third of UTIs are caused by bacteria that don’t produce nitrate reductase, the enzyme that converts nitrates to nitrite, so your urine, even if you have a UTI, maybe negative for nitrites, however, it should be positive for white cell esterase if you have a significant infection.
In summary, to diagnose a probable UTI you need white cells and possibly nitrites to be positive on the dipstick. Other abnormalities that can be found with UTIs are a raised protein and red blood cells, which are also detected on most commercial dipsticks. However, positive protein and red blood cells in the absence of the white cells and nitrites are not indicative of a UTI and can be caused by other pathologies.
If you have doubt about interpreting the dipstick you can always take a photograph of it and send it to your MS nurse, GP or neurologist for interpretation. If you have a UTI it is advisable to get your urine cultured in a laboratory and to start a course of antibiotics. The antibiotics can be changed if the culture grows a bacteria that is resistant to the antibiotic you are on. To get a culture done you need to drop-off fresh urine to your GP that needs to be sent to the laboratory within two hours. Please note you will have to collect a prescription for antibiotics from your GP. I personally like you to start your antibiotics for at least 24 hours before starting steroids.
If you are overweight or obese and have a family history of diabetes it is also worthwhile getting your blood glucose checked. We don’t want to give high-dose steroids to someone who has uncontrolled diabetes. Blood glucose is checked using a finger prick test that can be done by your GP or anyone who has a glucose home testing kit.
Will high-dose oral steroid put you at risk of COVID-19 or severe COVID-19?
I don’t know the answer to this question. However, significant immunosuppression is only considered to occur with a prolonged course of steroids, i.e. longer than 3 weeks at a dose of greater than 20mg of prednisone per day or equivalent. Therefore the level of immunosuppression with a short 5-day course of high-dose 500mg/day of methylprednisolone is relatively low. Although this is medical dogma there is good scientific evidence that high-dose steroids blunt innate immune responses, i.e. neutrophil and monocyte/macrophage responses to infection, which is why short-term steroids can cause UTIs to become systemic. The blunting of the innate immune response may be important in the early stages of COVID-19. Because of this, I am telling my patients who opt for steroid treatment to self-isolate for a period of 14 days after completing the 5-day course. The logic of this is simple; with a lack of evidence, it is better to be safe than sorry.
In addition to 500mg/day of methylprednisolone for 5-days, I also prescribe lansoprazole 30mg daily for 14 days to protect you from steroid-induced gastritis. I am aware that not all neurologists prescribe gastric protection with high-dose steroids. Steroid-induced gastritis is not an uncommon problem and the last thing you need is an upper GI bleed that needs hospitalisation.
If you have diabetes and/or hypertension it is important to monitor your blood sugars levels and blood pressure whilst you are on steroids in case your medications need to be adjusted.
The one side effect that worries me the most is steroid-induced hypomania, psychosis and depression. I have a handful of patients in my career that have had to be sectioned because of psychosis. It is important to be mindful of the mood-altering effects of steroids and if necessary seek help. I always warn partners or family members of the possibility of hypomania, psychosis and depression and that it is better to address these as soon as possible if they occur. The good news is that steroid-induced psychosis tends to respond to treatment relatively quickly.
Another side effect that is common is steroid-induced insomnia. If you have a history of this please ask for a short course of sedatives to help you sleep. The sedatives are only needed for 4 to 5 days and shouldn’t be taken for longer than this.
As you can see assessing and treating relapses remotely is possible, but on balance we should try and avoid using steroids.
If you any queries I will happy to ask them. I will also post this information to MS-Selfie, my COVID-19 and MS microsite.
I received this email, which may be of value to you all.
