36 people with long COVID tested a potential treatment. Here's what the study found

San Francisco Chronicle​

22-05-2025

With COVID-19 subsiding and the public health emergency over, most people no longer dwell on the virus that so recently terrified the world.
Yet millions are still forced to do so because of debilitating post-COVID symptoms, including persistent fatigue, pain or cognitive confusion. They hold out hope that science will solve the mystery of 'long COVID' and offer a cure.
In 2023, 36 people with long COVID allowed UCSF researchers to inject them with monoclonal antibodies — lab-made proteins designed to attack the specific version of the coronavirus that had sickened them in the first place. Although 12 of those volunteers got a placebo, no one, not even the scientists, knew who received the real drug and who did not.
Then everyone crossed their fingers. The hope was that the drug would kill any remaining bits of the virus that might be causing their symptoms — and that they would go away.
On Friday, study leader Dr. Michael Peluso of UCSF revealed the results to fellow long COVID researchers.
'I'm sad to say we did not detect a significant difference' between those who got the drug and those who did not, said Peluso, who reported the disappointing outcome during a webinar sponsored by the PolyBio Research Foundation, which focuses on chronic post-viral diseases such as long COVID, Lyme disease and ME/CFS, often called chronic fatigue syndrome, and helped support the UCSF trial.
Nevertheless, said Peluso, researchers learned much from the study — the first rigorous, placebo-controlled examination of monoclonal antibodies on long COVID — that can help propel new clinical trials in directions more likely to succeed.
There is currently no treatment for long COVID, an insidious illness that can affect every organ system and rob people of the ability to think clearly, wake up refreshed, exercise or even breathe deeply. Even children are vulnerable. Of the 15 million to 20 million Americans diagnosed with long COVID, two-thirds have been women, according to multiple reports.
The World Health Organization defines long COVID as 'the continuation or development of new symptoms three months after the initial SARS-CoV-2 (coronavirus) infection, with these symptoms lasting for at least two months with no other explanation.'
Most long COVID researchers study causes rather than treatments, often because funders are reluctant to pour money into potential cures without data showing they are likely to succeed.
That has been especially frustrating for patients. So when reports of improvement from monoclonal antibodies popped up in Florida and Texas a few years ago, patients and scientists alike perked up.
'But they had never really been tested in a controlled way,' Peluso told the Chronicle earlier this week.
That's what the UCSF study did. 'The most important message for people to hear is that monoclonal antibodies are not likely to be of benefit for everyone with long COVID,' Peluso said in an interview.
The researchers found that some people improved in both groups — the 24 who received the monoclonal antibodies and the 12 who did not. Others saw no improvement.
'Now we have to figure out why,' said Peluso, noting that the researchers feel 'disappointed but not discouraged. We knew this was never going to be an easy problem, and we're committed to figuring it out.'
One lesson learned is that monoclonal antibodies are safe to take, he said.
But their failure to vanquish the participants' symptoms could mean that 'viral persistence' — the ongoing presence of bits of the coronavirus — simply isn't causing them, Peluso said.
Peluso and other researchers aren't convinced that that is true, and the current study did not prove that.
Alternatively, Peluso said in his presentation, 'we think only a subset of people have viral persistence.' In future such studies, he said, researchers will need to confirm whether each participant has a biomarker of viral persistence.
'We cannot ignore this anymore,' Peluso told the audience. 'We need this for the field to move forward.'
Another possibility in the current study is that the monoclonal antibodies had lost potency. Known as AER002, the drug was manufactured by Aerium Therapeutics in Boston and aimed at the version of the virus that attacked people before 2022, Peluso said.
'Or maybe a single dose just didn't work,' he said. 'Maybe multiple doses are needed.'
The researchers 'unblinded' the study in February, meaning that everyone finally learned who got the real drug vs. the placebo.
'I was shocked,' said Shelley Hayden, the third person to be infused. 'I think I said swear words.'
Hayden, a marketing executive from Oakland whose post-COVID symptoms forced her to stop working shortly after the pandemic began in 2020, had gotten a placebo.
'I was 100% sure I'd gotten the monoclonal,' she said, because she felt feverish afterward.
Also, she improved over the next three months, feeling more energetic and having fewer stomach problems. Even her post-COVID eye twitch seemed to lessen.
'But nothing went away entirely,' said Hayden, 57. 'I'm not cured.'
Neither is Michael Dahl of San Francisco, a retired computer professional and the first to be infused.
Dahl, 69, got the real deal. 'But no,' he said. 'I didn't feel any benefit.'
His symptoms are neurological. 'Headachy, nausea, dizziness and real fatigue,' he said. 'My body says, 'sleep, sleep sleep.'
Since his infusion, 'I have gotten slightly worse. Maybe more than slightly,' said Dahl, adding that he knows of only one drug that definitely helps.
'Aspirin.'
Far fewer people get COVID these days, based on wastewater evidence reported by the CDC. But among those who do get sick, a portion still get long COVID.
'It's probably less common than it was in the early days,' said Peluso, who estimates that the occurrence is down to about 2% or 3% of people with COVID.
'But that's still a lot of people' among everyone infected, he said.
Other studies of potential long COVID treatments have also fallen short recently, including a pair out of Stanford and Yale that looked at whether Paxlovid, the drug that helps diminish acute COVID symptoms, is helpful. It isn't, though larger studies could still find otherwise, Peluso said.
In 2020, Congress set aside $1.15 billion to study long COVID through the RECOVER initiative overseen by the National Institutes of Health. Studies are continuing throughout the country.
Beyond viral persistence, two potential culprits are widely suspected of causing long COVID: ongoing inflammation caused by the coronavirus, and autoimmunity — when the body's own immune system turns on itself.
At UCSF, Peluso and Dr. Steven Deeks are planning three new studies through their long COVID research program, LIINC, for 'Long-term Impact of Infection with Novel Coronavirus.'
One study will look at whether the rheumatoid arthritis drug, Baricitinib, can help long COVID patients who have cognitive dysfunction. Another, funded by the Department of Defense, will test Bezisterim, under development for neurological conditions. The third will see whether boosting the immune system can ease long COVID.
'We're attacking this from multiple angles,' Peluso said. 'We're not giving up.'