Links to Exploration step
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Predictive factors for pneumonia development and progression to respiratory failure in MERS-CoV infected patients</title><author><name sortKey="Ko, Jae Hoon" sort="Ko, Jae Hoon" uniqKey="Ko J" first="Jae-Hoon" last="Ko">Jae-Hoon Ko</name><affiliation><nlm:aff id="aff1">Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 135-710, Republic of Korea</nlm:aff></affiliation></author><author><name sortKey="Park, Ga Eun" sort="Park, Ga Eun" uniqKey="Park G" first="Ga Eun" last="Park">Ga Eun Park</name><affiliation><nlm:aff id="aff1">Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 135-710, Republic of Korea</nlm:aff></affiliation></author><author><name sortKey="Lee, Ji Yeon" sort="Lee, Ji Yeon" uniqKey="Lee J" first="Ji Yeon" last="Lee">Ji Yeon Lee</name><affiliation><nlm:aff id="aff1">Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 135-710, Republic of Korea</nlm:aff></affiliation></author><author><name sortKey="Lee, Ji Yong" sort="Lee, Ji Yong" uniqKey="Lee J" first="Ji Yong" last="Lee">Ji Yong Lee</name><affiliation><nlm:aff id="aff1">Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 135-710, Republic of Korea</nlm:aff></affiliation></author><author><name sortKey="Cho, Sun Young" sort="Cho, Sun Young" uniqKey="Cho S" first="Sun Young" last="Cho">Sun Young Cho</name><affiliation><nlm:aff id="aff1">Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 135-710, Republic of Korea</nlm:aff></affiliation></author><author><name sortKey="Ha, Young Eun" sort="Ha, Young Eun" uniqKey="Ha Y" first="Young Eun" last="Ha">Young Eun Ha</name><affiliation><nlm:aff id="aff1">Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 135-710, Republic of Korea</nlm:aff></affiliation></author><author><name sortKey="Kang, Cheol In" sort="Kang, Cheol In" uniqKey="Kang C" first="Cheol-In" last="Kang">Cheol-In Kang</name><affiliation><nlm:aff id="aff1">Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 135-710, Republic of Korea</nlm:aff></affiliation></author><author><name sortKey="Kang, Ji Man" sort="Kang, Ji Man" uniqKey="Kang J" first="Ji-Man" last="Kang">Ji-Man Kang</name><affiliation><nlm:aff id="aff2">Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea</nlm:aff></affiliation></author><author><name sortKey="Kim, Yae Jean" sort="Kim, Yae Jean" uniqKey="Kim Y" first="Yae-Jean" last="Kim">Yae-Jean Kim</name><affiliation><nlm:aff id="aff2">Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea</nlm:aff></affiliation></author><author><name sortKey="Huh, Hee Jae" sort="Huh, Hee Jae" uniqKey="Huh H" first="Hee Jae" last="Huh">Hee Jae Huh</name><affiliation><nlm:aff id="aff3">Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea</nlm:aff></affiliation></author><author><name sortKey="Ki, Chang Seok" sort="Ki, Chang Seok" uniqKey="Ki C" first="Chang-Seok" last="Ki">Chang-Seok Ki</name><affiliation><nlm:aff id="aff3">Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea</nlm:aff></affiliation></author><author><name sortKey="Jeong, Byeong Ho" sort="Jeong, Byeong Ho" uniqKey="Jeong B" first="Byeong-Ho" last="Jeong">Byeong-Ho Jeong</name><affiliation><nlm:aff id="aff4">Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea</nlm:aff></affiliation></author><author><name sortKey="Park, Jinkyeong" sort="Park, Jinkyeong" uniqKey="Park J" first="Jinkyeong" last="Park">Jinkyeong Park</name><affiliation><nlm:aff id="aff5">Department of Critical Care Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea</nlm:aff></affiliation></author><author><name sortKey="Chung, Chi Ryang" sort="Chung, Chi Ryang" uniqKey="Chung C" first="Chi Ryang" last="Chung">Chi Ryang Chung</name><affiliation><nlm:aff id="aff5">Department of Critical Care Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea</nlm:aff></affiliation></author><author><name sortKey="Chung, Doo Ryeon" sort="Chung, Doo Ryeon" uniqKey="Chung D" first="Doo Ryeon" last="Chung">Doo Ryeon Chung</name><affiliation><nlm:aff id="aff1">Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 135-710, Republic of Korea</nlm:aff></affiliation></author><author><name sortKey="Song, Jae Hoon" sort="Song, Jae Hoon" uniqKey="Song J" first="Jae-Hoon" last="Song">Jae-Hoon Song</name><affiliation><nlm:aff id="aff1">Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 135-710, Republic of Korea</nlm:aff></affiliation></author><author><name sortKey="Peck, Kyong Ran" sort="Peck, Kyong Ran" uniqKey="Peck K" first="Kyong Ran" last="Peck">Kyong Ran Peck</name><affiliation><nlm:aff id="aff1">Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 135-710, Republic of Korea</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">27519621</idno><idno type="pmc">7112644</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7112644</idno><idno type="RBID">PMC:7112644</idno><idno type="doi">10.1016/j.jinf.2016.08.005</idno><date when="2016">2016</date><idno type="wicri:Area/Pmc/Corpus">000E65</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000E65</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Predictive factors for pneumonia development and progression to respiratory failure in MERS-CoV infected patients</title><author><name sortKey="Ko, Jae Hoon" sort="Ko, Jae Hoon" uniqKey="Ko J" first="Jae-Hoon" last="Ko">Jae-Hoon Ko</name><affiliation><nlm:aff id="aff1">Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 135-710, Republic of Korea</nlm:aff></affiliation></author><author><name sortKey="Park, Ga Eun" sort="Park, Ga Eun" uniqKey="Park G" first="Ga Eun" last="Park">Ga Eun Park</name><affiliation><nlm:aff id="aff1">Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 135-710, Republic of Korea</nlm:aff></affiliation></author><author><name sortKey="Lee, Ji Yeon" sort="Lee, Ji Yeon" uniqKey="Lee J" first="Ji Yeon" last="Lee">Ji Yeon Lee</name><affiliation><nlm:aff id="aff1">Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 135-710, Republic of Korea</nlm:aff></affiliation></author><author><name sortKey="Lee, Ji Yong" sort="Lee, Ji Yong" uniqKey="Lee J" first="Ji Yong" last="Lee">Ji Yong Lee</name><affiliation><nlm:aff id="aff1">Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 135-710, Republic of Korea</nlm:aff></affiliation></author><author><name sortKey="Cho, Sun Young" sort="Cho, Sun Young" uniqKey="Cho S" first="Sun Young" last="Cho">Sun Young Cho</name><affiliation><nlm:aff id="aff1">Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 135-710, Republic of Korea</nlm:aff></affiliation></author><author><name sortKey="Ha, Young Eun" sort="Ha, Young Eun" uniqKey="Ha Y" first="Young Eun" last="Ha">Young Eun Ha</name><affiliation><nlm:aff id="aff1">Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 135-710, Republic of Korea</nlm:aff></affiliation></author><author><name sortKey="Kang, Cheol In" sort="Kang, Cheol In" uniqKey="Kang C" first="Cheol-In" last="Kang">Cheol-In Kang</name><affiliation><nlm:aff