How should you treat Covid?

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As the prime minister announces more steps out of the lockdown, with restaurants and pubs getting back into business (partially), Dr Andrew Bamji completes his three part series on Covid-19 with answers to more of your questions.

In part 1 he talked about “Where are we going ?” and in part 2 he began to answer some of your questions. The questions now continue :

How should you treat Covid-19?

First, can you spot it coming? Probably. The oxygen level in the blood is important. A marked fall is highly suggestive. A developing cytokine storm also causes some blood test abnormalities. If you are in a position to request these in hospital, they are serum ferritin and D-dimer.

The next question is whether what you have, and what the doctors are seeing, is a direct effect of the virus in cells, or the cytokine storm, or both. It isn’t clear yet but by analogy with other conditions, if a cytokine storm is coming it needs to be headed off early.

What research is going on to treat SARS-CoV-2 and Covid-19?

I have never seen such an outpouring of work on a single topic in such a short time. The effort is international; some very convincing stuff is coming from China, Russia, Italy and the USA. There is some in the UK. The research has worked out the virus structure, has uncovered some interesting and possibly relevant genetic factors and noted that some groups appear to be protected to some extent.

These include patients on drugs that block cytokines (we rheumatologists are particularly familiar with these).  You will have read that a UK trial has shown that dexamethasone is effective.  The full results of the trial, called RECOVERY, aren’t out yet; it’s testing various combinations of drugs and time will tell which are the best.  There remains a fear that using steroids may compromise patients by allowing bacterial or fungal infections to get worse.  However, when the body is trying to deal with a serious infection the adrenal glands can’t secrete enough cortisone and adding more may help.

Some drug trials included in RECOVERY have been cytokine blockers, or biologics. Names you will hear commonly are anakinra and tocilizumab.  My personal view is that several trials are using the wrong drugs in the wrong combinations at the wrong time, so may fail to show benefit.

Other trials have used an antiviral drug, remdesivir. This kills the virus, but does not have as much effect on Covid-19 as we might have hoped, possibly because so much of Covid-19 is due to what the virus does to the immune system rather than the virus itself. A recent study showed that the anti-inflammatory drug ibuprofen might be useful, although earlier studies showed the opposite. This may be because doses and timings were different.  So it’s a confused and confusing picture.

What about hydroxychloroquine, which President Trump was taking?

An early study showed it worked, then was heavily criticised; another suggested it didn’t and caused too dangerous side-effects anyway. However, the doses used were high (usually the higher the dose, the more likely you are to get side-effects). Also it may have been employed too late; theoretically it might help because of the way it modulates the immune system.

But the uncertainty highlights what I said earlier; the facts can change or the trials may not be properly set up. If a drug doesn’t appear to work it may be because it’s used in the wrong dose at the wrong time.

And Vitamin D?

There is a little (disputed) evidence that having good Vitamin D levels may be protective. Certainly taking a small dose cannot do you any harm (although if you have been spending time during lockdown sitting in the sun you are probably OK!).  The Royal College of Physicians does not at present think there is any evidence to support the use of high-dose Vitamin D.

Why don’t we hear much about drug trials?

Very good question! Probably because the committee advising the government (SAGE) is made up of medics who specialise in infectious disease and public health, but does not contain any front line clinicians who understand how to manage acutely ill patients and in particular the cytokine storm syndrome. I have argued hard for inclusion of such doctors, but without success so far.

But if you go onto the website of the NHS Research Authority you will in fact find a whole series of trials are taking place here, and of course there are others worldwide.  As a follower of the “treat early and treat hard” philosophy I think personally that some of the trials are set up to fail, as they do neither. That said, some positive results do appear to be emerging and I have been wrong before.

Why is the death rate in the UK so high compared to other countries?

Many possible explanations for this one. First, are we comparing like with like? Are we over-reporting deaths? There is some evidence that we are. In the community, some deaths attributed to Covid-19 are not actually proven, only suspected. The same is true in Belgium, which has the highest death rate. Also population density may play a part; countries like Sweden have smaller cities, lower numbers of high-risk groups and different social behaviours.

Then some countries may be under-reporting deaths, either for political reasons or because testing is not widely available. The most useful number to look at is the number of deaths per 100,000 population. A large country with many people may have a huge number of deaths, but it’s the proportion of the population that matters.

Why have deaths been so high in care homes?

Put a large number of vulnerable people with major personal needs in close proximity and it is frankly inevitable. Cross-infection is difficult to stop with an agent as infectious as SARS-CoV-2. It’s very difficult to treat people with dementia in isolation; they get angry, upset and even more confused. Staff may have to rush between them and so spread it.

