In this weekly round-up, Richard Lehman looks at a personal selection of articles of relevance to clinicians dealing with covid-19
The Kung Fu of Covid
One third of a year has passed since the start of the covid-19 pandemic, but there is little sense of shared global wisdom. The Chinese sage Kǒng Qiū (551-479 BCE) would be saddened. Among the many sayings attributed to him are: “All people are the same; only their habits differ.” China, with the largest population in the world, is the only one which has come close to eliminating covid-19 within its borders (with the possible exceptions of New Zealand and Iceland, as we go to press). Among 1.4 billion people, daily deaths are zero. Why then isn’t the rest of the world rushing to adopt the habits of China? Another maxim of Confucius/Kung Fu is “Learn avidly. Question repeatedly. Analyze carefully. Then put what you have learned into practice intelligently.”
Dialogue concerning the two world systems
“The man who asks a question is a fool for a minute, the man who does not ask is a fool for life.”
Galileo wrote a dialogue to show you could not believe contrary things at once: either the sun revolved around the earth, or the earth revolved around the sun. Unfortunately the Pope was office-bound to believe the first, and Galileo’s book made him look a fool. Mistake. The pope remained a fool for life, and Galileo remained under house arrest for life. Now, with covid-19, any containment policy either revolves around the value of individual life, or it revolves around the economy. It cannot do both at the same time. China exemplifies the first, and Britain exemplifies the second. On 12 March our chief medical officer, chief scientific officer, and our prime minister Boris Johnson declared in favour of “herd immunity”, and nothing that has happened since shows serious intent to prevent the cull which that implies. Britain has already lost ten times more people per head of population than China during the whole of its epidemic. If we had started by valuing the individual, this would not have happened. And our economy would be less ruined too. Maybe there is time to mend our ways in the second wave.
“Do not impose on others what you yourself do not desire.”
So let’s say you have embraced the idea of herd immunity, without waiting for a vaccine. That means allowing the infection to spread through the population. It will kill those it is going to kill, but in a “controlled avalanche” that will be spread out to allow some to return to normal economic activity and health provision. That sounds like a good British compromise, though in fact the following model comes from Israel. “Individuals whose probability of developing serious health conditions is low (i.e. 20-49 years old with no comorbidities) will be offered the option to be voluntarily exposed to the virus under controlled supervision, and will then be issued ‘immunity certificates’ if they are confirmed to have developed SARS-CoV-2 antibodies.” I can see that having some appeal, especially to altruistic health professionals who have already voluntarily exposed themselves to covid-19 risk through lack of protective equipment. What I can’t understand is how the modellers come to the conclusion that this “reduces the overall mortality by 43%, reduces the maximum number of people in need for ICUs by 62%, and decreases the time required for release of 50% of the low-risk population by more than 2 months.” How can any controlled infection strategy reduce the virulence and case-fatality rate of the infection itself?
“If you make a mistake and do not correct it, this is called a mistake.”
When you put on a mask in public, you lose a lot of face. You also stop a lot of droplets. But this is at the cost of adopting a habit that many people in English-speaking countries seem to find repellent. I think they lose more face by insisting on randomised controlled trial evidence than they ever would by just putting on a mask. No RCT is ever going to be as good for detecting harms as a natural experiment involving 2 billion people. No cluster randomised trial of sufficient scale is going to be able to adjust for confounders any better than an observational comparison. Every population observation we have favours masking. Then triangulate this with some simple, common sense physical experiments, such as this: “We found that most home fabrics substantially block droplets, even as a single layer. With two layers, blocking performance can reach that of surgical mask without significantly compromising breathability. Overall, our study suggests that most double-layered cloth face coverings may help reduce droplet transmission of respiratory infections.” I do wish that some EBM-loving friends would admit that some ideas that have face validity are in fact valid until proven otherwise. On faces, even.
“To know what you know and what you do not know, that is true knowledge.”
