Positive signs are now emerging from research into this most miserable and lingering of diseases, writes Prof Luke O’Neill
Something significant happened on Thursday in relation to Covid-19. The RTÉ website has what’s called a strapline across the top of the screen, with words like ‘News’, ‘Climate Change’ and ‘Ukraine’. On Thursday ‘Covid-19’ disappeared. It’s a topic that is now part of the general news. This is a sure sign that we are indeed emerging from the pandemic.
Watch this space though, because the winter surge might lead to Covid-19 going back up into the strapline. A surge seems to be starting in the UK, with hospital admissions for Covid-19 up 48pc in England last week. This is a concern. We should therefore see a rise in hospitalisations here too. We can be hopeful that the HSE’s plan to help the hospitals, which involves increased capacity and staff, will protect us.
There was also news last week regarding long-Covid. Any discussion of our current Covid situation must involve the legacy of suffering associated with this. Covid-19 is not just a disease that might make you very sick and potentially kill you. It is also a disease that can give rise to persistent symptoms that lead to great suffering and disability.
Long-Covid is a set of symptoms that persist long after the infection is gone. These include fatigue and brain fog, but also things like heart problems and even diabetes.
A huge amount of research has been happening into long-Covid because there are so many people to study. At least one in 10 people who have had Covid-19 will develop long-Covid, although some studies concluded that the number is closer to one in three. Some will develop a very severe and debilitating disease that makes their lives a misery.
Long-Covid continues to be a source of largely unaddressed despair, especially for what are called “first-wave” infected people. They are people who became infected very early in the pandemic and had no immunity against the virus. Two years later, many are unable to return to work and are often not listened to by employers. There is an irony in this, because many are healthcare workers who were on the frontline of this disease. It reminds me of the wounded veterans who returned from Vietnam and were neglected.
The first piece of good news is that it does seem to be abating somewhat. Data from the UK has shown that the number of people with long-Covid is beginning to fall, from a peak of two million in May to about 1.8 million. This means some people are gradually recovering.
While the Omicron BA.5 variant can give rise to long-Covid, there appear to be fewer new cases, so perhaps the newer strains are less likely to cause it. Singapore, which had a large number of Omicron cases, is reporting quieter Covid-19 clinics. It could be that the decreased force of Omicron and its siblings is due to immunity from infection and/or vaccination in the people who become infected, but we don’t yet know if that is the case.
It would be very useful if a diagnostic blood test could be carried out to identify people with long-Covid — and that is the next area where there are good signs. A test is useful for two reasons. First, it might dictate what kind of therapy to use. Second, it can be shown to employers, as, sadly, sometimes people with long-Covid are not listened to.
A team in Yale University has uncovered what are called biomarkers which indicate the presence of long-Covid. The Yale scientists reported clear biomarkers in people with long-Covid, but not in healthy people.
This included low cortisol — a hormone involved in control of the stress response — and evidence that Epstein-Barr virus had been reactivated. Both are important. The low cortisol might explain the awful fatigue that can afflict people. But the reactivation of Epstein-Barr virus is especially noteworthy. This virus causes glandular fever, which has symptoms just like long-Covid. It can become hidden in our bodies in a process called latency. Could it therefore be that Covid-19 wakes up the slumbering virus, which then causes symptoms? Targeting Epstein-Barr virus could well protect or even treat long-Covid, which would be a very exciting prospect.
A similar study has been carried out by scientists in University College London. They compared levels of more than 90 blood proteins in 54 healthcare workers with Covid-19 and a group of healthy staff. They found several proteins were disrupted for up to six weeks. Twenty of them predicted the risk of developing long-Covid. Most were linked to blood clotting and inflammation, with names like Hemopexin and MASP2.
The researchers even used artificial intelligence to scan proteins in the blood samples — and successfully identified the 11 infected health workers who went on to develop long-Covid. Dr Wendy Heywood, one of the scientists involved said: “If we can identify people who are likely to develop long-Covid, this opens the door to trialling treatments early to see if it can reduce the risk of later long-Covid.”
The link to blood clotting had been seen before in Covid-19. This is something my own lab is interested in, and we’ve been studying clotting during Covid-19 and trying to come up with new ways to stop it. Early in the pandemic it was noticed that a Covid-19 infection increases the risk of blood clots, and that people who have had the disease have a greater risk of related conditions including stroke and heart attacks. Research from South Africa has found that people with long-Covid have clots, while studies in the UK suggested almost one-third of long-Covid patients have clotting abnormalities. These so-called ‘microclots’ differ from normal clots that form, for example, when you cut yourself.
A trial is now running with anticoagulants (blood thinners) to determine whether they might be useful. One group is given the current limited treatments that are available, the second an antihistamine, the third the anti-clotting drug, and the fourth an anti-inflammatory drug because inflammation is likely to play an important role. In three months’ time, there should be an answer as to whether any of these approaches work.
In another study, 1,118 patients in hospital with Covid-19 who are newly diagnosed have been recruited, with half receiving blood thinners. This trial is designed to determine if stopping clotting early might prevent long-Covid developing in the first place.
Finally, there is even a trial running to see if the immune system in people with long-Covid can be boosted. All the evidence suggests the immune system in sufferers is exhausted, just like the rest of their body. But now a brand-new approach involving the immune stimulants IL-2 and anti-PDL1 is being tested, and initial results are promising. So many scientists are trying to crack long-Covid that we have grounds for optimism. And progress there might be useful for other post-infection conditions such as chronic fatigue syndrome. If we can make the same progress for long-Covid as we did with Covid vaccines, this important and somewhat neglected aspect of the disease might also yield to the sword of science.
Luke O’Neill is professor of biochemistry in the school of biochemistry and immunology at Trinity College Dublin