Much of the print news and online commentary to date seems to fundamentally miss the point regarding why the drug combination of hydroxychloroquine and azithromycin might be very effective for treating and/or preventing severe cases of COVID-19 infection.
Even worse, many well-known media seem to be suffering from a derangement syndrome and have been promoting stories that clearly misrepresent the potential utility of hydroxychloroquine and azithromycin.
The important question that’s not being asked and answered is why would an antiparasitic (hydroxychloroquine) and an antibiotic (azithromycin) alone or in combination have antiviral activity against this specific coronavirus? It would be extremely unlikely that two old antimicrobial drugs with historically different (typically non-antiviral activities) would, by serendipity, have a direct antiviral effect (i.e., have direct antiviral biological activity) against the COVID-19 virus.
Furthermore, why are most COVID-19 cases simply like a “common cold” but in other patients (not just old people) there’s a rapid unexplained progression that often leads to death?
One explanation is that the coronavirus potentially activates a preexisting mycobacteria in a coinfection scenario (see my article on Medium for a more technical discussion).
In other words, hydroxychloroquine and azithromycin work together to treat or prevent severe presentations of COVID-19 cases (when administered early enough) because they are treating (suppressing) a preexisting mycobacterial infection that has been activated by the COVID-19 infection.
The azithromycin is working as an antibiotic to treat a bacterial infection (i.e., the activated mycobacterial infection) that is attacking the lungs as well as other organs in the body. The combination with hydroxychloroquine is important because it enhances the antibiotic activity of azithromycin (by increasing the pH of the cellular micro-environment).
Some have asked, “Why are antibiotics and not anti-virals quelling the COVID-19 coronavirus” and have independently surmised that it’s potentially because of a preexisting mycobacterial infection (see the March 2 Bill Sardi article on LewRockwell.com based on an interview with Lawrence Broxmeyer, M.D.).
The recent National Institutes of Health (NIH) announcement of April 21 regarding the guidance for use of hydroxychloroquine and azithromycin in patients with COVID-19 infection seems ambiguous and is misplaced (I think).
On the one hand the guidance states that “[t]here are insufficient data to recommend either for or against the use of any antiviral or immunomodulatory therapy in patients with COVID-19 who have mild, moderate, severe, or critical illness (AIII).” [emphasis added]
And in particular, NIH states that “[t]here are insufficient clinical data to recommend either for or against using chloroquine or hydroxychloroquine for the treatment of COVID-19 (AIII) … [and] [w]hen chloroquine or hydroxychloroquine is used, clinicians should monitor the patient for adverse effects (AEs), especially prolonged QTc interval (AIII).”
But also in the same guidance it states: “The COVID-19 Treatment Guidelines Panel (the Panel) recommends against the use of hydroxychloroquine plus azithromycin for the treatment of COVID-19, except in the context of a clinical trial (AIII) … [because] [c]hloroquine and hydroxychloroquine for COVID-19 have been used in small randomized trials and in some case series with conflicting study reports … [and] [t]he combination of hydroxychloroquine and azithromycin was associated with QTc prolongation in patients with COVID-19.” [emphasis added]
The apparent ambiguity in the NIH guidance appears because it states that there’s not enough information to make a recommendation “for or against” the use of any antiviral or immunomodulatory therapy—which necessarily includes the drug combination—but then recommends “against” use of the drug combination outside of a (formal) clinical trial.
The guidance “against” use of the drug combination is misplaced, because it’s well accepted that drugs and therapies are used “off-label” routinely by competent medical practitioners to the benefit of patients without the requirement of instituting and running a formal clinical trial.
It’s not clear to me that the available evidence regarding the use of hydroxychloroquine in combination with azithromycin supports a “risk/benefit” assessment that warrants a blanket recommendation against off-label use.
The NIH guidance is also misplaced, in view of the fact that treating physicians know that if certain “at risk” patients (particularly older patients) progress to intubation/ventilation it will be in most cases essentially a death sentence. Bloomberg, for example, reporting on a study of New York patients, wrote, “The [mortality] rate was particularly awful for patients over 65 who were placed on a machine, with just 3% of those patients surviving, according to the results.”
At risk patients on a case-by-case basis should be allowed and encouraged (with their treating physician) to assess and to choose between the potential risk of QTc prolongation from off-label use of the hydroxychloroquine in combination with azithromycin and the alternative risk of almost certain terminal outcomes if there is progression to intubation/ventilation therapy.
Understanding that the coronavirus pandemic morbidity may be attributable at least in part to a preexisting mycobacterial infection may be critical to identifying and deploying in the short-term cost-effective off-the-shelf counter measures (e.g., the combination of hydroxychloroquine and azithromycin) that will immediately save lives and potentially arrest the panic associated with extreme manifestations of the COVID-19 pandemic.
John D. Peabody III has a Ph.D. in organic chemistry and holds a law degree from George Mason University. He is the founder and president of PersisPharma LLC.