During our phone interview, Professor Brendan Delaney, chair in medical informatics at Imperial College London, suddenly apologises: ‘Sorry about the pauses,’ he says, ‘but I’m still learning to concentrate on both what I am saying and on my breathing’.
Professor Delaney was one of the early victims of long Covid after catching Covid-19 in March 2020.
Previously a very fit cyclist, two weeks after he’d ‘recovered’ from Covid, he was struck with intense fatigue.
Even a brief phone call could exhaust him. He also had difficulty breathing, muscle pains, brain fog and a recurring fever.
Three months later he’d recovered sufficiently to return to work part-time but still had brain fog.
‘I couldn’t function at my normal level,’ he says. ‘I wasn’t seeing the connection between things.’
Research just published by Imperial College London suggests as many as two million people in England alone are affected
Long Covid is defined as having symptoms lasting more than 12 weeks. The growing number of those affected with a condition for which there is currently no cure is shaping up to be the next major threat to the health service and the economy.
Last October, NICE (the National Institute for Health and Care Excellence) estimated there were 60,000 cases of long Covid in the UK. In June, the Office for National Statistics put it at one million.
Now research just published by Imperial College London suggests as many as two million people in England alone are affected.
One U.S. study has suggested that as many as 30 per cent of infected Covid patients could go on to suffer the long version of the infection (10 per cent of the patients in the study had been hospitalised but the majority were outpatients with mild illness, reported the journal JAMA Network Open).
List of symptoms getting longer
While the numbers of those affected has shot up, so, too, has the number of symptoms linked to it. At the end of last year, NICE issued a relatively short list, with the main signs being shortness of breath, severe fatigue, brain fog, and heart and lung conditions.
This year, the list of symptoms has mushroomed to 200, according to an international study of long Covid sufferers published in the Lancet journal EClinicalMedicine.
These now include visual hallucinations, tremors, itchy skin, changes to the menstrual cycle, sexual dysfunction, memory loss, diarrhoea and tinnitus.
The racing driver Lewis Hamilton recently revealed he’d suffered blurred vision as a result of long Covid. This, too, is now recognised as one of the neurological problems that 85 per cent of long Covid patients experience, as a study from the Northwestern Memorial Hospital in the U.S. has found.
This expansion of the symptoms makes diagnosing long Covid much harder and means that a far greater range of experts will be needed to treat them effectively.
Indeed, the lead author of the Lancet paper, Athena Akrami, a neuroscientist at University College London, says ‘tens of thousands’ of long Covid patients could be suffering in silence because they’re unsure if their symptoms are caused by the virus.
Exactly how the virus can have such a wide-ranging effect is unclear, but one theory is that it relates to an enzyme called ACE2 that helps with cell repair.
The lining of our blood vessels and a part of the brain (the brainstem) that controls many vital functions — such as breathing, heart rate, blood pressure and sleep — have a lot of ACE2 receptors.
The problem is that SARS- CoV-2, the virus that causes Covid-19, also attaches to these receptors, which reduces the enzyme’s effectiveness. This can damage both blood vessels and brainstem — and ‘the result of this can show up almost anywhere in the body’, explains Professor Delaney.
So what is being done to deal with this explosion of cases?
The plan, announced by NICE last October, was to set up two sorts of clinic: one to diagnose patients, the other to provide treatment. Assessment clinics are funded by the government and already £100 million has been spent setting up 89 such clinics in England. Treatment clinics are the responsibility of local health authorities.
The problem is that many of both types of clinic originally specialised in single disorders such as heart, lung or stroke, and have been repurposed for long Covid.
‘The result is that few of the diagnostic ones are properly equipped to provide the range of tests that these patients need,’ says Professor Delaney.
Patients miss out on right tests
Professeor Delaney says some of these diagnostic clinics ‘don’t have the resources to spot red flags such as low oxygen levels in the blood or a neurological problem such as vision issues’.
‘More important,’ he says, ‘is the lack of a “joined-up” pathway to arrange for detailed examination with CT or MRI scans if needed.
