Treatment with interferon beta-1b in combination with lopinavir/ritonavir and ribavirin was found to be safe and superior to lopinavir/ritonavir alone for reducing the duration of viral shedding and hospital stay in adults with coronavirus disease 2019 (COVID-19).

The prospective, open-label phase 2 trial included 127 adults with mild to moderate COVID-19 who were admitted to Hong Kong hospitals between February 10 and March 20, 2020. Patients were randomized 2:1 to receive either lopinavir 400mg/ritonavir 100mg plus ribavirin 400mg every 12 hours and up to 3 doses of 8 million international units of interferon beta-1b on alternate days (n=86; combination group) or lopinavir 400mg/ritonavir 100mg every 12 hours (n=41; control group), both for 14 days. 

All patients received standard of care including ventilation support, dialysis support, antibiotics, and corticosteroids; study treatment was initiated, on average, 5 days after symptom onset. The primary end point of the study was time to a negative nasopharyngeal swab for SARS-CoV-2, the virus that causes COVID-19.

Findings showed that the median time from start of treatment to negative nasopharyngeal swab was 7 days for the combination group vs 12 days for the control group (hazard ratio [HR] 4.37; 95% CI, 1.86-10.24; P =.001). Additionally, the combination group met key secondary end points achieving significant clinical improvements, including shorter time to alleviation of symptoms (4 days vs 8 days; HR 3.92; 95% CI, 1.66-9.23; P <.0001), SOFA (sequential organ failure assessment) score of 0 (3 days vs 8 days; HR 1.89; 95% CI, 1.03-3.49; P =.041), and shorter average hospital stay (9 days vs 14.5 days; HR 2.72; 95% CI, 1.2-6.13; P =.016) vs the control group, respectively. 

Continue Reading

With regard to safety, both treatment arms demonstrated similar adverse events including nausea, diarrhea and fever. There were no deaths reported in the study and 1 patient in the control group discontinued lopinavir/ritonavir due to biochemical hepatitis.

Related Articles

The study had several limitations including the open-label design that also lacked a placebo group. Moreover, the researchers noted that the findings were likely confounded by a subgroup of patients in the combination group who were admitted 7 or more days after symptom onset and who were not offered interferon beta-1b. The study also did not include critically ill COVID-19 patients.

“Our trial demonstrates that early treatment of mild to moderate COVID-19 with a triple combination of antiviral drugs may rapidly suppress the amount of virus in a patient’s body, relieve symptoms, and reduce the risk to healthcare workers by reducing the duration and quantity of viral shedding,” said Professor Kwok-Yung Yuen from the University of Hong Kong who led the research. “Despite these encouraging findings, we must confirm in larger phase 3 trials that interferon beta-1b alone or in combination with other drugs is effective in patients with more severe illness.”

For more information visit