Unconventional COVID-19 cures that might actually work

What do Viagra, vitamin C, honey, and head lice medication all have in common? They’re all currently being investigated as potential treatments for COVID-19. 

Sure, you’ve heard about homespun remedies like drinking liquid bleach and injecting yourself with Lysol. But, unlike those highly ill-advised “cures,” these proposed treatments have science and research to back them up. Plus, they’re all currently being investigated in actual clinical trials. 

Currently, nearly 950 clinical trials involving COVID-19 are underway. Of these, about 450 are actively recruiting patients. You’ve certainly heard about the most promising candidates like hydroxychloroquine, remdesivir, and convalescent plasma. But other treatments, with less notoriety, are also being investigated. On first glance, these unconventional, experimental medications may seem to be unlikely, even preposterous, therapies for a viral pulmonary infection. But, once you learn about how they would work, they might not seem so far-fetched after all. 

Viagra

The drug sildenafil, popularly known as Viagra, is used to treat erectile dysfunction. But, under the brand name Revatio, sildenafil is also used to treat pulmonary arterial hypertension. And pulmonary arterial hypertension is a well-known complication of acute respiratory distress syndrome (ARDS), which is a life-threatening finding in seriously ill people with COVID-19.  

Bear in mind that sildenafil dilates blood vessels and increases blood flow. So, the idea for this small clinical trial is that sildenafil may open up the vasculature in the lungs, reducing inflammation and helping to alleviate the ARDS that occurs in patients with severe cases of COVID-19. 

Interestingly, after the SARS outbreak in 2003, researchers reported that high nitric oxide levels (produced by drugs like sildenafil) had an antiviral effect on the replication cycle of the virus. The current clinical trial of sildenafil may provide similar evidence. 

Resistant starch

What is resistant starch? Unlike other starches, resistant starch isn’t easily digested. So it works in the body like dietary fiber and is used as a dietary supplement for digestive health. It travels through the small intestine undigested, but is fermented in the large intestine where it produces short-chain fatty acids, including acetate, propionate and, notably, butyrate.

How could resistant starch fight COVID-19? In animal studies, resistant starch has been shown to reduce systemic inflammation. In research in humans, it decreased rates of lower respiratory viral infections in bone marrow transplant recipients. Taken together, these studies suggest that resistant starch could have helpful effects in patients with COVID-19. 

“The idea behind using resistant starch is that it will increase butyrate levels in the body and there will be a reduction in inflammation secondary to the effects of butyrate on the lungs,” lead investigator Sherry Mansour, MD, MS, nephrologist at Yale School of Medicine, told MDLinx. 

In a multicenter, randomized clinical trial, Dr. Mansour and colleagues will recruit 1,500 non-hospitalized outpatients with COVID-19. Half will receive a dietary supplement containing about 20 grams of resistant starch twice daily for 14 days. The other half will receive a placebo. The goal will be to reduce hospitalizations, as well as speed recovery and decrease symptoms. 

Vitamin C

Vitamin C is well known as an antioxidant, but it also supports healthy immune function. Previous research has suggested that vitamin C can prevent the accumulation of neutrophils in the lungs caused by sepsis. Given this, researchers in Wuhan, China, have begun a clinical trial in 140 patients with COVID-19 to investigate the effect of intravenous vitamin C at a dose of 24 g/day for 7 days. The main goal is to see if it reduces the time patients are on a ventilator, as well as shortening their stay in the ICU and lowering mortality. 

The investigators face an uphill battle. In a recent preliminary study published in JAMA, US researchers reported that intravenous vitamin C offered no real improvement in patients with sepsis and ARDS, although there was a suggestion that it may have reduced mortality. 

Honey

Can honey help patients with COVID-19? Investigators in Egypt aim to find out. They point out that many studies have shown that honey has broad-spectrum antibacterial, anti-fungal, antiviral, and antimycobacterial effects. So, for their multicenter, randomized, controlled clinical trial, they are recruiting 1,000 patients with COVID-19. Half of these patients will receive standard care while the other half will receive standard care plus 1gm/kg/day of natural honey divided into 2 to 3 doses for 14 days.  

“The National Institute for Health and Care Excellence (NICE) and the Public Health England (PHE) guidelines recommended honey as a first line of treatment for acute cough caused by upper respiratory tract infection, which is currently a cornerstone symptom in COVID-19 infectious disease,” the researchers wrote. “Moreover, natural honey should no longer be used as ‘alternative’ and deserves to gain more attention by scientists and researchers.”

Head lice medication

Ivermectin is an anti-parasitic agent used to treat head lice and river blindness (onchocerciasis) in humans. It’s also used to prevent heartworm in dogs. But, how could an anti-parasitic be used against a virus like SARS-Cov-2? Researchers have shown that ivermectin also kills RNA viruses, and SARS-Cov-2 is an RNA virus. In fact, researchers at Australia’s Monash University recently published a study in which they found that ivermectin reduced SARS-Cov-2 RNA by 5,000-fold in 48 hours. (When news of this study broke, the FDA had to issue a warning that instructed people not to self-medicate with their dog’s heartworm medication to prevent COVID-19.)

But this was an in vitro experiment. Could it work in humans? Researchers in Iraq are now recruiting patients for a randomized clinical trial to find out. Patients with COVID-19 and pneumonia will receive either ivermectin 12 mg/weekly plus hydroxychloroquine and azithromycin daily, or placebo plus hydroxychloroquine and azithromycin. 

Despite the promising in vitro trial, the in vivo study is not a cinch to succeed. Some experts have recently pointed out that if the amount of drug used in the in vivo study were scaled up for humans, it would be about 100 times the approved dose of ivermectin in humans, and about 10 times higher than levels ever studied in humans.

Then again, maybe not as much drug is needed. In another recently published preliminary study, researchers administered a one-time 150mcg/kg dose of ivermectin to 704 patients with COVID-19 and compared their outcomes with 704 patients who didn’t receive the drug. Of those requiring mechanical ventilation, about two-thirds fewer patients in the ivermectin group died (7.3% vs 21.3%). Overall mortality rates were also lower in patients given ivermectin (1.4% vs 8.5%, HR: 0.20, CI 95%: 0.11-0.37, p<0.0001).

In unconventional times, unconventional solutions might be the answer. Only time, and experimentation, will tell if any of the treatments described here can stop COVID-19.