#MSCOVID19: Why is cladribine so misunderstood?

Because cladribine and alemtuzumab are classified as immune reconstitution therapies (IRTs), and probably work in a similar way, they are tarnished with the same brush. However, cladribine’s immune depletion and reconstitution, and adverse event profile are very different to alemtuzumab’s and therefore cladribine should be considered on its own when weighing up the risks and benefits of treating highly-active MS during the COVID-19 pandemic. For example, the advice that pwMS need to shield after cladribine treatment is a very harsh call and in my opinion unnecessary. Why? 

The following are the points concerning cladribine in the latest version (19-May-2020) of the ABN GUIDANCE ON THE USE OF DISEASE-MODIFYING THERAPIES IN MULTIPLE SCLEROSIS IN RESPONSE TO THE COVID 19 PANDEMIC

EXECUTIVE SUMMARY

5. The effect of DMTS on the risk of SARS-CoV2 infection and COVID 19 disease remains uncertain and we commend pwMS and MS teams to continue to submit data to the UK MS Register study of COVID 19. We recommend that patients are counselled on the effect of a DMT on their individualised risk of COVID 19 disease, taking into account its duration of action; any comorbidities; and also the DMT’s impact on the efficacy of any future SARS-CoV2 vaccine. Patients should be informed if their treatment choice requires shielding [especially cladribine and alemtuzumab].

11. Cladribine should be started cautiously on a case-by-case basis when the risk of SARS-CoV2 is very high. Re-treatment should be delayed until the risk of infection is level 3 or below.

14. pwMS with mild symptoms of COVID-19 should not stop first-line DMTs, but infusions [and cladribine administration] should be delayed until symptoms resolve.

C. THE RISK OF COVID-19 IN PEOPLE WITH MS [PWMS] ON DISEASE MODIFYING THERAPIES [DMTS] 

11. There is very limited experience4 of pwMS on cladribine becoming infected with SARS-CoV2 and the SmPC warns of herpetic viral infections being “common”. However, it may be considered on a case-by-case basis. When and where the rate of SARS-CoV2 infection is very high, the risks of increased infection for three months after cladribine administration, and the advice to shield, may outweigh its benefits.

D. DMTS IN PwMS WITH ACTIVE COVID 19 INFECTION

14. pwMS with mild symptoms of COVID-19 should not stop a first line DMT, but infusions [and cladribine administration] should be delayed until symptoms resolve.

We know that anti-SARS-CoV-2 immunity requires innate immune responses (neutrophils and macrophages) and T-cell responses (predominantly CD8+ responses) to clear the virus. Cladribine does not deplete monocytes and neutrophils and has a modest impact on CD8+ve T-cells. Therefore t is unlikely to have a major impact on anti-SARS-CoV-2 immunity. 

On cladribine, T lymphocytes are in general depleted by about 40% and the vast majority of patients don’t drop their counts below 500/mm3. In the T-cell compartment, the CD8+ T-cells are much less affected than CD4+ T-cells. This is important because CD8+ T-cells are the cells responsible for fighting viral infections and explains, apart from a small risk of herpes zoster reactivation, why we didn’t see an increase in viral infections compared to placebo in cladribine treated subjects in the phase 3 trial programme. 

In the phase 3 programme about a quarter of patients had a transient grade 3 or 4 lymphopaenia, but this tended to occur after the second course in year 2 in subjects who were redosed when their lymphocyte counts in year 1 had not yet recovered to above 800/mm3 (per-protocol dosing). We have used the trial data to model grade 3 and 4 lymphopaenia (<500/mm3), and estimate that less 7% of cladribine treated subjects will develop lymphocyte counts less than 500/mm3 if we stick to the cladribine redosing guidelines. This is important because most of the cases of zoster were in subjects who developed grade 3 or 4 lymphopaenia, which implies the risk of getting herpes zoster in real-life (post-marketing) is likely to be much lower than what we saw in the clinical trials.  

