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Covid-19 Immunity Risk transmission Vaccines

South African and UK: two Covid-19 variants – two countries in crisis ?

The UK and South Africa are two countries where the transmission of the virus has escalated. Last week a highly transmissible new strain was identified as the source in the UK. Three days ago, the explanation of a marked upswing in cases in South Africa was also shown to be related to a new genetic variant of the Covid-19 virus. Indeed, in an unpleasant twist, two cases of this variant were also yesterday reported to the UK. The outbreak caused by these new variants will be much more challenging to control, both within these countries and beyond.

(I hadn’t intended blogging again before the holiday, but these new data are sufficiently concerning I thought readers would want some of this background!)

Some comments on terms!

  1. Mutation – a change in one of the genes of the virus as it multiplies
  2. Variant – as a consequence of one or more mutations, a different version of the virus appears with slightly different genes from the initial version
  3. Strain – often refers to when a particular variant becomes an important cause of some or all of the cases in a particular outbreak

Thus the new UK strain has some 23 separate mutations and this variant has become the dominant strain causing infection in much of this country

What do we know about the new South African strain?

  • South Africa has seen a marked  increase recently in the number of new cases of Covid-19 
  • Around 90% of new cases in that country are due to a new strain, based on a number of mutations
  • As well as the 2 UK cases, the South African variant has now been found in Australia and Switzerland
  • No doubt as other countries undertake the necessary complex genetic analysis this strain will also be identified in many other countries

Concern in younger people

  • At the beginning of the epidemic less than 0.5% of cases in South Africa were in people under 30 (which may be related to who was being tested)
  • In some South African provinces the peak age is now in the 15-19 year age group
https://www.plenglish.com/index.php?o=rn&id=62600&SEO=south-africa-affected-by-second-wave-of-covid-19
  • As with the new UK strain, the new South African one multiplies much more quickly than the previous common strains
  • The problem is that those infected with these strains then produce much larger amounts of virus.
  • Thus, the concern is young people infected with these strains have higher levels of virus than they did with the previous strain: the latter of which only rarely led to a severe illness.
  • The greater viral load with the new strain could make them sicker
  • Indeed, there are a few unconfirmed reports from South Africa, of young people with no pre-existing illnesses who became seriously ill with this strain
  • It is too early to know how big these numbers are

How close are the South African and UK strains?

  • Both strains are quite different variants
  • Both however contain a number of mutations in the spike protein region, thought to be responsible for the increase in transmission
  • Thus both the South African and the new UK strain carry the same ‘N501Y’ mutation in the spike protein
  • It is likely that that these two variants have arisen spontaneously in different countries, but by chance both of them are particularly highly transmissible
  • We may see other countries reporting on other highly transmissible strains

For the UK variant, is there any new analysis of its impact?

  • In my post last week I thought it was highly likely that the UK strain would result in an increase in R
  • The graph below, from an epidemiology modelling unit in Oxford shows that the transmission rate, R, is now well over 1.0
 
http://epidemicforecasting.org/country-rt-estimates?region=GB
  • It is fairly definite that the increase in R is because of the UK’s new strain (now called B117 or VUI-202012/0)
  • What is interesting is that South Africa and the UK are two countries which, despite all the current lockdowns and mitigations, have two of the highest estimated R values in the world
    • UK R=1.26
    • South Africa R=1.33
  • As a comparison the estimates for other high prevalence countries are lower
    • USA R= 1.03
    • France R = 1.06
    • Italy R = 0.88

Conclusions about these new strains remain the same

  • New strains occurring during a pandemic are not unusual
  • The fact that these strains are more likely to transmit infection does not mean that the infection is more serious, but this will need to be monitored
  • Most experts also still expect the new vaccines to be effective, as the antibodies generated by these vaccines should still ‘work’ against even the mutant forms of the spike protein
  • As I mentioned last week, if necessary new vaccines can be made very easily against a new strain
  • Indeed, one sensible suggestion this week was that even if the vaccines turn out to be less effective against any new strain, that wouldn’t necessarily be a big problem
  • Given what is known about the effectiveness and safety of existing vaccines, it may be possible for regulators to approve slightly modified new vaccines without the need for additional lengthy trials

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Covid-19 Risk transmission

Covid-19 can survive on mobile phones for 28 days: is it time to reappraise risk from surfaces?

Widely reported in the media on Monday this past week were the results from an Australian study which showed that in the laboratory the Covid-19 virus can survive for 28 days on a wide range of surfaces from bank notes to mobile phone screens, in an amount considered sufficient to cause infection.  How worried should we be and what is the best estimate about the role of surfaces in increasing infection risk?

What was known about the risk of surfaces before Covid-19?

  • For over 40 years it has been known that the flu virus can survive on non-porous surfaces such as stainless steel for perhaps 24-48 hours Many other viruses have since been shown to  survive on a variety of surfaces and be a potential source of the transmission of infection
  • More relevant is that for most corona viruses that have been studied, including the ones responsible for the SARS pandemic in 2002-04 and the MERS epidemic in 2012, it has been shown in the laboratory that they could survive for more than a few hours on a variety of surfaces
  • The early advice about surfaces with Covid-19 was based on that laboratory evidence from other viruses 
  • Thus, it is reasonable to ask specifically about Covid-19: “can it survive on surfaces and, if so:
    • which surfaces?
    • for how long?”

