To fight against SARS-CoV-2, Chinese researchers have announced promising results on a two-week antiviral triple therapy combined with standard care.
- A trial of antiviral triple therapy has given promising results against Covid-19
- But this trial did not include severe cases of the disease
If France begins its deconfinement, the coronavirus is still far from being defeated. Also, studies to find an effective treatment for SARS-CoV-2 continue around the world. Friday, May 8, researchers announced promising results on a two-week antiviral triple therapy (interferon beta-1b, lopinavir-ritonavir and ribavirin) combined with standard care, in their study published in the journal The Lancet. However, these results do not include severe cases of Covid-19. Also, larger phase 3 trials will be needed to ensure the efficacy of this triple combination in critically ill patients.
In 2003, during the SARS epidemic, previous research had already shown that a combination of oral lopinavir-ritonavir (originally used to treat HIV) and ribavirin (a drug to be taken by mouth against hepatitis C) effectively reduced respiratory failure and mortality in patients. Interferon beta-1b, developed to treat multiple sclerosis (MS), was later shown to be useful in reducing viral load and improving lung problems in animal studies of MERS (Respiratory Syndrome) coronavirus infection. of the Middle East) appeared in 2012.
The current study took place in Hong Kong, where anyone who tests positive for Covid-19 is admitted to hospital. The researchers followed 127 patients with an average age of 52 with mild to moderate symptoms of Covid-19 in six public hospitals. They began to treat them on average five days after the appearance of clinical signs. Participants were randomly assigned to 14 days of oral triple combination lopinavir-ritonavir and ribavirin every 12 hours. They were also given up to three doses of injectable interferon beta-1b on alternate days. The control group received lopinavir-ritonavir every 12 hours.
A combination that seems “safe and well tolerated by patients”
In parallel, both groups of patients received standard care as well as support with ventilation, dialysis, antibiotics and corticosteroids. During the study, the researchers looked at clinical progression of symptoms and changes in lab results, as well as the viral spread of patients through regular testing.
They were thus able to observe that the viral load of patients treated with triple therapy disappeared more quickly than that of the control group, treated with lopinavir-ritonavir alone. Moreover, 52 subjects who underwent a combination treatment with interferon beta-1b within seven days after the first symptoms showed better clinical and virological results than the control group treated within the same period. In contrast, for people treated seven or more days after the onset of symptoms, the researchers observed no difference between the results of the combined treatment and control groups. Finally, no difference was observed in side effects between the treatment groups.
“Our trial demonstrates that early treatment of mild to moderate Covid-19 with a triple combination of antiviral drugs can rapidly reduce the amount of virus in a patient’s body, relieve symptoms and reduce risk to caregivers by reducing the duration and amount of viral dispersal (when virus is detectable and potentially transmissible). In addition, the combination of treatments appeared to be safe and well tolerated by patients”comments Professor Kwok-Yung Yuen of the University of Hong Kong.
“We will need to confirm the results in larger phase 3 trials”
This could be explained because, like the flu, the viral load of Covid-19 peaks at the time of the onset of symptoms. What’s more, a combination of antivirals could minimize the risk of drug resistance.
However, the researchers admit some limitations to their work. Indeed, this is an open study in which scientists and patients know the treatment they are receiving. Moreover, there was no placebo group and no critically ill patients were included in the trial. So the job is far from over.
“Despite these encouraging results, we need to confirm in larger phase 3 trials that interferon beta-1b alone or in combination with other drugs is effective in patients with more severe disease (in whom the virus had more time to replicate)”concludes Kwok-Yung Yuen, whose work had already shown that, in some cases, SARS-CoV-2 can replicate up to 100 times in 48 hours, compared to 10 to 20 times with the 2003 SARS-CoV.
If they are the first to associate ribavirin, the Hong Kong researchers are not the only ones to be interested in the combination lopinavir / ritonavir and interferon beta. This treatment is notably studied within the framework of the European trial Discovery. In this study conducted on thousands of patients in ten European countries, the subjects followed are divided into five groups. In addition to the group which is administered the combination lopinavir / ritonavir and interferon beta, another receives lopinavir / ritonavir only while other subjects test the hydroxychloroquine so vaunted by Professor Didier Raoult, and remdesivir, an experimental antiviral initially developed by the American Gilead against Ebola which has just been urgently authorized in the United States by the FDA or even conventional care, without an experimental molecule. Unfortunately, we still do not know when the results of the study will be revealed, the latter having taken a long time. In particular because of the difficulty of European countries to tune their violin.
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