Should we be so hung up about the lymphocyte count? When we explore the safety data of oral cladribine, from both the trial programme and post-marketing surveillance, we really don’t see a significant viral infection signal in cladribine-treated subjects. The viral infections that did occur tended to be non-specific upper respiratory tract infections and were mild to moderate. The following presentation is data that we recently presented at the AAN and EAN meetings and illustrates how uncommon viral infections are in pwMS treated with cladribine. 

Based on these data I really don’t think it is necessary to for pwMS to shield during the current pandemic. All they need to do is maintain social distancing, practice good personal hygiene and avoid contact with potentially infectious people. This means that pwMS working in high-risk professions (healthcare and care sector workers with direct patient contact) who are treated with cladribine should not have direct patient-facing activities until they have recovered their lymphocyte counts to a safe level (>500/mm3 in people less than 60 years of age and >800/mm3 in those older than 60 years). 

Although, cladribine is a remarkably good depleter of B-cells the B-cell numbers return quite quickly. The reconstituted B-cells are initially naive B-cells, which come from the bone marrow and are not memory B-cells. This is important for vaccine-readiness if a SARS-CoV-2 vaccine does emerge.

In comparison to cladribine, ocrelizumab and rituximab are given as maintenance or continuous therapy there is a small increase in the incidence of serious infections over with time and the development of hypogammaglobulinaemia, which is not seen with cladribine. Once the immune system reconstitutes post-cladribine it can fight infections, immune survey the body for cancers and mount immune responses to new viral infections, such as SARS-CoV-2, and vaccines. In relation to vaccines both live and inactivated component vaccines can be given after cladribine. 

The other important thing about cladribine is the monitoring requirements are low. Once you have had a course you only need a full blood count to be done 3 and 7 months after starting treatment. The rationale for this is that the 3-month time-point is where the nadir occurs and the 7-month time point is to check for recovery of lymphocyte counts. 

Another advantage of cladribine is that as a small molecule it penetrates the CNS; cerebrospinal fluid (CSF) levels are about 25% of what is found the peripheral blood and at a level that would target B- and T-cells within the brain and spinal cord. I think this property of cladribine is very important and is one of the reasons why we are exploring cladribine as a treatment for progressive MS in the CHARIOT-MS trial. 

I think cladribine is a very misunderstood DMT and has been hard done by in the COVID-19 treatment guidelines which in general are not evidence-based nor are they necessarily based on basic immunological principles.

As the COVID-19 pandemic is likely to have a long tail with a vaccine 18 to 24 months away I think we the MS community should reconsider our position on oral cladribine as cladribine addresses many of the issues of treating highly active MS in these troubling times and it has the added advantage of leaving people with MS with a reconstituted vaccine-ready immune system if and when a SARS-CoV-2 vaccine arrives. 

Please note that I am not saying cladribine is safe; no DMT is safe. However, cladribine has a very well-defined risk-benefit profile that is less risky than what is been suggested in the ABN guidelines. The risk-benefit profile of cladribine simply allows you to counsel patients with highly-active MS about their treatment options during the COVID-19 pandemic and cladribine deserves to be part of that discussion. 

CoI: multiple, but in particular I was the principal investigator on the oral cladribine phase 3 trial and have been involved with the development of oral cladribine as a treatment for MS since 2002. 

East Africa and MS

COVID-19 impact has extended to East Africa. Instead of a face-to-face meeting, the East African Neurologists have moved their CPD (continuing professional development) online in the form or regular webinars. In the past, I would probably have had to travel to East Africa to give a guest lecture at their annual meeting. Post-COVID-19 I can now do this online, which is a much cheaper and greener option for the environment and much more time-efficient for all concerned.

The other advantage of webinars is that the CPD event doesn’t have to be geographically limited in that people can register and log-in from all over the world. This is taking the democratisation of knowledge and learning to the next level and is one of the reasons that motivated me to start triMS.online.

So if you are not from East Africa and you want to attend the webinar below please do not hesitate to register online and log-in tomorrow. Places are limited.

CoI: multiple

#MSCOVID19 Anti-CD20 therapies and vaccines

Have we optimised the dose of anti-CD20 therapies to target the real MS or smouldering MS, i.e. disease progression independent of relapse activity (PIRA)?

