According to a new study published in American Journal of Epidemiology, early outpatient treatment is the most effective for treatment of coronavirus patients. The study, which was led by Dr. Harvey A Risch of Yale University, suggests that late stage studies missed the point about effective usage of hydroxychloroquine. Dr. Risch says immediate and early ramping-up of treatment for high-risk COVID-19 patients is key to controlling the coronavirus pandemic crisis.
To date, more than 1.6 million Americans have been infected with SARS-CoV-2 and >10 times that number carry antibodies to it. High-risk patients presenting with progressing symptomatic disease have only hospitalization treatment with its high mortality.
According to the abstract of the study, which has not yet been peer-reviewed, Dr. Risch said an outpatient treatment that prevents hospitalization is desperately needed. To date, two candidate medications have been widely discussed: remdesivir, and hydroxychloroquine+azithromycin. “Remdesivir has shown mild effectiveness in hospitalized inpatients, but no trials have been registered in outpatients. Hydroxychloroquine+azithromycin has been widely misrepresented in both clinical reports and public media, and outpatient trials results are not expected until September,” Dr. Harvey A Risch of Yale University, said.
In a 29-page report, the study suggests that early outpatient illness is very different than later hospitalized florid disease and the treatments differ. Evidence about use of hydroxychloroquine alone, or of hydroxychloroquine+azithromycin in inpatients, is irrelevant concerning efficacy of the pair in early high-risk outpatient disease.
Five studies, including two controlled clinical trials, have demonstrated significant major outpatient treatment efficacy. Hydroxychloroquine+azithromycin has been used as standard-of-care in more than 300,000 older adults with multicomorbidities, with estimated proportion diagnosed with cardiac arrhythmias attributable to the medications 47/100,000 users, of which estimated mortality is <20%, 9/100,000 users, compared to the 10,000
The great majority of infected people are at low risk for progression or will manifest the infection asymptomatically. For the rest, outpatient treatment is required that prevents disease progression and hospitalization. Exposures will occur as isolation policies are lifted and people begin to mix, even with various degrees of public isolation such as mask usage and physical separation still in place. Thus, the key to returning society toward normal functioning and to preventing huge loss of life, especially among older individuals, people with comorbidities, African Americans and Hispanics and Latinos, is a safe, effective and proactive outpatient treatment that prevents ORIGINAL hospitalization in the first place.
In reviewing the current evidence, Dr. Risch said this:
Based on laboratory and other preliminary evidence to-date, among many others, two candidate medication regimens have been widely discussed for outpatient treatment: remdesivir (Gilead Sciences, Inc., Foster City, California), and hydroxychloroquine (HCQ) plus azithromycin (AZ). Remdesivir has been studied extensively in laboratory work and in animals (8) and for other viral diseases and has good biological properties, suggesting utility for SARSCoV-2 infection. In a study of remdesivir compassionate use in 53 hospitalized patients with severe disease (9), 13% died, which appears lower than what might have been expected without treatment, though greater than the deaths in the placebo arm of the Adaptive COVID-19 Treatment Trial (more below).
Dr. Risch went on to talk about hydroxychloroquine and said this:
The other suggestion is the combined regimen of HCQ+AZ (or its variant HCQ+doxycycline). The FDA has recently issued guidance (15) to physicians and the general public advising that the combination HCQ+AZ should not generally be used except by critically ill hospital inpatients or in the context of registered clinical trials. The NIH panel for Covid-19 treatment guidelines say essentially the same (16), and a similar statement has been released by the major cardiology societies (17). Numerous reviews of HCQ efficacy and adverse events have been and continue to be published. To my knowledge, all of these reviews have omitted the two critical aspects of reasoning about these drugs: use of HCQ combined with AZ or with doxycycline, and use in the outpatient setting. For example, the Veterans’ Administration Medical Centers study (18) examined treated hospitalized patients and was fatally flawed (19). The same point about outpatient use of the combined medications has been raised by a panel of distinguished French physicians (20) in petitioning their national government to allow outpatient use of HCQ+AZ. It appears that the FDA, NIH and cardiology society positions have been based upon theoretical calculations about potential adverse events and from measured physiologic changes rather than from current real-world mortality experience with these medications and that their positions should be revised.
In reviewing all available evidence about hydroxychloroquine, Dr. Risch said this:
In reviewing all available evidence, I will show that HCQ+AZ and HCQ+doxycycline are generally safe for short-term use in the early treatment of most symptomatic high-risk outpatients, where not contraindicated, and that they are effective in preventing hospitalization for the overwhelming majority of such patients. If these combined medications become standard-of-care, they are likely to save an enormous number of lives that would otherwise be lost to this endemic disease.
Dr. Risch concluded with the following:
I conclude that HCQ+AZ and HCQ+doxycycline, preferably with zinc (47) can be this outpatient treatment, at least until we find or add something better, whether that could be remdesivir or something else. It is our obligation not to stand by, just “carefully watching,” as the old and infirm and inner city of us are killed by this disease and our economy is destroyed by it and we have nothing to offer except high-mortality hospital treatment. We have a solution, imperfect, to attempt to deal with the disease. We have to let physicians employing good clinical judgement use it and informed patients choose it. There is a small chance that it may not work. But the urgency demands that we at least start to take that risk and evaluate what happens, and if our situation does not improve we can stop it, but we will know that we did everything that we could instead of sitting by and letting hundreds of thousands die because we did not have the courage to act according to our rational calculations.
“Americans now dying each week. These medications need to be widely available and promoted immediately for physicians to prescribe,” the study concludes.
The full report can be found at Oxford University Press website