key: cord-0933850-0er3153o authors: Kenmoe, S.; Kengne-Nde, C.; Ebogo-Belobo, J. T.; Mbaga, D. S.; Fatawou Modiyinji, A.; Njouom, R. title: Systematic review and meta-analysis of the prevalence of common respiratory viruses in children < 2 years with bronchiolitis reveal a weak role played by the SARS-CoV-2 date: 2020-09-01 journal: nan DOI: 10.1101/2020.08.28.20183681 sha: 5ff05b81b4177396988005916f66fdcbe8ac7c93 doc_id: 933850 cord_uid: 0er3153o Introduction The advent of genome amplification assays has allowed description of new respiratory viruses and to reconsider the role played by certain respiratory viruses in bronchiolitis. This systematic review and meta-analysis was initiated to clarify the prevalence of respiratory viruses in children with bronchiolitis in the coronavirus disease 2019 pandemic context. Methods We performed an electronic search through Pubmed and Global Index Medicus databases. We included observational studies reporting the detection rate of common respiratory viruses in children with bronchiolitis using molecular assays. Data was extracted and the quality of the included articles was assessed. We conducted sensitivity, subgroups, publication bias, and heterogeneity analyses using a random effect model. Results The final meta-analysis included 51 studies. Human respiratory syncytial virus (HRSV) was largely the most commonly detected virus 59.2%; 95% CI [54.7; 63.6]). The second predominant virus was Rhinovirus (RV) 19.3%; 95% CI [16.7; 22.0]) followed by Human bocavirus (HBoV) 8.2%; 95% CI [5.7; 11.2]). Other reported viruses included Human Adenovirus (HAdV) 6.1%; 95% CI [4.4; 8.0]), Human Metapneumovirus (HMPV) 5.4%; 95% CI [4.4; 6.4]), Human Parainfluenzavirus (HPIV) 5.4%; 95% CI [3.8; 7.3]), Influenza 3.2%; 95% CI [2.2; 4.3], mild Human Coronavirus (HCoV) 2.9%; 95% CI [2.0; 4.0]), and Enterovirus (EV) 2.9%; 95% CI [1.6; 4.5]). HRSV was the predominant virus involved in multiple detection and most codetections were HRSV + RV 7.1%, 95% CI [4.6; 9.9]) and HRSV + HBoV 4.5%, 95% CI [2.4; 7.3]). Conclusions The present study has shown that HRSV is the main cause of bronchiolitis in children, we also have Rhinovirus, and Bocavirus which also play a significant role. No study has reported the presence of Severe Acute Respiratory Syndrome Coronavirus-2 in children with bronchiolitis to date. During the last two decades, the increase in use of Polymerase Chain Reaction (PCR) assays 14 for the detection of respiratory viruses has led to a reassessment of the role played by viruses 15 such as RV in acute respiratory infections. 7,8 These molecular detection assays have also 16 revealed new respiratory viruses such as HMPV and HBoV, and some RV and HCOV species. 9-17 Covid-19 spread rapidly worldwide and is now present in 188 countries in the 5 continents. At 25 August 22, 2020, more than 20 million of cases have been confirmed and about 800 thousand 26 deaths due to Covid-19 were recorded 21 . The objective of this study was to report the detection 27 rate of viral agents using PCR and the associated risk factors with bronchiolitis in children ≤ 2 28 years in the era of 30 . CC-BY-NC 4.0 International license It is made available under a perpetuity. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted September 1, 2020. . https://doi.org/10.1101/2020.08.28.20183681 doi: medRxiv preprint Methods 31 32 This systematic review was conducted according to the principles of the Centre for Reviews 34 and Dissemination. 22 The methodological standards of the PRISMA declaration have been 35 applied for this review (S1 Table) . 23 The protocol for this review has been registered in the 36 PROSPERO is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted September 1, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted September 1, 2020. . https://doi.org/10.1101/2020.08.28.20183681 doi: medRxiv preprint The quality of the studies was estimated as low (8-10), moderate (5-7), and high (0-4) risk of 76 bias using the Hoy et al. assessment tool (S3 Table) . 24 is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted September 1, 2020. . https://doi.org/10.1101/2020.08.28.20183681 doi: medRxiv preprint The literature search provided a total of 3777 articles and 154 duplicates were excluded. 96 Selection based on titles and abstracts excluded 3370 irrelevant articles. We therefore examined 97 253 complete texts and excluded 203 for multiple reasons (Fig 1, S4 is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted September 1, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted September 1, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted September 1, 2020. Table) . Substantial heterogeneity was detected in overall prevalence and 125 sensitivity analyses for all viruses. Publication bias was detected for HMPV and Influenza meta-126 analyses (S6 Table and is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted September 1, 2020. . https://doi.org/10.1101/2020.08.28.20183681 doi: medRxiv preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted September 1, 2020. . https://doi.org/10.1101/2020.08.28.20183681 doi: medRxiv preprint most studies report that HRSV is the major agent in cases of bronchiolitis with rates ranging 152 from 50 to 80%. 80 RV, that is the second most common virus in this study, has long been 153 considered a cause of benign respiratory infection such as the common cold. 82 is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted September 1, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted September 1, 2020. It is important to mention that the small number of studies in some subgroups analyses restricts 215 our ability to draw definitive conclusions. A second limitation in our study is that we did not 216 consider multiple other factors that could further explain the variability in the prevalence of 217 viruses in bronchiolitis such as comorbidities, anti-HRSV prophylaxis and the number of virus 218 types sought in studies for multi-species such as mild HCoV and HPIV. It is also known that 219 bronchiolitis case definitions show great variability in terms of age limit and constellation of 220 clinical symptoms according to geographic area and time that we did not consider in this study. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted September 1, 2020. . https://doi.org/10.1101/2020.08.28.20183681 doi: medRxiv preprint in bronchiolitis. We report the data obtained in almost all WHO regions from the PCR that 226 currently represent the most commonly used assays in diagnosing respiratory viruses, which is 227 another major asset of this work. We also have conducted multiple sensitivity analyses that 228 further strengthen the robustness of our results on multiple important aspects such as children 229 hospitalization, age range, and design and quality of studies. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted September 1, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted September 1, 2020. . https://doi.org/10.1101/2020.08.28.20183681 doi: medRxiv preprint . CC-BY-NC 4.0 International license It is made available under a perpetuity. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted September 1, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted September 1, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted September 1, 2020. . https://doi.org/10.1101/2020.08.28.20183681 doi: medRxiv preprint . 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