I did an iWiMS webinar on Wednesday covering anti-CD20 therapies and the risk of COVID-19 and severe COVID-19. I covered vaccine responses and how to be vaccine-ready or vaccine responsive to a future SARS-CoV-2 vaccine if you are on an anti-CD20 therapy.

I also discussed optimising the dose of anti-CD20 therapies making the point we may need much higher doses than what we currently use to treat MS. The latter is because we have been blinkered by the impact of anti-CD20 therapy on focal inflammatory events, i.e. relapses and MRI lesions, when the real MS (disability/smouldering MS) appears to more responsive to higher doses of anti-CD20 therapies.

I re-recorded my lecture to spend more time on why these issues are important for people with MS. I have also shared my slides below.

CoI: multiple

#MSCOVID19 info wars

It is one thing calling for scientists to turbocharge the development of a coronavirus vaccine but quite another to get the population to have the vaccine. The anti-vaxxers are organising rapidly and have started circulating content with false information to achieve their aims. The movie plandemic is one example and is covered in a very good article in the New York Times today.  

The primary reason I started this blog was to counteract anti-science movements and to provide people with MS and their families a rational interpretation of MS-related research. It is interesting to note that there is now good data science to show how anti-science movements, despite having very few initial supporters, get their message across and sow enough confusion to get undecided people to support their movement. 

What I find fascinating, albeit scary, is how dynamic and multifaceted the anti-vaccination campaigns are, which explains their explosive growth in recent times (see figure and paper below). It also shows how gullible people are in general. The study below highlights why we scientists need to fight back using the same tactics. Simply sitting in our ivory towers using traditional media and unidirectional channels will not be good enough to fight the anti-vaccination and other anti-science movements. 

I have a vested interest in this. One of our lines of research is to use an anti-EBV vaccine to prevent MS. If people don’t want vaccines how are we going to get this prevention strategy adopted by funders, ethics committees and more importantly the general population? 

Can you help? Yes, please help fight fake news, by reporting it and calling it out for what it is. And don’t believe the fabricated conspiracy theories that are peddled to support these anti-science movements. The vast majority of conspiracy theories are wrong.

Image from Johnson et al. The online competition between pro- and anti-vaccination views. Nature published: 13 May 2020.

Johnson et al. The online competition between pro- and anti-vaccination views. Nature published: 13 May 2020

Distrust in scientific expertise is dangerous. Opposition to vaccination with a future vaccine against SARS-CoV-2, the causal agent of COVID-19, for example, could amplify outbreaks, as happened for measles in 2019. Homemade remedies and falsehoods are being shared widely on the Internet, as well as dismissals of expert advice. There is a lack of understanding about how this distrust evolves at the system level. Here we provide a map of the contention surrounding vaccines that has emerged from the global pool of around three billion Facebook users. Its core reveals a multi-sided landscape of unprecedented intricacy that involves nearly 100 million individuals partitioned into highly dynamic, interconnected clusters across cities, countries, continents and languages. Although smaller in overall size, anti-vaccination clusters manage to become highly entangled with undecided clusters in the main online network, whereas pro-vaccination clusters are more peripheral. Our theoretical framework reproduces the recent explosive growth in anti-vaccination views, and predicts that these views will dominate in a decade. Insights provided by this framework can inform new policies and approaches to interrupt this shift to negative views. Our results challenge the conventional thinking about undecided individuals in issues of contention surrounding health, shed light on other issues of contention such as climate change, and highlight the key role of network cluster dynamics in multi-species ecologies.

CoI: we are planning to do an anti-EBV vaccine study to prevent MS

#MSCOVID-19: how to prevent yourself from getting COVID-19 in your own home

What can do I to prevent myself from being infected with coronavirus if someone in my household gets COVID-19? 

This is a topic that I have not covered directly, but it is obviously very important and an oversight on my part. Apologies. 

