COVID-19: Clinical Pathways to Pandemic Relief

By Graeme Gardner, Ph.D.

In a pandemic scenario, it is very important to remember that fear and lack of understanding of a problem often exacerbates it. The novel SARS-CoV-2 virus, which originated in the Wuhan Province in China and has now spread to almost 200 countries worldwide, is putting governments and healthcare organizations on their heels, and has been met with a highly politicized response. Intellectual debates are ongoing surrounding the trade-off between the economic disruption of government-mandated lockdowns and their ability to slow the rate of growth of infections. Meanwhile, the observation of a case mortality rate exceeding 9% in Italy and the lack of adequate inventory of key medical equipment such as oxygen masks, ventilators, and PPE in hospitals is a source of anxiety for many. 

What is important to keep in mind, however, is that there are probably a vast number of asymptomatic carriers of the virus – which is in part responsible for such a fast spread – and therefore the true mortality rate for this disease is likely much lower than what is currently reported. In addition, following the recommended guidelines from places like the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC) in the US is critical to containing the outbreak since these are the experts who have access to raw data internationally. Finally, it cannot be emphasized enough that performing more tests will lead to a much greater understanding of the disease spread and true rates of infection and mortality. The current data coming from Germany for instance, where the government implemented an “early-and-often” approach, with high-capacity and random testing, tracking person-to-person interactions with those who have tested positive, and targeted isolation of infection hot-spots, shows a mortality rate of ~0.5% out of a total of 34,055 cases after testing up to 120,000 people per week. With this benchmark in mind, it is possible for the rest of the world to start implementing more effective strategies. Due to the FDA’s Emergency Use Authorization (EUA) of in vitro diagnostics for COVID-19, some of which include more rapid tests from Roche, Thermo Fisher, and Abbott Laboratories, testing is expanding rapidly in the USA, with over 400,000 results reported as of March 25, 2020.

Potential Treatments

Going hand-in-hand with increased testing is the development of successful treatments for infected patients. The pharmaceutical and healthcare industries, with aid from the WHO and CDC, have been responding in full force, with many having plans for vaccine development or anti-virals, but these could have lead times of up to 18 months. There are currently no FDA-approved drugs specifically for the treatment of patients with COVID-19. However, there have been some promising clinical trials based upon investigational drugs or those approved for other indications that could help with chemoprophylaxis or curative treatment of COVID-19. Many of these drugs have shown promise in in vitro studies initially and were quickly adopted for clinical testing by physicians in China and France (see below).

In early clinical findings from China, patients with COVID-19 associated pneumonia in more than 10 hospitals treated with chloroquine phosphate exhibited superior outcomes compared to those of the control patients. These included remediation of the effects of pneumonia, shortened hospital stays, and higher rates of virologic cure. Although the study size initially reported was small (e.g. “more than 100 patients”), the data was significant enough to cause the National Health Commission of the People's Republic of China to recommend treatment with chloroquine phosphate for ten days for patients diagnosed with mild, moderate, and severe cases. Motivated by the results of this Chinese study, scientists in France recently conducted an expedited clinical trial in which patients with COVID-19 were given hydroxychloroquine to evaluate the drug’s anti-SARS-CoV-2 activity, as this chloroquine analog has a better safety record and can be given at higher doses. Patients were given a dose of 600 mg per day over the course of ten days, and by day six, 70% of participants were virologically cured as compared to 12.5% observed in the control group. To prevent bacterial superinfection, some of the group were also given azithromycin in combination with hydroxychloroquine and this proved even more effective with a 100% virologic cure at day six (Fig 1). As with the Chinese studies, the sample size was small (<50 total), but the results were promising and the quick turnaround as well as detailed study information allows the international community of doctors a more thorough glance into the possible benefits of these types of treatments. 

Effect of hydroxychloroquine or hybroxychloroquine/azithromycin combination on detection of SARS-CoV-2 virus in previously infected patients.

Fig. 1. Effect of hydroxychloroquine or hybroxychloroquine/azithromycin combination on detection of SARS-CoV-2 virus in previously infected patients. Source: Figure 2 from Gautret, P. et al. (2020), Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial, International Journal of Antimicrobial Agents, 105949.

Although the above published studies regarding chloroquine phosphate and hydroxychloroquine were not from properly designed clinical trials, the percentage of patients being cured of the virus and/or the statistical significance of the findings generated much hope among our elected officials. As of March 25th, the FDA has cleared the use of hydroxychloroquine treatment for COVID-19 in New York State on a “compassionate use” basis. Further, there are currently Phase III clinical trials open to enrollment for select patients diagnosed with COVID-19 to obtain treatment with Remdesivir (Gilead Sciences Inc.) and the FDA has allowed the use of and is facilitating access to convalescent plasma, an antibody-rich transfusion blood product donated from people who recovered from the disease.

The COVID-19 pandemic has been an elusive problem from the very beginning, with the lack of coherency among the response efforts of countries driving most of the panic and propagation of misinformation. The WHO and CDC have been beacons of sound advice, as have epidemiologists and NIH officials who have the expertise necessary to make appropriate policy recommendations. As we move forward in trying to remediate the problem in the United States, we can learn a lot from the contrasting efforts of China, Germany and South Korea, and Italy and Spain. A data-driven scientific approach in the wake of an epidemic is invaluable in terms of stemming the spread, alleviating fear, and ultimately curing the disease.

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