key: cord-0010131-qcfts6fu authors: Antalis, Emmanouil; Oikonomopoulou, Zacharoula; Kottaridi, Christine; Kossyvakis, Athanasios; Spathis, Aris; Magkana, Maria; Katsouli, Aikaterini; Tsagris, Vassileios; Papaevangelou, Vassiliki; Mentis, Andreas; Tsiodras, Sotirios title: Mixed viral infections of the respiratory tract; an epidemiological study during consecutive winter seasons date: 2018-01-17 journal: J Med Virol DOI: 10.1002/jmv.25006 sha: 1038b97923cff88c849b94467976ba1f93a3ceda doc_id: 10131 cord_uid: qcfts6fu The current study aimed to describe the molecular epidemiology of mixed respiratory viral infections during consecutive winter seasons in a tertiary care hospital. Patients with symptoms of respiratory tract infection were evaluated during the 2009‐2011 and 2013‐15 winter seasons. A clinical microarray technique was used for viral detection. Clinical and epidemiological data were correlated with mixed viral detection and the need for hospitalization. In 332 out of 604 (54.4%) evaluated patients (17.6% children) a respiratory virus was identified. Mixed viral infections were diagnosed in 68/332 (20.5%) patients with virus detection (66.2% mixed Influenza‐RSV infections). Mixed viral infections were more commonly detected in children (OR 3.7; 95%CI 1.9‐5.6, P < 0.01) and patients with comorbidities. In logistic regression analyses, mixed viral infections were associated with younger age (mean age 30.4 years vs. 41.8 years, P ≤ 0.001) and increased rates of fever (OR: 2.7; 95%CI 1.04‐7.2, P < 0.05) but no adverse outcomes or increased rates of hospitalization. High rates of mixed viral infections were noted during all winter seasons (especially Influenza and RSV) and were more common in younger patients. The clinical significance of mixed respiratory viral infection needs further elucidation. The current study aimed to describe the molecular epidemiology of mixed respiratory Mixed viral infections were more commonly detected in children (OR 3.7; 95%CI 1.9-5.6, P < 0.01) and patients with comorbidities. In logistic regression analyses, mixed viral infections were associated with younger age (mean age 30.4 years vs. 41.8 years, P ≤ 0.001) and increased rates of fever (OR: 2.7; 95%CI 1.04-7.2, P < 0.05) but no adverse outcomes or increased rates of hospitalization. High rates of mixed viral infections were noted during all winter seasons (especially Influenza and RSV) and were more common in younger patients. The clinical significance of mixed respiratory viral infection needs further elucidation. Care testing and newer available molecular techniques have improved our ability to detect diverse viruses causing respiratory infections. 4 In a recent study evaluating two different multiplex kits 14.2% of samples tested, harbored viral co-infections. 4 Limited studies have evaluated the presence of mixed viral infections at the clinical setting for adult populations. Significant rates of mixed infections have been reported in several studies mainly involving pediatric populations 5-14 while very little data exist regarding adult patients. [15] [16] [17] [18] The clinical significance of mixed viral infections is a matter of debate with some data supporting a role for increased illness severity and adverse outcomes including hospitalizations 5,15 and some not. 9, 10, 16 Further, most of the studies are biased towards studying hospitalized subjects 9, 10, 19, 20 and very little data exist regarding outpatients. [16] [17] [18] The current study aimed to describe the molecular epidemiology of mixed respiratory viral infections in both adults and children within the context of acute respiratory illness. The study was part of a molecular epidemiology study of respiratory viruses detection in patients presenting with acute respiratory symptoms during consecutive winter seasons, in a tertiary care hospital Emergency Room (ER), in a large metropolitan area. The study's main aim was to identify the prevalence of such infections within the population sampled. An additional aim was to correlate the detection of mixed respiratory viral infection with baseline clinical and epidemiological data, including the decision to hospitalize due to severe illness. We identified very few cases of other respiratory viral pathogens (Table 2) . Human metapneumovirus (hMPV) infections were more common in children (OR 5.9, 95%CI 1.8-19.6, P = 0.006, Table 2 ). Both RSV infections and human metapneumovirus infections were more frequent in children aged <5 years old (P < 0.001 for all associations). Thirty-four (5.6%) patients were hospitalized. The presence of any comorbidity was significantly associated with hospitalization (P = 0.001). In logistic regression models adjusting for all potential confounders higher age (beta: 0.03, OR 1.03, 95%CI 1.009-1.04, P < 0.01) and presence of a cardiovascular disease (beta: 0.99, OR 2.7, 95%CI 1.3-5.5, P < 0.01) were associated with a higher chance of hospitalization. A significant number of mixed viral respiratory infections was observed in the current study evaluating adults as well as children. Most mixed infections observed herein were RSV-influenza co-infections. Mixed viral infections were associated with younger age and increased rates of fever but were not associated with increased rates of hospitalization. We could not associate the presence of mixed infections with underlying comorbidities; however mixed viral infections appeared to be more frequent occurring than single infections in patients with comorbidities, patients with COPD and patients with cardiovascular disease. Nevertheless, it seems that our study did not have the power to elicit important differences in this regard. In the current study, single as well as mixed viral infection was more common in children than adults. Multiple pediatric studies as well as a recent Greek study identified significant rates of mixed viral infections in the evaluated children population. [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] If higher percentages of pediatric population were included in our study mixed viral infection rates could have been higher. 21 this co-circulation has been also confirmed in other efforts. 7 Our study results concur with these of other studies showing rates of respiratory virus detection from 38.8% to as high as 52.1% in adults with upper respiratory infection or influenza like illness. 17, 18 The higher percent of viral infections in children was not unexpected. 21, 22 In particular, infections due to RSV and hMPV were more frequently observed in children compared to adults. Regarding the higher rates of RSV detection in children, RSV is well known to be a common pathogen in respiratory tract infections in children. Although not seen in our study, RSV can be a devastating pathogen in children that are very young or that have underlying illnesses 23, 24 ; more severe clinical outcomes and hospitalization have been described for children with RSV infection in our country. 25 Human metapneumovirus was also more frequently seen in children in our study; as a virus it is known to affect younger children suffering from lower respiratory infections. 23 however we did not see this association in our cohort. The role of RSV in producing a more severe disease especially in the adult population is a matter of debate. 30 In general, RSV appears to be associated with milder illness compared to influenza 31 mixed viral infections in a significant fraction of our population. Although data from our study concur with data from several published pediatric studies, we believe that our study's main strength is that it is one of the very few epidemiological studies examining mixed respiratory viruses in adults. Further, as an epidemiological study it does not attempt to explain a hypothesis; rather it assists in generating hypotheses regarding the role of mixed viral infections in the adult population and points out the lack of data in this significant research area. Further work is necessary to elucidate the pathogenic role of mixed infections due to respiratory viruses and their local and systemic effects. This research received no specific grant from any funding agency, commercial or not-for-profit sectors. No financial or other conflict of interest exists, that might be construed to influence the contents of the current manuscript, including the results or interpretation of publication. 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