#MSCOVID19: wow!

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I am on call at the Royal London Hospital and sitting in my office digesting some of my daily COVID-19 reading. However, something has just hit me between the eyes and I have to say wow aloud! 

WOW!!

The paper and editorial below show you just how infective SARS-CoV-2 really is and why we are not going to win this battle for our vulnerable people without an effective anti-viral and/or vaccine. It also tells me that if we don’t get a vaccine things will not normalise for a very long time. 

Who said the R0 (R-zero) for this virus was less than 3 and therefore we would get herd immunity at about a 60% seroprevalence rate? Not me! 

R-zero or the basic reproduction number for SARS-CoV-2 is the expected number of cases infected by one case in a population where all individuals are susceptible to infection. The original calculations were based on symptomatic index cases and symptomatic contacts with positive swabs. The fact that a large number of people (possibly up to 50%) have now been shown to get asymptomatic infections and that the test for the virus is not 100% specific. This means that approximately 25% of cases with COVID-19 defined by clinical definition have negative nasopharyngeal (nose & throat) swabs; i.e. 25% of infected people who may be shedding are not detected with the swab test. Based on these assumptions I have estimated that in normal life (no social distancing) that the R-zero is likely to be somewhere between 6 and 7. This means that to get herd immunity, a point when natural transmission in the population stops, you need somewhere between 80% and 86% of the population to have immunity. 

However, the study below just published in the New England Journal of Medicine makes me think this may even be an underestimate. In a well done ‘classic’ epidemiology study in a nursing home in Seatle, 23 days after the first positive test result in a resident, 64% tested positive for SARS-CoV-2; more than half (56%) of the residents were asymptomatic at the time of testing. Only half of these residents then went on to develop symptoms a few days later. A quarter of shedders never became symptomatic and most of these ‘asymptomatic shedders’ were shown to shedding viable virus. Tragically of the 57 residents who were shown to be infected with SARS-CoV-2 infection 15 died; a mortality rate of 26%. 

Why is this so important? In short, a high or very high R-zero means that the government policy of relying on herd immunity to protect the vulnerable is not going to work.

Let me explain. Whilst we are socially distancing we reduce the R-zero of SARS-CoV-2 to less than 1 and hence the number of new cases falls and we flatten the curve. This is what is happening in the UK and many other countries at present. However, as soon as we stop the lockdown and allow social interaction the R-zero will rise above one and we will get more cases. But because this virus is so infectious we may need herd immunity to be well above 80% (possibly 90%) for the epidemic to peter out. At which time point the government is hoping to let vulnerable people remerge from self-isolation and feel confident that they will not be susceptible to being infected and dying from severe COVID-19. 

The bad news is that 15.2% of the UK population is over 70 years of age (data from Age Concern) the government definition of the vulnerable population based on age. This is not taking into account all the other vulnerable groups who are less than 70 years of age, i.e. those who are obese and/or have diabetes, cardiovascular, respiratory diseases. This means that by the time we get herd immunity many more people will die from COVID-19. This is why the scientific community needs to push for anti-virals and an effective vaccine. But herein lies a problem. 

To develop and test an effective vaccine we really need an 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. This is why we the rich-world may need to go to parts of the world where social distancing etc. is not feasible and the R-zero remains high, i.e. the squatter camps, shantytowns, favelas or slums of the low and middle-income countries of the world.

We, the rich world, may have no choice but to take this low/middle-income route for the sake of the world. But if ‘we’ do take this route to develop an effective vaccine we have to make it ethical. We will have to offer these countries priority access to the vaccine. If we don’t it will be a travesty. I can imagine the headlines in the press if we don’t. ‘Vaccine Imperialism: How the Rich World Exploited The Poor!’

What are the implications for you if you have multiple sclerosis. If you are vulnerable you need to be prepared to self-isolate/shield for a very long time. If you are not vulnerable then you really need to prepare yourself for becoming infected with SARS-CoV-2 and getting COVID-19. I have a section on MS-Selfie that addresses this issue. I will be updating this section over the weekend as there are additional things you can do as an individual and as a family to help derisk your chances further. 

