There are many studies on the effectiveness of hydroxychloroquine (HCQ) in treating COVID-19, but only a handful of them adhere to the highest scientific standards. Even those, however, fail to answer some of the most pressing questions.
The debate over HCQ turned into an information tug of war after President Donald Trump endorsed its potential early on. Each side now accuses the other of getting swayed by politics.
Each side has its arguments, but when they’re all put together, it turns out that some of the most crucial questions still haven’t been definitively answered. For example, is there a way to use HCQ to prevent the most at-risk people from dying of COVID-19, if caught early?
In theory, HCQ should be helpful in inhibiting COVID-19 by prying open the infected cells to allow zinc, which is naturally present in the human body, to enter the cell and slow the replication of the virus.
Several doctors who have been both vocal and successful in using HCQ to treat hundreds of patients have explained that the point of using the drug is not necessarily to cure a patient or suppress all symptoms. Their argument is that HCQ can slow the virus down and allow the body to build up immunity against it so that the body can get over it on its own.
But none of these studies are both controlled and randomized, which diminishes their value. For a study to match the scientific golden standard, it needs to be conducted on a sufficiently large number of truly random people so the specific makeup of the group (such as its demographics) doesn’t influence the results. The group is then divided in half. One half gets the drug and the other, the control group, gets a placebo. The outcomes for the two groups are then compared.
But other experts remain unconvinced, pointing to the handful of randomized controlled trials of HCQ that do exist. None of them showed statistically significant benefits in treating COVID-19 with the drug.
Some of the studies looked at hospitalized patients in serious conditions. But in those cases, it was already too late for HCQ to help, Risch argued. Others looked at people in early stages of the disease, but most of their participants were people under 50 without serious health issues. These people usually go through COVID-19 without serious complications anyway.
None of the studies used the HCQ-zinc-azithromycin combo that appears to have been the most effective in clinical practice.
Also, some of the studies included only a minority of people who’d actually tested positive for COVID-19. Other participants were included based on symptoms (such as cough, fatigue, headache, or fever) and risk of contact with the virus (such as by sharing workplace with somebody who’d tested positive). The virus that causes COVID-19, SARS-CoV-2, isn’t the only one causing such symptoms, leaving the possibility that some of the people didn’t have COVID-19 to begin with.
Furthermore, the studies used much higher doses of HCQ than what clinicians on the ground seem to recommend.
Zelenko prescribes 200 milligrams (mg) of HCQ every 12 hours for five days.
In contrast, the controlled randomized studies mostly used doses ranging from 1,200 mg to 2,400 mg in the first 24 hours, followed with 600 mg to 1,200 mg daily for the next 4 to 21 days.
This didn’t sit well with Meryl Nass, a physician and chemical toxicity expert.
Moreover, it takes about a month for a human body to excrete half the ingested drug, “so the cumulative amount is important,” Nass said.
The 1979 paper notes that a daily base dose of 1,200 mg (about 1,550 mg in pills) “has been tolerated for at least a few days.” But it adds that this dosage “appears to be a limit which should not be exceeded.”
Nass called these dosage regimens “non-therapeutic, toxic, and potentially lethal.”
Neither Nass nor representatives for the Solidarity trials respond to requests for comment.
Peter Horby, contact for the Recovery trial and Oxford professor of Emerging Infectious Diseases and Global Health, responded with the following comment:
“The loading dose and maintenance doses of hydroxychloroquine used in the RECOVERY trial were carefully selected based on knowledge of the absorption and distribution of the drug and the drug concentrations needed to inhibit the SARS-CoV-2 virus. The dose selection was done with a world recognised expert in the pharmacology of antimalarial drugs. ... The doses were designed to achieve the concentrations needed to inhibit the virus as quickly and safely as possible. We looked carefully at data on hydroxychloroquine toxicity. The doses used in RECOVERY are very unlikely to cause toxicity. ... Regarding the long half-life of hydroxychlroquine, the regimen we used is predicted to result in concentrations that are at the upper end of those observed in the treatment of rheumatoid arthritis.”