id="aff1">Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 135-710, Republic of Korea</nlm:aff></affiliation></author><author><name sortKey="Kang, Ji Man" sort="Kang, Ji Man" uniqKey="Kang J" first="Ji-Man" last="Kang">Ji-Man Kang</name><affiliation><nlm:aff id="aff2">Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea</nlm:aff></affiliation></author><author><name sortKey="Kim, Yae Jean" sort="Kim, Yae Jean" uniqKey="Kim Y" first="Yae-Jean" last="Kim">Yae-Jean Kim</name><affiliation><nlm:aff id="aff2">Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea</nlm:aff></affiliation></author><author><name sortKey="Huh, Hee Jae" sort="Huh, Hee Jae" uniqKey="Huh H" first="Hee Jae" last="Huh">Hee Jae Huh</name><affiliation><nlm:aff id="aff3">Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea</nlm:aff></affiliation></author><author><name sortKey="Ki, Chang Seok" sort="Ki, Chang Seok" uniqKey="Ki C" first="Chang-Seok" last="Ki">Chang-Seok Ki</name><affiliation><nlm:aff id="aff3">Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea</nlm:aff></affiliation></author><author><name sortKey="Jeong, Byeong Ho" sort="Jeong, Byeong Ho" uniqKey="Jeong B" first="Byeong-Ho" last="Jeong">Byeong-Ho Jeong</name><affiliation><nlm:aff id="aff4">Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea</nlm:aff></affiliation></author><author><name sortKey="Park, Jinkyeong" sort="Park, Jinkyeong" uniqKey="Park J" first="Jinkyeong" last="Park">Jinkyeong Park</name><affiliation><nlm:aff id="aff5">Department of Critical Care Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea</nlm:aff></affiliation></author><author><name sortKey="Chung, Chi Ryang" sort="Chung, Chi Ryang" uniqKey="Chung C" first="Chi Ryang" last="Chung">Chi Ryang Chung</name><affiliation><nlm:aff id="aff5">Department of Critical Care Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea</nlm:aff></affiliation></author><author><name sortKey="Chung, Doo Ryeon" sort="Chung, Doo Ryeon" uniqKey="Chung D" first="Doo Ryeon" last="Chung">Doo Ryeon Chung</name><affiliation><nlm:aff id="aff1">Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 135-710, Republic of Korea</nlm:aff></affiliation></author><author><name sortKey="Song, Jae Hoon" sort="Song, Jae Hoon" uniqKey="Song J" first="Jae-Hoon" last="Song">Jae-Hoon Song</name><affiliation><nlm:aff id="aff1">Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 135-710, Republic of Korea</nlm:aff></affiliation></author><author><name sortKey="Peck, Kyong Ran" sort="Peck, Kyong Ran" uniqKey="Peck K" first="Kyong Ran" last="Peck">Kyong Ran Peck</name><affiliation><nlm:aff id="aff1">Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 135-710, Republic of Korea</nlm:aff></affiliation></author></analytic><series><title level="j">The Journal of Infection</title><idno type="ISSN">0163-4453</idno><idno type="eISSN">1532-2742</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Summary</title><sec><title>Background</title><p>After the 2015 Middle East respiratory syndrome (MERS) outbreak in Korea, prediction of pneumonia development and progression to respiratory failure was emphasized in control of MERS outbreak.</p></sec><sec><title>Methods</title><p>MERS-CoV infected patients who were managed in a tertiary care center during the 2015 Korean MERS outbreak were reviewed. To analyze predictive factors for pneumonia development and progression to respiratory failure, we evaluated clinical variables measured within three days from symptom onset.</p></sec><sec><title>Results</title><p>A total of 45 patients were included in the study: 13 patients (28.9%) did not develop pneumonia, 19 developed pneumonia without respiratory failure (42.2%), and 13 progressed to respiratory failures (28.9%). The identified predictive factors for pneumonia development included age ≥45 years, fever ≥37.5 °C, thrombocytopenia, lymphopenia, CRP ≥ 2 mg/dL, and a threshold cycle value of PCR less than 28.5. For respiratory failure, the indicators included male, hypertension, low albumin concentration, thrombocytopenia, lymphopenia, and CRP ≥ 4 mg/dL (all <italic>P</italic> < 0.05). With ≥ two predictive factors for pneumonia development, 100% of patients developed pneumonia. Patients lacking the predictive factors did not progress to respiratory failure.</p></sec><sec><title>Conclusion</title><p>For successful control of MERS outbreak, MERS-CoV infected patients with ≥ two predictive factors should be intensively managed from the initial presentation.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Zumla, A" uniqKey="Zumla A">A. Zumla</name></author><author><name sortKey="Hui, D S" uniqKey="Hui D">D.S. Hui</name></author><author><name sortKey="Perlman, S" uniqKey="Perlman S">S. Perlman</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Kim, Y" uniqKey="Kim Y">Y. Kim</name></author><author><name sortKey="Lee, S" uniqKey="Lee S">S. Lee</name></author><author><name sortKey="Chu, C" uniqKey="Chu C">C. Chu</name></author><author><name sortKey="Choe, S" uniqKey="Choe S">S. Choe</name></author><author><name sortKey="Hong, S" uniqKey="Hong S">S. Hong</name></author><author><name sortKey="Shin, Y" uniqKey="Shin Y">Y. Shin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cowling, B J" uniqKey="Cowling B">B.J. Cowling</name></author><author><name sortKey="Park, M" uniqKey="Park M">M. Park</name></author><author><name sortKey="Fang, V J" uniqKey="Fang V">V.J. Fang</name></author><author><name sortKey="Wu, P" uniqKey="Wu P">P. Wu</name></author><author><name sortKey="Leung, G M" uniqKey="Leung G">G.M. Leung</name></author><author><name sortKey="Wu, J T" uniqKey="Wu J">J.T. Wu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nishiura, H" uniqKey="Nishiura H">H. Nishiura</name></author><author><name sortKey="Endo, A" uniqKey="Endo A">A. Endo</name></author><author><name sortKey="Saitoh, M" uniqKey="Saitoh M">M. Saitoh</name></author><author><name sortKey="Kinoshita, R" uniqKey="Kinoshita R">R. Kinoshita</name></author><author><name sortKey="Ueno, R" uniqKey="Ueno R">R. Ueno</name></author><author><name sortKey="Nakaoka, S" uniqKey="Nakaoka S">S. Nakaoka</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chowell, G" uniqKey="Chowell G">G. Chowell</name></author><author><name sortKey="Abdirizak, F" uniqKey="Abdirizak F">F. Abdirizak</name></author><author><name sortKey="Lee, S" uniqKey="Lee S">S. Lee</name></author><author><name sortKey="Lee, J" uniqKey="Lee J">J. Lee</name></author><author><name sortKey="Jung, E" uniqKey="Jung E">E. Jung</name></author><author><name sortKey="Nishiura, H" uniqKey="Nishiura H">H. Nishiura</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Park, G E" uniqKey="Park G">G.E. Park</name></author><author><name sortKey="Ko, J H" uniqKey="Ko J">J.H. Ko</name></author><author><name sortKey="Peck, K R" uniqKey="Peck K">K.R. Peck</name></author><author><name sortKey="Lee, J Y" uniqKey="Lee