‘Instead, they run basic tests such as lung X-rays or ECGs, to monitor the heart rhythm. These aren’t sensitive to typical post-Covid conditions, such as heart muscle inflammation or clots in small blood vessels.’
The result is that patients coming in with a range of Covid-19 symptoms can have various tests and be told nothing is wrong.
This is a problem recognised in the latest long Covid guidelines issued in June by the Centers for Disease Control and Prevention in the U.S., which state specifically that: ‘A lack of laboratory abnormality does not invalidate the existence or the severity or the importance of a patient’s symptoms or conditions.’
A snapshot of long Covid patients’ experience of the NHS clinics was recently published by the largest global patient group — Long Covid Support — which has 42,000 members in 100 countries (Professor Delaney is one of them).
Nearly 900 members were quizzed on their experiences of the new NHS clinics. The survey found that 37 per cent of recently diagnosed patients had not been referred to one by their GP, while 11 per cent who were referred were turned away — among the reasons were ‘having too many symptoms’.
It is precisely because of this wide range of symptoms that treatment clinics need to be staffed by a wide range of experts.
‘Long Covid is a multi-system disorder that can affect the brain and the body,’ explains Elizabeth Murray, a professor of e-health and primary care at University College London, where she runs a treatment clinic called Living With Covid Recovery.
‘These patients need specialists who know about rehabilitation. We don’t yet have treatments for many of long Covid’s effects, but we do know how to help patients with common symptoms such as fatigue, brain fog, breathlessness and anxiety. They need such rehab specialists as occupational therapists, physiotherapists, dietitians and psychologists.’
Not enough experts to help
What happened to one patient illustrates the pros and cons of the current system.
In May last year, George, a 57-year-old train driver from just outside London, ‘developed all the classic Covid-19 symptoms — fever, cough, fatigue’.
‘Two days after the symptoms had all greatly improved, I suddenly felt as if a switch had been flipped,’ he says. ‘I just collapsed with terrible fatigue.’
This worsened over the next six months until ‘eventually I couldn’t go out without a wheelchair’, says George, who is on sick leave and spoke on condition of anonymity. It took a year before George, a father of one, was able to see a GP in person.
‘I had various blood tests, but they mostly came back normal. My GP never mentioned long Covid.
‘I was eventually diagnosed over the phone by my work doctor.’
Using health insurance, George saw a cardiologist and a respiratory consultant who told him he’d be better in two months.
‘When I wasn’t, they referred me to an occupational therapist, who was very helpful,’ he says. ‘She’d had long Covid herself and taught me all about how to pace myself.
‘She also provided simple energy-saving equipment such as stools to rest on in the kitchen and a really helpful bath lift.’
When George’s GP finally asked if he wanted to be referred to a long Covid clinic, he says: ‘I almost fell over. I’d been asking for a referral for months.’
George is still waiting to be seen at the clinic.
But even when a patient is correctly diagnosed, long Covid is so new that there is great uncertainty about how best to treat it. ‘There’s no magic bullet because its effects are so widespread,’ says Professor Delaney. ‘We have drug treatments for some of the symptoms, such as high blood pressure, but there is a huge gap between the advice from official bodies, such as NICE, and the experience of clinicians and patients.’
So what does work for it?
NICE recommends using existing treatments for dangerous symptoms involving the heart, lungs or a lack of oxygen.
It is also spending £30 million on investigating the effectiveness of various drugs, rehabilitation, dietary changes and weight-loss management.
‘The problem is that NICE and other NHS bodies rely on analysing trials to gather evidence for treatments. But there aren’t any good trials yet of treatments that work,’ says Professor Delaney.
In an attempt to speed things up, Professor Delaney has gathered 35 UK clinicians with experience of treating long Covid patients to discuss treatment combinations that have worked for their patients and then to pool the results.
The results of their efforts have just been published in the British Journal of General Practice.
Combining drugs with yoga
One surprise to emerge from this collaborative effort is to use drug treatments in combination with complementary therapies.