Time will tell whether the seed for care home infections was the discharge of infected care home residents from hospital, where they had already acquired it. It is a probable, but not certain explanation, but one of my still-working friends tells me that in his hospital there was a large number of staff who tested positive but had no symptoms, so before everyone working in hospitals got tested it it’s quite possible that someone without symptoms did transmit it.

Other viruses spread like wildfire in closed environments; norovirus is a classic one, only it doesn’t kill people like SARS-CoV-2. It’s interesting that the Diamond Princess cruise ship outbreak of SARS-CoV-2 in Japan was extensive and rapid, but later analysis of the data shows clearly that cross-infection dropped dramatically after proper isolation measures were adopted.

A recent outbreak occurred in a German abattoir, an environment where there is a lot of cool mist from washing down, so any virus in the air would have had a field day.

What is meant by excess deaths, something which has being quoted in the news?

Every week and month the number of deaths in the UK is reported. The figures go back many years. One can therefore look at a month, say March, and compare it to the figures from March in previous years. From this you can calculate a difference between now, and what went before. Often the monthly numbers are averaged over 5 years and the comparison made with that number. However it’s a crude measure, as it doesn’t take every circumstance into account.

Thus the monthly figures for any year will be higher if some epidemic is going on; we might, therefore, be better comparing March and April 2020 with an epidemic flu peak pair of months, which might be October/November in a previous year. Also it’s important to remember that if lots of vulnerable people die now, but would have been likely to die in the succeeding months because of illness or frailty, then monthly figures for later in the year could be lower than expected.  Indeed in some areas the current death rate has dropped to below the average, which does not surprise me.

Now the numbers of cases and deaths are falling, does that mean we can go back to normal?

Yes but no. Returning to normal may cause a flare-up in infection rates. It’s happened already in some countries.  Does that matter? If there is no treatment for the severe disease, then yes (or maybe). If there is treatment that stops SARS-CoV-2 turning into Covid-19, then no. But we aren’t there yet. Until we are, precautions still need to be taken.

Wearing a mask and keeping a safe distance remain important, though how one defines a safe distance is tricky.  Possibly different parts of the country have a very low risk; in East Sussex that’s the case, but it could still be imported by visitors and tourists.

The economy has been badly affected by the lockdown. Has anything like this happened before?

No. There has never been a lockdown to my knowledge since the Spanish Flu epidemic of 1918, and that was country-specific. To put this pandemic in context, the 1968 flu epidemic killed over 80,000 people. There was no lockdown and not much fuss. It was then accepted that people would die. This lockdown is as much a function of media pressure as it is of the fact that we can treat people today whom we could not have treated in 1968, thanks to advances in drugs and medical technology.

Opinion is split. There are those who say the lockdown should have begun earlier, which would have reduced the initial number of cases (as in South Korea and New Zealand) , but there are also those who think it’s a complete waste, that it won’t have controlled the virus but has seriously damaged the economy. Many of these latter quote Sweden, which did not lock down, but the death rate there has been climbing, and is now well above Denmark and Norway, which did.

What do you think?

The lockdown and isolation measures saved the NHS from being overwhelmed. That was the key objective, and it succeeded, but at a cost. However it has become clear with the partial release that many people, particularly in the younger age groups, are ignoring distancing measures and gathering in large groups again. You cannot enforce distancing when it’s unobserved on a large scale. Quarantining travellers is also impossible to enforce.  If we can introduce a test that produces a result within hours then it’s probably unnecessary

Could you argue that all the vulnerable who were going to die have now done so? No. Will there be a second peak of infection? Probably. Does that matter? Maybe; it depends on whether we have managed to stop an infection from going bad and causing death.

Lastly, what about vaccination? We are told that the country won’t be safe until one has been developed.

There is no vaccine against the human immunodeficiency virus (HIV) which causes AIDS after 40 years of trying to find one. So I am not sure we can rely on one for SARS-CoV-2. It may anyway take years to develop, but then again it may not. It has to be tested for efficacy and safety, and given the falling level of infection in the UK this will have to be an international effort. I would prefer to work on treating the severe consequence of infection, the Covid-19 syndrome. HIV can be treated and so is no longer the panic-inducing problem that it began with.

One thing is certain.  You need to get advice from experts.  But it’s not easy to pick the right experts and, as this saga has shown, even the experts can disagree.

I hope this short series has been helpful. You may wish to look at my blog (https://bamjiinrye.wordpress.com) but I would be happy to try and answer any other readers’ questions.  I have had to revise this part just in the two weeks since the first, so there may yet be changes to come!

Image Credits: Rye News library .

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