Clinical Trials
There is now substantial evidence that many Long Covid patients have a chronic SARS-CoV-2 infection. Long haulers may be sick because they cannot fully clear the initial infection.
This could provide a treatment opportunity for patients with Long Covid. If long haulers can clear the virus, they may be able to recover much of their prior health.
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Treating Chronic Infections
Medicine has a long track record of treating chronic infections, and transforming previously life ending disease into manageable illnesseses.
Human Immunodeficiency Viruses (HIV). When HIV emerged in the early 1980s, becoming HIV positive was a death sentence. The turning point came with the development of powerful antiviral drugs, which are used in combinations to suppress the virus, and let patients live long, normal lives.
Hepatitis C. An RNA virus, like SARS-CoV-2. If untreated causes chronic illness and can be fatal. Today the disease is treated with multi month courses of antiviral drugs, which are able largely to clear the infection and help most patients recover.
Feline Infectious Peritonitis (FIP). FIP involves a coronavirus that infects cats, which becomes chronic in a subset. Untreated FIP is fatal within a year. FIP can now be treated with 3 month courses of antivirals, which clear the infection in 90%+ of cats. The antivirals used are the same drugs approved for COVID-19 - GS441524 (closely related to Remdesivir) and Molnupiravir.
In each of these cases, the disease is treated with long courses of combinations of antiviral drugs. Combinations are important because they utilize drugs with complementary mechanisms of action, attacking the virus from multiple angles. Monotherapies are often not effective.
We believe that the most urgent trials for Long Covid are long courses of combination antivirals, aiming to clear chronic SARS-CoV-2 infections, and ideally resolve symptoms for many Long Covid patients. These treatments could also be combined with other drugs that may support viral clearance: e.g. immunomodulators (which modulate the immune system to help the body fight the infection, or to recover) or drugs that work on repairing the vasculature.
Few Promising Clinical Trials Are Happening
“The enormity of these costs implies that policies to address long COVID are urgently needed. With costs this high, virtually any amount spent on long COVID detection, treatment, and control would result in benefits far above what it costs.”
David Cutler, Harvard, July 2022
The biggest challenge is funding. Almost no large funders have stepped up to take meaningful action; where they have, the money has not always been optimally allocated.
Government. The US government, via the NIH's RECOVER initiative, has announced $275m a year over 4 years to study Long Covid. Given the scale of Long Covid this is a fraction of the level of funding required. Moreover, the initiative has allocated minimal funding to clinical trials, with only one trial of a single antiviral announced and no results so far. No other national government has provided meaningful research funding.
Pharma, philanthropy and public health funders. With the exception of Vitalik Buterin, almost no large philanthropists or public health funders have stepped up. Pharma companies have not yet engaged in a significant way.
Types of clinical trial we need
Our approach initially is to focus our support on the following types of clinical trials:
Root cause treatments: trials of interventions with the highest potential to help Covid long haulers clear the chronic infection (e.g. antivirals) or address fundamental drivers of the pathology (e.g. vascular damage, coagulopathy).
Drug repurposing: trials of drugs that already have regulatory approval for other indications - particularly for the treatment of acute Covid-19. There are a number of promising drugs that can be tried for Long Covid very quickly.
Large scale adaptive platform trials and smaller scale experimental medicine: large scale but low cost adaptive trials, pioneered early in the pandemic for acute Covid-19 (e.g. the TOGETHER trial and the UK's Recovery trial), typically looking at low cost easily accessible drugs, should be repeated for Long Covid. Long Covid also needs smaller scale studies that examine in detail the impact of certain treatments on patients' pathophysiology.