For instance, the treatment of symptoms such as breathing difficulties might combine yogic breathing (put simply, a form of deep inhalation techniques), meditation, supplements and acupuncture with established drugs, including the heart medications beta-blockers and ivabradine, which reduces the heart rate and so may help with fatigue.
One of the motives behind this project was Professor Delaney’s own experience of being a patient in a long Covid clinic.
‘I quickly realised that no one knew anything about what was happening,’ he says. ‘So I started linking up with other doctors with similar symptoms, and it seemed to us we had overactive immune cells — specifically, mast cells.’
This is one of the more intriguing approaches. It seems SARS-CoV-2 can trigger the mast cells, which produce histamine and cause the itching and inflammation associated with allergies. Professor Delaney says when he started taking over-the-counter antihistamine pills, which dampen down the immune response, his symptoms improved (he also found that yogic breathing helped with his breathlessness).
The new recommendations suggest antihistamines and steroids (a standard combination for allergy) should be combined with a low-histamine diet (see panel, right).
Separately from this project, Dr Joseph Kwan, a consultant physician in stroke medicine at Charing Cross Hospital, London, is looking at another nutritional approach for the brain fog of long Covid by tackling homocysteine.
This is an amino acid we make from food. High levels are linked to damaging levels of inflammation in the brain, which has been seen in some Covid patients (high homocysteine has previously been linked to Alzheimer’s).
‘The only way to bring it down is by supplementing with very high levels of B vitamins,’ says Dr Kwan. ‘It’s worth testing.’ Dr Kwan, who has a nutrition qualification from Cornell University in the U.S., believes other diets could be worth investigating, including a very low-carb ‘keto’ diet, as high levels of insulin and glucose (one of the effects of a high-carb diet) are linked to increased levels of inflammation and breathing disorders.
For some patients, it’s not a case of multiple tests and new lifestyle and drug combinations. Sometimes something as simple as exercise — at the right intensity and speed — can do the trick.
Gillian Fowmes, 52, an IT manager from Reading, had a bad case of Covid-19 in April last year, with shortness of breath, ‘horrendous headaches’, crippling fatigue and chest pain, she says.
‘Even so, I thought that it would be a two-week thing and then I would be better.’
In fact, 14 weeks later, when Gillian finally got to see a doctor, she was still in trouble: ‘I really struggled to cover the 20m from the car to the surgery room and arrived totally breathless. A blood test showed I had high levels of markers for inflammation.’
She was referred to a clinic specialising in lung problems but not long Covid, but says she was ‘impressed’ by the treatment. ‘I was seen within a month and had X-rays and fitness and breathing tests, while my heart rate was monitored and I was checked to see I had adequate levels of oxygen.’
Gillian was put on an exercise programme for ten weeks that encouraged (but never forced) her to go out of her comfort zone.
‘To start with, having a shower was all I could manage in a day. But by the end I could walk comfortably for 30 minutes,’ she says. ‘And I’m still improving.’
can this APP help recovery?
In another effort to understand what works for long Covid, the clinic at University College London has an app that allows patients to feed in details about their treatment so that clinicians can see who is improving — and also pass on to other patients information about what works.
It’s already being used by 850 patients in 15 Covid clinics across the country. Professor Murray says: ‘We believe that it could increase the number of patients we can deal with between ten and 50 times, because the app speeds up communication between clinicians and patients, allowing them to review and treat many more.’
It’s the sort of improvement that is badly needed.
Saved by hayfever pills and cutting out cheese
Absolutely desperate to improve the crushing mental and physical fatigue she suffered as a result of long Covid, Clare Richardson made a concerted effort to eat ‘healthy’ foods, turning to spinach smoothies, fermented cabbage kimchi and avocados.
But the foods she thought would help get her back on her feet — literally, as she was wheelchair-bound for eight months — made the problem worse, she now believes.
For Clare, 48, who lives in Carmarthen, west Wales, with her husband Sam, 45, a farmer, and their two children, later learned she’d chosen foods that were high in histamine, a natural chemical also released by the body during an allergic reaction.
