Balancing coronavirus risks – its all in the genes

Two excellent articles from BBC online published recently, and one from “Unherd” exemplify some of the issues I have been thinking about over the last few months. The articles are too long to summarise succinctly, but I will try and curate the key themes and issues. All well worth reading in full from the links.

I have yet to read an exact explanation as to why so many people infected with Covid-19 have no symptoms at all or only mild symptoms, while others quickly become dangerously ill, often leading to death.

Covid-19 is on the way out ? – Sunetra Gupta

However, the theory of resistance or “hidden immunity” expounded by Professor Sunetra Gupta in Unherd does go someway to explaining why so many people are unaffected by coronavirus.

Covid-19 is either a deadly disease that only a small fraction of our populations have so far been exposed to, or it is a much milder pandemic that a large percentage of people have already encountered, and is already on its way out. I guess there are wide range of options in-between.

If Professor Neil Ferguson of Imperial College is the figurehead for the first opinion, then Sunetra Gupta, Professor of Theoretical Epidemiology at the University of Oxford, is the representative of the second. Her group at Oxford produced a rival model to Ferguson’s back in March which speculated that as much as 50% of the population may already have been infected and the true Infection Fatality Rate may be as low as 0.1%.( that’s 1 in 1,000)

As she sees it, the antibody studies, although useful, do not indicate the true level of exposure or level of immunity. First, many of the antibody tests are “extremely unreliable” and rely on hard-to-achieve representative groups. But more important, many people who have been exposed to the virus will have other kinds of immunity that don’t show up on antibody tests — either for genetic reasons or the result of pre-existing immunities to related coronaviruses such as the common cold.

Observing the very similar patterns of the epidemic across countries around the world has convinced Professor Gupta that it is this hidden immunity, more than lockdowns or government interventions, that offers the best explanation of the Covid-19 progression:

“In almost every context we’ve seen the epidemic grow, turn around and die away — almost like clockwork. Different countries have had different lockdown policies, and yet what we’ve observed is almost a uniform pattern of behaviour which is highly consistent with the SIR (Susceptible, Infectious, Recovered) model. To me that suggests that much of the driving force here was due to the build-up of immunity. I think that’s a more parsimonious explanation than one which requires in every country for lockdown (or various degrees of lockdown, including no lockdown) to have had the same effect.”

Click here for full Unherd interview and article

Coronavirus – How scared should we be ? Its all about balancing risk.

People want to be safe. But the problem is we are no longer as safe as we once were. After all, there is a new virus around that can have catastrophic consequences to any of us – we just don’t know if it you or me or our immediate family. So, what is the risk ?

Why you should not expect to be 100% safe

Prof Devi Sridhar, chair of global public health at Edinburgh University, says the question we should be asking is whether we are “safe enough”.

“There will never be no risk. In a world where Covid-19 remains present in the community it’s about how we reduce that risk, just as we do with other kinds of daily dangers, like driving and cycling.”

Lone cyclist in Cardiff
daily risks of cycling or driving

If we are not in hospital or a care home our best guide to the risk of infection comes from the government’s surveillance programme run by the Office for National Statistics.The data published this week suggests around one in 400 people is currently infected.

The chances of coming into close contact with one of those individuals – certainly as we are practising social distancing even when out and about – is considered to be pretty slim. And the hope is that level of infection will reduce even further in time if the government’s test, track and trace programme keeps the virus suppressed.

Then if we do become infected, the fact remains that for most people, coronavirus is a mild-to-moderate illness – only one in 20 people who shows symptoms is believed to need hospital treatment.

How to quantify your risk?

Those with pre-existing health conditions are most at risk. Deaths among under-65s with no illnesses are “remarkably uncommon”, research shows.Perhaps the easiest way is to ask yourself to what extent you are worried about the thought of dying in the next 12 months.

What is remarkable about coronavirus is that if we are infected our chances of dying seems to mirror our chance of dying anyway over the next year, certainly once we pass the age of 20.

Chart

For example, an average person aged 40 has around a one-in-1,000 risk of not making it to their next birthday and an almost identical risk of not surviving a coronavirus infection. That means your risk of dying is effectively doubled from what it was if you are infected. And that is the average risk – for most individuals the risk is actually lower than that, as most of the risk is held by those who are in poor health in each age group.

So coronavirus is, in effect, taking any frailties and amplifying them. It is like packing an extra year’s worth of risk into a short period of time.If your risk of dying was very low in the first place, it still remains very low.

As for children, the risk of dying from other things – cancer and accidents are the biggest cause of fatalities – is greater than their chance of dying if they are infected with coronavirus.  During the pandemic so far three under 15s have died. That compares to around 50 killed in road accidents every year.

Click for full BBC article

Coronavirus – “Baffling” observations from the front line

For the unlucky few (approx 1 in 20  5%) who are severely affected by coranavirus and  are hospitalised, many requiring  significant intensive care, the situation is very different.

When you talk to intensive care doctors across the UK, the phrase that emerges time after time is, “We’ve never seen anything like this before.” “We’ve yet to fully understand this condition, it is baffling,”   

Hospital bed
We have never seen anything like this before

“We still don’t really know why some patients feel OK to begin with, even though they have incredibly low levels of oxygen in their blood,” It is one of the many mysteries of Covid-19 on which more research is urgently required.

For the critically ill, this is a disease of such severe inflammation and blood clotting that it attacks multiple organs and causes life-threatening problems that cascade around the body.

Another measure of the risk of clotting, a blood protein known as D-dimer, has also been off the scale. Normal levels are measured in the tens or hundreds, whereas  levels of 60,000 – 80,000 have been measured with covid-19. ” D-dimers can also be a marker of an infection so severe that it triggers a lethal over-reaction from the body’s immune system. 

Cytokines are small molecules produced by the body as part of its defence against infection. A chemical warning system. They lead to inflammation, and up to a certain level that is good for you. It allows you to fight an infection and hopefully get rid of it. But in some patients, Covid-19 provokes what is known as a cytokine storm.

Many ICU doctors think it is highly likely that genetics plays a part in some people becoming critically ill with Covid-19, but they can’t yet say for sure.

“It could be partly responsible for the disproportionate effect it has had on people of African and Asian origin, It may also be responsible for the differences in the response of individuals.” It is possible, for example, that the genetic variation that makes you more susceptible to getting high blood pressure or diabetes also makes you more susceptible to the virus.

Click for full BBC article

Summary

So what are we to make of all this evidence ? Government policy has always said – “We will be led by the Science”, but as we see here and from previous posts, the views of scientists and epidemiologists differs significantly. So which Science do we follow ?

In general, as shown by the statistics above, an individual’s risk of of contracting covid-19 severely is very low. For the young and healthy, the risk of dying from covid-19 within one year is the same as the normal risk of dying from any other cause.

It all seems to boil down to our age, our immunity and the genes we were born with that determines whether or not we breeze through covid-19, or whether it is terminal.  For 95% of us, our immune system or acquired resistance kicks in and the symptoms of covid-19 are mild or even non existent (including the majority of children).

 For the other 5%, mainly the elderly whose immune systems are already reduced, but in some cases, particularly younger people, their immune systems go into overdrive triggering a lethal over-reaction from the immune system known as a cytokine storm. 

Lets hope Professor Gupta is right that the worst is over and that Lockdowns in the four Nations of the UK can be lifted as soon as possible and also be harmonised to a single policy of “the New normal”. What about a second wave you may ask ? that’s for another day.

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