What had we learnt in the first 6 months?

  • Given the findings from other corona viruses, from the start of the current pandemic there was a considerable amount of research on the survival of Covid-19  on different surfaces. 
  • The studies are tricky undertake and there are  lots of different ways to do such research 
  • Perhaps not surprisingly, the results varied but there was  broad conclusion that this virus can survive on a wide range of surfaces for a reasonable amount of time after say a sufferer has coughed 
  • In general, the virus survived much shorter times on porous surfaces such as clothing than shiny surfaces
  • Somewhat surprisingly the virus also survived for a few days on non-shiny surfaces such as wood, paper and cardboard
  • Given results such as these, many public health authorities recommended stringent approaches to cleaning
  • Businesses and members of the public then to varying extents adopted mitigation practices which ranged from stringent wiping of surfaces in health care settings to some households removing the front pages of a newspaper prior to reading. 

Are there limitations to the conclusions that can be drawn from such studies?

  • Absolutely! 
  • The studies have to be undertaken in laboratory conditions, but these do not necessarily replicate daily  life
  • Temperature, humidity, UV light all can alter virus survival 
  • The nature of the sample of virus spread on these surfaces was not the same that would be spread from an infected individual, for example from a patient coughing
  • The fact that the virus could be cultured did not necessarily mean there was sufficient virus on the surface to be harmful to health 
  • Furthermore, taking a sample ‘scrape’ from the surface is very different for example from what a person can pick up by touching the surface.
  • Thus, my conclusion was that the virus can survive on surfaces but that was not proof that in the form it survives it is capable to causing infection

What does this new Australian study add?

  • I thought the study was impressive!
  • The research ‘infected’ the surfaces with the concentration and form of the virus that would be typical of (say) that infected patient cough
  • They allowed the liquid preparation of the virus to dry
  • They studied a large range of materials (see table below).  The items listed are those directly studied  or referred to as relevant  in the research report 
Polymer bank note
Paper bank note
100% pure cotton
Brushed stainless steel
Glass
  • They studied the virus survival at ‘real life’ humidity and temperatures
  • They measured how much of the virus they could grow from 1-28 days
  • This is what they found:
    • On some surfaces such as cotton there was an immediate absorption of virus
    • Even on cotton virus could still be grown after 14 days
    • On all the other surfaces virus could still be grown 28 days later
  • The rate that the virus disappeared was calculated by how many days would be needed to lose (i) 50% and (ii)90% of the dose that was present after the initial application. 
  • The results (which I have drawn below) show that for all the materials half of the virus that had been applied was still present at 2 days 
  • Further although 90% had been lost by a week, that meant there was still 10% of the original amount of virus left, which was sufficient to cause infection
  • The authors argued, based on their findings, that common objects such as mobile telephones, ATM machines and even modern and old bank notes could still be a risk for transmission after gaps of several days
  • One major criticism of the study is that all objects were kept in the dark, given that UV light exposure would have reduced the amount of the virus (although from a research perspective it made sense to control that aspect)

Should these findings change behaviour?

  • Studies such as this are undertaken by virologists (indeed the results appeared in a publication with the not very surprising title  Virology Journal!)
  • Virologists in research of this type are addressing questions on “can the virus survive on surfaces?” and even (as in this article) “following a typical exposure to an infected person, can the virus survive for so many days that it could be an important source of transmission?”
  • An epidemiologist asks as different set of questions: we know that surfaces can be a source of transmission for these periods but how likely is this to happen in the ‘real world’?
  • As examples there are several potential health hazards that can happen following common health related activities (with no prior history) 
    • Haemorrhage after tooth extraction
    • Severe allergic reaction after paracetamol (USA acetaminophen)
    • Similar reactions after certain foods
  • And in the non-health sector:
    • Tyre blow-out whilst travelling at speed
    • Domestic kitchen appliance catching fire
  • These are all rare and we take the view that the risks are acceptably low and we don’t change our behaviour

Do we know how likely is it that transmission can occur from surfaces?

  • The short answer is no!
  • It is very challenging, outside a local outbreak with a single source, to know what was the route of transmission for any individual Covid-19 infected patient
  • There are anecdotal  reports in the media of a person who contracted the infection after touching a door handle or whatever, but the existence of one case does not allow us to calculate the numerical level of risk
  • Logically it is impossible to test all the surfaces that such an individual may have been in contact with over the previous 10 days
  • It was ‘easy’ with Novichok and the Salisbury poisoning, but that entailed closing down a whole town and a military style exercise!
Source Daily Mail
  • For sure transmission in hospitals in the early phase of the pandemic could be traced to high concentrations of the virus on surfaces, exhaled from patients and probably staff
  • Outside health care settings the likelihood of transmission from surfaces, I would conclude, is lower, probably substantially lower, than most other risks I would accept – including travel on a flight
  • The good news is that infection cannot occur by absorption through the skin, so if I am worried from any surface, I just wash my hands or use hand gel and I’m happy reading  the front page of news

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Categories
Risk transmission

Lockdown for the many or the few: when experts disagree!

