Key messages
We do not know whether immunoglobulins (a preparation made with antibodies from people who have recovered from respiratory syncytial virus) reduce deaths in very young children who are in hospital with a respiratory syncytial virus lung infection.
Immunoglobulins have little to no effect on the time young children who are in hospital with a respiratory syncytial virus lung infection spend there.
All eight studies included in this review investigated young children at study sites in high-income countries where the rate of death from this condition is low, with only two studies also including a study site in a middle-income country. As such, we do not know how effective the treatment is for young children in low-income countries where the rate of death from respiratory syncytial virus lung infection is higher.
The current evidence does not support the use of immunoglobulins as a treatment for young children who are in hospital with a respiratory syncytial virus lung infection.
What is respiratory syncytial virus (RSV)?
Respiratory syncytial virus (RSV) is a common virus that can infect the lungs and airways. In infants and very young children infection with RSV can result in symptoms of fever, cough, runny nose, wheezing, shortness of breath, and feeding difficulty. This may result in hospitalisation, admission to an intensive care unit, and death.
What did we want to find out?
We wanted to find out if immunoglobulins are an effective and helpful treatment for very young children who are admitted to hospital with an RSV lung infection confirmed by laboratory tests.
We were interested in:
- death from any cause occurring during the time the child was in hospital or after they had left hospital;
- the length of time children spent in hospital; and
- unwanted effects of the immunoglobulin treatment.
What did we do?
We searched for studies that compared immunoglobulins (of any type) with a dummy medicine that did not contain any active ingredients (placebo) in infants and young children up to the age of three years. The studies could be conducted in any location in the world.
We compared and summarised the results of the studies. Where possible we pooled (combined) the studies’ results to analyse them. We used a standardised method to rate our confidence in the evidence, which is based on study features such as how the study was designed and the number of people included.
What did we find?
We found eight studies that included 906 infants and young children. Five of the studies were conducted at one or more study sites in a high-income country. Three studies were conducted at sites in different countries. All three of these studies included sites in high-income countries, with only two studies also including a study site that was in a middle-income country.
We are very uncertain whether or not immunoglobulins affect the risk of death during the time a child is in hospital or after they leave hospital.
We found that immunoglobulins resulted in little to no difference in the time infants and young children with RSV lung infection spent in hospital.
We found that there may be little to no difference in unwanted effects between immunoglobulins and the dummy treatment.
What are the limitations of the evidence?
We are very uncertain about the effects of immunoglobulins on deaths because of the small number of deaths that occurred in the studies. We need to have studies with many hundreds or even thousands of infants and young children included to find out if immunoglobulins affect the risk of death amongst infants and young children in hospital for an RSV lung infection.
We are more certain about the evidence for the effects of immunoglobulins on the length of time spent in hospital, but there were some concerns about the way the studies were designed and conducted.
The studies primarily investigated young children in high-income countries (with only two studies including a study site in a middle-income country), so the results might not apply to infants and young children in low-income countries where the risk of dying from RSV lung infection is higher.
There were differences in the types of immunoglobulin treatments used in the studies and differences in how unwell the children included in the studies were. We were not able to investigate whether these factors affected how the treatment worked because of the small number of studies included in the review.
How up-to-date is this evidence?
This is the third version of our review. The evidence is up-to-date to 2 December 2022.
We are very uncertain about the effect of immunoglobulins on mortality. We are moderately certain that use of immunoglobulins in hospitalised infants and children may result in little to no difference in the length of hospitalisation. Immunoglobulins may result in little to no difference in adverse events, the need for or duration of mechanical ventilation, supplemental oxygen, or admission to the intensive care unit, though we are less certain about this evidence and the true effect of immunoglobulins on these outcomes may differ markedly from the estimated effect observed in this review. All trials were conducted in high-income countries, and data from populations in which the rate of death from RSV infection is higher are lacking.
Millions of children are hospitalised due to respiratory syncytial virus (RSV) infection every year. Treatment is supportive, and current therapies (e.g. inhaled bronchodilators, epinephrine, nebulised hypertonic saline, and corticosteroids) are ineffective or have limited effect. Respiratory syncytial virus immunoglobulin may be used prophylactically to prevent hospital admission from RSV-related illness. It may be considered for the treatment of established severe RSV infection or for treatment in an immunocompromised host, although it is not licensed for this purpose. It is unclear whether immunoglobulins improve outcomes when used as a treatment for established RSV infection in infants and young children admitted to hospital. This is an update of a review first published in 2019.
To assess the effects of immunoglobulins for the treatment of RSV-proven lower respiratory tract infections (LRTIs) in children aged up to three years, admitted to hospital.
For this 2022 update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), which contains the Cochrane Acute Respiratory Infections Specialised Register, Ovid MEDLINE, Embase, CINAHL, and Web of Science (from inception to 2 December 2022) with no restrictions. We searched two trial registries for ongoing trials (to 2 December 2022) and checked the reference lists of reviews and included articles for additional studies.
Randomised controlled trials comparing immunoglobulins with placebo in hospitalised infants and children aged up to three years with laboratory-diagnosed RSV lower respiratory tract infection.
Two review authors independently selected trials, assessed risk of bias, and extracted data. We assessed evidence certainty using GRADE.
In total, we included eight trials involving 906 infants and children aged up to three years. We included one new trial in this update. The immunoglobulin preparations used in these trials included anti-RSV immunoglobulin and the monoclonal antibody preparations palivizumab and motavizumab. Five trials were conducted at single or multiple sites within a single high-income country (four in the USA, one in Qatar). Three trials included study sites in different countries. All three of these trials included study sites in one or more high-income countries (USA, Chile, New Zealand, Australia, Qatar), with two trials also including a study site in a middle-income country (Panama). Five of the eight trials were "supported" or "sponsored" by the trial drug manufacturers.
The evidence is very uncertain about the effect of immunoglobulins on mortality (risk ratio (RR) 0.87, 95% confidence interval (CI) 0.14 to 5.27; 4 studies, 309 participants). There were four deaths - two amongst 98 children receiving immunoglobulins, and two amongst 98 children receiving placebo. One additional death occurred in a fourth trial, however the study group of the child was not known and the data were not included in the analysis (very low-certainty evidence).
The use of immunoglobulins in infants and children admitted to hospital with RSV proven LRTI probably results in little to no difference in the length of hospitalisation (mean difference (MD) −0.13 days, 95% CI −0.37 to 0.12; 6 studies, 737 participants; moderate-certainty evidence).
Immunoglobulins may result in little to no difference in the number of children who experience one or more adverse events of any severity or seriousness compared to placebo (RR 1.18, 95% CI 0.78 to 1.78; 5 studies, 340 participants; low-certainty evidence) or the number of children who experience one or more adverse events judged by study investigators to be serious in nature, compared to placebo (RR 1.08, 95% CI 0.65 to 1.79; 4 studies, 238 participants; low-certainty evidence).
Certainty of evidence for secondary outcomes was low. This evidence suggests that use of immunoglobulins results in little to no difference in the need for, or duration of, mechanical ventilation and the need for, or duration of, supplemental oxygen. The use of immunoglobulins does not reduce the need for admission to the intensive care unit (ICU) and when children are admitted to the ICU results in little to no difference in the duration of ICU stay.