Investigators Rush to Find Treatments for Novel Coronavirus

As the COVID-19 pandemic upends daily life and economies across the globe, investigators are hurrying to test and develop potential treatments for the coronavirus.

The ideal treatment for rapid distribution would be one that is already approved and widely available, so some research teams are looking at low-cost generic drugs in hopes that they could help treat the illness. According to Reuters, a trial began this week at the University of Minnesota to test hydroxychloroquine, a malaria treatment, in 1500 participants.¹ It is also being tested in China, Australia, and France.

Although malaria is caused by a parasite, hydroxychloroquine has demonstrated efficacy in preventing the spread of viral illnesses, including severe acute respiratory syndrome, which is caused by a different type of coronavirus than the new one causing COVID-19.²

Other investigative teams are looking to new and existing antivirals, alone or in combination, as potential therapy options. A report in the New England Journal of Medicine (NEJM) describes the treatment course and outcome of the first COVID-19 case in the United States, a 35-year-old man in Washington.³ On the evening of his seventh day of hospitalization, clinicians began treatment with intravenous remdesivir, a novel antiviral being developed by Gilead Sciences. His clinical condition began to improve the next day, and as of January 30 he was still hospitalized but his symptoms had resolved except for his cough, which was improving.

The scientific community now awaits results from a phase 3 trial of remdesivir that is underway in China. However, because it is an experimental drug, it would take months for enough supply to become available for treating large numbers of patients.

While some drugs are showing promise, others are being ruled out as answers to the COVID-19 crisis, including lopinavir and ritonavir, 2 antiviral drugs used to treat HIV. Results of a randomized trial of lopinavir-ritonavir treatment in 199 hospitalized patients with coronavirus infections showed that the treatment was not associated with differences in mortality, time to clinical improvement, and percentage of patients with detectable viral RNA compared with usual care.⁴ The investigators, writing in NEJM, noted better outcomes among those treated within 12 days of symptom onset, raising the question of whether earlier treatment with lopinavir-ritonavir could have clinical benefits.

An accompanying editorial in NEJM applauded the “heroic effort” of the trial investigators despite the disappointing results.⁵ The work of the investigators proves the feasibility of quickly and carefully conducting high-quality clinical trials among the unprecedented stress of pandemic conditions.

“The results of such trials, providing either convincing positive or convincing negative findings, will be central to clinical care as the dangerous coronavirus outbreak continues,” the editorial concluded.

References

1. Beasley D. Two generic drugs being tested in U.S. in race to find coronavirus treatments. Reuters website. reuters.com/article/us-health-coronavirus-usa-treatments/two-generic-drugs-being-tested-in-u-s-in-race-to-find-coronavirus-treatments-idUSKBN2161QQ. Published March 19, 2020. Accessed March 19, 2020.

2. Vincent MJ, Bergeron E, Benjannet S, et al. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virology J. 2005;2:69. doi: 10.1186/1743-422X-2-69.

3. Holshue ML, DeBolt C; Lindquist S, et al; Washington State 2019-nCoV Case Investigation Team. First case of 2019 novel coronavirus in the United States. N Engl J Med. 2020;382(10):929-936. doi: 10.1056/NEJMoa2001191.

4. Cao B, Wang Y, Wen D, et al. A trial of lopinavir-ritonavir in adults hospitalized with severe COVID-19 [published online March 18, 2020]. N Engl J Med. doi: 10.1056/NEJMoa2001282.

5. Baden LR, Rubin EJ. Covid-19—the search for effective therapy [published online March 18, 2020]. N Engl J Med. doi: 10.1056/NEJMe2005477.