antiviral drug combination for COVID-19

Hong Kong researchers investigated a triple antiviral drug combination for COVID-19 treatment in patients with mild to moderate illness.

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has affected more than 230 countries, with over three million cases and 200,000 deaths confirmed, according to WHO estimates at the beginning of May 2020. The majority of the human population remains vulnerable to this novel virus, which has a significant mortality rate, particularly in the elderly or those with other underlying medical conditions. Apart from the huge impact on healthcare systems around the world, the economic consequences of the pandemic are enormous.

In addition to vaccine development programs, researchers are working hard to find effective antiviral treatments for COVID-19 patients. It may take years to produce new drugs specifically targeting the SARS-CoV-2 virus. Existing antiviral drugs for other viral infections are being repurposed to treat COVID-19 patients. This provides a more rapid route to discovering antiviral drugs, either alone or in combination, that are effective and safe for COVID-19 treatment. Researchers in Hong Kong compared a triple antiviral drug combination for COVID-19 with a single antiviral therapy in treating patients with mild to moderate COVID-19 illness. They recently reported their findings in The Lancet.

Repurposing currently available antivirals may provide effective COVID-19 treatment

Experience with influenza suggests that treating hospitalized patients with a combination of antiviral drugs is more effective than single therapy and reduces drug resistance.  Influenza has a high viral load (amount of virus in the body) around the time that symptoms appear, and a similar pattern is seen with COVID-19 infection.  Because of this, the researchers considered that the treatment approach of combining several antiviral drugs might also be effective in COVID-19 patients.

In an open, prospective, randomized, controlled study, the researchers recruited 127 COVID-19 patients from six public hospitals in Hong Kong. In addition to standard care for COVID-19, patients were randomly assigned (at a 2 to 1 ratio) to receive either a 14 day course of triple combination antiviral therapy of interferon beta-1b, lopinavir-ritonavir and ribavir (86 patients), or lopinavir-ritonavir alone (41 patients). Patients were followed-up to measure time to test negative for the SARS-CoV-2 virus. COVID-19 symptoms, length of hospital stay and adverse effects were also closely monitored.

The triple antiviral drug combination therapy group had a shorter duration of viral shedding compared with single antiviral therapy (average 7 days vs 12 days). COVID-19 symptoms and length of hospital stay were also reduced in the triple therapy group compared to the single therapy group. There was no difference in adverse effects between the two groups.

Triple antiviral drug combination for COVID-19 appears effective and safe

The researchers concluded that early treatment of COVID-19 patients with mild to moderate illness with this triple combination of antiviral drugs rapidly suppressed the amount of virus in patient’s body and relieved symptoms, and was superior to single antiviral therapy. The treatment combination was safe and well-tolerated. The triple antiviral therapy may also reduce healthcare workers’ risk of infection by reducing the duration and quantity of viral shedding from patients. However, the team caution that further studies are needed to confirm the initial promising findings.

Further analysis of the study findings suggested that the antiviral drug interferon beta-1b may be a key component of the combination treatment. “Interferons are naturally occurring proteins, produced in response to viral infection and the hope is that interferon beta-1b will boost the body’s ability to fight SARS-Cov-2,” commented study author Dr. Jenny Lo (Ruttonjee Hospital, Hong Kong).

Professor Kwok-Yung Yuen (University of Hong Kong) who led the research added, “Despite these encouraging findings, we must confirm in larger trials that interferon beta-1b alone or in combination with other drugs is effective in patients with more severe illness in whom the virus has had more time to replicate.”

Written by Julie McShane, MA MB BS

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1. Hung IFN, Lung KC, Tso EYK, et al. Triple combination of interferon beta-1b, lopinavir-ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial. Published online. Lancet May 8, 2020 doi:10.1016/S0140-6736(20)31042-4.

2. The Lancet. Press release, 8 May 2020. “The Lancet: New triple antiviral drug combination shows early promise for treating COVID-19 in phase 2 randomized trial.”  

Image by Masum Ali from Pixabay 

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