A phase-2 trial found that COVID-19 patients with mild to moderate illness had no detectable virus seven days after treatment with a three-drug regimen — oral lopinavir-ritonavir, ribavirin and injectable interferon beta-1b. The control group took 12 days to clear the virus.
A phase-2 trial involving participants with mild to moderate COVID-19 illness found no detectable virus within an average seven days of starting treatment with a three-drug regimen compared with 12 days in people in the control group. Samples tested for the virus comprised nasopharyngeal swab, posterior oropharyngeal saliva, throat swab, and stool samples.
Clinical improvement was also significantly better in those who received the three-drug regimen. Complete alleviation of symptoms was achieved in four days in the intervention group and eight days in the control group. The average hospital stay was also significantly shorter (nine days) in participants who received the three-drug therapy than in the control group (14.5 days). The three-drug regimen was found to be safe.
Analysis of secondary outcomes revealed that 52 participants in the intervention group who started treatment less than seven days after onset of symptoms showed better clinical and virological outcomes than in the control group consisting of 24 participants.
The trial was carried out in six public hospitals in Hong Kong between February 10 and March 20. The team of researchers was led by Prof. Kwok-Yung Yuen from the University of Hong Kong, and the results were published in The Lancet. The safety and efficacy of the three-drug regimen have to be tested in a phase-3 trial involving more people.
The 127 participants were randomly assigned to either the intervention group or a control group. The intervention group had 86 participants and the control group had 41. Participants in the intervention group received oral lopinavir-ritonavir, ribavirin and injectable interferon beta-1b, while the control group received only lopinavir–ritonavir. Treatment in both groups started within seven days of symptoms showing up.
Lopinavir-ritonavir is used for treating HIV, ribavirin for treating chronic hepatitis C virus, and injectable interferon beta-1b is used by multiple sclerosis patients. The researchers had earlier demonstrated that a combination of lopinavir–ritonavir and ribavirin significantly reduced mortality and respiratory failure in patients during the 2003 SARS outbreak. And interferon beta-1b has previously been shown to reduce viral load and improve lung problems in animal studies of Middle East respiratory syndrome (MERS) coronavirus infection.
Early treatment with the three drugs that are modestly active was found to be appropriate for the treatment of COVID-19 because the viral load peaks at around the time of symptom onset.
Since all COVID-19 patients in Hong Kong should necessarily stay in hospital until they have negative test results on two consecutive days. Hence, most patients were admitted to hospital within seven days of symptom onset.
“It is important to note that the studied population had mild or moderate disease at the time of enrolment. Whether similar results are reproducible in populations with severe COVID-19 is unknown and should be explored in future studies,” Dr Sarah Shalhoub from Western University in Canada writes in an accompanying Comment piece.