key: cord-1007310-wqperk54 authors: Hwang, Hyunjung; Kim, Yujin; Park, Jeong-Woong; Jeong, Sung Hwan; Kyung, Sun Young title: A Retrospective Study Investigating Risks of Acute Respiratory Distress Syndrome and Mortality Following Human Metapneumovirus Infection in Hospitalized Adults date: 2017-05-31 journal: Korean J Crit Care Med DOI: 10.4266/kjccm.2017.00038 sha: ddf5a29103d06a6ab0fef7f8c15c169050e493c2 doc_id: 1007310 cord_uid: wqperk54 BACKGROUND: Human metapneumovirus (hMPV) is a relatively recently identified respiratory virus that induces respiratory symptoms similar to those of respiratory syncytial virus infection in children. The characteristics of hMPV-infected adults are unclear because few cases have been reported. METHODS: We conducted a retrospective review of hospitalized adult patients with a positive multiplex real-time polymerase chain reaction assay result from 2012 to 2016 at a single tertiary referral hospital in South Korea. We analyzed clinical characteristics of the enrolled patients and divided patients into an acute respiratory distress syndrome (ARDS) group and a non-ARDS group. RESULTS: In total, 110 adults were reviewed in this study. Their mean age was 61.4 years, and the majority (n = 105, 95.5%) had comorbidities or were immunocompromised. Most of the patients had pneumonia on chest X-ray (n = 88, 93.6%), 22 (20.0%) had ARDS, and 12 (10.9%) expired during hospitalization. The mortality rate for patients with ARDS was higher than that of the other patients (36.4% vs. 5.7%, P = 0.001). The risk factor for hMPV-associated ARDS was heart failure (odds ratio, 5.24; P = 0.044) and laboratory values were increased blood urea nitrogen and increased C-reactive protein. The acquisition site of infection was divided into community vs. nosocomial; 43 patients (39.1%) had a nosocomial infection. The risk factors for nosocomial infection were an immunocompromised state, malignancy and immunosuppressive treatment. CONCLUSIONS: These data suggest that hMPV is one of the important respiratory pathogens important respiratory pathogen that causes pneumonia/ARDS in elderly, immunocompromised individuals and that it may be transmitted via the nosocomial route. to RSV [3] . Furthermore, hMPV is a major contributor to the burden of wintertime respiratory illness in older adults that is peak incidence at 65 years of age and immunocompromised individuals [2, 4, 5] . hMPV infections in children are usually mild and self-limiting, but in elderly and immunocompromised patients, the clinical course can progress to acute respiratory distress syndrome (ARDS) [6] . Studies of patients with hMPV who develop severe illness have focused on children; few have involved adults [7, 8] . Nosocomial infection has been reported in several studies as a mode of transmission [5, [9] [10] [11] . Nosocomial hMPV infection of adults occurs predominantly in human immunodeficiency virus-infected persons [12] . There are few studies on hMPV infection of adults in Korea. And the number of immunocompromised patients is increasing in hospitals. These patients are also vulnerable to previously neglected pathogens. Therefore, we designed a retrospective review of hMPV-infected adults. The clinical characteristics of the patients-including demographic data, comorbidities, presence of pneumonia or ARDS, acquisition site (community-acquired or nosocomial), and risk factors for ARDS-were reviewed. This study was a retrospective review of medical records; institutional review board approval was obtained We reviewed the medical records of the patients to identify those admitted to the intensive care unit (ICU) with a nosocomial infection and who met the criteria for ARDS using the Berlin definition [13] . The incubation period is estimated to be 4 to 6 days [14] . Nosocomial infection was defined as an infection that occurred up to 5 days after discharge or more than 5 days in admission. Death information of patients was confirmed using hospital medical record and obliterated information of national health insurance service which means death. Clinically relevant parameters were identified on the day of execution of mRT-PCR and admission to the ICU or ward; these included temperature, respiratory rate, applied fraction of inspired oxygen, partial pressure of arterial oxygen, white blood cell count, blood urea nitrogen (BUN)/creatinine, total bilirubin, C-reactive protein (CRP) level, and procalcitonin level. The patients were divided into non-ARDS and ARDS groups, and the risk factors and laboratory values for ARDS were assessed. All data analyses were performed using SPSS version 20.0 (IBM Corp., Armonk, NY, USA). Categorical variables were compared by Fisher exact test, and continuous variables by Wilcoxon's rank-sum test. The