Scientists around the world are racing to develop effective treatments for COVID-19. There are currently at least 12 potential treatments being tested, including some existing medications for treating malaria and HIV. Instead of developing new treatments, repurposing those that are known to be safe can save precious time and lives. Hopefully, more than one drug will turn out effective so that we can have several treatments available for different stages of the infection.
Among them, hydroxychloroquine has received high hopes as President Trump claimed to “feel good” about its “very encouraging” early results. A few days later, the director general from the World Health Organization (WHO), Tedros Adhanom Ghebreyesus, clarified that raising false hope using limited evidence can do more harm than good.
A study in cell culture showed that hydroxychloroquine can handicap the virus. However, the doses needed to be very high, which could cause cellular toxicity and health concerns. Clinical evidence so far remains unclear as more than 20 studies using chloroquine or hydroxychloroquine in China have not yet published the data.
The study that President Trump was referring to is a small trial of 20 patients, published by a French team on the International Journal of Antimicrobial Agents. The trial concluded that a combination of hydroxychloroquine and the antibiotic azithromycin could reduce viral load in nasal swabs. Although reduced viral load is one indicator of increasing odds of survival, the trial was not randomized and did not report clinical outcomes such as recoveries or deaths. In addition, a small (30 patients) but randomized controlled trial in China reported no difference in recovery rates with hydroxychloroquine. In fact, one patient treated with hydroxychloroquine had severely worsened symptoms, and four other patients developed diarrhea and signs of liver damage. Therefore, President Trump’s optimism for hydroxychloroquine is hardly justified.
Importantly, self-medication of hydroxychloroquine or chloroquine is very dangerous as it has led to reports of poisoning. Last week, a couple died of taking chloroquine phosphate, an additive used to clean fish tanks because they believed in President Trump’s confidence in the drug.
Unfortunately, hydroxychloroquine has well-documented side effects, including:
- Heart complications: irregular heart beat or arrhythmia
- Kidney damage
- Psychiatric side effects: anxiety, insomnia, nightmares, paranoia, hallucinations, personality changes, suicidal thoughts
Therefore, both individuals and healthcare practitioners are urged to be cautious and stop using or prescribing hydroxychloroquine for people concerned about COVID-19.
Remdesivir was developed to combat Ebola viruses by interfering with viral replication. Although it did not help with Ebola, the researchers have previously shown that the drug may inhibit SARS and MERS viruses.
Since Remdesivir can be incorporated directly into virual RNA, thus preventing viral replication, it is considered to be the most promising option by some experts. Currently, Remdesivir is in Phase 3 clinical studies and is part of WHO’s SOLIDARITY trial.
Lapinavir and ritonavir are anti-HIV drugs that are being repurposed to combat COVID-19. The combination is part of the WHO’s SOLIDARITY trial and has been in the spotlight. Anecdotal evidence has been reported, but clinical trials are still underway. Unfortunately, the first dataset on 199 Chinese patients published on the New England Journal of Medicine reported no significant benefit of lapinavir-ritonavir over standard care. The researchers said that the patients were very ill already when the treatment was given, which may have reduced the potency of the drug.
A timing dilemma
For many anti-viral drugs, the dilemma is that most countries are running short on supplies and experiencing a healthcare overload during this sudden pandemic. Drugs like remdesivir is an expensive intravenous drug. It is tricky to use them on early stage patients who may not develop severe symptoms. But when you do give medications at a critical stage, it might be too late.
Unfortunately, we do not yet have an approved medication or standard protocol for treating COVID-19. The evidence on hydroxychloroquine, remdesivir, and lapinavir-ritonavir is still limited at this stage, but many clinical trials are due to finish in April. It is very dangerous to believe what the media reports and self-medicate at this stage, without considering the validity of the claims and potential side effects. Patients with heart, liver, kidney, and immune conditions are particularly prone to experience severe side effects when medications are used inappropriately. Elderly people should be extremely careful. We will have to wait patiently for clinical trials to finish and base judgements on sound scientific findings.