In this weekly round-up, Richard Lehman looks at a personal selection of articles of relevance to clinicians dealing with covid-19
Poppy and Mandragora
“Patients have intense dreams as deep as any experience in an opium den. Mine include a conviction that I can recite in great detail. One positions me in a London bakery; another persuaded me that there was a black magic exorcism under way in the hospital. Friends, family and colleagues who talked to me in this period can attest that I was off my head.” (Roger Boyes, The Times 18 Apr 2020) The trouble with ventilator delirium is that you remember some of it, and the nightmares are such that few ever want to go there again. Some of it may be due to the drugs, because ICUs are in fact dens full of opioids. To poppy, Shakespeare added mandragora, but this ancient combination of an opioid with an atropinic (mandrake extract) was more likely to kill than to “medicine thee to that sweet sleep” and it was certain to produce hallucinations. I wonder if there is a safe medicine that could make ventilation free of visions that affright? It would certainly make me less scared of it.
Try this at home?
“Home care of covid-19: a descriptive review” is the paper I’m most keenly awaiting. At present this wish would have to filed under “Pending: no articles found.” You may say that patients with covid-19 who stay at home can’t be properly ill, or they would be in hospital. Think about it, and you’ll see this isn’t necessarily true. These people still need kind and careful care: they may be dying of covid-19, or something else, or too frightened to go in, or simply have decided that if it comes to it, they would like to take their chances and die in their own bed. They may have been turned away by some triage system. NHS England has been trying to issue guidance without committing to any set model. For a week or two there was talk of “virtual wards” at home. There are lots of suggestions about palliative care and models of communication. There is even talk of training families and carers to maintain syringe drivers. Much of this sounds like improvisation driven by lack of staff and resources, but I would love to hear from readers about achieved solutions: my e-mail is not hard to find. In fact a group of us are planning to set up a website to share ideas and experiences.
Even before covid-19 came along, I lived in a state of permanent irritability, due to hypertension. No, you fool, not due to a disease called hypertension! There is no such disease! Can’t you see it’s a continuous physiological variable that is only relevant in the context of total cardiovascular risk! Then along came covid-19, which seems to enjoy killing people with elevated blood pressure. Why? Perhaps because so many of them take ACE inhibitors and ARB drugs that increase the number of ACE receptor sites, which the coronavirus uses to gain entry to human cells of many kinds. You can read all about this—and almost everything else you need to know about covid-19 as a systemic illness—in a terrific summary just published in Circulation. The presumption, therefore, has been that people continuing to take ACE inhibitors or angiotensin-receptor blockers to lower blood pressure in hospital might have a higher mortality than those taking other BP-lowering drugs. But in the biggest observational series published so far, from nine hospitals in the Hubei province of China, the opposite is true. Those taking these drugs had a mortality rate of less than half of those who did not (HR 0.37). Now you could do a whole graduate class on this observational study and its potential sources of confounding and bias, but my conclusion would still be that these drugs are safe in severe covid, and may even be beneficial.
In the North of England in the 1950s, every child was surrounded with several orbital rings of bodies who came to tea, called antis (people from the South using the long A will not understand this). As with electrons surrounding an atomic nucleus, aunties were quantum objects: any knowledge about their exact position was gained at the expense of ignorance about their momentum, so that some aunties were real relatives, whereas others existed in a state of quantum uncertainty. Some came often, some came seldom, and others just wrote at Christmas. I got a similar feeling of childlike consternation when I read a truly masterly review of coronavirus antibodies which has just appeared. The questions it poses are all the ones you most need answers to: for example, do people who have more severe disease mount stronger antibody responses after infection? Will infection protect you from future infection? How long will immunity last? This review provides a solid scholarly foundation for answering these questions, but only once the wave function of uncertainty has collapsed. I hope this article is the beginning of a cumulative real-time review that will give us all the emerging photons the moment they are emitted.
In certain parts of Paris there arises a characteristic aroma often attributed to a deficiency in French plumbing, Occasionally the same smell comes from a local restaurant which specialises in andouillettes. But whatever these sausages may do to the nostril, they are not known to transmit SARS-CoV-2. Human stools, on the other hand, can. An article called Time course quantitative detection of SARS-CoV-2 in Parisian wastewaters correlates with COVID-19 confirmed cases claims that you can sniff out the progress of an urban epidemic by measuring the amount of coronavirus RNA in its sewage outlets. John Snow, the inventor of urban epidemiology, would be rather thrilled. He must have grown very familiar with a certain odour as he studied contamination in the water supplies of London in the 1850s. Ah, les andouillettes!
I saw three ships
John Snow would certainly be thrilled to read a new study of how the novel coronavirus spread through the cruise ship Diamond Princess “We collected the daily number of 197 symptomatic cases, and that of the 146 passenger cases in two categories, i.e. those who stayed and did not stay in the same stateroom. We obtained the design of air conditioning and sewage treatment of the ship from literature. We back-calculated the dates of infection from the epidemic curve and compared with the start of on-board quarantine.” Golly, no more using up shoe-leather on the streets of Soho when you can do it by using up RAM on somebody’s laptop. “We infer that the ship central air conditioning system did not play a role, i.e. the long-range airborne route was absent in the outbreak. Most transmission appears to have occurred through close contact and fomites.”
These cruisers were of course mostly elderly people. But two other big ships that became covid-19 laboratories were full of young men. Le Figaro reports on “1081 marins positifs” on the French battleship Charles De Gaulle. The US aircraft carrier Theodore Roosevelt also turned into a positive marinade when the coronavirus came aboard and spread through its crew of 4,800. Among fighting fit mariners, French or American, confirmed SARS-CoV-2 infection seems to be asymptomatic in over 50% of cases. Even among the very different passengers on the Diamond Princess, the figure was over 40%.
Five weeks ago, when I began writing these reviews, everyone was aghast at the challenge of covid-19 and thrilled how it was dynamizing all the usual slow processes of medical knowledge exchange. In the intervening century, we have become more weary and circumspect. Each day brings another few hundred open-access articles about epidemiology, 17 new rapid meta-analyses of hydroxychloroquine, several deep algorithms that prove covid-19 has peaked, is peaking, won’t peak for another 8.3 months. We luxuriate in opinion pieces about masks, ventilators, patient narratives, animal models, political ineptitude. Lots of useful sites try to keep track of these (except the last), but few attempt to aggregate and appraise them and provide a dependable search engine. So thank goodness for CORD-19 which promises to organise the mechanistic literature, and the wider-ranging and easily searched McMaster guide to covid-19 evidence sources. Grown-ups, we need you more than ever.
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.