We have been caught in a drug war. This has nothing to do with cartels, turf battles or addictive chemicals. This is a war of words about hydroxychloroquine (HCQ), a really old malaria drug being repurposed to treat the coronavirus. When we first started writing about treatments for COVID-19 in March, we were intrigued by preliminary in vitro (test-tube) data. It appeared to us that hydroxychloroquine works by interfering with viral replication. That was the first hint that this medication might be helpful against SARS-CoV-2, the virus that causes COVID-19.
Since our initial notification about the potential benefits of HCQ in vitro, there have been numerous human studies. Some showed hydroxychloroquine works to reduce mortality while others demonstrated no improvement. Most have been observational rather randomized controlled trials (RCTs).
Everyone agrees that randomized, double-blind, placebo-controlled studies are the gold standard for determining a drug’s true effectiveness. Because so many people recover from COVID-19 on their own, it becomes hard to prove that a treatment is better than nothing unless there are large RCTs. But there is also value in well-conducted observational trials.
Italian Researchers Say that Hydroxychloroquine Works:
A new observational study from Italy suggests that hydroxychloroquine can reduce the risk of death in hospitalized patients with COVID-19. The research was published in the European Journal of Internal Medicine (Aug. 25, 2020).
The investigators reviewed the records of 3,451 coronavirus patients in 33 Italian hospitals between late February and late May, 2020. They all had laboratory-confirmed SARS-CoV-2 infection. Three fourths of these patients were given hydroxychloroquine while they were hospitalized. Most received the drug within one day after admittance. The rest got HCQ within three days. As far as we can tell, neither zinc or azithromycin were part of the standard drug regimens.
The death rate per 1,000 patient days was 8.9 for people on hydroxychloroquine and 15.7 for those who did not get the drug. After adjustment for confounding variables, people who received HCQ had a 30% lower risk of death. Those who had high levels of the inflammatory marker, C-reactive protein, when they entered the hospital were especially likely to benefit from this old malaria drug.
The Italian authors report that hydroxychloroquine works:
“Our findings provide clinical evidence in support of guidelines by Italian and several international Societies suggesting to use HCQ therapy in patients with COVID-19. However, the observed associations should be considered with caution, as the observational design of our study does not allow to fully excluding the possibility of residual confounders. Large randomized clinical trials in well-defined geographical and socio-economic conditions and in well-characterized COVID-19 patients, should evaluate the role of HCQ before any firm conclusion can be reached regarding a potential benefit of this drug in patients with COVID-19.”
The lead author, Augusto Di Castelnuevo, is a respected epidemiologist.
He clarified the findings of this study (Istituto Neurologico Mediterraneo Neuromed I.R.C.C.S. in Medical Press, Aug. 25, 2020):
“Our data were subjected to extremely rigorous statistical analysis, taking into account all the variables and possible confounding factors that could come into play. The drug efficacy was evaluated in various subgroups of patients. The positive results of hydroxychloroquine treatment remained unchanged, especially in those patients showing a more evident inflammatory state at the moment of admission to hospital.”
The researchers suggest that hydroxychloroquine works best at lower doses. They point out that:
“Very recently, a large RCT has become available as a pre-print publication, reporting no beneficial effect of HCQ in patients hospitalized with COVID-19. However, the dose of HCQ used in that trial was almost the double of that administered in our real life conditions. A reduced mortality was also observed by other observational studies using low or intermediate doses of HCQ.”
After a loading dose, most patients received 200 mg twice a day for five to ten days.
The Italians Conclude that Hydroxychloroquine Works:
We find these results promising.
We agree with the authors that:
“Within the limits of an observational study and awaiting results from randomized controlled trials, these data do not discourage the use of HCQ in inpatients with COVID-19.”
We will continue to report the results of clinical trials of hydroxychloroquine as they become available. Please stay tuned. In the meantime, you may wish to listen to our interview with Matt Richtel. If you have been a bit confused about reports of antibodies, T cells, and other aspects of the immune system, this podcast is a must listen! Matt Richtel has written a most amazing book: An Elegant Defense: The Extraordinary New Science of the Immune System: A Tale in Four Lives. We think you will find this podcast both compelling and informative. If you agree, we hope you will share it with friends and family.
Show 1170: What Makes Your Immune System an Elegant Defense?
You might imagine your immune system as an army fighting off invaders. What if it behaved more like a peacekeeping force to maintain harmony?