The following advice is pretty intuitive and has been hacked from an amazing website, by the Univesity of Southampton, called Germ Defence. If you have the time can I suggest you ignore this post and go through Germ Defence’s short online programme? Although not COVID-19 specific it gives out generic and very sensible advice and only takes 10 minutes to complete. 

Image from Germ Defence, University of Southampton.

Ideally, the person who has COVID-19 should spending as much in their own space so that you are less likely to come in contact with them. This could be in their own room or a room in the house that other people should not enter. I am aware that this may not be feasible depending on your circumstances. 

It is important not to share a bed with the person who has COVID-19 or you think may have coronavirus.

Please open your windows and limit the amount of time you are in a room with the person who has COVID-19. Also, try to spend time outdoors if you can. 

If possible socially distance at home; i.e. try and keep 2 meters away from the person with COVID-19. 

Try and organise your home so that you have more space between seats. If it is possible arrange to use shared areas of your home, for example, the bathroom, at different times, so that only one person is in there at any time. 

Try and kill any viruses by frequent cleaning. It may be impossible to avoid shared areas of the home, such as kitchens and bathrooms, so keeping them clean, very clean, is important. Try and use a disinfectant to clean surfaces that the affected person may touch, e.g. taps, fridge, door handles, toilet seat, toilet handle, remote controls, computer keyboards, gaming consoles, etc. Wipe down surfaces such as tables, kitchen tops, fridge and freezer doors, seats, remote controls, keyboards, etc. 

Place bottles of disinfectant in key areas of the house so that they are quick and handy to use. 

Try to avoid sharing or touching things that other people have used, e.g. bottles, kettle, towels, fridge, taps, toothpaste, remote controls, telephone, etc., unless you know that they have been cleaned recently with disinfectant. 

It can take up to 3 days (72 hours) for the coronavirus to completely die on hard surfaces. So if there are things that you can’t clean, can you put them somewhere out of the way for 3 days before you use them. If 3 days isn’t possible, then aim for as long as possible. 

The person with COVID-19 should wear a mask. Similarly, if you need to spend time with the person who has COVID-19 then wearing a mask can stop you breathing any infectious particles that are spread through coughing and sneezing. 

Try and not touch your face, in particular your nose and mouth. This is very hard so you need to concentrate and train yourself to be aware of what your hands and fingers are doing. 

Try to limit the time you spend close to other people in the house as well. They may be incubating and shedding the virus asymptomatically. 

CoI: none

#MSCOVID19 ocrelizumab

Roche is the first company to publish their data on how patients with MS are doing with COVID-19 who are being treated with ocrelizumab. Please note the data is on the first 100 cases that have been reported to Roche via their adverse event (AE) reporting mechanisms. Twenty-six of the cases have been reported as being severe with 5 being critical (see table below). These figures are pretty much in line with what happens in the general population in relation to COVID-19 outcomes with a similar proportion of severe and critical cases.  The one caveat is that ocrelizumab-treated patients may be younger and have fewer comorbidities than the general population.

Some of my colleagues have accused Roche of hiding data and selective reporting. Why would they do that? Pharma’s pharmacovigilance systems are transparent and open to audit by the regulators. It is not in Roche’s interests to not be open and frank about their data. At the end of the day, the data is what it is and we need to use it to help us make decisions about treatment.

I agree the data is full of warts and open to interpretation. It is likely to be biased in that clinicians are more likely to report hospitalised and severe cases as AEs and miss the milder cases. For example, I have collected 9 patients who have likely had COVID-19 over the last 8-10 weeks. Only one of these nine patients was admitted to a hospital with moderate COVID-19. In this case, the COVID-19 syndrome was confirmed on chest x-ray and other clinical features and her nasopharyngeal swab was positive for SARS-CoV-2. She was fortunately discharged after 4 days well and didn’t need any ventilatory support. The other 8 patients with MS all self-isolated and recovered at home and had no swabs taken. Only the admitted patient is part of the UK’s official figures the other 8 cases are not. Patients with COVID-19 who have mild disease, who don’t come to the hospital to get swabbed don’t get counted in the official figures. The same phenomenon is almost certainly happening with ocrelizumab and our other DMTs. Mild cases are not getting swabbed, diagnosed and reported. I, therefore, suspect that the Roche data represents the worse end of the spectrum. 

