“Frankly Scarlett I don’t give a damn!” — Rhett Butler, Gone With The Wind
As of this writing, the virus has infected more than two million people worldwide and caused more than 130,000 deaths … and counting.
Frankly, at this point in time, and to quote Rhett Butler, no one gives a damn what the cure is or where it comes from, but they must find something, and fast.
Critics can mock President Donald Trump for mentioning malaria drugs all they want, but if actually does work, who cares. Shut up, and take a backseat to science.
The good news is the World Health Organization (WHO) recently launched a large international trial called Solidarity to test four existing therapies, Tanya Lewis of Scientific American reported.
They are the previously mentioned malaria drugs chloroquine and hydroxychloroquine; the antiviral medication remdesivir (developed to treat Ebola); the antiviral combination of lopinavir and ritonavir (used for HIV); and those two HIV drugs plus the anti-inflammatory small protein interferon beta.
The US Food and Drug Administration has approved remdesivir for treating Covid-19 patients under the compassionate-use protocol. And the agency has granted an emergency use authorization for chloroquine and hydroxychloroquine.
“None of these therapies are proven,” says Stanley Perlman, a professor of microbiology and immunology at the University of Iowa.
Here is what we how so far.
Chloroquine and Hydroxychloroquine
President Trump has repeatedly touted the malaria drugs chloroquine and hydroxychloroquine as a treatment for COVID-19 — despite a lack of clinical evidence, Scientific American reported.
The president’s comments set off a scramble to obtain the drugs — which are frequently used to treat rheumatoid arthritis and lupus — and there is now a shortage. But some experts say the widespread usage of these drugs is premature.
“The clinical support is very, very minimal,” says Maryam Keshtkar-Jahromi, an assistant professor of medicine at the Johns Hopkins University School of Medicine. “The drugs do “not show strong evidence at this point,” she adds.
A controversial small, nonrandomized trial of hydroxychloroquine combined with the antibiotic azithromycin in France suggested that Covid-19 patients given the treatment had less virus. The jury appears to be split on the study’s validity, however.
Cardiac toxicity is also a concern — there have been some reports of myocarditis, or inflamed heart tissue, in people with Covid-19 who have not taken chloroquine or hydroxychloroquine.
“It’s a double-edged sword,” says Sina Bavari, chief science officer of Edge BioInnovation Consulting in Frederick, Md. “We are not saying, ‘Don’t [prescribe chloroquine].’ We are saying, ‘More data is needed to better understand how the drug works—if it works.’”
This experimental antiviral drug was developed to treat Ebola, and it has been shown to be safe for use in humans. It is a broad-spectrum antiviral that blocks replication in several other coronaviruses, Scientific American reported.
In addition to the WHO investigation, at least two trials in China and one in the US are currently evaluating remdesivir.
“As of this moment, we don’t have data for remdesivir in human Covid-19 disease,” says Barry Zingman, a professor of medicine at Albert Einstein College of Medicine and clinical director of infectious diseases at Montefiore Health System’s Moses Campus.
The two related institutions, both located in New York City, recently joined a nationwide clinical trial of the drug.
“Our patients are randomized, so we don’t know who’s getting the drug or a placebo. [But] we have seen some patients do remarkably well,” Zingman says. Trial results are on track for publication sometime in the next six to eight weeks, he adds.
Remdesivir works by inhibiting an enzyme called an RNA-dependent RNA polymerase, which many RNA viruses — use to replicate their genetic material.
Timothy Sheahan of the University of North Carolina at Chapel Hill and his colleagues have shown the drug is effective against severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). The team is in the process of testing the drug’s efficacy against SARS-CoV-2.
“Remdesivir has some chance,” Perlman says. “If we can give [the drug] early in the disease course, it could work.”
Ritonavir and Lopinavir
The HIV drugs ritonavir and lopinavir (sold as a combination therapy by AbbVie under the brand name Kaletra) have been tested against Covid-19 in a few clinical trials. The initial data have not shown them to be effective, however, Scientific American reported.
A study in the New England Journal of Medicine found they conferred no benefit beyond standard care.
The drug combination is what is known as a protease inhibitor, and it works by blocking an enzyme involved in viral replication. But its action is specific to HIV and so is unlikely to work for SARS-CoV-2, Perlman says.
“If you have the key to a car, and you try to put it in your car, the odds of it working are one in a million,” he says. “Kaletra [targets] a completely different lock” than the one for Covid-19.
Nevertheless, the WHO trial includes a group of Covid-19 patients who will receive these drugs on their own — and another group that will receive them in combination with interferon beta, a small cell-signaling molecule used to treat multiple sclerosis.
