Following the emergence of a novel coronavirus in Wuhan, China, in the last month of 2019, it has spread globally to produce the first pandemic of the 21st century. The virus, called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has already affected over 2.5 million and killed more than 177,000 people as of April 22, 2020.
More than three months into the pandemic, there are few signs of any immediate relief from the viral pneumonic illness called COVID-19, which appears to spread fast and cause disproportionate mortality in the older age group as well as those with underlying medical conditions. Without a specific vaccine or therapeutic agent to help counter the virus, public health authorities have resorted to social and physical distancing, quarantine for suspected or confirmed contacts of COVID-19 cases, and lockdowns of entire regions or countries, in many cases.
Drive-through coronavirus COVID-19 testing location. Image Credit: Supamotion / Shutterstock
Many questions have come up during the course of attempting to deal with this pandemic, which has so far appeared to overwhelm the best that modern medicine has to offer. One such question concerns the use of hydroxychloroquine (HCQ), a drug used for certain other medical conditions, but which has been touted to be effective against COVID-19.
The drug has shown its ability to produce antiviral effects in cultured cells in the laboratory, but there is little experimental proof of its real-time efficacy against the SARS-CoV-19 virus. A new study aims to summarize the available evidence for and against the use of this drug in this illness, to help make a more informed decision on its use.
How was the study done?
The researchers searched databases of PubMed, Scopus, Embase, Cochrane Library, Web of Science, and Google Scholar (intitle) as well as preprint database of bioRxiv and medRxiv up to April 5, 2020, to look for articles dealing with the use of HCQ in COVID-19. All the selected studies were either clinical or observational trials, or studies reporting the effects of the drug in human COVID-19 patients. Animal studies, reviews and case reports, and in vitro studies were not covered.
Six studies were found that fit the criteria for the meta-analysis. All studies were evaluated for quality and bias, using appropriate checklists. There were three clinical trials and three observational studies.
The number of participants in each sample ranged from 11 to 62, with 139 participants in total.
What does the study show about HCQ treatment for COVID-19?
The meta-analysis showed no significant difference between patients who were treated with HCQ plus standard care and those who received standard treatment without the drug. The relative risk for adverse outcomes was 1.44, but the difference was not significant.
In the clinical trials, an improvement in CT scanning was observed in about 60% vs. 52% of the treated and control groups, respectively. In comparison, the rt-PCR test of nasopharyngeal swabs showed negative results in 76% vs. 57% of treated and control groups, respectively.
With respect to the observational studies, the hospital discharge rate was 75%, while 3% required intensive care, and 1% died. Nasopharyngeal swab cultures were rt-PCR negative in over 60% of cases, with an improvement in CT scan findings being seen in almost the same proportion of cases.
Why was HCQ considered a promising therapeutic candidate for COVID-19?
A study of the pathogenetic mechanisms of the SARS-CoV-2 viral illness suggests that much of the mortality in this disease is due to the occurrence of cytokine storms, that is, the excessive and prolonged release of inflammatory cytochemicals from cells in the lungs that are infected by the virus. The known anti-inflammatory activity of HCQ promised to help mitigate this condition.
The drug has long been used in autoimmune disorders, and laboratory studies of the effects of the drug have suggested an inhibitory effect of the drug on viral infection in vitro. Other researchers have recommended that the drug be used to prevent infection before and after exposure to the virus, for healthcare personnel working in situations where they are exposed to the infectious agent.
However, other scientists have protested, quoting the harmful effects or at best ineffectiveness of the drug. They cite the similar use of chloroquine as an empirical treatment of Chikungunya, which resulted in harm to the patients. Others have concluded that the combination of azithromycin with HCQ has neither sufficient antiviral activity or clinical benefit, and should not be recommended.
Meanwhile, another group shows that HCQ could trigger the need for mechanical ventilation rather than offering clinical benefit. Moreover, the rush to buy HCQ after one paper was published in March 2020 has led to a shortage of the drug for patients who actually need it, such as those with systemic lupus erythematosus and rheumatoid arthritis. In these conditions, HCQ has been shown to be a disease-modifying drug, preventing the progression of the disease.
As a result, say the authors of the last-mentioned paper, medical professionals need to be careful before recommending a drug, especially in the absence of adequate evidence, and when the drug is already in widespread use for other conditions.
There is no evidence of any significant effect on mortality or the need for mechanical ventilation following the use of HCQ in patients with COVID-19. The small sample size precludes a final conclusion. The study, therefore, calls for comprehensive randomized controlled trials to analyze the safety profile and efficacy of HCQ in this condition. More than 100 trials of the value of this drug for COVID-19 are ongoing, and their results will be crucial to arrive at an informed decision regarding its use.
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
Shamshirian, A., Hessami, A., Heydari, K., et al. (2020). Hydroxychloroquine Versus COVID-19: A Rapid Systematic Review and Meta-Analysis. medRxiv. doi: https://www.medrxiv.org/content/10.1101/2020.04.14.20065276v1