The Wry Observer’s Covid-19 update (12)

Last night much was made of the statistic that the latest weekly number of deaths is the highest for the week since 2000.  It’s a pity that the weekly death figures for that year don’t seem to be available on the Office of National Statistics (ONS) website but my immediate thought was that like was not being compared with like.  Week for week, by calendar dates, I am sure the statement is correct.  But if you took the week from 2000 that compared directly in terms of the time of the flu outbreak I suspect the figures may differ.  In 2008/9, swine flu time, there was a rise of 25% in the December and January over the usual 42,000 or so monthly deaths but it had dropped back to the usual numbers by March.  Making a comparison between the height of the Covid-19 outbreak (April) and the tail-end of the 2009 swine flu outbreak, also in April, overstates the excess rate.  There is an expectation that the death rate from/with Covid-19 will peak in a couple of weeks, but it would seem sensible to line up the comparative graphs with the peaks and not with the calendar dates.  This has, of course, been the basis of comparisons between countries in the current epidemic.

There is also apparent growing puzzlement over the non-respiratory aspects of Covid-19, including renal and cardiac failure.  (see https://www.medscape.com/viewarticle/928929?nlid=135090_864&src=WNL_mdplsfeat_200421_mscpedit_rheu&uac=308617HG&spon=27&impID=2355197&faf=1).  But if the mechanism for severe “everything failure” is a cytokine storm it should not be at all surprising – indeed it is exactly what you would expect.  The effect is supposed to have been the cause of the rapid downhill path of patients with “Spanish Flu” in 1918, not that such things could be found back then, as there was no immunology, but the descriptions are remarkably like those today in Covid-19.  I have personally seen a cytokine storm as a side-effect of medication (sulfasalazine in rheumatoid arthritis) and it presented exactly the signs described in the article.  So were those of the Northwick Park drug trial where an experimental drug, TG-1412, designed to stimulate white blood cells, did so all too dramatically.  My patient recovered, but her kidneys were not far off complete failure, and the X-ray appearance of her lungs was horrific.  And if indeed this is the mechanism of acute deterioration then shutting off the cytokine pathway should work.  Interleukin-6 is part of that pathway.  We shut it down in rheumatoid arthritis with a drug called tocilizumab.

Strangely I was contacted by a newspaper for an instant comment at the time of the Northwick Park episode and believe I was the first to postulate the cytokine storm theory.  It may be that those who suffer a storm with some stimulus have had their immune system altered by something – perhaps a previous infection.  It would certainly explain why some suffer a storm and some don’t.  There’s a good exposition of this at https://www.outsourcing-pharma.com/Article/2007/01/29/Northwick-trial-tragedy-scientists-reveal-how-cytokine-storm-started.

It remains to be seen if tocilizumab turns out to be the Holy Grail of Covid-19 management.  The more time passes the more it does look as though the devastating downhill course seen in some patients is a cytokine phenomenon and so blocking that should shut off the damage, allowing clinicians to provide appropriate support (I do wonder whether high dose steroids might be appropriate; my series of one recovered on that).  Initial reports are encouraging but there have been many false dawns. If toclizumab does work one could offer it to anyone developing serious respiratory symptoms, as it appears that these precede a storm; those who are asymptomatic, one might presume, have not had their immune system wound up ready to uncoil like a spring.  And if it does work it may obviate the need for strict lockdowns; it won’t matter so much if some have a severe illness if there is a treatment.

I used a lot of steroids, more than many rheumatologists, but also wearing my rehabilitation hat when patients with multiple sclerosis came in moribund with an infection.  It took us a while, but we worked out that many of them had acute adrenal insufficiency and could not mount an effective steroid response to the insult of infection.  I would be interested to learn whether Covid-19 patients show the appropriate investigation results to confirm that they too may have this as an additional reason for failure to recover.  Could steroids do any harm?  I doubt it.  Might be worth a trial (blind, of course!).

Reinventing wheels etc

In the BMJ of 23rd April are listed the finalists for the BMJ Neurology team of the year awards, which include the Multiple Sclerosis team of UCLH for its integrated service.

Reinvention of the wheel? Failure of institutional memory? Left hand not knowing what right hand is doing?  All three possibilities come to mind when I read the nomination which “to everyone’s surprise” showed that urinary infections were the commonest cause of admission in patients with MS.

I am certainly surprised it was a surprise.  Indeed when I read this I was almost speechless.  I have known, and taught this for nearly 30 years.  I took over a Young Disabled Unit in 1985.  Over the next ten years I and my multidisciplinary team turned it from a long-stay unit with 15 residents to a dynamic rehabilitation unit with some 300 clients, the majority of whom had MS.  We provided a regular inpatient respite service, a helpline and regular outpatient review, which was supplemented in later years with bladder ultrasound.  The superb nursing staff were also alert to admissions of our clients to acute beds, from which they would be extracted as soon as possible – or at the very least they would make a trip to the acute ward to advise.  I taught all the trainee doctors that patients presenting to A&E with a sudden deterioration in their MS had an infection (usually urinary, but sometimes chest) until proved otherwise.  While deterioration was rapid, so was recovery if effective treatment was instituted rapidly.  I might add that, as a clinical point that will save some lives if anyone reads this, some patients with an acute infection regularly developed severe hyponatraemia which we attributed to acute adrenal insufficiency, and recovered with hypertonic saline and hydrocortisone; whether this phenomenon was related to previous high dose steroid treatment for relapses we never did determine.

We also provided an effective pressure sore service. Regular physiotherapy helped prevent contractures and maintain mobility.  Occupational therapy home visits were a sine qua non. Our service was entirely integrated.  Our local district nurses involved in home care regularly exchanged information.  If a patient “went off” suddenly then infection testing was arranged at home.  Not infrequently I would write the antibiotic prescription.  Unit emergency admissions were organised not by GPs but by family or the district nurses by direct contact.  In this way we actually kept MS patients out of acute hospital beds.  All of this was done without any input from neurologists.

To return to my opening paragraph it appears to me that the UCLH team have reinvented the wheel.  I regret that my teaching in a suburban district general hospital never permeated to the centre to provide a lasting institutional memory, but perhaps the most damning indictment is that, until relatively recently, it was rehabilitationists who dealt with long-term MS patients and not neurologists, who concentrated on diagnosis (once made, there was little treatment, so many, though not all, lost interest). So the crossover of information from left to right hand was as limited as in a patient whose corpus callosum has been transected.  It is thus encouraging to see the growing interest and enthusiasm of neurologists in integrated long-term management.

Though our model was highly effective, and much appreciated by patients and their families, it was expensive.  The Unit kept afloat as much through my political lobbying as through its care success. Within a year of my retirement it had been closed down.