A month ago the question on everyone’s mind was how many very sick covid-19 patients would have to be turned away from ventilators. For some of us older people, there was also the question of whether it was worth going on to a ventilator at all. In fact it seems that very few ventilator rationing decisions have had to be made in the UK, and thanks to the brilliant work of ICNARC we know that the mortality of ventilated patients in the UK is 67%. This is based on a much larger sample than from any other country. A more pertinent question may be: which patients really need ventilation and which might do better with a non-invasive strategy? Since continuous positive airways pressure was first proposed as an alternative, surprisingly little seems to have appeared about it in the clinical literature. Meanwhile, high flow nasal cannulas are making an appearance. I hope someone sorts all this out before I arrive on an ICU.
“No matter how busy you make think you are you must find time for reading, or surrender yourself to self-chosen ignorance.”
I may have been reading the wrong journals, but so far I’ve found little about the varied natural histories of the illness called covid-19. For sure, there have been plenty of symptom lists and time-course diagrams and so forth, but nothing that’s helped me understand the transition from what I’ve called benign covid into malignant covid. Now a very comprehensive review of the world literature has appeared in medRxiv.
This divides covid-19 into three stages: “the time of infection (Stage I), sometimes progressing to pulmonary involvement (Stage II, with or without hypoxemia) and less frequently to systemic inflammation (Stage III).” The hard-working authors go on to attempt to map therapy on to each stage. That is certainly the central challenge, though it seems hardly addressable in the present state of ignorance.
PM Question Time
“The essence of knowledge is, having it, to use it.”
Now let’s look at the few who die. Remember that modern medicine was not built on numbers but on observation: living patients reviewed on a daily basis, and then examined post mortem should they get unlucky. Autopsy just means seeing for yourself. I am baffled that medicine today should employ so many statisticians and so few gross pathologists. A new article tells us about the lung findings in 38 patients from Northern Italy. Terminal covid-19 is a systemic disease, but I guess it’s better to know about the lungs than about nothing. They are a mess, of course. “The features of the exudative and proliferative phases of Diffuse Alveolar Disease (DAD) were found: capillary congestion, necrosis of pneumocytes, hyaline membrane, interstitial oedema, pneumocyte hyperplasia and reactive atypia, platelet-fibrin thrombi.” There is lots about those thrombi in small arterial vessels, confirming that coagulopathy often dominates the end-stage of covid-19. In 4 patients, there were multiple small lung abscesses caused by bacterial infection.
“Success depends upon previous preparation, and without such preparation there is sure to be failure.” Two and a half millennia later, this Confucian saying reappeared on the lips of Louis Pasteur (1822-95) as “Fortune favours the prepared mind”. Pasteur’s experiments with yeast and cotton wool had prepared his mind to discover that infectious diseases were transmitted by filterable micro-organisms. Before long, other people discovered that certain infectious diseases, like smallpox, were spread by organisms that seemed to be invisible and pass through filters. Subsequently, with better filters and stronger microscopes, these viruses appeared in their full glory. The image of a blob covered in a mass of collar studs that you see everywhere is a triumph of cumulative science. Forget post-modernism. This represents knowledge that is certain and will never go away. Soon it will lead us to an effective vaccine. There is no reason to doubt that: the only question is when and which of the 115+ candidate vaccines it will be. And then it will all seem so straightforward. “Anyone can find the switch after the lights are on.”
No, Confucius did not really say that. There is no record that he invented the electric light in 500 BCE. Yet you can find it in a list of his sayings on Google.
Competing interests: None declared
Articles from MedRxiv get special prominence in these reviews. MedRxiv is a completely free site for the rapid exchange of knowledge which was launched last year as a joint initiative by The BMJ, Cold Spring Harbor Laboratory and the Yale University Open Data Access project. All MedRxiv articles carry the caveat: This article is a preprint and has not been certified by peer review. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice. This review is intended as a quick source of information in a readable form. While every effort has been made to be accurate, the opinions are those of the author and should not be relied on without reading the full articles cited in the context of current NHS guidance.