The search for treatments against long covid has reached an important turning point: it is not a single disorder and there is not a single cause.
After three years of pandemic, research on possible cures against the long covid, the name given to the set of ailments that persist for months after a SARS-CoV-2 infection, seems to have gained at least one fixed point. There is finally scientific consensus that the long covid is not a single syndrome with a single causebut rather a group of diseases grouped for simplicity under the same umbrella term, and with different origins.
More causes… Estimates on the number of long covid patients vary, but according to a review of studies published in January 2023 in Nature it could be around 65 million, just under the population of France. As explained in an article on the international version of Wiredthe possible causes of the aftermath of CoViD-19 are many.
In some people it could be linked to an autoimmune reaction triggered by covid. In others, from fragments of SARS-CoV-2 that still roam the body and keep the immune system “on its toes”, now exhausted after such a long activation. In other cases, the reported ailments could depend on damage to the organs affected by CoViD-19; or again, the infection with the new coronavirus could have reactivated latent viruses that the body had already encountered in the past and of which we remain carriers, such as that of Epstein-Barr, responsible for mononucleosis.
…and more symptoms. These hypotheses are not mutually exclusive and in some people they could also manifest themselves together: precisely the variety of triggering conditions would explain the wide range of symptoms of long covid. Fatigue, mental fog, widespread pain, tachycardia, difficulty concentrating, depression are some of the most common, but about 200 have been catalogued.
Learning in the field. Since there are more causes, there will also be more possible treatments, and it will be the clinical studies that have already begun on patients that will clarify which type of treatment is more suitable in the various circumstances. Since there is such a great urgency to relieve the symptoms of those affected by it, research on the origins of long covid and on drugs to deal with it are proceeding in parallel. Complicated by the fact that there is no agreement on what defines long covid, nor an official test or indicator (such as a blood marker) to diagnose.
Who does it work on? And why? Akiko Iwasaki, an immunologist at Yale University internationally appreciated for her studies on long covid, has a clinical study underway on a hundred patients to ascertain whether Pfizer’s Paxlovid antiviral used to treat symptomatic cases of covid has effect also on long covid, as reported by some people who suffer from it.
The clinical hypothesis on which the research is based is that of viral reserve: if the drug really works, it could be because it manages to eliminate every residual trace of the covid virus from the body.
A detective job. Iwasaki already knows that the drug won’t benefit everyone, but this is precisely the element that interests her: understanding which patients it is indicated for and why. The trial should naturally include patients with long covid deriving from different causes, whose immune characteristics will be monitored (for example, hyperactive T cells or spike protein residues of SARS-CoV-2) and who will receive Paxlovid or a placebo in a randomized way (with random assignment). In this way it will be possible to see precisely at the end of the treatment which are the most common biomarkers in people who have felt better. And then trace the triggering cause, at least for some.
Symptomatic drugs. Other ongoing clinical trials target different mechanisms, such as the widespread inflammation left in the body by covid. Still others try to relieve symptoms while not necessarily tracing the root cause: University College London’s Stimulate-ICP trial which has so far recruited 500 people will use an anticoagulant, rivaroxaban, to treat microclots in the blood resulting from covid that hinder the arrival of oxygen to the tissues and which according to some could contribute to the long covid. If the drug worked, however, it wouldn’t tell us anything about what caused the microclots.
A gain for everyone. The success of studies like these depends not only on the fate of patients with long covid, but also that of people affected by other complex and still little known conditions, such as chronic fatigue syndrome, which could share some dynamics and causes with long covid triggers.