I am sorry for bringing you bad news at the beginning of the weekend, but as always I feel it is important, to be honest, and frank.

The information in this post is quite complex so if you have any questions please feel free to ask. 

Gandhi et al. Asymptomatic Transmission, the Achilles’ Heel of Current Strategies to Control Covid-19. NEJM  April 24, 2020 DOI: 10.1056/NEJMe2009758

Arons et al. Presymptomatic SARS-CoV-2 Infections and Transmission in a Skilled Nursing Facility. NEJM April 24, 2020 DOI: 10.1056/NEJMoa2008457

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can spread rapidly within skilled nursing facilities. After identification of a case of Covid-19 in a skilled nursing facility, we assessed transmission and evaluated the adequacy of symptom-based screening to identify infections in residents.

METHODS: We conducted two serial point-prevalence surveys, 1 week apart, in which assenting residents of the facility underwent nasopharyngeal and oropharyngeal testing for SARS-CoV-2, including real-time reverse-transcriptase polymerase chain reaction (rRT-PCR), viral culture, and sequencing. Symptoms that had been present during the preceding 14 days were recorded. Asymptomatic residents who tested positive were reassessed 7 days later. Residents with SARS-CoV-2 infection were categorized as symptomatic with typical symptoms (fever, cough, or shortness of breath), symptomatic with only atypical symptoms, presymptomatic, or asymptomatic.

RESULTS: Twenty-three days after the first positive test result in a resident at this skilled nursing facility, 57 of 89 residents (64%) tested positive for SARS-CoV-2. Among 76 residents who participated in point-prevalence surveys, 48 (63%) tested positive. Of these 48 residents, 27 (56%) were asymptomatic at the time of testing; 24 subsequently developed symptoms (median time to onset, 4 days). Samples from these 24 presymptomatic residents had a median rRT-PCR cycle threshold value of 23.1, and viable virus was recovered from 17 residents. As of April 3, of the 57 residents with SARS-CoV-2 infection, 11 had been hospitalized (3 in the intensive care unit) and 15 had died (mortality, 26%). Of the 34 residents whose specimens were sequenced, 27 (79%) had sequences that fit into two clusters with a difference of one nucleotide.

CONCLUSIONS: Rapid and widespread transmission of SARS-CoV-2 was demonstrated in this skilled nursing facility. More than half of residents with positive test results were asymptomatic at the time of testing and most likely contributed to transmission. Infection-control strategies focused solely on symptomatic residents were not sufficient to prevent transmission after SARS-CoV-2 introduction into this facility.

CoI: none for this post

About the author

Prof G

Professor of Neurology, Barts & The London. MS & Preventive Neurology thinker, blogger, runner, vegetable gardener, husband, father, cook and wine & food lover.

41 comments

    • By who, the British Government? Do vulnerable people know they may have to self-isolate for 12 months or longer? I wouldn’t assume the general population know this.

  • Yes. This is depressing means we are going to see another wave with more death before life goes back to normality. Isn’t finding treatments for the disease more important and better strategy then a vacine? Surely there must be a anti viral out there that can mute the seriousness of this virus? If not then surely this points to this virus coming from lab and not nature? Coincidently China have cloned the anti bodies. Amazing feat given the blood is filled with anti bodies and isolating the correct protein so quickly is a little strange don’t unthink? Anyways if this true then isn’t injecting this anti body the best option?

    • Using modern technology antibody cloning is now quite a routine procedure. It can be done in weeks to months. I am not surprised they have cloned it. I don’t buy the conspiracy theories. The genomic evidence suggests this virus hopped from a bat into humans with no lab interference.

      • Thanks Prof G. On slightly different tangent, UK army helping with coronavirus have been advised to take vitamin d (okay makes sense and is in line with your recommendation). Oddly been told to spray insecticide. Given my fellow country men are not eccentric or loopey especially the British army for its size one of the most formidable makes me think I should not discount this advise. In your opinion is there any benefit apart from killing the virus on your skin. Oh yeah in fairness to stable geniuses that support Trump drinking disinfectant stupid or unhinged!

