Key messages
- We do not know whether antibodies (the body’s natural defence against disease) made in a laboratory and all the same as one another (monoclonal) and designed to target COVID-19, are an effective treatment for COVID-19 because we assessed only six studies exploring different treatments in different types of patients.
- We identified 36 ongoing studies that will provide more evidence when completed.
- We will update this review regularly as more evidence becomes available.
What are ‘monoclonal’ antibodies?
Antibodies are made by the body as a defence against disease. However, they can also be produced in a laboratory from cells taken from people who have recovered from a disease.
Antibodies that are designed to target only one specific protein – in this case, a protein on the virus that causes COVID-19 – are ‘monoclonal’. They attach to the COVID-19 virus and stop it from entering and replicating in human cells, which helps to fight the infection. Monoclonal antibodies have been used successfully to treat other viruses. They are thought to cause fewer unwanted effects than convalescent plasma, which contains a variety of different antibodies.
What did we want to find out?
We wanted to know if COVID-19 specific monoclonal antibodies are an effective treatment for COVID-19. We looked at whether they:
- reduced the number of deaths from any cause;
- improved symptoms or made them worse;
- increased admissions to hospital; and
- caused any serious or other unwanted effects.
What did we do?
We searched for studies that investigated one or more monoclonal antibodies to treat people with confirmed COVID-19 compared with placebo (sham treatment), another treatment or no treatment. Studies could take place anywhere globally and include participants of any age, gender or ethnicity, with mild, moderate or severe COVID-19.
We compared and summarised the results of the studies and rated our confidence in the evidence, based on factors such as study methods and size.
What did we find?
We found six active studies including a total of 17,495 people. Four studies investigated non-hospitalised people with no symptoms or mild COVID-19. Two studies investigated hospitalised people with moderate to severe COVID-19. Studies took place across the world. Three studies were funded by pharmaceutical companies. The monoclonal antibodies they studied were bamlanivimab, etesevimab, casirivimab and imdevimab, sotrovimab, regdanvimab. We did not identify data for mortality at 60 days and quality of life.
Non-hospitalised people, with no symptoms or mild COVID-19 (four studies)
One study investigated different doses of bamlanivimab (465 people), compared to placebo.
We don’t know whether bamlanivimab:
- increases or reduces the number of deaths because no participants died within 30 days of treatment;
- causes more or fewer serious unwanted effects because there were few events.
Bamlanivimab may reduce the number of admissions to hospital within 30 days of treatment compared to placebo.
- May cause slightly fewer unwanted effects than placebo.
- We did not find data for improved symptoms or worsened symptoms.
One study investigated a combination of bamlanivimab and etesevimab (1035 people), compared to placebo.
- Bamlanivimab and etesevimab may reduce the number of deaths and admissions to hospital.
- May cause slightly more unwanted effects.
- May cause more serious unwanted effects.
For treatment with bamlanivimab alone or in combination with etesevimab we did not find data for improved symptoms or worsened symptoms.
One study (phase 1/2 with 799 people) investigated different doses of casirivimab combined with imdevimab, compared to placebo.
- Casirivimab combined with imdevimab may reduce the number of hospital admissions or death.
- We don't know whether casirivimab and imdevimab causes more unwanted (grades 3 and 4) and serious unwanted effects than placebo because there were too few deaths to allow us to make a judgment.
- We did not find data for the number of people who died at day 30 and development of severe symptoms.
- We did not include results from phase 3 (5607 people) of this study, because of high risk of bias, as it was not clear which participants were included in the analysis.
One study (583 people) investigated sotrovimab, compared to placebo.
We don't know whether sotrovimab:
- increases or reduces the number of deaths and people requiring invasive mechanical ventilation or dying, because there were too few deaths to allow us to make a judgment.
- Sotrovimab may reduce the number of people requiring oxygen, unwanted (grades 3 to 4) and serious unwanted effects;
- may have little or no effect on unwanted effects (all grades).
Another study (327 people) investigated different doses of regdanvimab (40 mg/kg and 80 mg/kg), compared to placebo.
- Regdanvimab at either dose may reduce the number of admissions to hospital or death.
- May increase unwanted events (grades 3 to 4).
- Regdanvimab at a dose of 80 mg/kg may reduce unwanted effects (all grades) and 40 mg/kg may have little to no effect.
- We don't know whether regdanvimab increases or decreases the number of deaths, requirement for invasive mechanical ventilation, and serious unwanted effects, because there were too few events to allow us to make a judgment.
Hospitalised people with moderate to severe COVID-19 (2 studies)
One study (314 people) investigated bamlanivimab compared to placebo.
