The antimalarial drug hydroxychloroquine (HCQ), widely touted last year as a potential treatment for COVID-19, causes damage to DNA in mouse cell cultures at common dosages. This makes it possible that consumption could have long-term harmful effects, including a heightened risk of cancer. Given HCQ's long history of use against a variety of diseases, the consequences cannot be too common, or they would already have been detected. Nevertheless, the discovery emphasizes the recklessness of widespread, indiscriminate consumption of HCQ, based on preliminary and flawed studies.
It seems an age ago now, but last year the promotion of HCQ as a wonder-drug, both for preventing COVID-19 infection and treating those who had it, was unprecedented. The circus started when a very small, non-random trial reported HCQ and the antibiotic azithromycin eliminated the presence of SARS-CoV-2, but went into high gear when President Trump tweeted about it and subsequently promoted it more than 50 times. HCQ then became the center of a culture war, with certainty HCQ did or did not work becoming a way to demonstrate loyalty to a political tribe. Meanwhile, doctors frantically tried to point out there was little reliable evidence for or against its effectiveness against COVID-19.
Gradually the weight of evidence accumulated that HCQ offered little or no benefit against COVID. At the same time, some rare but potentially serious side effects were detected, beyond those already known. Now, a study in DNA Repair has suggested the possibility of more serious, delayed consequences.
“The uproar over HCQ drew our group’s attention, and we realized that, although the drug has been widely used for the treatment of diseases ranging from malaria to rheumatoid arthritis, its exact mechanisms of action are only beginning to be understood,” said Professor Ahmad Besaratinia of the University of Southern California in a statement. “Most importantly, there was no data on whether HCQ has adverse effects on the genome.”
Besaratinia set out to correct that, applying HCQ to a culture of embryonic mouse cells. “[M]any in vitro experiments administer unrealistically high levels of a drug for testing, we used therapeutic doses of HCQ that are actually given to patients,” he said. At these doses, HCQ roughly doubled the frequency of certain cell mutations.
Just as many treatments that work well on rodents or other animals fail when applied to humans, not all side-effects may translate either. Moreover, Besaratinia acknowledged his work is only in culture, so living mice may be less affected. Nevertheless, the findings are certainly alarming.
Besaratinia stresses HCQ remains the best option for some conditions; “If a patient’s need for HCQ outweighs the risks of using the drug, it makes perfect sense to prescribe it,” he said. However, volunteers in clinical trials, let alone those taking the drug on an extended basis for touted protective effects, should be aware of the dangers.
Eventually, the caravan of deceit rolls on. Now politicians, media figures, and social media commentators are more likely to be promoting ivermectin than HCQ, despite similar problems with the studies favoring it. However, the HCQ story remains a cautionary tale about the dangers of drug fads. Whether or not cancer or other conditions result from the HCQ craze remains to be seen, but we know enormous damage was done by people who risked exposure, believing this drug would save them from COVID-19.