        • If the Guardian is right it seems they bave purchased citronella…maybe someone,II suspect the trumpster, has told Downing street COVID is transmitted by biting insects…I suspect it was the Trumpster

        • No idea about insecticide unless it is one that is known to disrupt vesicles, i.e. it has detergent in it.

          Re: Yes, important to keep yourself vD replete and make sure your also have zinc.

  • When you say ‘if you are vulnerable….’ which people with MS are you referring to? All of us? Or those you have mentioned as being in the shielded category previously?

    • The only people who are vulnerable are those who have been treated with alemtuzumab, HSCT and possibly cladribine in the last 3-6 months. However, if you fall into this group and you are young <60, have no comorbidities, are a non-smoker and have a total lymphocyte count of >500/mm3 then you are not vulnerable. If you are older, i..e. >=60, have comorbidities and/or you smoke I would suggest you wait for your lymphocyte counts to go above 800/mm3 before you consider yourself non-vulnerable.

      Other vulnerable pwMS are those who are older than 70, comorbidities and with advanced MS with swallowing and breathing problems.

      • Mhmm, that’s interesting. I thought that you were classed as vulnerable if the count was less than 800. Or was that a general cover all.

      • Care home at the end of my street and the staff are still going home at the end of their shifts then coming back the next day. They are out shopping and some of the bigger shops around here are letting them in early for shopping with the NHS workers. That could be a way for the corona to get in…

  • I’m about to enter my 6th week of not leaving my home. I’m not classed as extremely vulnerable by the government probably because half my medical records have disappeared into cyberspace when hospitals changed to EPR. My DNA is all over the place I research labs and tissue in the Biobank. I’ve met Professor Stephen Powis and have a lot of respect for him, and I also admire Sir Chris Whitty. After the revelations today as who is in the Sage group, I believe the safest thing for me to do is follow my own guidelines for as long as it takes.

      • Well, what I’m finding strange is for someone who has suffered with mental health issues throughout my life, at the moment I’m okay. I’ve been treated with psychotherapy not drugs in dark times, this meant at times when things have been tough physically(not MS), I’ve coped very well. I’m surprised that friends who are very active are struggling even though they are able to exercise outside and go shopping and it’s me helping them. I cannot leave my home without assistance, not wheelchair bound, but a user. When I see a new HCP I hand them my medical history, it’s completely up to date, I keep it with me at all times. I’ve been keeping a journal since lockdown, this not only encourages me to fill my day, it keeps a record of my day to day health. FaceTime, WhatsApp, zoom, email, text and the good old fashioned telephone helps.

        • Today 7/5/2020, I’ve just received a government text telling me I’m extremely vulnerable and I should be shielding. I suppose better late than never, or could they have saved me the grief trying to get my shopping delivered?

  • Is it possible that in different age groups the virus has a different Ro?
    For example, children don’t seem to get COVID19 and don’t seem to infect others suggesting they aren’t shedding as asymptomatically. People over 70 do seem to be particularly susceptible as indicated in this paper (with and without symptoms). So is it possible that in the community with people aged across the whole rang, the true Ro is an average of whatever it is across the age ranges?

    • I wonder if Govenrments will be using children as the dirty bombs to try and infect the young (under 50s), back to school infect the parents and keep grannie and grandad in-doors

      • From what I’ve seen out of my window. The elderly are not exactly following the distancing guidelines. Why are they using buses, when I definitely know neighbours have offered help? Chatting to people strolling along the pavement, side by side(not same household). It’s painful and lonely I know, but there have been leaflets in our doors and surprisingly good support out there. I’ve had so many kind offers from people I barely know. This is London, who would have guessed?