J">J.Y. Lee</name></author><author><name sortKey="Lee, J Y" uniqKey="Lee J">J.Y. Lee</name></author><author><name sortKey="Cho, S Y" uniqKey="Cho S">S.Y. Cho</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cho, S Y" uniqKey="Cho S">S.Y. Cho</name></author><author><name sortKey="Kang, J M" uniqKey="Kang J">J.M. Kang</name></author><author><name sortKey="Ha, Y E" uniqKey="Ha Y">Y.E. Ha</name></author><author><name sortKey="Park, G E" uniqKey="Park G">G.E. Park</name></author><author><name sortKey="Lee, J Y" uniqKey="Lee J">J.Y. Lee</name></author><author><name sortKey="Ko, J H" uniqKey="Ko J">J.H. Ko</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mizumoto, K" uniqKey="Mizumoto K">K. Mizumoto</name></author><author><name sortKey="Endo, A" uniqKey="Endo A">A. Endo</name></author><author><name sortKey="Chowell, G" uniqKey="Chowell G">G. Chowell</name></author><author><name sortKey="Miyamatsu, Y" uniqKey="Miyamatsu Y">Y. Miyamatsu</name></author><author><name sortKey="Saitoh, M" uniqKey="Saitoh M">M. Saitoh</name></author><author><name sortKey="Nishiura, H" uniqKey="Nishiura H">H. Nishiura</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Corman, V M" uniqKey="Corman V">V.M. Corman</name></author><author><name sortKey="Albarrak, A M" uniqKey="Albarrak A">A.M. Albarrak</name></author><author><name sortKey="Omrani, A S" uniqKey="Omrani A">A.S. Omrani</name></author><author><name sortKey="Albarrak, M M" uniqKey="Albarrak M">M.M. Albarrak</name></author><author><name sortKey="Farah, M E" uniqKey="Farah M">M.E. Farah</name></author><author><name sortKey="Almasri, M" uniqKey="Almasri M">M. Almasri</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Feikin, D R" uniqKey="Feikin D">D.R. Feikin</name></author><author><name sortKey="Alraddadi, B" uniqKey="Alraddadi B">B. Alraddadi</name></author><author><name sortKey="Qutub, M" uniqKey="Qutub M">M. Qutub</name></author><author><name sortKey="Shabouni, O" uniqKey="Shabouni O">O. Shabouni</name></author><author><name sortKey="Curns, A" uniqKey="Curns A">A. Curns</name></author><author><name sortKey="Oboho, I K" uniqKey="Oboho I">I.K. Oboho</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Majumder, M S" uniqKey="Majumder M">M.S. Majumder</name></author><author><name sortKey="Kluberg, S A" uniqKey="Kluberg S">S.A. Kluberg</name></author><author><name sortKey="Mekaru, S R" uniqKey="Mekaru S">S.R. Mekaru</name></author><author><name sortKey="Brownstein, J S" uniqKey="Brownstein J">J.S. Brownstein</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Saad, M" uniqKey="Saad M">M. Saad</name></author><author><name sortKey="Omrani, A S" uniqKey="Omrani A">A.S. Omrani</name></author><author><name sortKey="Baig, K" uniqKey="Baig K">K. Baig</name></author><author><name sortKey="Bahloul, A" uniqKey="Bahloul A">A. Bahloul</name></author><author><name sortKey="Elzein, F" uniqKey="Elzein F">F. Elzein</name></author><author><name sortKey="Matin, M A" uniqKey="Matin M">M.A. Matin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Banik, G R" uniqKey="Banik G">G.R. Banik</name></author><author><name sortKey="Alqahtani, A S" uniqKey="Alqahtani A">A.S. Alqahtani</name></author><author><name sortKey="Booy, R" uniqKey="Booy R">R. Booy</name></author><author><name sortKey="Rashid, H" uniqKey="Rashid H">H. Rashid</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Madani, T A" uniqKey="Madani T">T.A. Madani</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Oboho, I K" uniqKey="Oboho I">I.K. Oboho</name></author><author><name sortKey="Tomczyk, S M" uniqKey="Tomczyk S">S.M. Tomczyk</name></author><author><name sortKey="Al Asmari, A M" uniqKey="Al Asmari A">A.M. Al-Asmari</name></author><author><name sortKey="Banjar, A A" uniqKey="Banjar A">A.A. Banjar</name></author><author><name sortKey="Al Mugti, H" uniqKey="Al Mugti H">H. Al-Mugti</name></author><author><name sortKey="Aloraini, M S" uniqKey="Aloraini M">M.S. Aloraini</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Woolf, B" uniqKey="Woolf B">B. Woolf</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Al Ghamdi, M" uniqKey="Al Ghamdi M">M. Al Ghamdi</name></author><author><name sortKey="Alghamdi, K M" uniqKey="Alghamdi K">K.M. Alghamdi</name></author><author><name sortKey="Ghandoora, Y" uniqKey="Ghandoora Y">Y. Ghandoora</name></author><author><name sortKey="Alzahrani, A" uniqKey="Alzahrani A">A. Alzahrani</name></author><author><name sortKey="Salah, F" uniqKey="Salah F">F. Salah</name></author><author><name sortKey="Alsulami, A" uniqKey="Alsulami A">A. Alsulami</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Modjarrad, K" uniqKey="Modjarrad K">K. Modjarrad</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chan, J F" uniqKey="Chan J">J.F. Chan</name></author><author><name sortKey="Yao, Y" uniqKey="Yao Y">Y. Yao</name></author><author><name sortKey="Yeung, M L" uniqKey="Yeung M">M.L. Yeung</name></author><author><name sortKey="Deng, W" uniqKey="Deng W">W. Deng</name></author><author><name sortKey="Bao, L" uniqKey="Bao L">L. Bao</name></author><author><name sortKey="Jia, L" uniqKey="Jia L">L. Jia</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Min, C K" uniqKey="Min C">C.K. Min</name></author><author><name sortKey="Cheon, S" uniqKey="Cheon S">S. Cheon</name></author><author><name sortKey="Ha, N Y" uniqKey="Ha N">N.Y. Ha</name></author><author><name sortKey="Sohn, K M" uniqKey="Sohn K">K.M. Sohn</name></author><author><name sortKey="Kim, Y" uniqKey="Kim Y">Y. Kim</name></author><author><name sortKey="Aigerim, A" uniqKey="Aigerim A">A. Aigerim</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Arabi, Y M" uniqKey="Arabi Y">Y.M. Arabi</name></author><author><name sortKey="Arifi, A A" uniqKey="Arifi A">A.A. Arifi</name></author><author><name sortKey="Balkhy, H H" uniqKey="Balkhy H">H.H. Balkhy</name></author><author><name sortKey="Najm, H" uniqKey="Najm H">H. Najm</name></author><author><name sortKey="Aldawood, A S" uniqKey="Aldawood A">A.S. Aldawood</name></author><author><name sortKey="Ghabashi, A" uniqKey="Ghabashi A">A. Ghabashi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Guery, B" uniqKey="Guery B">B. Guery</name></author><author><name sortKey="Poissy, J" uniqKey="Poissy J">J. Poissy</name></author><author><name sortKey="El Mansouf, L" uniqKey="El Mansouf L">L. el Mansouf</name></author><author><name sortKey="Sejourne, C" uniqKey="Sejourne C">C. Sejourne</name></author><author><name sortKey="Ettahar, N" uniqKey="Ettahar N">N. Ettahar</name></author><author><name sortKey="Lemaire, X" uniqKey="Lemaire X">X. Lemaire</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Choi, K W" uniqKey="Choi K">K.W. Choi</name></author><author><name sortKey="Chau, T N" uniqKey="Chau T">T.N. Chau</name></author><author><name sortKey="Tsang, O" uniqKey="Tsang O">O. Tsang</name></author><author><name sortKey="Tso, E" uniqKey="Tso E">E. Tso</name></author><author><name sortKey="Chiu, M C" uniqKey="Chiu M">M.C. Chiu</name></author><author><name sortKey="Tong, W L" uniqKey="Tong W">W.L. Tong</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lupovitch, A" uniqKey="Lupovitch A">A. Lupovitch</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yang, M" uniqKey="Yang M">M. Yang</name></author><author><name sortKey="Ng, M H" uniqKey="Ng M">M.H. Ng</name></author><author><name sortKey="Li, C K" uniqKey="Li C">C.K. Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Le, V B" uniqKey="Le V">V.B. Le</name></author><author><name sortKey="Schneider, J G" uniqKey="Schneider J">J.G. Schneider</name></author><author><name sortKey="Boergeling, Y" uniqKey="Boergeling Y">Y. Boergeling</name></author><author><name sortKey="Berri, F" uniqKey="Berri F">F. Berri</name></author><author><name sortKey="Ducatez, M" uniqKey="Ducatez M">M. Ducatez</name></author><author><name sortKey="Guerin, J L" uniqKey="Guerin J">J.L. Guerin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ying, T" uniqKey="Ying T">T. Ying</name></author><author><name sortKey="Li, W" uniqKey="Li W">W. Li</name></author><author><name sortKey="Dimitrov, D S" uniqKey="Dimitrov D">D.S. Dimitrov</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chu, H" uniqKey="Chu H">H. Chu</name></author><author><name sortKey="Zhou, J" uniqKey="Zhou J">J. Zhou</name></author><author><name sortKey="Wong, B H" uniqKey="Wong B">B.H. Wong</name></author><author><name sortKey="Li, C" uniqKey="Li C">C. Li</name></author><author><name sortKey="Chan, J F" uniqKey="Chan J">J.F. Chan</name></author><author><name sortKey="Cheng, Z S" uniqKey="Cheng Z">Z.S. Cheng</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Assiri, A" uniqKey="Assiri A">A. Assiri</name></author><author><name sortKey="Al Tawfiq, J A" uniqKey="Al Tawfiq J">J.A. Al-Tawfiq</name></author><author><name sortKey="Al Rabeeah, A A" uniqKey="Al Rabeeah A">A.A. Al-Rabeeah</name></author><author><name sortKey="Al Rabiah, F A" uniqKey="Al Rabiah F">F.A. Al-Rabiah</name></author><author><name sortKey="Al Hajjar, S" uniqKey="Al Hajjar S">S. Al-Hajjar</name></author><author><name sortKey="Al Barrak, A" uniqKey="Al Barrak A">A. Al-Barrak</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chan, J F" uniqKey="Chan J">J.F. Chan</name></author><author><name sortKey="Lau, S K" uniqKey="Lau S">S.K. Lau</name></author><author><name sortKey="To, K K" uniqKey="To K">K.K. To</name></author><author><name sortKey="Cheng, V C" uniqKey="Cheng V">V.C. Cheng</name></author><author><name sortKey="Woo, P C" uniqKey="Woo P">P.C. Woo</name></author><author><name sortKey="Yuen, K Y" uniqKey="Yuen K">K.Y. Yuen</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">J Infect</journal-id><journal-id journal-id-type="iso-abbrev">J. Infect</journal-id><journal-title-group><journal-title>The Journal of Infection</journal-title></journal-title-group><issn pub-type="ppub">0163-4453</issn><issn pub-type="epub">1532-2742</issn><publisher><publisher-name>The British Infection Association. Published by Elsevier Ltd.</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">27519621</article-id><article-id pub-id-type="pmc">7112644</article-id><article-id pub-id-type="publisher-id">S0163-4453(16)30209-2</article-id><article-id pub-id-type="doi">10.1016/j.jinf.2016.08.005</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Predictive factors for pneumonia development and progression to respiratory failure in MERS-CoV infected patients</article-title></title-group><contrib-group><contrib contrib-type="author" id="au1"><name><surname>Ko</surname><given-names>Jae-Hoon</given-names></name><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author" id="au2"><name><surname>Park</surname><given-names>Ga Eun</given-names></name><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author" id="au3"><name><surname>Lee</surname><given-names>Ji Yeon</given-names></name><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author" id="au4"><name><surname>Lee</surname><given-names>Ji Yong</given-names></name><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author" id="au5"><name><surname>Cho</surname><given-names>Sun Young</given-names></name><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author" id="au6"><name><surname>Ha</surname><given-names>Young Eun</given-names></name><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author" id="au7"><name><surname>Kang</surname><given-names>Cheol-In</given-names></name><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author" id="au8"><name><surname>Kang</surname><given-names>Ji-Man</given-names></name><xref rid="aff2" ref-type="aff">b</xref></contrib><contrib contrib-type="author" id="au9"><name><surname>Kim</surname><given-names>Yae-Jean</given-names></name><xref rid="aff2" ref-type="aff">b</xref></contrib><contrib contrib-type="author" id="au10"><name><surname>Huh</surname><given-names>Hee Jae</given-names></name><xref rid="aff3" ref-type="aff">c</xref></contrib><contrib contrib-type="author" id="au11"><name><surname>Ki</surname><given-names>Chang-Seok</given-names></name><xref rid="aff3" ref-type="aff">c</xref></contrib><contrib contrib-type="author" id="au12"><name><surname>Jeong</surname><given-names>Byeong-Ho</given-names></name><xref rid="aff4" ref-type="aff">d</xref></contrib><contrib contrib-type="author" id="au13"><name><surname>Park</surname><given-names>Jinkyeong</given-names></name><xref rid="aff5" ref-type="aff">e</xref></contrib><contrib contrib-type="author" id="au14"><name><surname>Chung</surname><given-names>Chi Ryang</given-names></name><xref rid="aff5" ref-type="aff">e</xref></contrib><contrib contrib-type="author" id="au15"><name><surname>Chung</surname><given-names>Doo Ryeon</given-names></name><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author" id="au16"><name><surname>Song</surname><given-names>Jae-Hoon</given-names></name><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author" id="au17"><name><surname>Peck</surname><given-names>Kyong Ran</given-names></name><email>krpeck@skku.edu</email><xref rid="aff1" ref-type="aff">a</xref><xref rid="cor1" ref-type="corresp">∗</xref></contrib></contrib-group><aff id="aff1"><label>a</label>Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 135-710, Republic of Korea</aff><aff id="aff2"><label>b</label>Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea</aff><aff id="aff3"><label>c</label>Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea</aff><aff id="aff4"><label>d</label>Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea</aff><aff id="aff5"><label>e</label>Department of Critical Care Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea</aff><author-notes><corresp id="cor1"><label>∗</label>Corresponding author. Fax: +82 2 3410 0064. <email>krpeck@skku.edu</email></corresp></author-notes><pub-date pub-type="pmc-release"><day>9</day><month>8</month><year>2016</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on .</pmc-comment>