Overall the Roche data is in keeping with the Italian, French and other registry data that people with MS on ocrelizumab don’t appear to be at higher risk of getting severe COVID-19. This also needs to be interpreted in the context of the immunology of COVID-19 and SARS-CoV-2. It looks as if innate immunity (monocytes and macrophages) and T-cells, in particular CD8+ T-cells, are the most important lines of defence against SARS-CoV-2. The fact that two patients with X-linked agammaglobulinaemia recovered from COVID-19 and that anti-CD20 treated patients with no B-cells in the peripheral blood are recovering from COVID-19 tells you that B-cells are not essential for the antiviral response. The latter is also in keeping with the trial data that patients on B-cell depleting therapies don’t seem to have a problem dealing with viral infections. 

Could there be an upside to B-cell depletion? Yes, I suspect there may be. As the humoral or antibody response emerges antibody-mediated damage to lung with complement activation may be responsible for some of the delayed tissue damage that occurs in COVID-19. This is why it will be important to get more data and better-defined comparator groups to see if anti-CD20 therapy treated patients may be doing better than expected. The recently presented Swedish data suggests not. However, the Swedish data is on rituximab, and not ocrelizumab, and the rituximab doses used in Sweden may not be high enough to block antibody responses to SARS-CoV-2 and hence the data can’t simply be extrapolated to ocrelizumab or vice versa. For those of you who don’t know ocrelizumab is a much more potent B-cell depleter than rituximab. 

Now, what about vaccine readiness? Are people on ocrelizumab less likely to develop an antibody response after COVID-19 and if they do is the antibody response good quality, i.e. capable of neutralizing the virus and preventing reinfection? We are in the process of validating an ultrasensitive assay and doing an antibody study to answer this question. So watch this space. 

Even if antibody responses to SARS-CoV-2 are blunted in ocrelizumabers, who have had COVID-19, this doesn’t mean they are not immune to reinfection. Cellular responses are likely to be sufficient to prevent reinfection. The latter has been shown to occur with the measles virus. 

Vaccine readiness may become a real issue if a vaccine for SARS-CoV-2 emerges. However, I suggest crossing that bridge when we get there. With anti-CD20 therapies, all you will have to do is miss a dose or two, wait for naive B-cell reconstitution and then have the vaccine. We have very good data that after 3 or 4 courses of ocrelizumab missing infusions for the next 12-18 months is unlikely to affect MS disease activity. The latter observation is why we are still planning to do an adaptive-dosing study in the UK (ADIOS Study). 

I personally want to congratulate and thank Roche for putting their data into the public domain so rapidly. I have asked other Pharmaceutical companies to do the same. Having access to this data alongside other real-life data sets is what we and others are using to adjust treatment guidelines and is why we as an MS treatment centre are starting and redosing patients with MS with ocrelizumab. At last, we can say our practice is evidence-based rather than opinion-based. 

Hughes et al. COVID-19 in persons with multiple sclerosis treated with ocrelizumab – a pharmacovigilance case series. MSARDs Available online 16 May 2020, 102192.

CoI: Multiple. Importantly I am a steering committee member on the ocrelizumab phase 3 development programme and I am PI on the ORATORIO-HAND study of ocrelizumab in PPMS.

#MSCOVID19 Boris Johnson is obese

Obesity has taken centre stage after Boris Johnson admitted that his recent coronavirus scare may have been related to his obesity. He is now pledging to do something about it. His sudden interest in the UK’s obesity problem is getting a lot of ink space in both the tabloids & broadsheets and airtime on radio & TV. Andrew Marr even covered it this morning on his BBC talk show. Will anything become of it? 

A few weeks ago when I was on the medical wards there was a social media shit storm when Krispy Kreme doughnuts pledged to give NHS staff free doughnuts and dropped off a free delivery to the Royal Free staff. The issue, raised by many critics, is that Krispy Kreme (big business) and doughnuts (ultra-processed foods) represent the problem with our food environment.