  • So the CDC says

    The virus that causes COVID-19 is spreading very easily and sustainably between people. Information from the ongoing COVID-19 pandemic suggest that this virus is spreading more efficiently than influenza, but not as efficiently as measles, which is highly contagious

    https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/how-covid-spreads.html

    And again

    High Contagiousness and Rapid Spread of Severe Acute Respiratory Syndrome Coronavirus 2

    Assuming a serial interval of 6–9 days, we calculated a median R0 value of 5.7 (95% CI 3.8–8.9). We further show that active surveillance, contact tracing, quarantine, and early strong social distancing efforts are needed to stop transmission of the virus.

    https://wwwnc.cdc.gov/eid/article/26/7/20-0282_article

    The wikipedia says

    Measles Airborne 12–18[2]
    Chickenpox (varicella) Airborne 10–12[3]
    Mumps Airborne droplet 10–12[4]
    Polio Fecal–oral route 5–7
    Rubella Airborne droplet 5–7
    Pertussis Airborne droplet 5.5[5]
    Smallpox Airborne droplet 3.5–6[6]
    COVID-19 Airborne droplet 1.4–5.7[7][8][9][10]

    https://en.wikipedia.org/wiki/Basic_reproduction_number#cite_note-10

    A bit outside of the box was you always like to be

    😉

  • If immunity to SARS-CoV-2 is permanent, the virus could disappear for five or more years after causing a major outbreak

    Long-term immunity consistently led to effective elimination of SARS-CoV-2 and lower overall incidence of infection. If SARS-CoV-2 induces cross immunity against HCoV-OC43 and HCoV-HKU1, the incidence of all betacoronaviruses could decline and even virtually disappear (Fig. 3D). The virtual elimination of HCoV-OC43 and HCoV-HKU1 would be possible if SARS-CoV-2 induced 70% cross immunity against them, which is the same estimated level of cross-immunity that HCoV-OC43 induces against HCoV-HKU1.
    Low levels of cross immunity from the other betacoronaviruses against SARS-CoV-2 could make SARS-CoV-2 appear to die out, only to resurge after a few years

    Even if SARS-CoV-2 immunity only lasts for two years, mild (30%) cross-immunity from HCoV-OC43 and HCoV-HKU1 could effectively eliminate the transmission of SARS-CoV-2 for up to three years before a resurgence in 2024, as long as SARS-CoV-2 does not fully die out (Fig. 3E).

    To illustrate these scenarios (Fig. 3), we used a maximum wintertime R0 of 2.2, informed by the estimated R0 for HCoV-OC43 and HCoV-HKU1 (table S8). This is a low but plausible estimate of the basic reproduction number for SARS-CoV-2 (41). Increasing wintertime R0 to 2.6 leads to more intense outbreaks, but the qualitative range of scenarios remains similar (fig. S8).

    We varied the peak (wintertime) R0 between 2.2 and 2.6 and allowed the summertime R0 to vary between 60% (i.e. relatively strong seasonality) and 100% (i.e. no seasonality) of the wintertime R0, guided by the inferred seasonal forcing for HCoV-OC43 and HCoV-HKU1 (table S8).

    We used the open critical care capacity of the United States, 0.89 free beds per 10,000 adults, as a benchmark for critical care demand (2). We simulated epidemic trajectories based on an epidemic establishment time of 11 March 2020. We simulated social distancing by reducing R0 by a fixed proportion, which ranged between 0 and 60%. We assessed ‘one-time’ social distancing interventions, for which R0 was reduced by up to 60% for a fixed duration of time (up to 20 weeks) or indefinitely starting two weeks after epidemic establishment. We also assessed intermittent social distancing measures, for which social distancing was turned ‘on’ when the prevalence of infection rose above a threshold and ‘off’ when it fell below a second, lower threshold, with the goal of keeping the number of critical care patients below 0.89 per 10,000 adults. An ‘on’ threshold of 35 cases per 10,000 people achieved this goal in both the seasonal and non-seasonal cases with wintertime R0 = 2.2. We chose 5 cases per 10,000 adults as the ‘off’ threshold. These thresholds were chosen to qualitatively illustrate the intermittent intervention scenario; in practice, the thresholds will need to be tuned to local epidemic dynamics and hospital capacities. We performed a sensitivity analysis around these threshold values (figs. S10 and S11) to assess how they affected the duration and frequency of the interventions. We also implemented a model with extra compartments for the latent period, infectious period, and each hospitalization period so that the waiting times in these states were gamma-distributed instead of exponentially distributed (see the supplementary materials and methods and figs. S16 and S17). Finally, we assessed the impact of doubling critical care capacity (and the associated on/off thresholds) on the frequency and overall duration of the social distancing measures

