Whatever your standpoint on whether the pandemic is over, or what “living with the virus” should mean, it is clear some manifestation of Covid-19 will be with us for some time to come. Not least for the estimated 1.7 million people in the UK living with long Covid.
And lest any who made a full and rapid recovery from infection still wonder whether long Covid might be a self-reported creation of the indolent, this is a now a large, well-documented, convergent cluster of clear physiological symptoms, and it is common to every part of the globe affected by Covid-19. Many sufferers of my acquaintance were keen cyclists, runners, skiers and dancers, but are now disabled and deprived of their former passions, while some are unable to resume their former professions. Doctors and scientists the world over now consider this a recognised part of the Sars-CoV-2 symptom profile.
Many of the most severe and enduring “long-haulers” derive from the first UK infection wave just before the initial lockdown in March 2020. Even though it was clear from the outset that the risk of long Covid was not correlated simply with the severity of infection, there was every reason to hope that with the large-scale rollout of effective vaccines, and more recent waves of infection dominated by a somewhat less severe variant, there would be few additions to the sufferers joining long Covid support groups.
We thought that the number of long Covid cases developing might be lower when most cases were breakthrough cases in the vaccinated, or infections in vaccinated or partially vaccinated children. Sadly, far from any subsidence in new long Covid cases, the big, ongoing caseloads of the Delta, Omicron and BA.2 waves have brought a large cohort of new sufferers.
From published data, the chances of long Covid in those who are vaccinated but suffer breakthrough infections may be halved, but when you apply this to the huge waves we’ve experienced – 3.5 million people infected at a given time – each 3.5 million cases becomes another 175,000 people with long Covid.
These waves have disproportionately affected primary and secondary schools, and many of the new sufferers are children. Sammie Mcfarland at LongCovidKids.org reports a constant stream of new members across its support services, many developing long Covid after two, three or four bouts of reinfection, having escaped it first time round.
Also, the symptom spectrum may be shifting from the earlier waves, with more reports of sight, hearing and motor-function deficits, alongside gastrointestinal pain, joint pain, rashes, swelling and fatigue. This is a tangible price being paid for turning a blind eye to the high incidence of cases in schools over recent months.
With such large numbers having been infected at any given time in recent months, many suffering repeat infections at three- or four-week intervals, the potential legacy of chronic, disabling illness is an aspect making this utterly different from most other winter respiratory pathogens – such as flu or colds. Nobody is certain whether long Covid from the current period will be quite the same as the early waves, but this is an experiment that none of us would wish to do on our children.
It has been consistently difficult to assess the trajectory of people’s recovery from persistent symptoms, which has entailed assessing those whose symptoms lasted three months but not six, compared with the smaller subset without improvement at 18-24 months. A team at the University of Toronto followed up patients with persistent symptoms after infection during the 2003 Sars outbreak. Many of these showed little recovery several years later. If this trend were extrapolated to our current Omicron wave, the effects on education, the workforce and healthcare provision would be huge.
It is still early days for long Covid research. The UK’s strength in epidemiology research through survey data, such as the Office for National Statistics, React2 and ZOE, put us at the forefront of counting and recognising the importance of long Covid, leading to the early push for dedicated clinics. This was important, but sufferers have understandably become weary of questionnaires and surveys, looking for tangible progress on mechanisms and therapeutic trials – the demand for less observation, more intervention.
In the early days of long Covid, we and others put forward working hypotheses to explain the disease process. These spanned the effects of the virus itself causing enduring damage and scarring in diverse body organs, viral persistence, autoimmunity causing a range of symptoms, and many more. Relatively small-scale studies have produced some interesting support for each of these, but we still lack the overarching paradigm – or way of understanding the disease – that would facilitate comprehensive diagnostic testing, bespoke care pathways and curative therapeutics.
People with long Covid led the charge to identify, characterise and trigger a research agenda for the new condition through hard work and proactive social media networks. Their attention (and wrath) is now focused on impatience to test potential treatments. There is pressure – sometimes manifest as patients travelling abroad for costly experimental treatments – to trial everything from antivirals and anti-spike monoclonal antibodies to anticoagulants and apheresis (a complex procedure to remove possible microclots from blood).
As was appreciated from the results of randomised, controlled trials (RCTs) for original Covid-19 treatments, sometimes approaches that have been heavily publicised do not pan out, while others are convincingly shown to work and change global management of patients’ symptoms – such as the drugs tocilizumab and dexamethasone.
Long Covid sufferers need a large-scale recovery trial, fast-tracked to offer them some answers about treatments. Many of the responses offered when they get to the front of the queue at long Covid clinics are about readjustment and rehabilitation in light of their new disability. They do not want readjustment, they want their lives back.
Some current research programmes offer initial steps in this direction. The Stimulate-ICP trial at University College hospital will compare effectiveness of antihistamines, rivaroxaban (an anti-clotting drug) and colchicine (an anti-inflammatory). A clinical trial at Oxford University is investigating whether a drug called AXA1125 can treat fatigue and muscle weakness.
Our thinking about Sars-CoV-2 and long Covid – and our response to it – has had to shift and readjust, virtually on a monthly basis. This is now a highly infectious, upper-respiratory virus able to reinfect repeatedly – an outcome that wasn’t expected early in the pandemic. If we renege on mitigations as each round of infection draws more of all ages into chronic disability, this may be the blunder that we rue for decades to come. Even after the original wave of lockdowns and deaths has become a distantly remembered nightmare.
Danny Altmann is a professor of immunology at Imperial College London. He has contributed advice to the Cabinet Office, the all-party parliamentary group on long Covid and the EU