<pub-date pub-type="ppub"><month>11</month><year>2016</year></pub-date><pub-date pub-type="epub"><day>9</day><month>8</month><year>2016</year></pub-date><volume>73</volume><issue>5</issue><fpage>468</fpage><lpage>475</lpage><history><date date-type="accepted"><day>5</day><month>8</month><year>2016</year></date></history><permissions><copyright-statement>© 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.</copyright-statement><copyright-year>2016</copyright-year><copyright-holder>The British Infection Association</copyright-holder><license><license-p>Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.</license-p></license></permissions><abstract id="abs0010"><title>Summary</title><sec><title>Background</title><p>After the 2015 Middle East respiratory syndrome (MERS) outbreak in Korea, prediction of pneumonia development and progression to respiratory failure was emphasized in control of MERS outbreak.</p></sec><sec><title>Methods</title><p>MERS-CoV infected patients who were managed in a tertiary care center during the 2015 Korean MERS outbreak were reviewed. To analyze predictive factors for pneumonia development and progression to respiratory failure, we evaluated clinical variables measured within three days from symptom onset.</p></sec><sec><title>Results</title><p>A total of 45 patients were included in the study: 13 patients (28.9%) did not develop pneumonia, 19 developed pneumonia without respiratory failure (42.2%), and 13 progressed to respiratory failures (28.9%). The identified predictive factors for pneumonia development included age ≥45 years, fever ≥37.5 °C, thrombocytopenia, lymphopenia, CRP ≥ 2 mg/dL, and a threshold cycle value of PCR less than 28.5. For respiratory failure, the indicators included male, hypertension, low albumin concentration, thrombocytopenia, lymphopenia, and CRP ≥ 4 mg/dL (all <italic>P</italic> < 0.05). With ≥ two predictive factors for pneumonia development, 100% of patients developed pneumonia. Patients lacking the predictive factors did not progress to respiratory failure.</p></sec><sec><title>Conclusion</title><p>For successful control of MERS outbreak, MERS-CoV infected patients with ≥ two predictive factors should be intensively managed from the initial presentation.</p></sec></abstract><abstract abstract-type="author-highlights" id="abs0015"><title>Highlights</title><p><list list-type="simple" id="ulist0010"><list-item id="u0010"><label>•</label><p id="p0010">Predictive factors for pneumonia progression in MERS patients were investigated.</p></list-item><list-item id="u0015"><label>•</label><p id="p0015">Clinical variables measured within three days from symptom onset were used.</p></list-item><list-item id="u0020"><label>•</label><p id="p0020">Six predictive factors for pneumonia development and respiratory failure were found.</p></list-item><list-item id="u0025"><label>•</label><p id="p0025">With ≥ two predictive factors for pneumonia, 100% of patients developed pneumonia.</p></list-item><list-item id="u0030"><label>•</label><p id="p0030">Patients lacking the predictive factors did not progress to respiratory failure.</p></list-item></list></p></abstract><kwd-group id="kwrds0010"><title>Keywords</title><kwd>Predictive factor</kwd><kwd>Pneumonia</kwd><kwd>Respiratory failure</kwd><kwd>Disease progression</kwd><kwd>Middle East respiratory syndrome coronavirus</kwd></kwd-group></article-meta></front><body><sec id="sec1"><title>Introduction</title><p id="p0035">Middle East respiratory syndrome (MERS) is an emerging lethal respiratory disease caused by a novel betacoronavirus (MERS-CoV).<xref rid="bib1" ref-type="bibr"><sup>1</sup></xref> From May to July 2015, there was a hospital-associated MERS outbreak in the Republic of Korea reporting 186 laboratory-confirmed cases, which is the largest recorded outbreak outside the Arabian Peninsula.<xref rid="bib2" ref-type="bibr">2</xref>, <xref rid="bib3" ref-type="bibr">3</xref>, <xref rid="bib4" ref-type="bibr">4</xref>, <xref rid="bib5" ref-type="bibr">5</xref>, <xref rid="bib6" ref-type="bibr">6</xref> The outbreak featured several super-spreading events with unexpectedly high human-to-human transmission rate: 136 of 186 cases (73.1%) were transmitted from only three patients.<xref rid="bib5" ref-type="bibr">5</xref>, <xref rid="bib7" ref-type="bibr">7</xref>, <xref rid="bib8" ref-type="bibr">8</xref>, <xref rid="bib9" ref-type="bibr">9</xref>, <xref rid="bib10" ref-type="bibr">10</xref> As these large transmission clusters were exclusively originated from patients with pneumonia, prediction of pneumonia development has been emphasized in control of MERS outbreak.<xref rid="bib9" ref-type="bibr"><sup>9</sup></xref> In addition, pneumonia progression to respiratory failure should be anticipated in advance to avoid urgent intubation or cardiopulmonary resuscitation which might break protection of healthcare workers. Although several studies analyzed prognostic factors for fatal outcome,<xref rid="bib11" ref-type="bibr">11</xref>, <xref rid="bib12" ref-type="bibr">12</xref>, <xref rid="bib13" ref-type="bibr">13</xref>, <xref rid="bib14" ref-type="bibr">14</xref>, <xref rid="bib15" ref-type="bibr">15</xref>, <xref rid="bib16" ref-type="bibr">16</xref> predictive factors for pneumonia development and progression to respiratory failure have not been reported. To identify factors which can predict pneumonia development and progression to respiratory failure at the early course of the disease, we evaluated MERS-CoV infected patients managed in a tertiary care center during the 2015 MERS outbreak in Korea.</p></sec><sec id="sec2"><title>Methods</title><sec id="sec2.1"><title>Study design and patient grouping</title><p id="p0040">To identify factors which can predict pneumonia development and progression to respiratory failure at the early course of the disease, we reviewed the electronic medical records of who were diagnosed with MERS-CoV infection and admitted at Samsung Medical Center, a 1950 tertiary care university hospital which managed the largest number of MERS-CoV infected patients as a single center during the 2015 Korean MERS outbreak. As it is still unclear whether initially asymptomatic patients would develop pneumonia or not,<xref rid="bib17" ref-type="bibr"><sup>17</sup></xref> we included all the MERS-CoV infected patients managed at our hospital during the outbreak regardless of symptoms presence. To avoid confusion with the case definition of MERS which did not included asymptomatic cases,<xref rid="bib18" ref-type="bibr"><sup>18</sup></xref> we used the term of ‘MERS-CoV infected patient’ rather than ‘MERS patients’ throughout the present paper. MERS-CoV infections were confirmed on the basis of rRT-PCR assays targeting upstream of the E gene and the open-reading frame gene 1a.