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16 September 2020

How Covid-19 is still confounding doctors after six months

A study found around 100 symptoms the virus may cause, but only a dozen or so are widely recognised. At this stage, we're not ruling anything out. 

By Phil Whitaker

Paul’s feet were burning. “It looks like there’s nothing wrong with them,” he told me on the phone, “but they feel like they’re on fire.”

There is really only one condition that gives rise to that symptom – peripheral neuropathy. Naming it is easy. The challenge is working out what is causing the nerves supplying the extremities to malfunction. Around half of cases in the UK are caused by diabetes or alcohol abuse, but Paul is a moderate drinker with no known sugar-control problems. There’s a long list of other potential causes – known as a differential diagnosis – but in at least a quarter of cases none is ever identified. These get lumped together under the label “idiopathic”, which is doctor-speak for “I haven’t got a clue”.

“Let’s book some blood tests,” I told him. “And bring you in to see me after.”

Paul’s results were pristine; in particular, none of the vitamins vital for nerve function were deficient, nor were there antibodies against Lyme disease, a tick-borne infection known to cause neuropathy months after the original illness. By the time he came in to be examined, however, things had progressed. He’d developed intermittent abdominal pain. And the burning sensation had spread to his arms, hands and face, and was even sometimes affecting his tongue.

“Do you want to try something to ease it?” I said. Certain antidepressants and anti-epileptic drugs have a fortuitous ability to dampen neuropathic pain. Paul shook his head. “I can cope with it. I just want to know what’s going on.” It was starting to worry me, too. Peripheral neuropathy affecting only the feet is something I’ve seen several times over the years but I had never before encountered this rapid progression, affecting nerves all over his body.

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“And I was sweating last night,” Paul told me. “My pyjamas were soaked through.”

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Night sweats are a hallmark of lymphoma, and cancers of the immune system are another possible cause of peripheral neuro-pathy. I examined Paul carefully, but found only a mild fever. I was wondering whether to request a CT scan to look for lymph gland swelling internally, when Paul asked: “Could it be anything to do with Covid?”

He’d had coronavirus during the first wave. It had dragged on for weeks, but eventually he’d recovered and had been well for months. “I’m not sure,” I told him. “We’re learning as we go. Let’s keep an open mind.”

His Covid-19 had occurred before community testing was available, so I recommended a swab test and sent off blood to check for antibodies. I’ve been in general practice more than 25 years and have never met a case like that with which Paul was presenting. If Covid-19 were responsible then either he’d been reinfected (there are now documented cases of this) or the protracted form of the disease – “long Covid” – was relapsing after a prolonged period of perfect health, which would itself be a new finding to me.

While awaiting Paul’s results, I did some burrowing online. I discovered research by Dr Natalie Lambert of the Indiana University School of Medicine, who in July teamed up with Survivor Corps, a grass-roots patient group helping to catalyse research and education into Covid-19. Lambert surveyed symptoms experienced by more than 1,500 long Covid sufferers. More than a quarter reported night sweats, and a quarter reported peripheral neuropathy. This kind of research has potential flaws, but as a confirmation that what was happening to Paul could be due to Covid-19 it was invaluable.

Elsewhere, research by the Collaborative Study of Covid Recurrences group in France has reported a case series of what appear to be reactivations of Covid-19 infection after a period of apparent recovery. We know this happens with some other viruses: our bodies never clear chickenpox, for example, and it reactivates later as shingles. So it may prove with Covid-19.

Both Paul’s swab and antibody tests were negative. While that made it harder firmly to attribute his symptoms to coronavirus, it didn’t rule it out. Early research suggests that around 80 per cent of long Covid patients do not mount an antibody response.

Nevertheless, Paul’s abdominal pains and night sweats completely resolved, and over a period of around a month his burning skin has substantially improved, though there are still residual symptoms. I am reasonably sure I have just seen my first case of Covid-19 peripheral neuropathy. Fascinatingly, many of the symptoms of long Covid – abnormally fast heart rate, labile blood pressure, diarrhoea, temperature dysregulation – may be attributable to neuropathy in the autonomic nervous system, a separate nerve network that controls the functioning of our organs and circulation.

During the crisis of the first wave, the NHS became an emergency-only service. Over the summer, we have been steadily reincorporating normal healthcare appointments and procedures. Paul’s case feels symbolic. Covid-19 has to be added to the long differential diagnosis of peripheral neuropathy. The Indiana study identified around 100 symptoms the virus may cause, far more than the dozen or so widely recognised at present, and coronavirus will need to be considered in all sorts of differentials from now on. Covid-19 has gone from being a separate, overwhelming threat to becoming yet one more part of medicine’s complexity – something we’re getting to grips with, albeit there is still much more to learn.

It has been a privilege to write weekly about the pandemic in the front pages of the New Statesman over these past six months. And it is now time to return to my former fortnightly rhythm alongside my fellow columnists in the Back Pages. There, I can resume writing about the whole of medicine – which now includes a new disease with a plethora of presentations and ramifications: Covid-19.