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Disease Severity and Clinical Outcomes of Community Acquired Pneumonia Caused by Non-Influenza Respiratory Viruses in Adults Early View Original article Disease severity and clinical outcomes of community acquired pneumonia caused by non- influenza respiratory viruses in adults: a multicenter prospective registry study from CAP- China Network Fei Zhou, Yimin Wang, Yingmei Liu, Xuedong Liu, Li Gu, Xiaoju Zhang, Zenghui Pu, Guoru Yang, Bo Liu, Qingrong Nie, Bing Xue, Jing Feng, Qiang Guo, Jianhua Liu, Hong Fan, Jin Chen, Yongxiang Zhang, Zhenyang Xu, Min Pang, Yu Chen, Xiuhong Nie, Zhigang Cai, Jinfu Xu, Kun Peng, Xiangxin Li, Pingchao Xiang, Zuoqing Zhang, Shujuan Jiang, Xin Su, Jie Zhang, Yanming Li, Xiuhong Jin, Rongmeng Jiang, Jianping Dong, Yuanlin Song, Hong Zhou, Chen Wang, Bin Cao Please cite this article as: Zhou F, Wang Y, Liu Y, et al. Disease severity and clinical outcomes of community acquired pneumonia caused by non-influenza respiratory viruses in adults: a multicenter prospective registry study from CAP-China Network. Eur Respir J 2019; in press (https://doi.org/10.1183/13993003.02406-2018). This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Copyright ©ERS 2019 Title page Short Title: Illness severity and clinical outcomes of CAP caused by non-influenza respiratory viruses Fei Zhou1, 2, 3, Yimin Wang1, 2, 3, Yingmei Liu1, 2, 3, Xuedong Liu4, Li Gu5, Xiaoju Zhang6, Zenghui Pu7, Guoru Yang8, Bo Liu9, Qingrong Nie10, Bing Xue11, Jing Feng12, Qiang Guo13, Jianhua Liu14, Hong Fan15, Jin Chen16, Yongxiang Zhang17, Zhenyang Xu18, Min Pang19, Yu Chen20, Xiuhong Nie21, Zhigang Cai22, Jinfu Xu23, Kun Peng24, Xiangxin Li25, Pingchao Xiang26, Zuoqing Zhang27, Shujuan Jiang28, Xin Su29, Jie Zhang30, Yanming Li31, Xiuhong Jin32, Rongmeng Jiang33, Jianping Dong34, Yuanlin Song35, Hong Zhou36, Chen Wang1, 2, 3, Bin Cao1, 2, 3,* and CAP-China network 1 Department of Pulmonary and Critical Care Medicine, Center for Respiratory Diseases, National Clinical Research Center of Respiratory Diseases, China-Japan Friendship Hospital, Beijing, China. 2 Clinical Center for Pulmonary Infections, Capital Medical University. 3 Tsinghua University-Peking University Joint Center for Life Sciences. 4 Department of Respiratory Medicine, Qingdao Municipal Hospital Group, Jiaozhou Road, Qingdao City, Shandong Province, China. 5 Department of Infectious Diseases, Beijing Chao-Yang Hospital, Capital Medical University, No 8, Gongti Road, Chaoyang District, Beijing, China. 6 Department of Infectious Diseases, Henan Provincial People's Hospital, Zhengzhou, China. 7 Department of Infectious diseases, YanTai Yu Huang-Ding Hospital, No. 20, Yu Huangding east Road, Yantai, China. 8 Department of Pulmonary and Critical Care Medicine, Weifang No. 2 People's Hospital, Yuanxiao Street, Weifang City, Shandong Province, China. 9 Department of Respiratory and Critical Care Medicine, Linzi District People’s Hospital, Shandong, China. 10 Department of Respiratory and Critical Care Medicine, Liangxiang Hospital, No. 45, Gongchen Road, Fangshan District, Beijing, China. 11 Department of Respiratory Medicine, Chuiyangliu Hospital Affiliated to Tshinghua University, No. 2, Chui Yangliu south Road, Beijing, China. 12 Department of Respiratory Medicine, Tianjin Medical University General Hospital, Tianjin, China. 13 Department of Respiratory, Emergency and Critical Care Medicine, First Affiliated Hospital of Soochow University, China. 14 Department of Respiratory, Beijing Huairou Hospital of University of Chinese Academy of Science, China. 15 Department of Pulmonary and Critical Care Medicine, West China Hospital, Sichan University, China. 16 Department of Respiratory, Fuxing Hospital, Capital Medical University, China. 17 Department of Pulmonary and Critical Care Medicine, Daxing Hospital Affiliated to Capital Medical University, China. 18 Department of Pulmonary and Critical Care Medicine, Beijing Luhe Hospital, Capital Medical University, China. 19 Department of Respiratory, First Hospital of Shanxi Medical University, China. 20 Department of Pulmonary and Critical Care Medicine, Shengjing Hospital of China Medical University, China. 21 Department of Respiratory, Xuanwu Hospital Capital Medical University, China. 22 Department of Respiratory, The Second Hospital of Hebei Medical University, China. 23 Department of Pulmonary and Critical Care Medicine, Shanghai Pulmonary Hospital, China. 24 Department of Respiratory, Beijing No.6 Hospital, China. 25 Department of Pulmonary and Critical Care Medicine, Beijing Changping Hospital, China. 26 Department of Pulmonary and Critical Care Medicine, Peking University Shougang Hospital, China. 