<xref rid="bib18" ref-type="bibr">18</xref>, <xref rid="bib19" ref-type="bibr">19</xref> Disease status of included patients was assessed at six weeks from their symptom onset and patients were divided into three groups depending on pneumonia development and progression to respiratory failure: patients without the development of pneumonia (group 1), patients who developed pneumonia without respiratory failure (group 2), and pneumonia patients who progressed to respiratory failure (group 3). For practical purposes, respiratory failure was defined as the need for mechanical ventilation (MV). The institutional review board of our hospital approved the present study.</p></sec><sec id="sec2.2"><title>Data collection and operational definitions</title><p id="p0045">We retrospectively collected data from electronic medical records and epidemiologic investigation. To identify factors which can predict pneumonia development and progression to respiratory failure at the early course of the disease, we evaluated clinical variables measured within three days from symptom onset. During the 2015 Korean MERS outbreak, fever was defined as body temperature ≥37.5 °C to increase sensitivity of screening and the same definition was used in the present analysis.<xref rid="bib9" ref-type="bibr"><sup>9</sup></xref> Thrombocytopenia was defined as a platelet count lower than 150 × 10<sup>3</sup> cells/mm<sup>3</sup>, lymphopenia as an absolute lymphocyte count lower than 1,000 cells/mm<sup>3</sup>, and hypoalbuminemia as albumin concentration lower than 3.5 g/dL. Lower respiratory tract specimens including sputum and endotracheal aspirates were used for MERS-CoV rRT-PCR. Cycle threshold (Ct) values of MERS-CoV rRT-PCR were used as a surrogate of viral load. Pneumonia development of MERS-CoV infected patient was defined as presence of parenchymal infiltration on chest X-ray with respiratory symptoms. Test days or events were counted from the day of symptom onset for each patient: day 1 was defined as the day of symptom onset. For asymptomatic patients, the day of diagnosis of MERS-CoV infection was considered as day 1.</p></sec><sec id="sec2.3"><title>Statistical analysis</title><p id="p0050">To identify predictive factors for pneumonia development and progression to respiratory failure, clinical variables measured within three days from symptom onset were compared. For evaluation of pneumonia development, patients who developed pneumonia (group 2 and 3) were compared to those who did not (group 1). For factors for respiratory failure, patients who progressed to respiratory failure (group 3) were compared to those who did not (group 1 and 2). Student's t-tests or Mann–Whitney U tests were used to compare continuous variables, and chi-square tests or Fisher's exact tests were used to compare categorical variables. Statistically significant continuous variables were re-categorized into binary factors using threshold values between mean of each group, which showed lowest <italic>P</italic> value. Statistically significant categorical variables and binary factors re-categorized from continuous variables were defined as predictive factors. For significant predictive factors, as a measure of association, odds ratio (OR) and 95% confidence interval (CI) for OR were calculated using the Woolf procedure.<xref rid="bib20" ref-type="bibr"><sup>20</sup></xref> Multivariate analysis was not performed due to the limited sample size. All <italic>P</italic>-values were two-tailed, and those <0.05 were considered to be statistically significant. IBM SPSS Statistics version 20.0 for Windows (IBM, Armonk, NY, USA) was used for all statistical analyses.</p></sec></sec><sec id="sec3"><title>Results</title><sec id="sec3.1"><title>Time course of pneumonia development and progression to respiratory failure</title><p id="p0055">A total of 45 MERS-CoV infected patients were hospitalized during the outbreak with 13 patients in group 1 (including 3 asymptomatic patients), 19 patients in group 2, and 13 patients in group 3. The clinical course of symptomatic MERS patients progressed serially: patients developed initial symptoms after a median 5-day incubation period (IQR 3.5–7.0), pneumonia after a median of 6 days from symptom onset (IQR 5.0–7.0), and respiratory failure after a median of 12 days from symptom onset (IQR 10.0–13.0). In group 3 patients, it took a median of 2 days from desaturation to respiratory failure (IQR 1–3 days). The development and progression of pneumonia by time sequence is depicted in <xref rid="fig1" ref-type="fig">Fig. 1</xref>. No one developed pneumonia before day 4 of symptom onset.<fig id="fig1"><label>Figure 1</label><caption><p><bold>The development and progression of pneumonia in patients with MERS-CoV infection depicted by time sequence</bold> MERS-CoV infected patients were divided into three groups: patients without the development of pneumonia (group 1), patients who developed pneumonia without respiratory failure (group 2), and pneumonia patients who progressed to respiratory failure (group 3). (<bold>a</bold>) <bold>Number of patients who developed pneumonia and who received endotracheal intubation due to respiratory failure by the days after symptom onset</bold>. Patients in group 3 developed pneumonia earlier than those in group 2, and progressed to respiratory failure sequentially. (<bold>b</bold>) <bold>Overall presentation of pneumonia development and progression</bold>. The development of pneumonia, desaturation, endotracheal intubation, and application of ECMO occurred step by step. Abbreviations: ECMO, extracorporeal membrane oxygenation.</p></caption><alt-text id="alttext0010">Fig. 1</alt-text><graphic xlink:href="gr1_lrg"></graphic></fig></p></sec><sec id="sec3.2"><title>Predictive factors for pneumonia development</title><p id="p0060">To evaluate predictive factors for pneumonia development, demographics, underlying diseases, and clinical variables of patients in group 2 and 3 were compared to those of patients in group 1 (<xref rid="tbl1" ref-type="table">Table 1</xref>, <xref rid="tbl2" ref-type="table">Table 2</xref>). Identified predictive factors are summarized in <xref rid="tbl3" ref-type="table">Table 3</xref>with odd ratios (OR). Increasing age was significantly associated with pneumonia development as a continuous variable (<italic>P</italic> = 0.015), and age older than 45 years was a predictive factor for the development of pneumonia (OR, 8.04; 95% CI, 1.52–42.43; <italic>P</italic> = 0.007). Although proportion of male also increased with progression of pneumonia (38.5%, 57.9%, and 84.6% for group 1, 2, and 3, respectively), statistically significant association between male sex and the pneumonia development was not identified (<italic>P</italic> = 0.097).<table-wrap position="float" id="tbl1"><label>Table 1</label><caption><p>Demographics and underling diseases of MERS-CoV infected patients compared depending on pneumonia development and progression to respiratory failure.