Hello, I'm Monaz Mehta, editor in the Cochrane Editorial and Methods department. Cochrane is producing a series of reviews to help decision makers respond to the COVID-19 pandemic. In September 2021, we published the first version of a Living Systematic Review on the effects of monoclonal antibodies for treating COVID-19 and in this podcast we speak to Nina Kreuzberger one of the lead authors, about the review, which was initiated in the Germany-wide joint projects "COVIM" and "CEOsys" and funded by the Federal Ministry of Education and Research of Germany.

Caroline: Many monoclonal antibodies are being investigated as potential therapies for COVID‐19 so perhaps you could begin by telling us what antibodies are and what they do?

Nina: Antibodies are made by the body to provide defence against infection. Following an infection, a range of antibodies are created that recognise different proteins on the microorganism or virus that caused the infection. To try to mimic this, monoclonal antibodies are produced in the laboratory from cells taken from people who have recovered from a disease. Each type of monoclonal antibody recognises a specific protein, or part of a protein, on a virus such as SARS-Cov-2, the cause of COVID-19; and they have been found to be effective for other illnesses.
For COVID-19, the hope is that SARS-CoV-2-neutralising monoclonal antibodies will treat the disease through what's called passive immunization. They would target the part of the spike protein that the virus would use to bind to a human cell and enter it, thereby preventing or suppressing the progress of the disease.

Caroline: Your living Cochrane review is investigating whether these monoclonal antibodies are effective and safe for a range of patient outcomes, including survival, clinical progression, quality of life and adverse events; using studies from anywhere in the world; in patients of any age, gender or ethnicity; and with any severity of COVID-19 disease. What did you find?

Nina: Based on our searches up to mid-June 2021, we found six eligible studies including a total of nearly seventeen and a half thousand people. Four studies investigated non-hospitalised people with no symptoms or mild COVID-19, and the other two studies were in hospitalised people with moderate to severe COVID-19. We also identified 36 ongoing studies, which we are regularly tracking.

Caroline: Let's start with the evidence on non-hospitalised people. What does that tell us?

Nina: In these people without symptoms or with only mild COVID-19, each of the four studies tested a different type of monoclonal antibody therapy, which means that we have low certainty in our findings for each of these therapies. We provide details for each drug and for the combinations that were tested in the review and, in general, the treatments seem to reduce hospital admissions but the effects on death are very uncertain, because so few patients in these trials died within 30 days of treatment. There were also mixed results for adverse events, with some monoclonal antibodies appearing to reduce these, while others increased them.

Caroline: Moving on to hospitalised people, what can the two studies you included tell us about the effectiveness and safety of the treatment with monoclonal antibodies?

Nina: Bamlanivimab was tested, but then dropped from, one of the so-called, platform trials for COVID-19. It may possibly increase adverse events and severe symptoms compared with placebo and have little to no effect on mortality. The other study was within the large platform trial called RECOVERY and tested the combination of casirivimab and imdevimab, which was found to probably have little to no effect on mortality or need for invasive mechanical ventilation when compared with usual care alone. However, the findings of both studies suggest that it might be worth taking a separate look at the effects in the subgroup of people who had, and had not, already made their own antibodies for SARS-CoV-2. 

Caroline: Given the generally low certainty in the findings, what is needed now?

Nina: We need further studies and mature data to confirm or refute the current findings. Some of this may come from the 36 ongoing trials that we identified. Publication of these studies might resolve some uncertainties and allow a clearer judgment on the effectiveness and safety of SARS-CoV-2-neutralising monoclonal antibodies for the treatment of COVID-19. But the main message is that we urgently need the findings from high-quality randomised trials with comparable study arms that are large enough to detect the effects on important clinical outcomes, and which we can then combine in future versions of our review.

Caroline: Thanks very much Nina. If our listeners would like to look at the finer detail in the review and watch for those future updates, how can they get hold of it?

Nina: The full review is available free online at Cochrane Library dot com. A simple search for 'monoclonal antibodies and COVID-19' will find it.