Immune System Inhibitors
Researchers are also considering a number of other therapies that tamp down the rampant immune response seen in severe Covid-19 cases. Such a flood of immune cells in the lungs — known as a cytokine storm — can lead to death, Scientific American reported.
Many of the sickest patients have elevated levels of an inflammatory protein called interleukin-6 (IL-6). Research in China has suggested that Actemra (tocilizumab), an IL-6-blocking antibody drug made by Roche, shows promise.
And Chinese authorities have recommended the drug in their treatment guidelines. Roche has since initiated a phase III randomized controlled clinical trial for the medication.
In the US, Michelle Gong — chief of the division of critical care at Montefiore and Albert Einstein — and her colleagues are among dozens of groups conducting a clinical trial of a related drug called sarilumab, approved for treating rheumatoid arthritis.
Sarilumab will only be given to the sickest individuals: to be part of the trial, patients must be hospitalized with Covid-19 and in severe or critical condition.
Another treatment approach involves injecting COVID-19 patients with blood plasma from people who have recovered from the illness. The FDA recently issued guidance on the investigational use of such “convalescent plasma,” which contains antibodies to the coronavirus, and clinical trials are underway, Scientific American reported.
Blood from disease survivors has been used as a treatment throughout history — from polio-infected horses in the 1930s to former Ebola patients in 2014.
“There is a long-lasting rationale for the use of convalescent plasma against any infectious disease,” Cortegiani says.
One problem, however, is that scientists do not know whether people develop strong immunity against SARS-CoV-2. And it is not easy to collect plasma containing enough antibodies, he adds.
Another issue is the shortage of eligible donors. Some companies are looking into ways to produce these antibodies artificially.
The anti-viral drug called Interferon Alfa-2B is produced in China, by a Cuban-Chinese joint venture ChangHeber, TheWeek reported.
Considered one of the stars of the Cuban biotechnology boom, the drug has reportedly been effective in the treatment of HIV, human papilloma virus, Hepatitis B and C.
According to reports, this Cuban drug has proven effective in treatment of viruses that show characteristics similar to the novel coronavirus.
While Ireland is considering bringing in Cuban drugs to combat Covid-19, Cuba has already sent its emergency contingent of doctors and nurses to fight the novel coronavirus in Italy.
Interferon drugs are man-made versions of the proteins that the human body creates. The drugs equip the body to tackle viruses, preventing them from multiplying in the body.
Interferon drugs first emerged for cancer therapy and have also been used in the treatment of HIV and AIDS.
Cuba manufactured its first interferon in 1981 and was used in the treatment of the dengue epidemic in Cuba the same year. The country later manufactured “recombinant” human interferon Alfa-2B in 1986.
This is not an anti-viral drug, per se, but researchers at the University of Waterloo are developing a DNA-based vaccine that can be delivered through a nasal spray, the school reported on its website.
The vaccine will work by using bacteriophage, a process that will allow the vaccine to replicate within bacteria already in the body and is being designed to target tissues in the nasal cavity and lower respiratory tract.
“When complete, our DNA-based vaccine will be administered non-invasively as a nasal spray that delivers nano-medicine engineered to immunize and decrease Covid-19 infections,” explains Roderick Slavcev, a professor in the School of Pharmacy.
“This research combines the expertise of many and leverages existing technology developed by my team, which we’re reconfiguring for a Covid-19 application.”
When completed, the researchers aim to have the DNA-based vaccine enter cells in targeted tissues and cause them to produce a virus-like particle (VLP) that will stimulate an immune response in people.
Additional design of components and further testing will take place later this year.
This antiviral drug Favipiravir was approved in 2014 in Japan mainly to treat novel influenzas, MacLeans Magazine reported.
It was considered a viable potential treatment option for Covid-19 because it is able to block the replication of RNA viruses, and Covid-19 is an RNA virus. Currently, it is being studied in human trials in China and Japan.
In March, Italy approved the drug for experimental use against COVID-19 and has begun conducting trials in regions most affected by the disease.
Zhang Xinmin, an official at China’s science and technology ministry, said favipiravir had produced encouraging outcomes in clinical trials in China involving 340 patients. Others have said the drug is not as effective in patients with more severe symptoms.
The key thing about favipiravir, says Dr. Lynora Saxinger, an infectious disease specialist with the University of Alberta, is they are more likely effective when used early on.
“In all of those antiviral drugs, the timing will become very important,” she says. “That’s challenging, because some people with Covid-19 don’t have many symptoms up front.”
The good news: no significant negative reactions were noted in patients on favipiravir, and it had significantly fewer side effects than other drugs.