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New private venture tackles the riddle of Long Covid—and aims to test treatments quickly


A new, privately funded venture announced today it has recruited more than 20 top scientists and is pouring $15 million raised so far into Long Covid research, with plans to launch clinical trials of treatments as soon as possible. The scientist who spearheaded the Long Covid Research Initiative (LCRI), microbiologist Amy Proal at the Washington state–based nonprofit PolyBio Research Foundation, says the goal is to bring in $100 million. Half would be dedicated to trials, which have thus far been sparse in the field.

When it comes to available funds, LCRI pales in comparison with the behemoth RECOVER initiative at the National Institutes of Health (NIH), which has more than $1 billion to fund Long Covid projects. But RECOVER has also come under fire for its sluggish pace and slow recruitment into its current flagship program, an observational study slated to enroll up to 40,000 people. Proal and others say different, quicker strategies are desperately needed, including more rapid distribution of funds and an embrace of higher risk, higher payoff research.

“We need a spark, we need a philanthropic organization that has a risk tolerance much greater than NIH,” says E. John Wherry, an immunologist at the University of Pennsylvania who is part of LCRI and has been an adviser on some RECOVER grants. Wherry compares NIH money to the bonds in an investor’s portfolio—“lumbering, slow-changing things that give you the core of what you need.” But, “Sometimes to make a rapid change or to pivot in your investment strategy, bonds are not going to be the tool you use,” he says.

NIH said in a statement that the agency welcomes the private initiative because “the public can only benefit from multiple research efforts.” However, the statement called RECOVER “unprecedented” in scale and aim, and said the giant effort will be crucial to giving researchers “a fighting chance at identifying the underlying mechanisms of Long COVID.”

LCRI was born after several patient advocates with Long Covid and a professional background in technology startups approached Proal early this year. “They were like, ‘We want to get better, we want to get better soon,’” Proal says. The advocates considered how to apply their startup mentality to the overwhelming challenge of Long Covid.

“The enormity of the problem really outweighs the size of the response,” says one advocate, LCRI co-founder Henry Scott-Green, a Google product manager. He contracted COVID-19 in August 2020 and subsequently developed Long Covid but has since improved.

The Centers for Disease Control and Prevention estimates more than 40% of U.S. adults have reported contracting COVID-19; of those, nearly one in five may have persistent symptoms. In the months after an infection with the SARS-CoV-2 coronavirus, Long Covid patients can experience crushing fatigue; difficulty thinking; shortness of breath, especially on exertion; and assorted other symptoms. Although Long Covid clinics have popped up in hospitals around the world, they have little to offer in the way of proven therapies. Pharmaceutical companies have been hesitant to invest in research on the syndrome, in part because there are no easy objective methods, such as blood tests, to gauge a treatment’s performance, Proal says.

After talking with the patient advocates, Proal and other Long Covid researchers began contacting additional scientists and initiated weekly meetings. The venture received $15 million from an investment fund led by Vitalik Buterin and from the Chan Soon-Shiong Family Foundation, led by Patrick Soon-Shiong, a billionaire scientist and businessperson. Additional commitments are expected soon, Proal says.

The first $15 million is committed for basic research and will be spread among participating scientists. It will focus on one key issue: whether SARS-CoV-2 persists in Long Covid patients and drives their symptoms. That, Proal says, is “the trend we see the most evidence for,” and she hopes multiple overlapping projects supported by LCRI can tackle the question. Studies will hunt for virus in intestinal, nerve, vascular, and other tissues, including from those procured from autopsies. In imaging studies, researchers will inject antibodies bound to radiotracers that can, in turn, bind to the SARS-CoV-2 spike protein and light up if virus is present in the body. Researchers will also dig deep into immune cell behavior that may reflect viral persistence.

If virus is lingering in the body, antiviral therapies might reduce symptoms. Proal hopes the collaborative can soon begin clinical trials of such therapies, and that its scientists can nail down the kind of biomarkers drug companies crave. “We really think there are tangible outcome measures” that will make assessing therapies more straightforward, Proal says. These could include certain immune signatures or other measures in blood. A working group is considering which drugs or supplements might be tested first.

NIH has said that it, too, expects to launch several Long Covid trials this fall that will include treatments aimed at viral persistence. Those involved in LCRI—and often RECOVER, too—stress that they want to complement each other, not work at cross-purposes. “Most of the people in the collective have a connection to RECOVER, so have an inside track on what’s happening,” says David Putrino, a neurophysiologist and rehabilitation medicine specialist at the Icahn School of Medicine at Mount Sinai. He is part of LCRI and also sits on a RECOVER subcommittee. Knowing what RECOVER is pursuing—and which proposals it’s rejecting—will likely prove useful, he says. “We can chase the things that people are saying ‘no’ to, that hold promise,” he says.

For Wherry, who studies how T cell behavior can be used as a proxy for viral persistence, the collaborative has appeal. He plans to apply to NIH for Long Covid funding but hasn’t yet, partly because grant applications are time-consuming and often rejected, and there can be a lengthy lag to learn the outcome. With LCRI, “in some ways you’re betting on the individual, the idea is so early you know you’ll have to pivot and adjust,” he says.

Putrino cares for Long Covid patients and has been critical of RECOVER in the past, but says he hopes at least for détente, if not friendly cooperation. “No matter what is happening and what’s gone before,” he says, “we need to swallow our pride and work together.”



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