Katherine rang her GP about her teenage daughter, who had Covid-19 symptoms of sore throat, cough and chest tightness. Partway through the call, Katherine’s older son, Patrick, came downstairs. For the past few days Katherine had noticed him being a bit breathless when moving around. She wasn’t particularly worried – he didn’t have the symptoms his sister had, and she had told him many times that he needed to do something about his weight, now the wrong side of 17 stone. Now though, he seemed markedly out of puff just from having descended the stairs. Katherine mentioned it to her GP, who was still on the line. An assessment was arranged at the local Covid “hot hub” where I was on duty.
Within minutes I was on the phone to the hospital: otherwise fit and well 23-year-olds with a resting pulse of 140 and oxygen saturation levels of 80-something per cent definitely need admission. He responded well to supplemental oxygen while waiting for the ambulance. What was surprising were the results of his CT scans later that day. There were peripheral signs of early Covid, but the principal problem was multiple blood clots blocking arteries in both of his lungs.
This was a little over a month ago, when we were still thinking of Covid-19 as a respiratory infection, albeit one that could set off a fulminant chain reaction inside the lungs, requiring ventilatory support and all too often resulting in death. It is a measure of the extraordinary research effort globally that just a few weeks later we are appreciating that Covid-19 can be an altogether more complex disease.
Coronavirus gains entry into human cells by binding to a cell-surface receptor called ACE2. This is present in large amounts in the linings of the upper airways, where it is thought most people’s infections take hold. It is abundant, too, in the tiny air sacs deep inside the lungs (alveoli) – the battleground in Covid-19 pneumonia. But ACE2 is also found on cells in many other tissues and organs, including the lining of blood vessels.
The formation of clots inside arteries and veins has long been recognised as a complication of any major illness, but so-called thromboembolic disease appears to affect 20-30 per cent of hospitalised Covid-19 patients – far more than in other serious infections. The mechanisms are still being elucidated, but it is possible that coronavirus can directly infect cells lining blood vessels, provoking inflammation that in turn causes clots to form. This evolving insight is leading to rapid changes in hospital practice: Covid patients are now routinely treated with blood-thinning injections in an attempt to prevent thromboembolism.
The distribution of ACE2 in other body tissues seems to explain alternative patterns with which Covid-19 can present. In the early phase of the pandemic, the dominant picture was of respiratory symptoms, but there is a definite gastrointestinal variant, characterised by nausea and diarrhoea. Sometimes these occur together with cough and chest tightness, but I’ve encountered several patients with isolated digestive tract problems, and case reports corroborate this.
We still have an imperfect understanding of how coronavirus is spread; a gastrointestinal variant could suggest an oral route of transmission in addition to the airborne one. And the presence of ACE2 in the heart muscle, kidneys, liver, and brain may explain the serious complications affecting these organs in the most severely unwell patients. Around a quarter of Covid patients on ICU require renal (kidney) support: again, a strikingly high proportion.
Out in general practice we are also learning important lessons. We are on heightened alert for “silent hypoxia”: patients who don’t feel particularly unwell, but whose oxygen levels prove dire when measured, possibly – as with Patrick – related to clot formation. And we are beginning to recognise a relapsing-remitting variant. Most patients recover from mild to moderate Covid over the course of one to two weeks, but there is a subset who continue to experience symptoms on a cyclical basis, recovering for a few days only to fall ill again. My longest-running patient has been intermittently unwell for over seven weeks now. At present, we don’t know whether these people represent an ongoing infection risk, periodically shedding the virus. It makes decisions about the duration of self-isolation challenging.
Some other viral infections can cause relapsing symptoms, the most common being glandular fever, which is an important precipitant of chronic fatigue syndrome (sometimes called ME). Our evolving experience with Covid-19 raises the spectre of a minority of patients suffering long-term effects. This will certainly be true for severe cases – recovery after prolonged ventilation takes many months – but it may also occur in some patients whose initial illness did not warrant hospitalisation.
As a novel infection, Covid-19 is tragic but professionally fascinating. The speed with which new knowledge is being disseminated by the global medical and scientific community is phenomenal. We have a growing appreciation of Covid as a multi-system disease, and further important questions are the subject of urgent enquiry. The chilling excess mortality among BAME patients may in part reflect the socioeconomic inequity these groups endure, but it seems likely that there are also ethnically determined genetic vulnerabilities. Understanding these, as well as the basis for Covid’s disproportionate impact on male patients, will reveal more about the biology of the virus and its effects on the human body.
Patrick was discharged on blood-thinning tablets to prevent further clot formation. It seems likely that his obesity – also recognised as a risk factor for Covid complications – was the reason he, rather than his sister, became the patient that day.
This article appears in the 06 May 2020 issue of the New Statesman, Remaking Britain