Yes, we have a massive problem in the UK. Well over 50% of calories consumed in the UK are from ultra-processed foods (see study below), which are produced by the large food companies. These foods increase dramatically the amount of free sugar we consume and hence drive up insulin levels and over time it causes the cascade that leads to obesity, impaired glucose tolerance, insulin resistance and the metabolic syndrome.

What needs to be considered is that the consumption of ultra-processed foods and the associated obesity epidemic are a core component of the social determinants of health (SDoH). For Boris Johnson to address obesity from a political perspective he is going to have tackled a much wider set of social issues. Is he up to it? I doubt it. However, I am hopeful that the COVID-19 epidemic, his near-death experience and resulting social consequences of the lock-down will give him the necessary motivation to support a ‘nanny state’ that he as always so despised in the past. 

Historians have been pointing out that it often takes an international crisis to bring people together for the common good and to make them realise that we are all in it together.  A good example is the NHS; it was created in response to the sense of togetherness induced by the national response to the second world war. I suspect the same thing will happen post-COVID-19. It is predicted that all politicians will move left and more money and resources will be lavished on social spending. Let’s hope this reduces inequality, improves education and the lived environment and tackles our reliance on cheap processed and ultra-processed food. The consequences could be slimming down of the national waistlines and a healthier nation. 

How is this relevant to MS? Getting ready for having COVID-19, which may be just around the corner for many of us, is maximising our chances of not getting the severe form of the disease. To do this you may have to improve your lifestyle and get all your comorbidities treated and under control. For some of us this may be shedding a few pounds. I am aware that this is easier said than done, which is why I would recommend you consider trying intermittent fasting or a low carbohydrate diet. The good thing about these two diet options is that they may have additional benefits for your MS.  

Fernanda Rauber et al. Ultra-Processed Food Consumption and Chronic Non-Communicable Diseases-Related Dietary Nutrient Profile in the UK (2008⁻2014). Nutrients. 2018 May 9;10(5):587.

We described the contribution of ultra-processed foods in the U.K. diet and its association with the overall dietary content of nutrients known to affect the risk of chronic non-communicable diseases (NCDs). Cross-sectional data from the U.K. National Diet and Nutrition Survey (2008⁻2014) were analysed. Food items collected using a four-day food diary were classified according to the NOVA system. The average energy intake was 1764 kcal/day, with 30.1% of calories coming from unprocessed or minimally processed foods, 4.2% from culinary ingredients, 8.8% from processed foods, and 56.8% from ultra-processed foods. As the ultra-processed food consumption increased, the dietary content of carbohydrates, free sugars, total fats, saturated fats, and sodium increased significantly while the content of protein, fibre, and potassium decreased. Increased ultra-processed food consumption had a remarkable effect on average content of free sugars, which increased from 9.9% to 15.4% of total energy from the first to the last quintile. The prevalence of people exceeding the upper limits recommended for free sugars and sodium increased by 85% and 55%, respectively, from the lowest to the highest ultra-processed food quintile. Decreasing the dietary share of ultra-processed foods may substantially improve the nutritional quality of diets and contribute to the prevention of diet-related NCDs.

CoI: multiple

#MSCOVID19 super-superspreader

A single man triggered a massive contact tracing exercise in Seoul, South Korea, after visiting 5 nightclubs in a Seoul neighbourhood on a weekend and later tested positive for COVID-19.

Not only does this case highlight the scope of the response which can be triggered by one infected individual but the willingness of Korean authorities to use mobile phone data, credit card data and CCTV footage to track down individuals who could have come into contact with the virus.

I wonder how citizens of other countries would feel about this? This is real big brother stuff.

Do you think the UK Government is up to the task of whack-a-mole to this degree?

The Korean Centers for Disease Control and Prevention said that as of 13th May, 119 new infections have been traced back to the 29-year-old and that 5,517 fellow clubgoers have been contacted in the process. This has led to 7,272 additional tests being administered on Tuesday (on top of the baseline of 4,000 to 5,000 tests carried out daily in the country) to patrons and their families/immediate contacts. Authorities said they had identified a total of more than 11,000 people who had been in the general area on the night in question.