impact of potential risk factors on the development of ARDS was analyzed with univariate logistic regression analysis. Statistically significant variables at univariate analysis were included into a multivariate logistic regression analysis with backward elimination to identify independent risk factors of ARDS. The independent influences of risk factors for ARDS were expressed as the odds ratio (OR) with their 95% confidence intervals. Significance was taken as P < 0.05. The mean age of the adult patients was 61.4 ± 16.6 years, and there was no difference according to sex (Table 1) . Overall, 19 patients (17.3%) had viral co-infections, and 22 (20.0%) had bacterial co-infections. Co-infection did not affect event of ARDS, nosocomial infection and mortality. Most patients (n = 105, 95.5%) had comorbidities; these included diabetes, malignancy, pulmonary disease, cardiac disease, ESRD, and liver cirrhosis and they were being treated with corticosteroid or immuno- (Table 2) . The non-ARDS group included 88 patients while the ARDS group included 22 patients. The mean age of the non-ARDS group was 59.8 years, while that of the ARDS group was 68.0 years (OR, 1.034; P = 0.040). However, multivariate logistic regression showed age was not significant ( Table 3 ). The pattern of viral and bacterial co-infection did not differ between the ARDS and non-ARDS groups ( Table 1 ). The rates of comorbidities in the hMPV-associated ARDS patients were similar in hMPVassociated ARDS patients, with the exception of congestive heart failure (OR, 5.249; P = 0.044) ( Table 3 ). The inhospital and 1-year all-cause mortality rates of the ARDS patients were 36.4% and 40.9%, respectively (Table 1) . Additional analysis showed Kendal rank correalation coefficient was 0.752 (P = 0.001) between in hospital mortality and 1-year mortality. Therefore 1-year all-cause mortality was not independent variable. Overall, 67 patients had community-acquired hMPV infections and 43 had nosocomial infections. The patients with nosocomial infection showed the presence of comorbidities (e.g., solid tumor, hematologic disorder, liver cirrhosis, and immunosuppressive therapy; P < 0.05). However, the rates of mortality and hMPV-associated ARDS were not different between the community-acquired and nosocomial infection groups (Table 4 ). Our study is the first to characterize ARDS and mortality in the adult patients with hMPV infections in Korea. [8] . Although the scope of the studies, it is necessary to focus on high ARDS incidence and high mortality rates. The increasing availability and broadened scope of viral respiratory polymerase chain reaction panels helps our understanding of viral pathogens. The mRT-PCR assay had a sensitivity and specificity higher than 88% and 98.6%. And the mRT-PCR could detect co-infecting respiratory viruses, even at low viral loads that cannot be detected using culture techniques [15] . During the study period, the peak incidence of hMPV infection was in April, after that of influenza which had peak in February. A study in a similar area conducted from 2000 to 2005 reported a peak incidence of hMPV infection in January to March [16] , and another in March to April [17] . In this study, 17% of the subjects had viral co-infections, most frequently with influenza virus (Table 4 ). This is in agreement with a previous report [4] . These The hMPV infection has been reported in immunocompromised patients, including lung transplant and hematopoietic stem cell transplant recipients [3, 19] . Moreover, outbreaks in healthcare facilities have been reported [2, 9] . When considering the implications of these findings, it should be noted that the risk of nosocomial hMPV infection is on the rise among patients with blood cancer or patients with a solid tumor [20] This study has multiple limitations. Whether hMPV was the pathogen in all patients enrolled in this study was unclear. However, the mRT-PCR assay used has high sensitivity and specificity. Also, the rate of co-infection with other pathogens was not high (Table 5) . Future studies should assess the clinical features of hMPV infection in adults, determine the clinical potential of the virus as a respiratory pathogen to induce severe ARDS, and develop novel antiviral agents or vaccines. In conclusion, this study suggests that hMPV is an important respiratory pathogen that causes pneumonia/ ARDS in elderly, immunocompromised individuals and that it is transmitted via the nosocomial route. Clinicians need to consider mMPV virus and sufficient attention is required. Hyunjung Hwang http://orcid.org/0000-0003-3688-0962 The online-only Supplement data are available with this article online: https://doi.org/10.4266/kjccm.2017.00038. 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