An art museum curator in Ahmedabad, India, Bhasha Mewar has been suffering from Long COVID symptoms since March 2020. Her life’s savings is nearly exhausted after seeing endless specialists in what has been a futile attempt to find relief.

Mewar is among millions languishing with a condition with no proven treatment. Fortunately, since researchers are homing in on what causes Long COVID, effective therapies targeting inflammation, blood clots, and/or remaining coronavirus fragments could be developed within a year, according to an article in Nature journal. Better yet, some of these potential therapies are repurposed medications, so they are already approved for widespread commercial use.*

Why the slow development?

A major barrier to treatment development has been the difficulty establishing Long COVID’s root cause(s). Currently, there are a handful of hypotheses that researchers are hopeful will get sorted out and lead to new treatments:

• Residual virus, or viral fragments, may be causing immune dysfunction.
• Antibodies from the virus may be mistakenly attacking the body long after initial infection.
• Microscopic blood clots caused by the virus may be inhibiting oxygen flow to tissues.
• The virus may disrupt the gut microbiome, affecting overall health.

There could be multiple reasons behind Long COVID, though each hypothesis represents a different avenue of relief (for example, using anticoagulants to break up blood clots). 

The problem is that, while research in support of these hypotheses is mounting, some investigators don’t think the links to Long COVID are strong enough to begin clinical trials. If Long COVID has multiple causes, a promising therapy could be overlooked if it’s tested on the wrong patients. Additionally, Long COVID has over 200 symptoms that are often difficult to measure and can come and go, as they have for Mewar. This makes it hard to enroll and then group participants for analysis.

Trials happening now

Despite the difficulties, some researchers are pressing on.

• Three trials are aimed at immune dysfunction, with some involving common anti-inflammatory drugs like colchicine, a gout therapy.
• Other trials involve steroids, immunosuppressant drugs like sirolimus, and antihistamines.
• The drug RSLV-132, effective against fatigue in Sjögren’s syndrome, is being tested for removing leftover viral RNA in the blood, believed to cause inflammation.
• The antidepressant drug vortioxetine, shown to boost cognition, is being studied for relief of brain fog.
• For cardiovascular impacts, a cocktail of drugs is slated to be tested against inflammation-related clot formation inside blood vessels.

Looking to the future

Some logical Long COVID drug candidates have yet to undergo robust testing, such as Paxlovid, an antiviral used to treat acute COVID-19, but there is movement to correct this. 

Ledford says that, later this year, Merck (maker of the antiviral drug molnupiravir) and Pfizer (maker of Paxlovid) will follow their treatment subjects for an additional six months, and Gilead Sciences is considering testing their antiviral drug remdesivir against Long COVID. As case numbers rise, experts say more pharmaceutical companies may see the value in pursuing Long COVID treatments.

Danny Altmann, an immunologist at Imperial College London, says that while the U.S. and U.K. have committed significant funds to Long COVID research, little has gone into treatment discovery. “I feel like there hasn’t been the kind of will from the top that we need.”

There are signs of change, however. The U.S. National Institutes of Health’s RECOVER initiative recently requested proposals for trials to test potential interventions, and the U.K.’s STIMULATE-ICP trial began enrollment this summer to test:

• Colchicine (anti-inflammatory),
• Famotidine and loratadine (antihistamines), and
• Rivaroxaban (anticoagulant)

Do-it-yourself treatment

In the meantime, Long COVID patients and their doctors continue trying different combinations of allopathic and naturopathic medicine and other healing modalities. 

As for Mewar, after two years, her Long COVID symptoms have begun to subside, but she knows they can return if she pushes too hard. After losing faith in traditional medicine, she now takes vitamins, and is considering traditional Indian medicine to manage her symptoms. 

*Ledford, H. (2022, August 9). Long-COVID treatments: why the world is still waiting. Nature, 608, 258-60. https://www.nature.com/articles/d41586-022-02140-w