- We don’t know whether bamlanivimab increases or decreases the number of deaths due to any cause up to 30 or 90 days after treatment because there were too few deaths to allow us to make a judgment (6 deaths with bamlanivimab and 4 deaths with placebo in 314 people).
- Bamlanivimab may slightly increase the development of severe COVID-19 symptoms five days after treatment and the number of people with unwanted effects.
- Bamlanivimab may have little to no effect on time until discharge from hospital.
- We don’t know whether bamlanivimab causes serious unwanted effects by day 30 because the study was small and reported few serious unwanted effects.
Another study (9785 people) investigated casirivimab combined with imdevimab, compared to standard of care.
- Casirivimab combined with imdevimab has probably little to no effect on the number of deaths, requirement for invasive mechanical ventilation or death, and hospital discharge alive.
- We did not find data for unwanted and serious unwanted effects.
What are the limitations of the evidence?
Our confidence in the evidence is low because we found only six studies, and they did not report everything we were interested in, such as the number of deaths within 60 days and quality of life. We found 36 ongoing studies. When they are published, we will add their results to our review. These results are likely to change our conclusions and will also help us understand how new variants affect how well monoclonal antibodies work.
How up to date is this evidence?
The evidence is up to date to 17 June 2021.
The evidence for each comparison is based on single studies. None of these measured quality of life. Our certainty in the evidence for all non-hospitalised individuals is low, and for hospitalised individuals is very low to moderate. We consider the current evidence insufficient to draw meaningful conclusions regarding treatment with SARS-CoV-2-neutralising mAbs.
Further studies and long-term data from the existing studies are needed to confirm or refute these initial findings, and to understand how the emergence of SARS-CoV-2 variants may impact the effectiveness of SARS-CoV-2-neutralising mAbs. Publication of the 36 ongoing studies may resolve uncertainties about the effectiveness and safety of SARS-CoV-2-neutralising mAbs for the treatment of COVID-19 and possible subgroup differences.
Monoclonal antibodies (mAbs) are laboratory-produced molecules derived from the B cells of an infected host. They are being investigated as a potential therapy for coronavirus disease 2019 (COVID‐19).
To assess the effectiveness and safety of SARS-CoV-2-neutralising mAbs for treating patients with COVID-19, compared to an active comparator, placebo, or no intervention. To maintain the currency of the evidence, we will use a living systematic review approach.
A secondary objective is to track newly developed SARS-CoV-2-targeting mAbs from first tests in humans onwards.
We searched MEDLINE, Embase, the Cochrane COVID-19 Study Register, and three other databases on 17 June 2021. We also checked references, searched citations, and contacted study authors to identify additional studies. Between submission and publication, we conducted a shortened randomised controlled trial (RCT)-only search on 30 July 2021.
We included studies that evaluated SARS-CoV-2-neutralising mAbs, alone or combined, compared to an active comparator, placebo, or no intervention, to treat people with COVID‐19. We excluded studies on prophylactic use of SARS-CoV-2-neutralising mAbs.
Two authors independently assessed search results, extracted data, and assessed risk of bias using the Cochrane risk of bias tool (RoB2). Prioritised outcomes were all-cause mortality by days 30 and 60, clinical progression, quality of life, admission to hospital, adverse events (AEs), and serious adverse events (SAEs). We rated the certainty of evidence using GRADE.
We identified six RCTs that provided results from 17,495 participants with planned completion dates between July 2021 and December 2031. Target sample sizes varied from 1020 to 10,000 participants. Average age was 42 to 53 years across four studies of non-hospitalised participants, and 61 years in two studies of hospitalised participants.
Non-hospitalised individuals with COVID-19
Four studies evaluated single agents bamlanivimab (N = 465), sotrovimab (N = 868), regdanvimab (N = 307), and combinations of bamlanivimab/etesevimab (N = 1035), and casirivimab/imdevimab (N = 799). We did not identify data for mortality at 60 days or quality of life. Our certainty of the evidence is low for all outcomes due to too few events (very serious imprecision).
Bamlanivimab compared to placebo
No deaths occurred in the study by day 29. There were nine people admitted to hospital by day 29 out of 156 in the placebo group compared with one out of 101 in the group treated with 0.7 g bamlanivimab (risk ratio (RR) 0.17, 95% confidence interval (CI) 0.02 to 1.33), 2 from 107 in the group treated with 2.8 g (RR 0.32, 95% CI 0.07 to 1.47) and 2 from 101 in the group treated with 7.0 g (RR 0.34, 95% CI 0.08 to 1.56). Treatment with 0.7 g, 2.8 g and 7.0 g bamlanivimab may have similar rates of AEs as placebo (RR 0.99, 95% CI 0.66 to 1.50; RR 0.90, 95% CI 0.59 to 1.38; RR 0.81, 95% CI 0.52 to 1.27). The effect on SAEs is uncertain. Clinical progression/improvement of symptoms or development of severe symptoms were not reported.