| Latest COVID-19 information for people with MS
UPDATE FROM MS NEUROLOGISTS – 08/04/20 Dear MS Stakeholder, We hope you are keeping safe and well since our last communication. In our last COVID-19 update to you on 27/03/20 we shared a statement prepared by an independent group of Australian and New Zealand neurologists. MS Research Australia continues to work closely with these experts and would like to share an update to the advice for people with MS provided at the end of March. The statement is outlined below, with the key updates to the previous information highlighted in red for your convenience. BACKGROUND Since December 2019 following cases emerging in and around Wuhan, China most regions of the world have now experienced cases of a novel respiratory illness (COVID-19) caused by a new coronavirus which has been identified as SARS-CoV-2. The mortality of this infection amongst cases displaying symptoms and confirmed to have the virus is in the order of 1-7%. National and International measures to reduce the risk of transmission of the virus have been implemented in most jurisdictions. It is likely that these measures will slow the rate of transmission, but at this point it is unclear if further spread can be prevented and it is unclear how long the present outbreak will last. At present there is no known effective treatment for COVID-19 and there is no vaccine. Older persons and those with pre-existing medical conditions (respiratory disease, heart disease, diabetes, cancer) have a higher risk of complications from COVID-19 infection. Men may also be at a slightly increased risk. At this stage, there is no evidence that being immunosuppressed increases a person’s risk of being infected with COVID-19 or developing complications, but there is a theoretical risk of both. In Australia, we are still in a containment phase where it is hoped that the measures being implemented will limit the number of people infected and the present risk of being infected with COVID-19 remains low. The latest data indicate that the number of new cases is declining. This suggests that the present transmission prevention efforts may be working. This is result of two main factors. The first is that the population of Australia has largely followed the recommendations of social distancing and personal protection. The second is the outstanding work undertaken by our Public Health team who have successful traced the source of 80-90% of cases and implemented testing, quarantine and self-isolation as necessary. This has been an amazing achievement and goes largely unnoticed. However, we need to remain vigilant as the situation may still change. We will continue to monitor this and change our advice accordingly. HOW CAN I PROTECT MYSELF FROM GETTING COVID-19? In order to minimise the risk of being infected by COVID-19, you should follow the standard precautions advised by the Australian Government. This is the best source of advice on how to keep yourself safe and will be updated daily. WHAT IF I DEVELOP SYMPTOMS OF COVID-19 INFECTION OR HAVE A CONFIRMED DIAGNOSIS OF COVID-19 INFECTION? If you develop symptoms of COVID-19 infection or have a confirmed diagnosis of COVID-19 infection you should:
WHO SHOULD I CONTACT IF I HAVE SYMPTOMS OF COVID-19 INFECTION? If you are concerned that you are developing symptoms of COVID-19 you can:
SHOULD I COME TO MY OUTPATIENT CLINIC, INFUSION, BLOOD TEST OR MRI APPOINTMENT? If you have visited a high-risk area, have symptoms of COVID-19 infection or have had close contact with someone who has been diagnosed with COVID-19 please do not attend your outpatient, infusion, blood test or MRI appointment. Please contact your specialist clinic, MRI department, infusion centre or MS Nurse to advise of your need to cancel the appointment and make alternative arrangements. Most neurology clinics have now moved to telephone or telehealth consultations. It is important to remember that MRI scans and blood test form an important part of the monitoring of your disease activity and potential side effects of medication. In some instances, there may be adverse consequences of delaying or cancelling these investigations. Please contact your neurologist before making any changes to your planned investigations. MRI departments in hospitals and private radiology practices have implemented measures to limit the risk of infection. Some private pathology services offer a home collection service. Please contact your pathology service for details. This may require the approval of your neurologist. SHOULD I TRAVEL OVERSEAS? Current travel advice is available on the Australian Smart Traveller website, but essentially all travel has now been banned. SHOULD I HAVE THE FLU AND PNEUMONIA VACCINATIONS? It is recommended that all persons with MS and related disorders have the flu vaccination when it becomes available in April. The Pneumococcal vaccination is also recommended. WHAT IF I AM A HEALTHCARE WORKER? At present we have no evidence of an increased risk of COVID-19 infection or its complications in people with MS or related conditions, even in those on treatment. However, as indicated below there are potential, theoretical risks with some medications and it would be sensible for healthcare workers on any of these therapies to avoid work environments that would bring them into direct contact with people either known to be or likely to be infected with COVID-19. If you require any documentation to this effect, please contact your neurologist who will be happy to assist. WHAT SHOULD I DO ABOUT MY MEDICATION? If you are on a regular medication for MS or a related condition, then it is recommended that you should continue to take this medication because of the very real risk of relapse when medication is ceased. With regards to specific therapies:
Signatories Simon Broadley Michael Barnett Todd Hardy FOR THE LATEST UPDATES VISIT THE COVID-19 INFORMATION FOR PEOPLE WITH MS HUB ON OUR PARTNER ORGANISATION MS AUSTRALIA’S WEBSITE
MS Research Australia |
The hypothesis that immunosuppression may protect you from severe COVID-19 is gaining traction. New data released on the 4th April 2020 from the UK’s Intensive Care National Audit & Research Centre suggests it may. When comparing 2249 patients admitted to ITU in the UK with severe COVID-19 the proportion of immunocompromised patients was 3.7x lower than the proportion of immunocompromised patients admitted to ITU with viral pneumonia (the comparator) between 2017 and 2019 (2.3% vs. 8.5%). This was a highly significant difference (p<0.00001).
This clearly justifies the current research strategy being tested across the planet to see if immunosuppressive therapies may improve disease outcome in patients with COVID-19.