Yesterday two groups of scientists sent conflicting open letters to those leading the national responses to the increasing number of cases in the 4 countries of the UK.  The issues raised in these letters are relevant to how other countries/regions in Europe, North America and beyond manage the outbreak. When scientists disagree, the public loses confidence in their opinion and governments are left wondering whose advice  to follow.

In this post I dissect the points raised and attempt to reconcile the different conclusions as to what  countries should do.

The 2 letters:

  • Both were led by epidemiology colleagues from Oxford University who work in the same department of Primary Care
  • The first arguing for a whole population approach was led by Professor Trish Greenhalgh which said:
    • Restrictions in terms of social distancing/lockdown should apply to everyone because:
    • Including everyone is the best way to reduce the incidence of infection 
    • There is too much uncertainty to have a targeted approach 
  • The second arguing for a targeted approach was led by Professor Carl Heneghan which said:
    • Restrictions in terms of social distancing/lockdown should apply to those who are the most vulnerable, such as the elderly because:
    • Limiting actions to contain the virus  to those for whom there is clear evidence that there is a measurable benefit 
    • In this way we minimise unnecessary harmful impacts on the economy, mental health and education 

Critique of the Greenhalgh letter 

Point made in the letterMy response
Everyone in the  population is at some risk:  even young people can have complications and long term health problemsIt is a ‘numbers game’ and the low rate of serious complications (for example) in young people should be taken into consideration
Cannot easily have different policies for vulnerable and non-vulnerable.  Example -grandparents often involved in child careThe data from several countries would suggest that the recent increasing incidence has been greater in younger people.  This suggests that shielding works
The letter argued against the targeted policy – that if a sufficient proportion of low risk people get infected – this  would lead to a degree of herd immunity.  This would then protect the (say) older people who have been shielding.   This letter argued that that such policy is flawed – based on the assumption that people cannot get re-infected, for which there is no evidence  The rates of a second infection thus far are very very low so it is plausible that we could achieve herd immunity whilst protecting the vulnerable.  But I agree that the achievement of herd immunity is unlikely to come from natural infection rather than vaccine
No evidence from other countries that having targeting policies is more effective than general restrictionsThis is true, but  it is probably unrealistic to expect to obtain definitive evidence.  The authors also write (next point) that we should not necessarily require such evidence 
Relying on high quality research on a single aspect to make decisions in a situation as complex as managing Covid-19 is dangerous and need to take a more balanced viewI don’t disagree

Critique of the Heneghan letter 

Point made in the letterMy response 
Current UK government policy does not have a clearly stated overall strategy, so impossible to judge if any policy is successful I agree, but not sure how we would reach agreement on what that policy should be
Having a policy just focusing on reducing deaths is too restrictedI am not sure that a policy of just reducing deaths has been stated. One problem is that deaths are the most easily measured and so the media in these situations focus on comparing death rates both within and between countries 
Mortality is concentrated in older people and those with pre-existing health problems. Therefore, this is the group that should be targeted for interventionsThe authors are arguing both ways on this, they argue above against focusing on those at increased risk of dying if they get Covid-19. 
Blanket lockdown policies on the whole population which are ‘unnecessary’ can as a side effect result in a reduced access to health care for non-Covid-19 diseases.  This can  lead, for example, to increased numbers with untreated heart disease or cancerI think this is a significant concern and countries will need to provide robust data on the consequence of lockdown on health care for other diseases.  But this is not a ‘zero sum’ game; ie countries can have high levels of lockdown for the general population and invest heavily in maintaining health care more widely
A previously widely discusused point on the economic costs of lockdown and that, for example the unemployment and other consequences have their substantial health risksThis has to be true, or at the very least is a testable hypothesis.  The results from available national data will take several months to gather.  Further, these health consequences may take decades and not just months to become apparent 

Conclusions

  • No-one suggests this is easy and the trade-off between the harmful impacts of Covid-19 and of strict lockdown are well known I am sure to all readers of this blog
  • These two open letters also identify that despite the fact we are 9 months into the pandemic, there are still so many unknowns
  • Not surprisingly there is scope for disagreement on interpretation of the available evidence 
  • These letters do bring into focus what are the key issues 
  • If I were forced to judge which letter provides the stronger argument, it would be that the targeted approach is likely to  win out in terms of the sum total effects on human health in our populations 

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Categories
Covid-19 Risk

How common is Covid-19 (and what is my risk?)

Is the rate going down or staying the same?

Every day we are told about the numbers of deaths and the number of new cases of infection (based on those who test positive) with Covid-19. As interesting as these data are, they do not give any real indication of how likely any of us are to contract the infection and whether the rate of new infections is going down. In this post I will discuss what the current epidemiological studies tell us.

The ‘headline results’ are:

  • Approximately 1/3500 people in England in the general population have evidence of being infected currently
  • This is down from 1/450 around 8 weeks ago.
  • There are probably around 1700 people newly developing the disease every day.
  • Over the past month, the rate of new infections is levelling off.