</p></caption><alt-text id="alttext0015">Table 1</alt-text><table frame="hsides" rules="groups"><thead><tr><th rowspan="2">Variables</th><th rowspan="2">Group 1<break></break><italic>Without pneumonia</italic><break></break>(n = 13)</th><th rowspan="2">Group 2<break></break><italic>Pneumonia</italic><break></break>(n = 19)</th><th rowspan="2">Group 3<break></break><italic>Respiratory failure</italic><break></break>(n = 13)</th><th colspan="2"><italic>P</italic> value<hr></hr></th></tr><tr><th>Pneumonia<break></break>(<italic>Group 1 vs 2 & 3</italic>)</th><th>Resp. failure<break></break>(<italic>Group 1 & 2 vs 3</italic>)</th></tr></thead><tbody><tr><td colspan="6"><bold>Demographics</bold></td></tr><tr><td>Age, years</td><td>37.3 ± 17.1</td><td>47.7 ± 14.0</td><td>55.2 ± 17.4</td><td>0.015</td><td>0.036</td></tr><tr><td> <italic>Age</italic> ≥<italic>45 years</italic></td><td>2 (15.4%)</td><td>10 (52.6%)</td><td>9 (69.2%)</td><td>0.007</td><td>0.098</td></tr><tr><td>Male sex</td><td>5 (38.5%)</td><td>11 (57.9%)</td><td>11 (84.6%)</td><td>0.094</td><td>0.045</td></tr><tr><td>BMI (kg/m<sup>2</sup>)</td><td>22.1 ± 8.6</td><td>23.4 ± 2.4</td><td>24.8 ± 4.0</td><td>0.524</td><td>0.275</td></tr><tr><td><bold>Underlying disease</bold></td><td>5 (38.5%)</td><td>9 (47.4%)</td><td>8 (61.5%)</td><td>0.514</td><td>0.337</td></tr><tr><td>Diabetes mellitus</td><td>1 (7.7%)</td><td>2 (10.5%)</td><td>2 (15.4%)</td><td>1.000</td><td>0.617</td></tr><tr><td>Hypertension</td><td>2 (15.4%)</td><td>1 (5.3%)</td><td>5 (38.5%)</td><td>1.000</td><td>0.021</td></tr><tr><td>Chronic heart disease</td><td>1 (7.7%)</td><td>2 (10.5%)</td><td>4 (30.8%)</td><td>0.654</td><td>0.168</td></tr><tr><td>Chronic lung disease</td><td>0 (0.0%)</td><td>0 (0.0%)</td><td>1 (7.7%)</td><td>1.000</td><td>0.289</td></tr><tr><td>Liver disease</td><td>0 (0.0%)</td><td>0 (0.0%)</td><td>1 (7.7%)</td><td>1.000</td><td>0.289</td></tr><tr><td>Renal disease</td><td>0 (0.0%)</td><td>1 (5.3%)</td><td>2 (15.4%)</td><td>0.546</td><td>0.196</td></tr><tr><td>Neurologic disease</td><td>0 (0.0%)</td><td>2 (10.5%)</td><td>1 (7.7%)</td><td>0.546</td><td>1.000</td></tr><tr><td>Solid cancer</td><td>2 (15.4%)</td><td>4 (21.1%)</td><td>2 (15.4%)</td><td>1.000</td><td>1.000</td></tr><tr><td>Hematologic disease</td><td>0 (0.0%)</td><td>2 (10.5%)</td><td>1 (7.7%)</td><td>0.546</td><td>1.000</td></tr><tr><td>Charlson's WIC</td><td>0 (0.0–1.0)</td><td>0 (0.0–2.0)</td><td>0 (0.0–2.0)</td><td>0.333</td><td>0.363</td></tr></tbody></table><table-wrap-foot><fn id="tspara0015"><p>Data are expressed as the number (%) of patients or mean ± SD. Continuous variables with statistical significance were re-categorized into binary factors which are presented in italics.</p></fn><fn id="tspara0020"><p>Abbreviations: Res., respiratory; BMI, body mass index; WIC, weighted index of comorbidity.</p></fn></table-wrap-foot></table-wrap><table-wrap position="float" id="tbl2"><label>Table 2</label><caption><p>Clinical presentation and initial laboratory findings of MERS-CoV infected patients compared depending on pneumonia development and progression to respiratory failure.</p></caption><alt-text id="alttext0020">Table 2</alt-text><table frame="hsides" rules="groups"><thead><tr><th rowspan="2">Variables</th><th rowspan="2">Group 1<break></break><italic>Without pneumonia</italic><break></break>(n = 13)</th><th rowspan="2">Group 2<break></break><italic>Pneumonia</italic><break></break>(n = 19)</th><th rowspan="2">Group 3<break></break><italic>Respiratory failure</italic><break></break>(n = 13)</th><th colspan="2"><italic>P</italic> value<hr></hr></th></tr><tr><th>Pneumonia<break></break><italic>(Group 1 vs 2 & 3)</italic></th><th>Resp. failure<break></break><italic>(Group 1 & 2 vs 3)</italic></th></tr></thead><tbody><tr><td colspan="6"><bold>Initial symptoms</bold></td></tr><tr><td>Fever ≥ 37.5 °C</td><td>2/11 (18.2%)</td><td>10/14 (71.4%)</td><td>7/9 (77.8%)</td><td>0.002</td><td>0.240</td></tr><tr><td>Myalgia</td><td>5 (38.5%)</td><td>10 (52.6%)</td><td>2 (15.4%)</td><td>1.000</td><td>0.088</td></tr><tr><td>Cough</td><td>4 (30.8%)</td><td>6 (31.6%)</td><td>5 (38.5%)</td><td>1.000</td><td>0.732</td></tr><tr><td>Sputum</td><td>4 (30.8%)</td><td>3 (15.8%)</td><td>3 (23.1%)</td><td>0.441</td><td>1.000</td></tr><tr><td>Diarrhea</td><td>0 (0.0%)</td><td>1 (5.3%)</td><td>2 (15.4%)</td><td>0.546</td><td>0.196</td></tr><tr><td colspan="6"><bold>Initial laboratory tests</bold><xref rid="tbl2fna" ref-type="table-fn">a</xref></td></tr><tr><td>WBC (/mm<sup>3</sup>)</td><td>5329 ± 1208</td><td>4230 ± 1588</td><td>4799 ± 3037</td><td>0.216</td><td>0.915</td></tr><tr><td>Hemoglobin (g/dL)</td><td>13.6 ± 1.6</td><td>13.0 ± 2.9</td><td>11.8 ± 4.2</td><td>0.255</td><td>0.352</td></tr><tr><td>Platelet (×10<sup>3</sup>/mm<sup>3)</sup></td><td>223 ± 47</td><td>156 ± 52</td><td>104 ± 69</td><td><0.001</td><td>0.003</td></tr><tr><td> <italic>Thrombocytopenia</italic></td><td>0/11 (0.0%)</td><td>5/14 (35.7%)</td><td>5/8 (62.5%)</td><td>0.007</td><td>0.023</td></tr><tr><td>ALC (/mm<sup>3)</sup></td><td>1487 ± 424</td><td>1006 ± 446</td><td>733 ± 577</td><td>0.003</td><td>0.026</td></tr><tr><td> <italic>Lymphopenia</italic></td><td>1/11 (9.1%)</td><td>7/14 (50.0%)</td><td>7/8 (87.5%)</td><td>0.003</td><td>0.006</td></tr><tr><td>Albumin (g/dL)</td><td>4.2 ± 0.5</td><td>4.2 ± 0.6</td><td>3.3 ± 0.8</td><td>0.184</td><td>0.003</td></tr><tr><td> <italic>Hypoalbuminemia</italic></td><td>1/8 (12.5%)</td><td>1/11 (9.1%)</td><td>5/8 (62.5%)</td><td>0.633</td><td>0.005</td></tr><tr><td>Total bilirubin (mg/dL)</td><td>0.3 ± 0.1</td><td>0.7 ± 0.7</td><td>0.6 ± 0.4</td><td>0.190</td><td>0.981</td></tr><tr><td>AST (IU/L)</td><td>28 ± 13</td><td>33 ± 18</td><td>32 ± 11</td><td>0.438</td><td>0.863</td></tr><tr><td>ALT (IU/L)</td><td>34 ± 19</td><td>28 ± 19</td><td>29 ±23</td><td>0.463</td><td>0.808</td></tr><tr><td>BUN (mg/dL)</td><td>10 ± 2</td><td>15 ± 5</td><td>20 ± 18</td><td>0.064</td><td>0.285</td></tr><tr><td>Creatinine (mg/dL)</td><td>0.8 ± 0.2</td><td>1.0 ± 0.5</td><td>1.2 ± 0.4</td><td>0.089</td><td>0.066</td></tr><tr><td>CRP (mg/dL)</td><td>0.7 ± 0.6</td><td>1.3 ± 1.5</td><td>6.8 ± 7.5</td><td>0.031</td><td>0.063</td></tr><tr><td> ≥ <italic>2 mg/dL</italic></td><td>0/11 (0.0%)</td><td>3/13 (23.1%)</td><td>5/8 (62.5%)</td><td>0.018</td><td>0.005</td></tr><tr><td> ≥ <italic>4 mg/dL</italic></td><td>0/11 (0.0%)</td><td>1/13 (7.7%)</td><td>4/8(50.0%)</td><td>0.078</td><td>0.002</td></tr><tr><td>LD (IU/L)</td><td>388 ± 86</td><td>412 ± 131</td><td>441 ± 168</td><td>0.554</td><td>0.545</td></tr><tr><td>Ct value of rRT-PCR</td><td>31.3 ± 3.2</td><td>26.2 ± 5.7</td><td>26.5 ± 3.5</td><td>0.025</td><td>0.405</td></tr><tr><td> <italic>Ct value</italic> <<italic>28.5</italic></td><td>1/8 (12.5%)</td><td>4/6 (66.7%)</td><td>2/3 (66.7%)</td><td>0.024</td><td>0.537</td></tr></tbody></table><table-wrap-foot><fn id="tspara0030"><p>Data are expressed as the number (%) of patients or mean ± SD. As missing values were also removed from the population parameter, variables with missing values are expressed with modified population parameters. Continuous variables with statistical significance were re-categorized into binary factors which are presented in italics.