Lower respiratory tract infection in the community: associations between viral aetiology and illness course

Abstract

Objectives: This study determined associations between respiratory viruses and subsequent illness course in primary care adult patients presenting with acute cough and/or suspected lower respiratory tract infection.

Methods: A prospective European primary care study recruited adults with symptoms of lower respiratory tract infection between November 2007 and April 2010. Real-time in-house polymerase chain reaction (PCR) was performed to test for six common respiratory viruses. In this secondary analysis, symptom severity (scored 1 = no problem, 2 = mild, 3 = moderate, 4 = severe) and symptom duration were compared between groups with different viral aetiologies using regression and Cox proportional hazard models, respectively. Additionally, associations between baseline viral load (cycle threshold (Ct) value) and illness course were assessed.

Results: The PCR tested positive for a common respiratory virus in 1354 of the 2957 (45.8%) included patients. The overall mean symptom score at presentation was 2.09 (95% confidence interval (CI) 2.07-2.11) and the median duration until resolution of moderately bad or severe symptoms was 8.70 days (interquartile range 4.50-11.00). Patients with influenza virus, human metapneumovirus (hMPV), respiratory syncytial virus (RSV), coronavirus (CoV) or rhinovirus had a significantly higher symptom score than patients with no virus isolated (0.07-0.25 points or 2.3-8.3% higher symptom score). Time to symptom resolution was longer in RSV infections (adjusted hazard ratio (AHR) 0.80, 95% CI 0.65-0.96) and hMPV infections (AHR 0.77, 95% CI 0.62-0.94) than in infections with no virus isolated. Overall, baseline viral load was associated with symptom severity (difference 0.11, 95% CI 0.06-0.16 per 10 cycles decrease in Ct value), but not with symptom duration.

Conclusions: In healthy, working adults from the general community presenting at the general practitioner with acute cough and/or suspected lower respiratory tract infection other than influenza impose an illness burden comparable to influenza. Hence, the public health focus for viral respiratory tract infections should be broadened.

Keywords: Disease burden; lower respiratory tract infection; primary healthcare; public health; respiratory tract infection; respiratory virus; symptom duration; symptom severity.

Fig. 1

Flow-chart patient exclusion as compared with the total number of patients included in the GRACE cohort [1]. CRF, case report form; PCR, polymerase chain reaction.

Fig. 2

Detected viral pathogens in included patients (n = 2957) and availability of follow-up data. CoV, coronavirus; hMPV, human metapneumovirus; IV, influenza virus; PiV, Parainfluenza virus; RV, rhinovirus; RSV, respiratory syncytial virus; Undet, influenza virus type undetermined. ∗ The following combinations of viral pathogens were found: CoV + RV (n = 10), IV + RV (n = 8), CoV + hMPV (n = 5), CoV + RSV (n = 4), RV + RSV (n = 4), IV + RSV (n = 3), CoV + IV (n = 2), hMPV + RV (n = 2), IV + PiV (n = 1), CoV + PiV (n = 1), RV + PiV (n = 1), RSV + PiV (n = 1). ∗∗ The following combinations of viral pathogens were found: CoV + RV (n = 5), IV + RV (n = 3), CoV + IV (n = 3), CoV + RSV (n = 1), RV + RSV (n = 1), IV + RSV (n = 1), RV + PiV (n = 1).

Fig. 3

Forest plots showing odds ratios (ORs) with 95% confidence intervals (CIs) on the log scale for coronavirus (CoV), human metapneumovirus (hMPV), influenza virus, parainfluenza virus (PiV), rhinovirus and respiratory syncytial virus (RSV) for a severe burden of individual symptoms at presentation (highest on four-point Likert scale). The reference category is no virus isolated. ORs are derived from logistic regression models (one model per symptom) with adjustment for bacterial and viral coinfections, age, gender, pulmonary comorbidities (asthma, chronic obstructive pulmonary disease and other lung diseases), hearth failure, current smoking, influenza vaccination during the preceding fall or winter and duration of symptoms before presentation. ∗ For fever and chest pain the scale on the x-axis was altered for visual purposes.

Fig. 4

Cox regression survival curves for the duration of symptoms rated moderately bad or worse in patients with lower respiratory tract infections (LRTIs) and a viral mono-infection (n = 2344), stratified by detected virus. The reference category is no virus detected. Survival curves are derived from multivariate Cox regression models with adjustment for bacterial coinfections, age, gender, pulmonary comorbidities (asthma, chronic obstructive pulmonary disease and other lung diseases), heart failure, current smoking, influenza vaccination during the preceding fall or winter and duration of symptoms before presentation. CoV, coronavirus; hMPV, human metapneumovirus; PiV, parainfluenza virus; RSV, respiratory syncytial virus.