State of Play : Covid-19

As this pandemic has progressed, so has its medical management.  Although largely drowned out by more sensational media ‘noise of numbers’, one thing is clear – Covid-19 treatment is getting much better.  Those infected since June are now far more likely to survive than those unluckily infected before June.  This is why.

ICU and infectious disease doctors have been on a steep ‘learning curve’ but they now know far more about Covid-19 than they did in the early days of the pandemic.  As a result, they are now treating their patients more effectively.

Although tragic for families who lost those they loved in the early months and who now think ‘if only ... ...’, those two words reflect the bittersweet reality of all medical learning curves: the more we learn, the better the outcomes.

There are five important things that we know now but didn’t know at the start.

1. Covid-19 was initially thought to kill by pneumonia ... and infection of the lungs.  As a result, ventilators seemed the best way to treat sick patients who couldn’t breathe.  We will all remember the scramble for [and the bitter debate over] ventilators in the US and Europe.

But importantly, it has become clear that the virus does not cause its worst damage through infective pneumonia, but rather by the formation of tiny blood clots inside blood vessels – primarily in the lungs.  These, in turn, cause the blood oxygen level to fall, rapidly leading to a condition known as ‘hypoxia’.  But the lungs are not the only target – small clots also form in other organs – like the kidneys.  These micro-clots, and not infection, are the key feature of Covid-19.

Simply providing oxygen by a ventilator is not the answer.  Rather, it is these micro-clots that need to be prevented and/or dissolved.  Blood-thinning drugs [like aspirin and heparin] that prevent clotting are now the core of Covid-19 treatment – we have learned that drugs that only treat infection do not work.

2. Early in the pandemic, patients died incredibly rapidly – often before they could reach hospital.  This sudden, frightening, and catastrophic pattern of death occurred when the blood oxygen level began to drop precipitously.  But why?

It seems that Covid-19 causes a rather strange type of hypoxia – oddly dubbed ‘happy hypoxia’.  In Covid-19, the blood oxygen level can fall gradually, without any symptoms, without the patient being ‘aware’ – at least not until a critical, near fatal level has been reached.  Normally we become breathless if our blood oxygen content [saturation] falls below about 90%.  But in Covid-19 patients, oxygen saturation can fall slowly, imperceptibly, to as low as 70% before the patient suddenly gets very sick, and collapses.  This is not unlike the way carbon monoxide kills ‘by stealth’, and why carbon monoxide monitors are now recommended if gas burners or open fireplaces are used at home.

Why breathlessness is not triggered in Covid-19 patients until very low oxygen levels are reached is not fully understood, but it does explain why so many very sick patients presented so very late in those earlier months.

Once ‘happy hypoxia’ was recognised, early intervention became possible.  Many countries now use a simple, cheap, pulse oximeter [those little black clamps they place on a fingertip before an anaesthetic] to home-monitor oxygen saturation in Covid-19 patients.  This allows patients to stay safely at home and only be transferred to hospital only if the blood oxygen saturation drops below 90%.  This simple management step is one key reason why survival is improving.

3. Early on, no drugs were able to ‘fight’ the coronavirus and most patients became severely ill.  Hypoxia could be countered with a ventilator, but this was a rear-guard action and was before we knew of the benefits of treating blood clots.

During those first few desperate global months, doctors began to learn!  Autopsies revealed the underlying clotting problem and led to the use of anti-clotting drugs.  Furthermore, two important anti-viral medicines, remdesivir and favipiravir, were found to be effective against Covid-19.  If used early and selectively in patients where oxygen levels had fallen below 90%, these drugs could prevent many patients from becoming severely unwell.  But, as both are scarce and expensive, they are held in reserve for those in greatest need.

4. Many Covid-19 patients do not die from the virus alone but are damaged by an overly-exuberant response from their own immune system – ‘cytokine storm’.  This exaggerated response can do as much (or more) damage than the virus itself.

Doctors did not know how to prevent this immune response until, in June, an Oxford team reported their success with dexamethasone – a cheap, available, long-used steroid.  This has allowed ‘cytokine storm’ to be blunted in most patients.

5. ICU patients on respirator support have traditionally been nursed flat on their backs, but ICU doctors now know that Covid-19 hypoxia improves best if patients are nursed flat on their tummies.  This simple but crucial difference was unknown early in the pandemic.

Recently, the Israelis have reported a chemical produced by white blood cells [alpha-defensin] as the cause of the micro-clots that clog the lungs and kidneys in Covid-19.  They found that a simple, common drug used to treat gout – colchicine – can counter alpha-defensin, though this intervention needs further confirmation.

In summary ... Covid-19 patients now have a better chance of surviving than those infected in the early, desperate months.  Furthermore, other useful treatment strategies may yet emerge as we frantically scramble for that elusive vaccine.

 Meanwhile, do not forget the three proven, simple precautions of infection control ... (1) wash hands, (2) wear masks, and (3) socially distance.  

John Agar MBBS, FRACP, FRCP[London], OAM
Conjoint Clinical Professor of Medicine [retired]