    Under current critical care capacities, however, the overall duration of the SARS-CoV-2 epidemic could last into 2022, requiring social distancing measures to be in place between 25% (for wintertime R0 = 2 and seasonality; fig. S11A) and 75% (for wintertime R0 = 2.6 and no seasonality; fig. S9C) of that time. When the latent, infectious, and hospitalization periods are gamma-distributed, incidence rises more quickly, requiring a lower threshold for implementing distancing measures (25 cases per 10,000 individuals for R0 = 2.2 in our model) and more frequent interventions (fig. S16).

    Marc Lipsitch
    Professor of Epidemiology
    Department of Epidemiology
    Department of Immunology and Infectious Diseases

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7164482/

  • This new coronavirus may affect individuals differently according to their DNA I heard, we don’t really know how much of a role children play in spreading the virus, why it appears to affect men and those from BAME backgrounds more severely, whether people can actually become immune and for how long… I think trying to draw any conclusions at this stage is very academic.

    • Social determinants are also very important. Poverty looks like being a more important risk factor than genetics.

  • Hi Prof G, thank you for your sobering info on COVID-19. If I have interpreted it correctly I understand that eventually isolating or not, covering up & sanitise – we will have to move on with our lives one way or another. The question is we hope, that a anti-viral or vaccine or both will be available to gives us faith & hope that we won’t be severely affected by the virus, but possibly a mild reaction.

    We are all grateful to all of you and your team, all NHS & front-line workers and we are all living in an anxious & dreadful time – if you have family or friends that have died or severely affected by the virus. I think we can all now know of someone that has had it or lost a relative or friend (me personally) but I can’t help but worry too – the anxiety & stress that we see reported daily about the numbers & facts (some correct – I hope – some unbelievable) that is adding to this pandemic. I live in a mixed area of young and elderly and I know the elderly (most) are extremely anxious. The worry about mixing & going out, rightly so, has taken away their laughter, smiles & most importantly trust away.

    It grieves me too – that the co-ordination that in some ways has been remarkable & commendable about cancelling healthcare appointments. The urgent want to send out letters advising these cancellations along with phone calls/emails to you, telling you that you are ‘severely vulnerable’ to not receiving one at all – and/or a completely different recommendation from you GP stating a different category! Heightens fear & worry.

    Whilst we fight this battle and like everything else, the world will go back to some normal ish soon as we humans evolve. Can we already start to plan medically, both physically & mentally – how to ensure the fall-out from this virus is as well organised as when we entered into it and are dealing with it. The media are dreadful at the amount of Corona Virus programmes/information and news channels that all this overkill (please don’t say this isn’t true – it is unbelievable) & the ignorance of people around the world, even in the top jobs, should surely see that the very problems of all the stress and anxiety can add pressure to your health condition. Is lack of education, empathy, too greedy, killing the planet, over crowded in certain countries, that these areas globally need addressing now. It might be possible that we can re-build, mend & help each other to become a better world. The money idiots spend on the ‘race to Mars’ – how about the race to save our world that is suffering (COVID-19 – happened!) we shouldn’t be eating certain things – pangolins/bats & keeping them in small unsanitised cages/markets – WE DON’T NEED TO DO THIS! Not in the 21st Century – and no-one is that desperate for that type of food/fool’s remedy!

    If we can work out how to support all of our vulnerable people, put in place a caring & well versed team to help lift people up & ensure that they are OK, to also ensure that if they’ve not gotten a medical issue dealt with, that this can be dealt with and this is how it is going to done…! Give people some hope & empathy.

