Next up is the underlying biology, of which we have a limited understanding. We know, for example, that clots form, but still not clearly why. We know that patients’ blood vessels are not normal, but not for how long this persists. And we know that some patients have prolonged inflammation, but we cannot predict who.
This makes it hard to choose therapies to trial and patients to include in those trials. It means we need to make some educated guesses who and when to treat, and with what.
Many patients recover, so should we enroll all patients when most of them will get better, pick out patients at higher risk of problems or wait until symptoms are established? No treatment comes without side effects. We need to minimize the chances of harming someone who was going to get better anyway.
Added to this, the group we are studying may change with the advent of acute treatments and vaccines. Early reports suggest a younger population in the current wave.
This can have big effects on clinical trials. If you set a trial up to pick up a signal with an assumption of a third of people having long-term problems, if this reduces, then your trial might not be able to answer the question.
So what can we do about all this? The first thing is to run trials that are big enough for definitive answers and flexible enough to react to evolving knowledge, by including extra treatment arms if evidence changes.
The second is to have a mix of trials looking at different populations. Post-hospital patients are almost definitely at higher risk of problems like clots or scarring than those that were never admitted. Prevention is always better than treatment, so therapies aimed early in the disease course are important. The community patients who are living with persistent problems may need different trials.
The good news is that a lot of funding is being released to point at the problem, even if we don’t yet know the best areas to focus on. Another positive is that big trials like the vaccine studies and the Recovery trial (the world’s biggest clinical trial to identify treatments for people hospitalised with COVID), have shown we can do big trials at pace and at scale.
Unfortunately, the current funding system is competitive, lacks coordination and doesn’t really reward collaboration. These big trials were the exceptions, not the rule. So we need pressure on funders and researchers to do things differently.
In the U.K., we have set up an early example of the sort of trials we think we need, called Heal-COVID. It already has around 100 centers in the U.K. involved and puts into practice some of the ideas above. If you had told me before the pandemic that this type of trial could be set up in weeks, I would not have taken you seriously.
Despite this, the long-term nature of the problems mean it will be months before trials start to report and we need to explain to the public why. There are a lot of people out there desperate for something/anything and this will be fertile ground for charlatans and opportunists. So in the meantime, if patients are going to experiment they must always ask who benefits, make sure the treatments are at least safe, and take heart that a lot of patients are still on a journey of improvement. There remains hope.
Mark Toshner is a lecturer in translational respiratory medicine at the University of Cambridge in the U.K. This piece originally appeared in The Conversation, a nonprofit news source dedicated to unlocking ideas from academia for the public.