Does this mean we can now assume that immunosuppression protects against severe COVID-19 and COVID-19-related ARDS (adult respiratory distress syndrome)? Not yet. The UK’s ITU cohort of severe COVID-19 is biased in that those patients who are deemed too frail and/or disabled may never get to ITU, which may include a disproportionate number of immunosuppressed patients. Whereas this specific bias is unlikely to apply to ITU admissions between 2017 and 2019 (viral pneumonia cohort) when there was no such pressure on resources.
Despite this caveat, this is an important tidbit of information that will allow pwMS on immunosuppression to sleep a bit easier. I sincerely hope the wider MS community will reconsider their advice about not giving MS DMTs that are if anything mildly immunosuppressive to patients with active MS. By not treating our patients we may unintentionally be increasing their chances of developing severe COVID-19. Could our guidelines be another example of the law of unintended consequences? Let’s hope the real-world data that is being collected at present will answer this question.
CoI: multiple
If you have MS and think you are vulnerable to severe COVId-19 have you asked the obvious question? How long do I shield or self-isolate for?
The impact of Boris Johnson’s admission to ITU with severe COVID-19 on the collective mind of the UK will be substantial. I suspect pwMS who think they are vulnerable will now go into shielding mode in an attempt to never get exposed to SARS-CoV-2. Is this a feasible long-term strategy?
Yes, trying to never get infected with SARS-CoV-2 and waiting for a vaccine is one feasible option if this was in-line with the governments COVID-19 strategy. However, at the moment the government strategy is not clear. Without aggressive testing, case and contact finding and local quarantine programmes we have to assume their current strategy is still trying to flatten-the-curve and extending-the-tail of the epidemic until herd immunity does the job and the COVID-19 epidemic fizzles out. This strategy will take many many months to run its course during which vulnerable people will need to remain shielded. Shielding has social and mental-health consequences that most of us have yet to appreciate.
Active surveillance and contact tracing are what is being done in China, Korea and Singapore. The downside of the latter is that it takes hard work. Already in Singapore, we have seen a second flare, i.e. the peak appeared to come and gone, but once social distancing regulations were being lifted the epidemic flared-up again.
I think there is some disagreement between public health officials, epidemiologists and politicians which is the best approach to take. It would help if we had better data on how many of the population had already been infected with the virus, but we don’t. Current estimates on the proportion of the population who may have already been infected vary wildly. A major blow is a laboratory study from Oxford showing that the point-of-care finger-prick antibody tests to see if you have had SARS-CoV-2 don’t work very well. This means we will have to resort to the doing standard laboratory tests for antibodies on whole blood samples. This doesn’t matter; it is better to get reliable data that will allow the modellers to work-out what is best for the UK to quell this epidemic and to allow us to get back to business, which for me is treating pwMS and studying MS.
I reviewed a patient with MS in my telemedicine clinic yesterday. He has classified himself as being vulnerable, which I don’t agree with, and has put himself into shielding. He is quite disabled and hence has stopped his carers coming into his house. He is now having to battle with doing his own domestic chores, cooking his own food and doing his own on-line shopping without help. This is complicated by the fact that he is often incontinent, which creates an extra burden on personal hygiene. He has a dog that needs walking, which he is battling to do in his small back garden. His is clearly under a lot of stress. I am not convinced his position is tenable for much longer. He is just one example of how the COVID-19 epidemic is affecting individuals with MS.
This is why we need to start planning an exit strategy for pwMS. When do we start derisking patients, i.e. taking them off the vulnerable list and managing them face-2-face, encouraging them to reconnect with their families and friends, and eventually the wider community? Do we wait for herd immunity? Do we wait for a vaccine? Do we wait for a reliable antibody test and derisk/reintegrate those that are antibody positive? Do we tell our low-risk patients that it is okay to get COVID-19 because once you have had the infection you are then immune to reinfection? Or do we wait for the government to say now is the time to get back to normal? When do we start redosing alemtuzumab and other DMTs and restart our HSCT programme? When do we restart our clinical trials? Many questions and no answers.
If I was in charge of government policy I would hedge my bets and implement both strategies, i.e. (1) case and contact finding with quarantine and (2) flattening-the-peak and extending the tail of the epidemic until we have herd immunity. Once the seroprevalence data comes in; i.e. what proportion of the population has been infected asymptomatically and have early data from vaccine trials we can then definitively commit to one of the two paths based on data.
At the moment I am very frustrated; we are fighting a tactical war without a longterm strategy in place. Sadly, with Boris Johnson in ITU will there be anybody in government, with the power and chutzpah, to make a strategic decision?