    The fear & worry – can bring a whole new lot of issues to people in 2020. Young & old. As so many people have slipped into ‘lock-down’ well and enjoying the quiet, pollution free, noisy world of germ filled work world – will find it hard to get back into a different gear to go back (me included :))

    I can only say that there needs to be more clarity on who should shield themselves & who should not – why some cancer patients are treated as ‘moderate’ & some ‘severe’ can cause concern in itself! How to ask people to ‘back off!’ when they come to close, that should be amusing on a trip to the dentist! But also, to not frighten people to come out of the lock-down without becoming, too anal, over zealous cleaner, mask, glove wearing, non-hugging & hand shaking, type of human being – that is now the ‘new norm!’

    Take care and keep safe Prof G – any clarity on a pwMS on ocrelizumab, stent fitted (angina diagnosed), asthma since age 3 (controlled as such, but stress & seasonally) along with chronic osteoarthritis, but apart from that healthy 🙂 would be classed as – ‘severe’ or ‘moderate’ in terms of keeping yourself safe from Coronavirus?

    God bless and take care,

  • Something I keep wondering about – is the fact that the virus transmits so easily down to the fact that asymptomatic individuals can infect others, or is there something else about the virus which helps it spread?

    • Not sure. What worries is me is our canine companions. There is no self-isolation or the social distancing of dogs. Just come for a walk on Clapham Common and you will see that everyone pats and plays with each others dogs. We know that a tiger in a zoo caught SARS-CoV-2 so why not dogs? I hope someone in the vet schools is looking into this.

      • That’s very true. Cats as well – around here there are quite a few, which roam around visiting different houses and gardens.

        • Not to mention Larry the cat from Downig Street which has/had a fair few covid cases.
          Matt Hancock was pictured stroking him the other day, good job he’s already had it.

      • The infectivity of dogs is much lower than for cats based on studies ACE2 receptor differences and infection studies from China, my brother has a ferret so he has to watch it? :-)…I can see the paper now testicular infectivity must tell to stop putting ferrets down your trousers…it’s a Yorkshire thing

        • As long as he doesn’t kiss it like so many do with their dog- right after they’ve licked their proverbials. Cats also lick themselves clean… Their fur could be full of fomites? I love animals, but hygiene needs to be given more consideration with pets in many cases…

      • Last week I saw a woman with an electric wheelchair and an assistance dog get off a bus. The dog did a poo on the pavement. The owner picked the item up with a plastic bag and put it in a neighbour’s bin. She then strapped herself back into the chair, no hand gel no gloves. When this lady’s carer arrives, who knows what lurks to be passed onto the next vulnerable person? This woman is going on a bus that essential workers use. When NHS workers are dying, it’s not always lack of PPE it’s irresponsible behaviour by the public.

        • I think it doesn’t need to be obvious inadequate hygiene that spreads this virus. Just an asymptomatic person who touches their slighly moist nose absentmindedly, without registering, then smears virus on a hand rail mounting the bus. Next person grips the same spot only seconds later, then has a problem with an eyelash.

  • Great post – I am sure this is a daft question but how do we go about applying more sub classification of the Vulnerable to establish whether we could get close to a 85% total infection position for the population in a slow, progressive and risk informed way ?

    • I am sure this is what the Government is planning at the moment; it is the gradual lifting of the lockdown and letting-out the least vulnerable first.

      • Assuming, of course that catching the virus stops you getting it again. If that isn.t the case (though I’d be surprise), all bets are off.

      • From what I’m hearing where I am in Scotland, there may be the possibility of certain regions in Scotland doing things differently.

  • Hmmm my prediction of this being the worst global event to happen in my lifetime is looking pretty accurate. I’m not thrilled about getting covid 19 without a guaranteed anti viral or other treatment being identified. I see little reason for schools to go back in session until the Drugs trials have been concluded as that would be a natural end point for fear and panic ( at least a drugs been identified). Currently this virus looks like it kills 1 in 200 people , I think the mental health drain alone of being told to go back into normal life with no defined treatment course is not acceptable given remdesivir and hydrozycholprquine looks strong candidates to prove efficacy and reduce mortality. I’m certainly unsatisfied with the prospect of 80% of the UK getting the disease..

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