ORIGINAL ARTICLE Respiratory Diseases https://doi.org/10.3346/jkms.2017.32.2.287 • J Korean Med Sci 2017; 32: 287-295 Characteristics of Adenovirus Pneumonia in Korean Military Personnel, 2012–2016 Hee Yoon,1 Byung Woo Jhun,2,3 Adenovirus (AdV) can cause severe pneumonia in non-immunocompromised host, but Hojoong Kim,2 Hongseok Yoo,3 limited data exist on the distinctive characteristics of AdV pneumonia in non- and Sung Bum Park4 immunocompromised patients. We evaluated distinctive clinico-laboratory and radiological characteristics and outcomes of AdV pneumonia (n = 179), compared with non-AdV 1Department of Emergency Medicine, Samsung Medical Center, Sungkyunkwan University School of pneumonia (n = 188) in Korean military personnel between 2012 and 2016. AdV Medicine, Seoul, Korea; 2Division of Pulmonary and pneumonia patients had a higher rate of consolidation with ground-glass opacity (101/152) Critical Care Medicine, Department of Medicine, in lobar distribution (89/152) on computed tomography (CT) (P < 0.001). Laboratory Samsung Medical Center, Sungkyunkwan University findings showed a higher incidence of unusual blood profiles such as leukopenia (55/179, School of Medicine, Seoul, Korea; 3Division of Pulmonary and Critical Care Medicine, Department P < 0.001) or thrombocytopenia (100/179, P < 0.001). The patients had more systemic of Medicine, The Armed Forces Capital Hospital, symptoms such as myalgia (82/179, P = 0.001) or diarrhea (23/179, P < 0.001), compared Seongnam, Korea; 4Department of Public Health with non-AdV pneumonia patients. Bacterial co-infection was identified in 28.5% of AdV and Operation, The Armed Forces Medical pneumonia. Most of the AdV isolates typed (69/72, 95.8%) were AdV-55. Patients with a Command, Seongnam, Korea pneumonia severity index ≥ class III were more commonly observed in AdV pneumonia Received: 15 August 2016 patients compared with non-AdV pneumonia patients (11.2% vs. 2.1%, P < 0.001), and Accepted: 1 November 2016 time to clinical stabilization from admission was longer in the AdV pneumonia patients compared with the non-AdV pneumonia patients (3.8 vs. 2.6 days, P < 0.001). Address for Correspondence: Byung Woo Jhun, MD Mechanical ventilation (n = 6) was only required in AdV pneumonia patients, one of whom Division of Pulmonary and Critical Care Medicine, Department died due to AdV-55. Our data showed that AdV pneumonia in non-immunocompromised of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, patients had distinct characteristics and most of the isolates typed in our study were AdV- Seoul 06351, Korea 55. It is suggested that AdV-55 is an important pathogen of pneumonia in Korean military E-mail: [email protected] personnel. Keywords: Adenovirus; Consolidation; Pneumonia; Thrombocytopenia INTRODUCTION monia (CAP) patients, admitted with varying severities of dis- ease, has increased annually; among these cases, the AdV isola- Adenoviruses (AdV) are non-enveloped, double-stranded DNA tion rates have been steadily increasing over recent years and viruses that can cause diseases of the respiratory tract, and gas- fatal cases have been reported since 2012 (15-17). Thus, physi- trointestinal and ocular systems (1). It is well-known that AdV cians have tried to identify the causative respiratory viral agents respiratory tract infections are usually mild and self-limiting in at an early stage to produce favorable outcomes, with these ef- a non-immunocompromised host, in contrast with immuno- forts, we have recently reported clinical data on the outcome of compromised hosts, in whom AdV infection can be fatal (2-4). administration of antiviral agents, and factors predictive of re- Since the fatal case of AdV pneumonia in a healthy adult was spiratory failure in AdV pneumonia (16,17). described in the 1960s (5), severe disease caused by AdV has However, there is limited data on the distinctive characteris- been reported among non-immunocompromised adults, es- tics of AdV pneumonia in non-immunocompromised patients, pecially in vulnerable populations, such as military recruits and which could help a physician to determine a diagnostic or treat- residents of health care facilities (6-9). Recent studies have also ment strategy during early presentation. Therefore, in the pres- described fatal cases of severe AdV pneumonia caused by par- ent study, we evaluated the characteristics of AdV-associated ticular serotypes, which provide insight into emerging, highly vs. non-AdV pneumonia cases among Korean military person- virulent serotypes, even in non-immunocompromised patients nel between 2012 and 2016, and additionally