27 Department of Respiratory, Beijing Shijingshan Hospital, China. 28 Department of Pulmonary and Critical Care Medicine, Shandong Province Hospital, China. 29 Department of Respiratory, Nanjing General Hospital of Nanjing Military Command, PLA, China. 30 Department of Respiratory, Beijing Tiantan Hospital, Capital Medical University, China. 31 Department of Pulmonary and Critical Care Medicine, Beijing Hospital, China. 32 Department of Respiratory, Beijing Pinggu Hospital, China. 33 The National Clinical Key Department of Infectious Disease, Beijing Ditan Hospital, Capital Medical University, China. 34 Department of Infectious diseases, Beijing Haidian hospital, Haidian section of Peking University Third Hospital, China. 35 Department of Respiratory, Zhongshan Hospital, Fudan University, China. 36 Department of Respiratory, Beijing electric power Hospital, China. FZ, YMW, YML, XDL, LG, XJZ, ZHP, GRY and BL contributed equally. * Correspondence to: Dr. Bin Cao ([email protected]) at Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital; National Clinical Research Center of Respiratory Diseases; Clinical Center for Pulmonary Infections, Capital Medical University; Tsinghua University-Peking University Joint Center for Life Sciences. Take home Message: The high incidence of complications in non-influenza viral pneumonia and similar impact of non-influenza viruses relative to influenza virus on disease severity and outcomes suggest more attention should be given to CAP caused by non-influenza viruses. Disease severity and clinical outcomes of community acquired pneumonia caused by non-influenza respiratory viruses in adults: a multicenter prospective registry study from CAP-China Network Abstract Although a wide knowledge of influenza viral pneumonia have been established, the significance of non-influenza respiratory viruses in community acquired pneumonia (CAP) and their impact on clinical outcomes remains unclear, especially in non-immunocompromised adult population. Hospitalised immunocompetent patients with CAP were prospectively recruited from 34 hospitals in Mainland China. Respiratory viruses were detected by molecular methods. Comparisons were conducted between influenza and non-influenza viral-infection groups. In total, 915 of 2336 adult patients with viral infection were enrolled in the analysis with influenza virus (28.4%) most frequently detected, followed by respiratory syncytial virus (3.6%), adenovirus (3.3%), human coronavirus (3.0%), parainfluenza virus (2.2%), human rhinovirus (1.8%), and human metapneumovirus (1.5%). Non-influenza viral infections accounted for 27.4% of viral pneumonia. Consolidation was more frequently observed in patients with adenovirus infection. The occurrence of complications such as sepsis (40.1% vs 39.6%, p = 0.890) and hypoxemia (40.1% vs 37.2%, p = 0.449) during hospitalization in influenza group didn’t differ from that of non-influenza group. Compared with influenza viral infection, the multivariable-adjusted odds ratios and 95% confidence intervals (CIs) of CURB-65 >3, PaO2/FiO2 <200 mmHg, and occurrence of sepsis or hypoxemia for non-influenza viral infection were 0.87 (0.26-2.84), 0.72 (0.26-1.98), 1.00 (1.63-1.58), and 1.05 (0.66-1.65), respectively. The hazard ratio and 95% CI of 90-day mortality was 0.51 (0.13-1.91). The high incidence of complications in non-influenza viral pneumonia and similar impact of non-influenza viruses relative to influenza virus on disease severity and outcomes suggest more attention should be given to CAP caused by non-influenza viruses. Keywords non-influenza viruses, community acquired pneumonia, complications, outcomes Abbreviations: CAP Community acquired pneumonia ICU Intensive care unit NP Nasopharyngeal ETA Endotracheal aspirates BALF Bronchoalveolar lavage fluid PCR Polymerase Chain Reaction UTM Universal transport medium IFV Influenza virus CoV Human coronavirus AdV Adenovirus HMPV Human metapneumovirus RSV Respiratory syncytial virus PIV Parainfluenza virus HRV Human rhinovirus MP Mycoplasma pneumoniae CP Chlamydia pneumoniae LP Legionella pneumophila ARDS Acute Respiratory Distress Syndrome COPD Chronic obstructive pulmonary disease WBC White blood cell AST Aspartate transaminase ALT Alanine aminotransferase LDH Lactate dehydrogenase BUN Blood urea nitrogen PCT Procalcitonin HR Heart rate PI Principle investigators IQR Inter quartile range OR Odds ratio HR Hazard ratio Introduction Community acquired pneumonia (CAP) is the leading cause of death worldwide among communicable diseases[1]. The development of molecular-diagnostic techniques has markedly improved the ability of virus identification, with numerous studies having reported a
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