ROCHESTER, Minn. -- With hundreds of drugs having been studied it has been hard to keep track of the experimental treatments investigated for the COVID-19 pandemic.
Scientific findings of unknown significance make the news daily, some of them in so-called "preprint" form, meaning their data have not been peer reviewed, and need to be adopted with caution.
Others are small studies, limiting their relevance. Still others lack a control group or some other key design element. Press releases raise hopes for new treatments in the pipeline, but often lack key data needed to draw strong conclusions.
With so many variables at work, as the U.S. embarks on mass vaccination, the treatment landscape is littered with dashed hopes and a handful of interventions that survived the test.
Repurposed drugs and supplements mostly faltered
- Legacy medications The latest update of the NIH COVID-19 treatment guidelines lists drugs of interest for arthritis, gout, malaria, diabetes, parasites and depression as all lacking necessary data showing effectiveness against the virus.
- Supplements Vitamin C, D and Zinc all lack endorsements at this time as well.
- Hydroxychloroquine and Ivermectin Some drugs that garnered widespread attention on social media, like hydroxychloroquine last year, and the parasitic drug Ivermectin this year, have taken on a life of their own within communities skeptical of official recommendations.
The panel recommended against the use of the antiviral agent hydroxychloroquine in 2020. Like hydroxychloroquine, Ivermectin has not shown the data needed to establish its effectiveness against COVID-19 in the eyes of health authorities.
A February update of the NIH COVID-19 Treatment Panel has categorized Ivermectin as possessing "insufficient data" to recommend for or against its use in the treatment of COVID-19.
The NIH also provides a table listing the methodological limitations of nearly a dozen studies of Ivermectin, research conducted mostly overseas.
- Read part 1 of the series: The future of COVID-19 series: It's all about the spike
- Convalescent plasma Although it was adopted by a host of large academic centers thanks to an international collaboration that arose early in the pandemic, the investigation of convalescent plasma now is received with reduced expectations in federal treatment guidelines.
The NIH Covid-19 Treatment Panel recommends against low-titer convalescent plasma in patients with COVID-19, as well as against any nontrial use of the blood products in those who are on a respirator.
Citing insufficient data, NIH reviewers have no recommendation on the use of convalescent plasma in nonhospitalized patients, or for those who are immunocompromised.
Four drugs that worked
Once you get beyond comfort-care measures for mild forms of the illness, there are essentially four medications with federal support for the care of COVID-19 at this time. They each provide usefulness during a limited window for the illness.
- Monoclonal antibodies (mAB) The drugs bamlanivimab plus etesevimab (made by Eli Lilly), and casirivimab plus imdevimab (made by Regeneron) have oddly spelled names, which is why they are often called monoclonal antibodies.
They are lab-engineered proteins that mimic the antibodies produced by our bodies. Delivered as infusions, they interfere with the ability of the spike protein to latch onto cells, and are given in one 2.5-hour infusion at outpatient treatment centers affiliated with participating medical centers.
They are effective at improving outcomes when given very early in the illness -- within first 7-10 days of infection -- but are not considered useful once a patient has entered the hospital.
For this reason, mAB are given preventively, after a positive diagnosis of infection by someone with risk factors for a poor outcome.
As Harvard University infectious disease expert Dr. Paul Edward Sax stated during a recent episode of the podcast Plenary Session, "giving an IV treatment to a person with a highly contagious infection who's an outpatient is extremely challenging."
To date, Mayo Clinic has treated over 5,400 patients with monoclonal antibodies, according to Dr. Raymund Razonable, using dedicated outpatient treatment centers and mobile units.
- Remdesivir If monoclonal antibodies are only effective before a patient develops a serious case of illness, Remdesivir is the next drug in the prescriber's tool box as a patient's condition worsens, and it is only helpful for early hospitalization.
The intravenous antiviral is "recommended for use in hospitalized patients who require supplemental oxygen," according to the NIH, but not those who are in need of ventilation.
It is shown to raise the likelihood of a faster time to recovery, from 15 to 10 days on average. It is given in five- and 10-day courses.
- Tocilizimab Should a patient worsen after Remdesivir, another monoclonal antibody comes into play, this one in use for almost a decade in the treatment of rheumatoid arthritis.
Tocilizimab blocks a receptor for a cytokine, a chemical released by the immune system. That gives it anti-inflammatory properties, which is vital given that advanced COVID-19 is considered an autoimmune disorder.
The immune system is responding over-aggressively to the virus, and that, apart from the effects of the spike protein on the vascular system, is causing patients to deteriorate.
For this reason, Tocilizimab is suitable for those in a hospital and are on supplemental oxygen, worsening and at risk of ICU care.
- Dexamethasone. Dexamethasone is a cheap, common steroid hormone first synthesized as cortisone by a pair of Mayo Clinic scientists in the late 1950s, and it is available worldwide. It is given for a variety of conditions but was first developed for rheumatoid arthritis.
Given systemically, it is possibly the most effective medication in the four-drug arsenal known to be effective against worsening COVID-19. It is given to patients on supplemental oxygen, where it helps somewhat, and patients on the respirator, where it helps even more.
Dexamethasone is not useful or recommended for patients who are not hospitalized.
"WHO emphasizes that dexamethasone should only be used for patients with severe or critical disease, under close clinical supervision," as WHO Director-General Dr. Tedros Adhanom Ghebreyesus stated last summer.
"There is no evidence this drug works for patients with mild disease or as a preventative measure, and it could cause harm."