The Etiological Role of Common Respiratory Viruses in Acute Respiratory Infections in Older Adults: A Systematic Review and Meta-analysis
Authors: Shi Ting , Arnott Andrew , Semogas Indre , Falsey Ann R , Openshaw Peter , Wedzicha Jadwiga A , Campbell Harry , Nair Harish ,   RESCEU Investigators, Nair Harish , Campbell Harry , Shi Ting , Zhang Shanshan , Li You , Openshaw Peter , Wedzicha Jadwicha , Falsey Ann , Miller Mark , Beutels Philippe , Bont Louis , Pollard Andrew , Molero Eva , Martinon-Torres Federico , Heikkinen Terho , Meijer Adam , Kølsen Fischer Thea , van den Berge Maarten , Giaquinto Carlo , Mikolajczyk Rafael , Hackett Judy , Tafesse Eskinder , Cai Bing , Knirsch Charles , Gonzalez Lopez Antonio , Dieussaert Ilse , Dermateau Nadia , Stoszek Sonia , Gallichan Scott , Kieffer Alexia , Demont Clarisse , Cheret Arnaud , Gavart Sandra , Aerssens Jeroen , Wyffels Veronique , Cleenewerck Matthias , Fuentes Robert , Rosen Brian , Nair Harish , Campbell Harry , Shi Ting , Zhang Shanshan , Li You , Openshaw Peter , Wedzicha Jadwicha , Falsey Ann , Miller Mark , Beutels Philippe , Bont Louis , Pollard Andrew , Molero Eva , Martinon-Torres Federico , Heikkinen Terho , Meijer Adam , Kølsen Fischer Thea , van den Berge Maarten , Giaquinto Carlo , Mikolajczyk Rafael , Hackett Judy , Tafesse Eskinder , Cai Bing , Knirsch Charles , Gonzalez Lopez Antonio , Dieussaert Ilse , Dermateau Nadia , Stoszek Sonia , Gallichan Scott , Kieffer Alexia , Demont Clarisse , Cheret Arnaud , Gavart Sandra , Aerssens Jeroen , Wyffels Veronique , Cleenewerck Matthias , Fuentes Robert , Rosen Brian 
Published: December 2018

Abstract
Acute respiratory tract infections (ARI) constitute a substantial disease burden in adults and elderly individuals. We aimed to identify all case-control studies investigating the potential role of respiratory viruses in the etiology of ARI in older adults aged ≥65 years. We conducted a systematic literature review (across 7 databases) of case-control studies published from 1996 to 2017 that investigated the viral profile of older adults with and those without ARI. We then computed a pooled odds ratio (OR) with a 95% confidence interval and virus-specific attributable fraction among the exposed (AFE) for 8 common viruses: respiratory syncytial virus (RSV), influenza virus (Flu), parainfluenza virus (PIV), human metapneumovirus (HMPV), adenovirus (AdV), rhinovirus (RV), bocavirus (BoV), and coronavirus (CoV). From the 16 studies included, there was strong evidence of possible causal attribution for RSV (OR, 8.5 [95% CI, 3.9–18.5]; AFE, 88%), Flu (OR, 8.3 [95% CI, 4.4–15.9]; AFE, 88%), PIV (OR, not available; AFE, approximately 100%), HMPV (OR, 9.8 [95% CI, 2.3–41.0]; AFE, 90%), AdV (OR, not available; AFE, approximately 100%), RV (OR, 7.1 [95% CI, 3.7–13.6]; AFE, 86%) and CoV (OR, 2.8 [95% CI, 2.0–4.1]; AFE, 65%) in older adults presenting with ARI, compared with those without respiratory symptoms (ie, asymptomatic individuals) or healthy older adults. However, there was no significant difference in the detection of BoV in cases and controls. This review supports RSV, Flu, PIV, HMPV, AdV, RV, and CoV as important causes of ARI in older adults and provides quantitative estimates of the absolute proportion of virus-associated ARI cases to which a viral cause can be attributed. Disease burden estimates should take into account the appropriate AFE estimates (for older adults) that we report.