The Etiological Role of Common Respiratory Viruses in Acute Respiratory Infections in Older Adults: A Systematic Review and Meta-analysis.

Ting Shi ,Harish Nair ,Andrew Arnott ,Peter Openshaw ,Ann R Falsey ,Indre Semogas ,Harry Campbell ,Jadwiga A Wedzicha ,Resceu Investigators

doi:10.1093/infdis/jiy662

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.

Highlights

From the 16 studies included, there was strong evidence of possible causal attribution for respiratory syncytial virus (RSV) (OR, 8.5 [95% confidence intervals (CIs), 3.9–18.5]; AFE, 88%), Flu (OR, 8.3 [95% CI, 4.4–15.9]; AFE, 88%), parainfluenza virus (PIV) (OR, not available; AFE, approximately 100%), human metapneumovirus (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 Acute respiratory tract infections (ARI), compared with those without respiratory symptoms or healthy older adults
Forty-three studies were excluded for a variety of reasons: no data specific to older adults ≥65 years old were available (n = 1), the case or control definitions were not fulfilled (n = 4), no applicable data for cases and controls were reported (n = 36), or serum was used as the clinical specimen (n = 2)
We demonstrated strong evidence in support of a potential causal attribution when a virus is identified in older adults presenting with ARI or pneumonia 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 [NA]; AFE, approximately 100%), human metapneumovirus (hMPV) (OR, 9.8 [95% CI, 2.3–41.0]; AFE, 90%), AdV (OR, NA; 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%)