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Little-noticed groups of medical researchers are racing to find treatments for COVID-19 in its early stages, hoping to keep infected people out of the hospital with everyday remedies like antidepressants or vitamins.

Instead of seeking new drugs, the researchers are pulling common generics off pharmacy shelves, and even eyeing the nutritional-supplement aisles, in search of agents with proven safety and, perhaps, hidden superpowers.

And they’re pioneering a new approach to medical research — mail-order clinical trials, in which patients can take the medication and monitor its effects without leaving home.

Even as vaccines gradually make their way to the public, these scientists point out that hospitals will continue to be overrun for weeks or months, and the coronavirus is likely to cause illness for many years, if not forever.

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“The numbers of new infections and deaths continue to go up — they’re higher than ever,” said Dr. Sarah Read, cochair of a working group developing studies of COVID-19 treatments at the National Institute of Allergy and Infectious Diseases. Read said the lack of outpatient treatment must be addressed, especially as the vaccine rollout proceeds more slowly than anticipated.

“For the time being we can’t take the foot off the gas,” she said. Early treatment, Read added, might eventually be shown to prevent the long-lasting symptoms that afflict some COVID survivors.

Even though the vast majority of COVID-19 patients ride out the illness at home, most of the research into treatments has focused on those in the hospital, where medical resources are already concentrated and a sense of urgency prevails.

The only outpatient treatments used outside of clinical trials are monoclonal antibodies, lab-made copies of the body’s immune-system fighters. These medications, though in limited supply, have been left largely untapped because of the logistical challenges, including the need for sick people to spend two hours at an infusion center.

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Progress has been painfully slow on finding other options. The COVID-19 Early Treatment Fund, which since its founding last spring has doled out $4 million to support such research, expected to have results by October, said Dr. Lisa Danzig, the fund’s chief medical adviser.

“None of us expected that in January 2021 we’d still be talking about raising money and starting more studies,” she said. But recruiting research subjects has proven exceptionally difficult.

Study participants typically must enroll within a few days of testing positive. But people with mild to moderate illness are scattered in the community, may not even be in touch with a doctor — and have been advised not to leave home. “Also, we don’t have a good clearinghouse,” Danzig said. “It’s really hard for people to get information about clinical trials.”

“With this surge right now, it’s fair to ask the world: let’s enroll all these trials in this next month,” Danzig said.

Hundreds of researchers are trying out drugs, supplements, and even over-the-counter medications. The National Institute of Allergy and Infectious Diseases has launched the ACTIV-2 trial, which aims to test several medications at once. Currently it is studying two monoclonal antibody formulations developed to treat COVID-19 and is considering including two antivirals, both repurposed drugs.

Dr. Eric J. Lenze, a psychiatrist and director of the Healthy Mind Lab at Washington University School of Medicine in St. Louis, is studying a surprising candidate for COVID-19 treatment — the antidepressant fluvoxamine, in use since the 1990s and so safe that even an overdose can’t kill you. Lenze has enrolled only about 60 of the needed 1,100 participants so far.

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Lenze got interested in fluvoxamine as a weapon against COVID-19 after reading a study showing it could tamp down sepsis in mice. Last year, he recruited a group of 152 COVID-positive patients; he gave fluvoxamine to 80 and a placebo to 72. Not a single one of the patients who took fluvoxamine got sicker during a 15-day period, while six who received a placebo deteriorated, developing shortness of breath or other symptoms.

His research, published in November, was the first placebo-controlled clinical trial to show that medication could prevent severe respiratory symptoms in COVID-19. But it was too small to allow firm conclusions, and Lenze needs to show it works on a larger group.

He is recruiting in all 50 states, employing the work-from-home version of medical research. Participants who have recently tested positive for COVID-19 receive the pills in the mail — they won’t know whether it’s fluvoxamine or a placebo — along with a fingertip pulse oximeter so they can measure their blood-oxygen levels, an indicator of breathing difficulties. They also fill out an online survey and speak daily by phone with a researcher.

Although normally used to treat mental illness, fluvoxamine would not induce mental illness in a healthy person, Lenze said; by raising serotonin levels, the drug might slightly and transiently improve sleep and energy, but its effects are likely to be limited by the short duration of use. In the first study, fluvoxamine did not affect participants’ anxiety levels, he said.

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Lenze is holding out hope that recruitment will be complete by early February (details can be found at https://stopcovidtrial.wustl.edu).

“As soon as recruitment is done, we’re only 15 days away from an answer,” he said. “If it’s positive, you can bet we will make that public as quickly as we can.”

Dr. Melisa Lai-Becker at the Cambridge Health Alliance is also looking at a long-used medication, NAC or N-acetylcysteine, a drug approved in the 1970s that treats acetaminophen overdoses and prevents exacerbations of emphysema.

The idea came to her on a fitful night as the second surge bore down on the Boston area. “I woke up with a start,” she recalled. “All I could think was NAC, NAC.” The drug has been used to treat viral pneumonias, and there’s evidence it can moderate the immune-system overreaction that leads to severe COVID-19.

Acting on a hunch, Lai-Becker, who is site chief of emergency medicine at CHA Everett Hospital, gave NAC to about 200 COVID-19 patients in the emergency department. They seemed to tolerate it well, and many found their breathing eased.

Lai-Becker won approval from the Cambridge Health Alliance to conduct a clinical drug trial, a rare endeavor for a community hospital.. But they’re doing it without any funding, relying on the volunteer efforts of a team of physicians. They can’t even afford to use a placebo, which costs $5 to $10 per capsule, compared with seven to 10 cents for NAC capsules.

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The study has enrolled 130 of the 200 patients sought (more information here: https://www.nacincovid.info).

Dr. JoAnn Manson, chief of the Division of Preventive Medicine at Brigham and Women’s Hospital, is intrigued by the potential of vitamin D to combat COVID-19, by boosting the immune system early in the infection and tamping down the inflammation that occurs when the immune system goes into overdrive. Her study is looking at whether vitamin D can reduce hospitalization and also whether it can prevent transmission to household contacts of those who are infected.

“It’s been shown in randomized trials to reduce the risk of other acute respiratory infections, especially in those who start out with vitamin D deficiency,” Manson said.

Several studies suggest that people with low levels of vitamin D are at greater risk for severe effects from coronavirus infections. But it’s not clear whether vitamin-D-deficient people merely have other characteristics that make them more susceptible.

Open to eligible patients within five days of a positive COVID-19 test, as well as their close contacts, the study plans to enroll 2,700 people. It too uses the trial-by-mail approach, with a finger-prick blood-sampling device. (Details here: www.vividtrial.org).

At the University of Massachusetts Medical School, Dr. Jonathan M. Gerber is studying a product of the human body — blood plasma donated by people who have recovered from COVID-19, known as convalescent plasma. UMass is participating in two national studies led by Johns Hopkins, one testing to see if the plasma can prevent infection in close contacts of COVID-19 patients, and the other seeing if it can prevent worsening of symptoms in those recently infected.

Convalescent plasma is already being used as an inpatient treatment, under an emergency use authorization. Gerber thinks it’s likely to be more effective earlier in the illness, when the immune system may need help fighting off the virus. But the study of outpatients has so far enrolled less than half the target number.





Felice J. Freyer can be reached at felice.freyer@globe.com. Follow her on Twitter @felicejfreyer.