An antibody combination reduces the number of deaths among patients hospitalised with severe COVID-19 when they are are unable to mount their own immune response, British researchers have announced.
Scientists involved in the RECOVERY (Randomised Evaluation of COVID-19 Therapy) trial have described the results, which could benefit one in three patients, as “very exciting”.
The treatment combines two monoclonal antibodies, casirivimab and imdevimab, that bind specifically to two different sites on the coronavirus spike protein and neutralise the virus’s ability to infect cells.
Previous studies in COVID-19 patients who were not hospitalised showed the treatment reduces viral load, shortens the time to resolution of symptoms, and significantly reduces the risk of hospitalisation or death.
Preliminary evidence in a small trial in hospitalised patients also suggested a clinical benefit in patients who had not mounted a natural antibody response of their own.
However, RECOVERY is the first trial that is big enough to establish definitively if the antibody combination reduces mortality in patients hospitalised with severe COVID-19.
The preliminary results are available as a pre-print on medRxiv and will be submitted to a peer-reviewed medical journal.
The study recruited 9785 hospitalised COVID-19 patients between 18 September 2020, and 22 May 2021, and they were randomly allocated to receive either usual care plus the antibody combination treatment of casirivimab 4g with imdevimab 4g by intravenous infusion, or usual care alone as part of the RECOVERY trial.
Of these, about one-third were seronegative at baseline, one-half were seropositive, and one-sixth had unknown serostatus.
The trial found that in the cohort of patients who received usual care alone, 28-day mortality was twice as high in those who were seronegative, at 30% compared with 15%.
However, the antibody combination significantly reduced 28-day mortality among patients who were seronegative at baseline by one-fifth compared with usual care alone, with 24% of patients in the antibody combination group dying compared with 30% of patients in the usual care group, a rate ratio 0·80; 95% confidence interval 0·70–0·91; p=0·001. This means for every 100 such patients treated with the antibody combination, there would be six fewer deaths.
The study found evidence that the effect of treatment in seronegative patients differed from that in seropositive patients (test for heterogeneity p=0·001).
When combining the larger seropositive group and those with unknown status with the seronegative patients, there was not a significant effect on 28-day mortality. Overall, 20% of patients in the antibody combination group died compared with 21% of patients in the usual care group, a rate ratio 0·96; 95% confidence interval 0·86–1·03; p=0·17.
Seronegative patients were in hospital for a shorter time, at a median of 13 days compared with 17, if they had received the antibody combination. The proportion of patients discharged alive by day 28 was also greater at 64% compared with 58%, a rate ratio 1·19, 95% confidence interval 1·08 to 1·30.
The researchers also found that seronegative patients not on invasive mechanical ventilation at baseline had a lower risk of progressing to invasive mechanical ventilation or death if they received the antibody combination compared to the usual care group, at 30% compared with 37%, a risk ratio 0·83, 95% confidence interval 0·75 to 0·92.
RECOVERY trial joint chief investigator Sir Peter Horby, Professor of emerging infectious diseases in the Nuffield Department of Medicine, University of Oxford, said: “These results are very exciting. The hope was that by giving a combination of antibodies targeting the SARS-CoV-2 virus we would be able to reduce the worst manifestations of COVID-19.
“There was, however, great uncertainty about the value of antiviral therapies in late-stage COVID-19 disease. It is wonderful to learn that even in advanced COVID-19 disease, targeting the virus can reduce mortality in patients who have failed to mount an antibody response of their own.”
Joint chief investigator Sir Martin Landray, professor of medicine and epidemiology at the Nuffield Department of Population Health, University of Oxford, added: “We now know that this antibody combination is not only bad for the virus but it is also good for the sickest patients who have failed to mount a natural immune response of their own. That is excellent news – it is the first time that any antiviral treatment has been shown to save lives in hospitalised COVID-19 patients.”
• Corticosteroids seem to be an effective treatment for children who develop multi-system inflammatory syndrome following COVID-19 infection, researchers at Imperial College, London, reported last night.
The findings, reported in the New England Journal of Medicine, come from analysis of more than 600 case reports indicating the success of treatments with corticosteroids or immunoglobin or both combined.
There were just 2% of deaths, making it impossible to identify a treatment that prevented death.
The researchers said 80% of the children met World Health Organisation criteria for diagnosis of the condition – and amongst these there was evidence of lower rates of death or organ failure from corticosteroid treatment.
Researcher Dr Elizabeth Whittaker said: “The finding that outcome is similar for patients treated with steroids alone as with those treated with steroids and immunoglobulin or immunoglobulin alone, suggests that steroids may be a cheaper and more available alternative to immunoglobulin.
“Corticosteroids are cheap and available worldwide whereas immunoglobulin is expensive, and there is a worldwide shortage of it. This is a particular problem in many low and middle income countries.“
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