Histamine is a powerful chemical released by mast cells (part of our immune system) in response to a threat, such as an allergen, causing symptoms such as itching and sneezing designed to flush out the dangerous substance. Histamine can cause inflammation in blood vessels and tissue around the body — and this has been proposed as one of the mechanisms of long Covid, with the infection triggering an over-response from the body, prompting it to release too much histamine and causing longer-term symptoms such as fatigue and brain fog.
Some doctors and dietitians believe patients with long Covid could benefit from antihistamine medication combined with a low-histamine diet.
The suggestion is that this may be particularly true for people with an underdiagnosed and recently recognised condition called mast cell activation syndrome (MCAS), where mast cells are already ‘faulty’ and easily stimulated to produce too much histamine.
There is no reliable test for MCAS and diagnosis relies on a doctor’s clinical judgment and an improvement after taking drugs that dampen down mast cell action.
But now antihistamines are set to form part of a major UK study into long Covid.
T he STIMULATE-ICP study, involving 4,500 people and led by University College London (UCL), will look at whether antihistamines and other existing drugs can reduce symptoms.
As the lead researcher, Professor Amitava Banerjee, a consultant cardiologist, told Good Health: ‘Patient experience and preliminary data has suggested for quite some time that histamine released from mast cells could be important in some of the symptoms of long Covid.’
He adds that research has already shown that people with long Covid have increased levels of histamine and mast cells.
And a recent study (with 49 long Covid patients) at the Physicians’ Clinic in London, found that 60 per cent of those treated with antihistamines experienced an improvement in their symptoms, compared to 24 per cent not given the medication.
Dr Paul Glynne, a consultant physician at the Physicians’ Clinic and University College London Hospital NHS Foundation Trust, was prompted to run the study after seeing many long Covid patients with symptoms similar to allergic reactions, including runny noses and rashes.
This approach is ‘potentially exciting, as antihistamines are cheap, easily available and very safe’, says Dr Glynne, adding that larger trials are needed.
Dr Tina Peers, a consultant doctor with special interests in women’s health, who runs the Menopause Consultancy clinic in Surrey, is already combining antihistamine medication with a low-histamine diet for her patients with long Covid.
She prescribes relatively high doses of well-known anti-histamines such as loratadine and fexofenadine (which block histamine receptors).
Foods thought to be high in histamine include some generally accepted as important to a healthy diet, such as tomatoes and avocados, and fermented food such as sauerkraut, and experts warn that patients should consult their GP before embarking on such a radical regimen and not follow it long-term because it excludes many foods that are vital for health.
Hannah Hunter, a specialist allergy dietitian at Guy’s and St Thomas’ NHS Foundation Trust, suggests long Covid patients could try a low histamine diet for two to four weeks, monitoring for any reactions.
‘Following a low-histamine diet means avoiding a lot of everyday foods, and that isn’t easy,’ she says.
‘Someone recovering needs a balanced, healthy diet, so this approach should only be undertaken with help from a dietitian or doctor.’
The British Dietetic Association also urges caution about ‘restrictive and time-consuming’ low-histamine diets, citing a lack of evidence. Yet Clare is convinced this approach helped her. She developed Covid in February 2020, and was ill at home for a month with fever, exhaustion and aches. Then, eight weeks after she’d recovered, she suddenly found herself engulfed with long Covid.
‘I could hardly make it out of bed and my brain ceased working. It was terrifying.’
Then, earlier this year, she learned about antihistamines via an online long Covid support group and contacted Dr Peers, who prescribed two stronger antihistamines, fexofenadine and famotidin — and a low-histamine diet.
‘It was no fun at all,’ says Clare. ‘For the first six months I ate just low-histamine veg, soft, fresh cheese, and rice. I started to reintroduce other foods a few months ago, starting with fish fingers with the breadcrumbs picked off.’
Clare is now better and eating more normally again. But she says: ‘I still won’t go near alcohol, coffee or fermented food as they make me react a bit.’