The role of viral co-infections in the severity of acute respiratory infections among children infected with respiratory syncytial virus (RSV): A systematic review and meta-analysis

摘要

BackgroundRespiratory syncytial virus (RSV) is the predominant viral cause of childhood pneumonia. Little is known about the role of viral-coinfections in the clinical severity in children infected with RSV.MethodsWe conducted a systematic literature review of publications comparing the clinical severity between RSV mono-infection and RSV co-infection with other viruses in children under five years (<5y). Clinical severity was measured using the following six clinical outcomes: hospitalisation, length of hospital stay, use of supplemental oxygen, intensive care unit (ICU) admission, mechanical ventilation and deaths. We summarised the findings by clinical outcome and conducted random-effect meta-analyses, where applicable, to quantitatively synthesize the association between RSV mono-infection/RSV co-infection and the clinical severity.ResultsOverall, no differences in the clinical severity were found between RSV mono-infection and RSV co-infection with any viruses, except for the RSV-human metapneumovirus (hMPV) co-infection. RSV-hMPV coinfection was found to be associated with a higher risk of ICU admission (odds ratio (OR)?=?7.2, 95% confidence interval (CI)?=?2.1-25.1; OR after removal of the most influential study was 3.7, 95% CI?=?1.1-12.3). We also observed a trend from three studies that RSV-hMPV coinfections were likely to be associated with longer hospital stay.ConclusionOur findings suggest that RSV-hMPV coinfections might be associated with increased risk for ICU admission in children <5y compared with RSV mono-infection but such association does not imply causation. Our findings do not support the association between RSV coinfections with other viruses and clinical severity but further large-scale investigations are needed to confirm the findings.Protocol registrationPROSPERO CRD42019154761.Respiratory syncytial virus (RSV) is the predominant viral cause of childhood pneumonia [1-3]. It is estimated that in the year of 2015, there were 33.1 million episodes of RSV-associated acute lower respiratory infections (ALRI) and 3.2 million RSV-ALRI hospital admissions in children under five years of age (<5y) globally [4]. RSV activity is found to be seasonal in most locales globally and associated with low temperature and/or high relative humidity [5]. Individual-level risk factors for RSV-ALRI include prematurity, low birth weight, being male, having siblings, maternal smoking, history of atopy, no breastfeeding and crowding [6].As new diagnostic techniques for respiratory pathogens became more widely available in research and clinical settings, co-detection of RSV with another respiratory virus is not uncommon. Studies have shown that co-detection of RSV with other respiratory viruses could account for 35%-40% of all RSV infections in young children [7-9]. However, the role of viral-coinfections remains unclear in the severity of RSV-associated respiratory diseases. Several systematic reviews suggest that there is no association between disease severity and viral co-infections (compared to mono-infections) but little was reported in these reviews regarding RSV-specific effects [10-13]. Therefore, we conducted a systematic review and meta-analysis to understand the role of viral-coinfections with RSV in the clinical severity in children <5y.