Out of the 5,517 people who authorities are seeking contact with, 1,982 have so far not replied, showing that even a sophisticated method is not perfect. Since the bars and clubs in question catered to gay audiences, Korea’s traditional stance on sexual identity could be hampering peoples’ will to come forward.

This case also redefines how infectious a superspreader can be. May be he should referred to as a super-superspreader?

#MSCOVID19 De-deployed

This is a very good news post and worth a quiet celebration. 

As you can see from the study and figure below that Barts Health NHS Trust, where we work, was at the epicentre, of the epicentre of the UK’s COVID-19 pandemic. London has had the most COVID-19 cases in the UK and it looks as if the majority of cases where managed in our four COVID active hospitals. This graph shows just is how effective the London lockdown has been in flattening the peak of the epidemic. 

The bars show you the proportion of asymptomatic HCPs (healthcare professionals) who tested positive for SARS-CoV-2 on consecutive weeks from March 23, 2020: 

28 of 396 HCPs (7.1%) in week 1
14 of 284 HCPs (4.9%) in week 2
4 of 263 HCPs (1.5%) in week 3
4 of 267 HCPs (1.5%) in week 4
3 of 269 HCPs (1.1%) in week 5

Importantly of the 44 HCPs who tested positive for SARS-CoV-2, 12 (27%) had no symptoms in the week before or after positivity. Although I was not one of the HCPs in this survey there is a chance that I have been exposed to SARS-CoV-2, which is why I am volunteering to get myself tested next week to see if I have antibodies to the virus. Knowing I have been infected or not will clearly affect my behaviour. This is why it is so important for widespread antibody testing to happen ASAP. 

If you generalise these results to the wider HCP population, then so-called asymptomatic SARS-CoV-2 infection rates among HCWs tracked the general population infection curve in London. This suggests that the rate of asymptomatic infection among HCPs more likely reflects general community transmission rather than in-hospital exposure. 

So if you are one of our, Barts-MS, patients these results should be very reassuring and as the overall epidemic wanes asymptomatic infection among us, your MS team is likely to be low and we are unlikely to be a major source of virus transmission. This means you need not fear us when we resume face-2-face consultations. 

The other good news is that we now have so few new COVID-19 admissions at the Royal London Hospital that we have started closing down some of the extra medical wards that were created to deal with the surge. This means my services as a make-shift general physician are not required anymore and I have been de-deployed back to being a neurologist and MSologist. I hope this means that we will be able to resume our MS services, albeit with adaptations to make sure social distancing is maintained, very soon. 

Treibel et al. COVID-19: PCR Screening of Asymptomatic Health-Care Workers at London Hospital. Lancet. 2020 May 8;S0140-6736(20)31100-4. 

CoI: I work at the Royal London Hospital, which is one of five hospitals of Barts Health NHS Trust.

#MSCOVID19 Endemic musings

Fudging the issues or bumbling along is how the public, opposition politicians and the journalists are interpreting the Government’s handling of the exit strategy for the COVID-19 epidemic in the UK. I don’t agree. I think the Government has a clear plan, which is being driven primarily by economic considerations. 

The primary objective of the lockdown was to protect the NHS and this has been successful. Well done! The primary objective of handling the epidemic’s tail is to get the country back to work and to try and turn COVID-19 into an endemic disease. 

For those of you who are not epidemiologists, an epidemic is the rapid spread of disease to a large number of people in a given population within a short period of time compared to endemic infection when that infection is maintained at a constant baseline level in the population.

Making COVID-19 endemic is like walking on a tightrope. By allowing very young children back to school first who are unable to self-isolate effectively is asking them to spread the infection amongst themselves, their siblings and their parents who will all be relatively young and at low risk of severe COVID-19. This will allow the gradual spread of infection to continue in the community and the gradual build-up of herd immunity. Most people I speak to don’t seem to understand this.

