Treatments for COVID-19: What works, doesn't work, and is still being tested

A year into the COVID-19 pandemic in Canada, doctors are learning how to help keep more patients alive, but the proven treatment options remain limited.

So what does work?

The U.K.'s ongoing Randomised Evaluation of COVID-19 Therapy, or RECOVERY trial, tests existing drugs as potential therapies to treat COVID-19. Its investigatorsproved that giving the widely available steroid medication dexamethasone to hospital patients severely ill with COVID-19 can save lives.

Back in June, RECOVERY released apress releasethat included key details for applying the information and the full study was published in the New England Journal of Medicine a month later.

Currently, steroids such as dexamethasone are the only drug treatments for COVID-19 listed as "most beneficial" in a review that's continually updated in theBMJ.

One thing researchers found was the benefitof usingsteroids to treat COVID-19depends on the severity of a person's case.The drug'sbenefits only outweighed the risks in patients who were sick enough to need oxygen treatment, not those recovering at home, the research suggests.

Dr. Lynora Saxinger, an infectious disease physician in Edmonton, follows the advances in treatments and how they're communicated.

"There's been a lot of pressure to say, 'Hey, we found something possibly useful, we should share it immediately," shesaid.

"Enthusiasm travels so quickly and becomes ingrained before you even have a chance to really support whether it's a good idea. Then you're facing a bit of a battle to actually calm down enthusiasm if the data are less strong than the press release really suggested."

Doctors who treat people with COVID-19 in hospital wards, intensive care units and out in the community continue to juggle conflicting clinical trial results sometimes for the same treatmentbased on studies in different countries most of which feature data from asmall numbers of patients.

To try to make sense of the small numbers, clinicians follow their training to assess what's known about the drug and apply it to their patients'cases. That's why "Show me the data" is a refrain doctors use when weighing treatment options for patients with COVID-19 in the face of promising press releases that are short on key details.

At this point in the pandemic,Saxinger said, the norm of presenting science by press release needs to be questioned because there's an alternative. That is, press releases can be accompanied by what are known as preprints, ordraft manuscripts that haven't been checked for errors andinclude all of the available data and astudy's methods, so clinicians can assess themeritsfor themselves, just as the RECOVERY trial investigators do.

Last week, for example, Canadian hospitals put out press releases about two potential treatments: a common blood thinner for patients with moderate COVID-19 and colchicine, an oral medication used to treat gout.

Both announcements were based on the results of clinical trials that haveyet to be peer reviewed or published in a medical journal.

Dr. Zain Chagla, an infectious disease physician in Hamilton, Ont., and an associate professor at McMaster University, recently experienced the mismatch between patient expectations for a new treatment and what he could offer firsthand.

"When you put out a press release on Friday night and your patients that test positive for COVIDon Saturday are saying, 'OK, where's my colchicine?' it's very hard ... to counsel them appropriately."

Given that the full manuscript now suggests about70 people would need to be treated withcolchicine to prevent one hospitalization, Chagla said the bottom line is to consider if the patient fits the profile of who might benefit most before prescribing it.

He said thiscould include individuals in their 50s with risk factors, such as diabetes. Doctors should also keepin mind the significant risk of gastrointestinalissues with colchicine, which could also lead to hospitalization and possible drug interactions.

Treatment hype

In the early days of the pandemic, when clinicians were trying to figure out what to do on the fly, enthusiasm led to missteps, Saxinger said.

Hydroxychloroquine, an anti-malarial drug, is an obviousexample. In the spring, U.S. President Donald Trump hailed itas a game-changer in the fight against COVID-19. But the RECOVERY trialshowedhydroxychloroquinedid not benefit hospitalized patients.

"I think the nail's in the coffin on that one," she said.

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Chaglaand Saxinger dividepotential treatments for COVID-19 into a few main categories:

• Antivirals such as those used to treat HIV, the virus that causes AIDS.
• Monoclonal antibodiesthat mimic a natural antibodyand were one of the treatments Trump received.
• Convalescent plasma, which is plasma from people who have recovered from COVID-19 that contains different types of antibodies to fight the virus.
• Immunomodulatorssuch as interferonthat aim to quell the "cytokine storm"that can lead to life-threatening complications withCOVID-19.

Saxinger puts these potential treatments in the too-soon-to-tell group because larger or better trials are still needed.

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COVID-19 vaccines have come fast but treatments for the disease are still limited. When a Canadian company developed Bamlanivimab, a new monoclonal antibody drug, Ottawa spent millions on doses. But after the rush to buy them they've sat on shelves for months, unused.

The RECOVERY trial recently closed recruitment for its convalescent plasma study. In Canada this week,Dr. Donald Arnold, a hematologist at McMaster University who is helpinglead Canada's Convalescent Plasma for COVID-19 Research, or CONCOR trial, saidthe study is ongoing.

Canadian Blood Services (CBS) and Hma Qubec supplyconvalescent plasma to doctors caring for patients with COVID-19 as part ofCONCOR. CBS has said not all plasma from those who haverecovered from the illnesscan be used as a therapy because some people might not have enough antibodies to protect others.

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Chagla and Saxinger both said ivermectin, an anti-parasite drug, also needs further study in clinical trials.

"For a single trial to be truly practice changing, it has to be pretty watertight," Saxinger said.

In the case of ivermectin, Saxinger said the research so far was based on a small number of people. Some participants were also given steroids, making it hard to tease out the impact of the anti-parasite portion of the treatment.

Also, earlier test tube-based research intoivermectin used much higher concentrations than what's given to humans, Saxinger said. Giving highly concentrated drugs to people can often be too toxic and result in side-effects.

Most large clinical trials for COVID-19 treatments that have reported results so far have been for patients hospitalized with the illness.

But most people recover at home.

Last week, Canadian and international researchers with theCOLCORONA study of colchicineput out a press release about the effects of the gout drug in outpatients with COVID-19. Saxinger said she's "provisionally excited" but awaits more data to draw any conclusions about the use of colchicine.

Chagla said outpatient COVID-19 studies arebeneficial because they keeppeople out of overburdened hospitals.

But such multi-centre studies running in multiple countries can also be difficult to set up, especially sincehealth-care systems are already stretched. Contracts and insurance paperwork can also bog down the trials and could be eased by regulators such asHealth Canada, he said.

"Outpatient trials are super hard to fund," Chagla said. "It's hard to navigate."

Blood thinners

Dr. Kwadwo Kyeremanteng, an intensive care and palliative care physician in Ottawa, said many patients critically ill with COVID-19 were having to go on dialysis due to blood clotting. It was a surprising feature of the disease last spring.

"We aggressively began putting blood thinners on board earlier in their course," Kyeremanteng recalled. "This is more subjective, I would say, but it appeared that patients were doing better as a result."

Blood thinners continue to be used to treat moderateCOVID-19 in hospitalized patients.

Despite all of the advances in treatments, Saxinger sees greater potential in prevention from public health measures such as physical distancing, masking and staying close to home whileCanada reaches better vaccine coverage.

"At the end of the day, medical treatments against a viral and inflammatory illness are always going to be disappointing compared to just preventing the illness," shesaid. "Any kind of treatment that reduces really severe outcomes doesn't actually reduce people getting sick and doesn't actually reduce people spreading it to others."