Bamlanivimab/etesevimab compared to placebo
There were 10 deaths in the placebo group and none in bamlanivimab/etesevimab group by day 30 (RR 0.05, 95% CI 0.00 to 0.81). Bamlanivimab/etesevimab may decrease hospital admission by day 29 (RR 0.30, 95% CI 0.16 to 0.59), may result in a slight increase in any grade AEs (RR 1.15, 95% CI 0.83 to 1.59) and may increase SAEs (RR 1.40, 95% CI 0.45 to 4.37). Clinical progression/improvement of symptoms or development of severe symptoms were not reported.
Casirivimab/imdevimab compared to placebo
Casirivimab/imdevimab may reduce hospital admissions or death (2.4 g: RR 0.43, 95% CI 0.08 to 2.19; 8.0 g: RR 0.21, 95% CI 0.02 to 1.79). We are uncertain of the effect on grades 3-4 AEs (2.4 g: RR 0.76, 95% CI 0.17 to 3.37; 8.0 g: RR 0.50, 95% CI 0.09 to 2.73) and SAEs (2.4 g: RR 0.68, 95% CI 0.19 to 2.37; 8.0 g: RR 0.34, 95% CI 0.07 to 1.65). Mortality by day 30 and clinical progression/improvement of symptoms or development of severe symptoms were not reported.
Sotrovimab compared to placebo
We are uncertain whether sotrovimab has an effect on mortality (RR 0.33, 95% CI 0.01 to 8.18) and invasive mechanical ventilation (IMV) requirement or death (RR 0.14, 95% CI 0.01 to 2.76). Treatment with sotrovimab may reduce the number of participants with oxygen requirement (RR 0.11, 95 % CI 0.02 to 0.45), hospital admission or death by day 30 (RR 0.14, 95% CI 0.04 to 0.48), grades 3-4 AEs (RR 0.26, 95% CI 0.12 to 0.60), SAEs (RR 0.27, 95% CI 0.12 to 0.63) and may have little or no effect on any grade AEs (RR 0.87, 95% CI 0.66 to 1.16).
Regdanvimab compared to placebo
Treatment with either dose (40 or 80 mg/kg) compared with placebo may decrease hospital admissions or death (RR 0.45, 95% CI 0.14 to 1.42; RR 0.56, 95% CI 0.19 to 1.60, 206 participants), but may increase grades 3-4 AEs (RR 2.62, 95% CI 0.52 to 13.12; RR 2.00, 95% CI 0.37 to 10.70). 80 mg/kg may reduce any grade AEs (RR 0.79, 95% CI 0.52 to 1.22) but 40 mg/kg may have little to no effect (RR 0.96, 95% CI 0.64 to 1.43). There were too few events to allow meaningful judgment for the outcomes mortality by 30 days, IMV requirement, and SAEs.
Hospitalised individuals with COVID-19
Two studies evaluating bamlanivimab as a single agent (N = 314) and casirivimab/imdevimab as a combination therapy (N = 9785) were included.
Bamlanivimab compared to placebo
We are uncertain whether bamlanivimab has an effect on mortality by day 30 (RR 1.39, 95% CI 0.40 to 4.83) and SAEs by day 28 (RR 0.93, 95% CI 0.27 to 3.14). Bamlanivimab may have little to no effect on time to hospital discharge (HR 0.97, 95% CI 0.78 to 1.20) and mortality by day 90 (HR 1.09, 95% CI 0.49 to 2.43). The effect of bamlanivimab on the development of severe symptoms at day 5 (RR 1.17, 95% CI 0.75 to 1.85) is uncertain. Bamlanivimab may increase grades 3-4 AEs at day 28 (RR 1.27, 95% CI 0.81 to 1.98). We assessed the evidence as low certainty for all outcomes due to serious imprecision, and very low certainty for severe symptoms because of additional concerns about indirectness.
Casirivimab/imdevimab with usual care compared to usual care alone
Treatment with casirivimab/imdevimab compared to usual care probably has little or no effect on mortality by day 30 (RR 0.94, 95% CI 0.87 to 1.02), IMV requirement or death (RR 0.96, 95% CI 0.90 to 1.04), nor alive at hospital discharge by day 30 (RR 1.01, 95% CI 0.98 to 1.04). We assessed the evidence as moderate certainty due to study limitations (lack of blinding). AEs and SAEs were not reported.