At the same time, the more vulnerable groups in the population have been asked to continue shielding and to be extra cautious about avoiding getting infected with SARS-CoV to reduce the risk of a second surge in the epidemic, protect the NHS and to keep the death rate relatively low. 

The Government is also putting in place the whack-a-mole strategy of active case finding and contact tracing to try and control local COVID flares. The whack-a-mole strategy is working well in China, South Korea and Singapore and it will almost certainly work well here if it is properly resourced.

The introduction of widespread antibody testing, with a reliable assay, to see who has been infected with SARS-CoV-2 will allow epidemiologists to track herd immunity and to finesse the Government’s strategy. The idea of getting a COVID-19 passport to show that you have been previously infected and are now immune to getting further infections, at least in the short-term, is unlikely to happen within the UK but may be required for safe international travel or to attend outpatient clinics or be admitted to cold (COVID-negative) hospitals for invasive procedures, etc. The latter is analogous to what happens with multi-drug resistant staphylococcus in clean surgical units in the NHS. Before you are allowed to be admitted for elective surgery you have a nasal swab taken to make sure you are not carrying the multi-drug resistant bacterium.

If the Government can allow herd immunity to gradually increase and to keep the R-value for the whole population at about 0.8 to 1.0 they will achieve their aims of making COVID-19 endemic, getting the economy going again and protecting the vulnerable. Clearly, this strategy will be a bit hit-and-miss and there will be collateral damage, i.e. people will continue to get severe COVID-19 and a proportion of them will die as a result. To expect anything else is unrealistic, which is why I find the posturing of the opposition politicians bewildering, to say the least. What is their solution; perpetual lockdown until we get a vaccine?

Most people think that a vaccine is the government’s end-game. I don’t want to disappoint you but there is no guarantee that a vaccine will work. I also worry that if the whole world exits lock-down with a trickle of cases we may not be able to test vaccines in an efficient manner. 

To develop and test an effective vaccine we really need the COVID-19 epidemic to be in full swing, i.e. on the upside of the curve and not on the tail. A vaccine trial is like a drug trial; subjects are randomised to an active or SARS-CoV-2 vaccine arm or a comparator arm (placebo or another vaccine) and then you see whether or not there are fewer cases of COVID-19 on the active arm compared to the comparator arm. However, if there are too few cases developing COVID-19 because of social distancing, using face masks, hygiene measures, etc. it will take too long to get enough events or trial subjects getting COVID-19, to show the vaccine is working. There is a way around this and that is to shift to an active-challenge vaccine paradigm, i.e. to get groups of young volunteers who are anti-SARS-CoV-2 antibody negative and to randomise them to receive the vaccine or placebo and to then challenge them with the live virus. This is how they test the effectiveness of the seasonal flu vaccine each year. You may ask why would anybody take the risk of getting COVID-19 and severe COVID-19 voluntarily? The answer is money. These volunteers tend to be paid very handsomely for their time. 

Another factor that may help the Government is that summer is on its way and as the temperature rises the less infectious coronaviruses become. SARS-CoV-2 viral particles are temperature sensitive and are viable for much shorter periods of time outside the body in hot climates. This may explain why we haven’t seen such rampant spread of the virus in warmer climates. 

I think Boris Johnson’s recent bumbling performances when questioned about the Government’s exit strategy is deliberate so as to avoid questions about herd immunity, whack-a-mole and collateral damage. The sad truth is that at some point we as a society are going to have to realise that quite a large number of people are still going to have to die from COVID-19 as part of the exit strategy to get us to a point when we can chop off the tail of the UK’s COVID-19 epidemic. The consequences of not doing this are potentially far worse for the UK in the longterm. For example, some epidemiologists predict that the increase in poverty and inequality that the COVID-19 epidemic has caused will result in more excess deaths than the number of people dying from severe COVID-19. This may be hard to comprehend, but the social determinants of health have a powerful effect on health, health outcomes and survival. The challenge for the government is getting the balance right, which is what they are trying to do.

I would be interested to know if any of you have any thoughts on these issues. 

CoI: none

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