described the char- (10-14). acteristics of the AdV pneumonia caused by the serotype of AdV- In the Armed Forces Capital Hospital, the largest military re- 55 which was most commonly isolated type. ferral center in Korea, the number of community acquired pneu- © 2017 The Korean Academy of Medical Sciences. pISSN 1011-8934 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. eISSN 1598-6357 Yoon H, et al. • Characteristics of Adenovirus Pneumonia in Military Personnel MATERIALS AND METHODS tory symptoms; 2) definite infiltration on radiography or comput- ed tomography (CT); and 3) evidence of AdV infection identified Study subjects by a respiratory virus PCR test from lower respiratory specimens We reviewed the medical records of 557 consecutive adult pa- including sputum or bronchoalveolar lavage fluid. When speci- tients who were admitted with acute febrile respiratory illness, mens sampled from the lower respiratory tract were considered between July 2012 and January 2016, to the Armed Forces Capi- inadequate, specimens from the upper respiratory tract, including tal Hospital, Korea. All patients were serving in the military ser- nasopharyngeal or oropharyngeal swabs, were obtained (16,17). vice and were non-immunocompromised with negative human The serotype of AdV-positive specimens was evaluated in some immunodeficiency virus infection tests. Of these patients, those patients. Before June 2014, serotype analysis was performed only with upper respiratory tract infection (URI) or bronchitis (n = 17), in severe cases based on the attending physician’s decision (16). and those who did not undergo a respiratory virus polymerase Between December 2014 and March 2015, because the number chain reaction (PCR) test (n = 173), were excluded. Consequent- of CAP patients had increased and more severe patients with ly, 367 patients with CAP were included in the analysis; of these, unusual blood profiles such as leukopenia or thrombocytope- 179 with AdV pneumonia and 188 with non-AdV pneumonia nia were referred to the Armed Forces Capital Hospital (Fig. 2), were identified and included in the analysis (Fig. 1). serotype analysis was more frequently performed cooperated The diagnosis of AdV pneumonia was considered confirmed by the Armed Forces Medical Command (17). During the same when the following findings were present: 1) acute lower respira- period, serotype analysis was also performed in some outpati- ents without pneumonia but who had severe symptoms based on the attending physician’s decision. The present study includ- Acute febrile respiratory illness (n = 557) ed previously published data on patients with AdV pneumonia URI or Bronchitis treated at the Armed Forces Capital Hospital (15-17). (n = 17) Community acquired pneumonia Patient management and data collection (n = 540) Patients who had persistent symptoms, or who deteriorated de- No respiratory virus PCR test spite appropriate empirical antibiotics for 2–3 days, and/or who (n = 17) had unusual blood profiles including leukopenia or thrombo- Respiratory virus PCR test cytopenia, were suspected of having atypical causative agents (n = 367) and underwent etiological investigations. Etiologies were eval- uated in blood, sputum, bronchoalveolar lavage fluids, naso- AdV pneumonia Non-AdV pneumonia pharyngeal or oropharyngeal secretions, and urine using mi- (n = 179) (n = 188) crobiological culture for bacteria; a multiplex real-time PCR test for bacterial agents including Streptococcus pneumoniae, Hae- Fig. 1. Patients included in the study analysis. URI = upper respiratory tract infection, PCR = polymerase chain reaction, AdV = ad- mophilus influenzae, Mycoplasma pneumoniae, and Chlamyd- enovirus. ia pneumoniae; a multiplex real-time PCR test for respiratory 150 150 Leukopenia Thrombocytopenia No-leukopenia No-thrombocytopenia 125 125 100 100 75 75 50 50 Patients (number) Patients (number) Patients 25 25 0 0 A B 2012-Jul.2012-Oct.2013-Jan.2013-Apr.2013-Jul.2013-Oct.2014-Jan.2014-Apr.2014-Jul.2014-Oct.2015-Jan.2015-Apr.2015-Jul.2015-Oct.2016-Jan. 2012-Jul.2012-Oct.2013-Jan.2013-Apr.2013-Jul.2013-Oct.2014-Jan.2014-Apr.2014-Jul.2014-Oct.2015-Jan.2015-Apr.2015-Jul.2015-Oct.2016-Jan. Fig. 2. Time trend of patient number with leukopenia (A) and thrombocytopenia (B) among admitted patients with CAP (patient number per 3 months) (n = 540). CAP = community acquired pneumonia. 288 http://jkms.org https://doi.org/10.3346/jkms.2017.32.2.287 Yoon H, et al. • Characteristics of Adenovirus Pneumonia in Military Personnel viruses; and a urinary antigen test for S. pneumoniae or Legio- RESULTS nella pneumophila. Antiviral therapy