Wednesday, April 22, 2020

Coronavirus Update 7

Various sources, e.g., CNN and the Washington Post, are reporting about a small pilot study to test the efficacy of hydroxychloroquine to treat the coronavirus infection. Hydroxychloroquine is approved for use to treat malaria, a parasite infection. The reported data is not from a randomized clinical trial. It is also not yet peer-reviewed. This data is only anecdotal, not the kind of evidence that constitutes solid evidence of safety or efficacy.

Two critically important thoughts to keep in mind are these:

1. Randomized, double- or triple-blinded, placebo controlled clinical trials are needed to assess safety and efficacy.

2. That an approved drug is safe enough for treating a specific disease does not mean that it is safe to treat a different disease. I will explain this in the context of hydroxychloroquine and coronavirus.


The data
The study included 368 male VA patients with coronavirus infections. That is considered to be a small study by experts, not a large study as Fox News is falsely reporting. This study is larger than past studies reported so far, but that doesn't make it a large study. Ninety-seven patients received hydroxychloroquine, 113 received hydroxychloroquine in combination with the antibiotic azithromycin, and 158 did not not receive hydroxychloroquine.


As reported by the WaPo, rates of death in both drug-treated groups were worse than the 158 who did not receive the drugs. The drugs produced no benefit for patients who were on ventilators in either drug-treated group.

The observed death rates were as follows:
No drug treatment: 11.4%
Hydroxychloroquine and azithromycin treated: 22%
Hydroxychloroquine treated: 27%


Failed pandemic politics
The president has politicized an weaponized the pandemic to serve his personal political re-election agenda. CNN's broadcast last night played about six short clips of the president repeatedly urging people to use hydroxychloroquine because he claims that ‘he heard good things about the drug’, or that ‘he heard very good things about the drug’. His ‘scientific rationale’ is based on posing questions such as, ‘what do you have to lose?’ and ‘why not try it because you have nothing to lose?’.

Unfortunately, it may turn out to be the case that people have their lives to lose.

Presumably, some people took the president’s idiotic advice and doing so could have killed some of them. If that turns out to be true, the president should be impeached and jailed for medical malpractice, gross incompetence and inexcusable arrogant stupidity. Dr. Trump’s unsound medical advice would have literally killed some people.


How hydroxychloroquine might be lethal in coronavirus infections 
The following is personal speculation about why it might turn out to be the case that hydroxychloroquine is lethally toxic for some coronavirus-infected patients. One study reported that when hydroxychloroquine is used to treat rheumatoid arthritis and systemic lupus erythematosus, it appears that it works by inducing a form of immune suppression, i.e., “down-regulation of the immune response against autoantigenic peptides.” Other research indicates that hydroxyquinoline modulates biological pathways that regulate immune responses by other mechanisms including  blocking inflammatory responses, e.g., “there is some evidence that antimalarials decrease secretion of monocyte‐derived pro‐inflammatory cytokines, such as tumour necrosis factor alpha (TNFα).”

Based on that, I speculate that it is possible that hydroxychloroquine-induce causes an immune suppression that (1) unleashes the virulence or replication capacity of coronavirus in lungs to a point that it becomes lethal, and/or (2) allows bacteria in the lungs to replicate and cause a lethal bacterial pneumonia. Anecdotal evidence for that is in the different death rates of the two drug-treated groups. People who also received the antibiotic azithromycin may have had a lower death rate than the group treated with hydroxychloroquine alone. If that turns out to be true, then the azithromycin may have prevented a lethal pneumonia in some of the patients, leading to a lower death rate. Azithromycin is used to treat various bacteria, including ones that that can cause pneumonia.

Again, all of this is personal speculation. I'm not an expert and thus my speculation may turn out to be completely wrong, e.g., because we still do not know much about coronavirus pathology at the molecular level. 

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