</p></fn><fn id="tspara0035"><p>Abbreviations: Res., respiratory; WBC, white blood cell; ALC, absolute lymphocyte count; AST, aspartate transaminase; ALT, alanine transaminase; BUN, blood urea nitrogen; CRP, C-reactive protein; LD, lactate dehydrogenase; Ct, threshold cycle; rRT-PCR, real-time reverse transcriptase polymerase chain reaction.</p></fn></table-wrap-foot><table-wrap-foot><fn id="tbl2fna"><label>a</label><p id="ntpara0010">Data are presented as mean value of day 1–3 ± SD.</p></fn></table-wrap-foot></table-wrap><table-wrap position="float" id="tbl3"><label>Table 3</label><caption><p>Predictive factors for development of pneumonia and respiratory failure in MERS-CoV infected patients.</p></caption><alt-text id="alttext0025">Table 3</alt-text><table frame="hsides" rules="groups"><thead><tr><th rowspan="2">Predictive factors</th><th colspan="2">Pneumonia<hr></hr></th><th colspan="2">Respiratory failure<hr></hr></th></tr><tr><th>OR (95% CI)</th><th><italic>P</italic> value</th><th>OR (95% CI)</th><th><italic>P</italic> value</th></tr></thead><tbody><tr><td>Age ≥45 years</td><td>8.04 (1.52–42.43)</td><td>0.007</td><td></td><td></td></tr><tr><td>Ct value <28.5</td><td>14.00 (1.14–172.65)</td><td>0.024</td><td></td><td></td></tr><tr><td>CRP ≥2 mg/dL</td><td>NA<xref rid="tbl3fna" ref-type="table-fn">a</xref></td><td>0.018</td><td></td><td></td></tr><tr><td>Fever ≥37.5 °C by day 3</td><td>12.75 (2.12–76.57)</td><td>0.002</td><td></td><td></td></tr><tr><td>Thrombocytopenia</td><td>NA<xref rid="tbl3fna" ref-type="table-fn">a</xref></td><td>0.007</td><td>6.67 (1.18–37.78)</td><td>0.023</td></tr><tr><td>Lymphopenia</td><td>17.50 (1.88–163.02)</td><td>0.003</td><td>14.88 (1.56–142.20)</td><td>0.006</td></tr><tr><td>Male sex</td><td></td><td></td><td>5.50 (1.05–28.88)</td><td>0.045</td></tr><tr><td>Hypoalbuminemia</td><td></td><td></td><td>14.17 (1.83–109.86)</td><td>0.005</td></tr><tr><td>CRP ≥4 mg/dL</td><td></td><td></td><td>23.00 (2.01–262.57)</td><td>0.002</td></tr><tr><td>Hypertension</td><td></td><td></td><td>6.04 (1.18–30.88)</td><td>0.021</td></tr></tbody></table><table-wrap-foot><fn><p>Abbreviations: OR, odds ratio; CI, confidence interval; Ct, threshold cycle; CRP, C-reactive protein; NA, not applicable.</p></fn></table-wrap-foot><table-wrap-foot><fn id="tbl3fna"><label>a</label><p id="ntpara0015">OR was not applicable as none of the group 1 patients reached thrombocytopenia or CRP values ≥2 mg/dL.</p></fn></table-wrap-foot></table-wrap></p><p id="p0065">Fever over 37.5 °C by day 3 were more frequently detected in patients with pneumonia (18.2%, 71.4%, and 77.8% in groups 1, 2, and 3, respectively), and was identified as a predictive factor for the development of pneumonia (OR, 12.75; 95% CI, 2.12–76.57; <italic>P</italic> = 0.002). Thrombocytopenia (OR, not applicable (NA); <italic>P</italic> = 0.007), lymphopenia (OR, 17.50; 95% CI, 1.88–163.02; <italic>P</italic> = 0.003), elevated C-reactive protein (CRP ≥ 2 mg/dL; OR, NA; <italic>P</italic> = 0.018), and high viral load (Ct value < 28.5; OR, 14.00; 95% CI, 1.14–172.65; <italic>P</italic> = 0.024) were distinctly observed in pneumonia patients from the initial presentation, and identified as predictive factors for pneumonia development.</p></sec><sec id="sec3.3"><title>Predictive factors for progression to respiratory failure</title><p id="p0070">To evaluate predictive factors for progression to respiratory failure, patients in group 3 were compared to those in group 1 and 2 (<xref rid="tbl1" ref-type="table">Table 1</xref>, <xref rid="tbl2" ref-type="table">Table 2</xref>, <xref rid="tbl3" ref-type="table">Table 3</xref>). Although the mean age of patients in each group tended to increase with progression of pneumonia (37.3, 47.7, and 55.2 years in groups 1, 2, and 3, respectively) and increasing age was significantly associated with respiratory failure as a continuous variable (<italic>P</italic> = 0.036), there was no statistically significant cut-off value for prediction of respiratory failure. Proportion of male also increased with progression of pneumonia, and male sex was a predictive factor for respiratory failure (OR, 5.50; 95% CI, 1.05–28.88; <italic>P</italic> = 0.045). Among underlying diseases, hypertension was identified as a predictive factor for respiratory failure (OR, 6.04; 95% CI, 1.18–30.88; <italic>P</italic> = 0.021).</p><p id="p0075">Initial symptoms including fever were not significantly different between patients who progressed to respiratory failure and those who did not. Among initial laboratory test results, thrombocytopenia (OR, 6.67; 95% CI, 1.18–37.78; <italic>P</italic> = 0.023), lymphopenia (OR, 14.88; 95% CI, 1.56–142.20; <italic>P</italic> = 0.006), hypoalbuminemia (OR, 14.17; 95% CI, 1.83–109.86; <italic>P</italic> = 0.005), and elevated CRP (CRP ≥ 4 mg/dl; OR, 23.00; 95% CI, 2.01–262.57; <italic>P</italic> = 0.002) were distinctly observed in group 3 patients, and identified as predictive factors for respiratory failure.</p></sec><sec id="sec3.4"><title>Predictability of predictive factors for pneumonia development and respiratory failure</title><p id="p0080">Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) by number of predictive factors were presented in <xref rid="tbl4" ref-type="table">Table 4</xref>. When patients presented with ≥ two of the predictive factors for pneumonia development, 100% of these patients developed pneumonia (sensitivity 56.3%, specificity 100.0%, PPV 100%, and NPV 48.1%). Patients lacking the predictive factors for respiratory failure did not progress to respiratory failure. When patients presented with ≥ two of these predictive factors, 50.0% of these patients progressed to respiratory failure (sensitivity 69.2%, specificity 75.0%, PPV 52.9%, and NPV 85.7%).<table-wrap position="float" id="tbl4"><label>Table 4</label><caption><p>Sensitivity, specificity, PPV and NPV by number of predictive factors for pneumonia development and progression to respiratory failure.</p></caption><alt-text id="alttext0030">Table 4</alt-text><table frame="hsides" rules="groups"><thead><tr><th rowspan="2">No. of factors</th><th colspan="4">Pneumonia<hr></hr></th><th colspan="4">Respiratory failure<hr></hr></th></tr><tr><th>Sensitivity</th><th>Specificity</th><th>PPV</th><th>NPV</th><th>Sensitivity</th><th>Specificity</th><th>PPV</th><th>NPV</th></tr></thead><tbody><tr><td>≥0</td><td>100.0</td><td>0.0</td><td>71.1</td><td>NA</td><td>100</td><td>0.0</td><td>28.9</td><td>NA</td></tr><tr><td>≥1</td><td>90.6</td><td>53.8</td><td>82.9</td><td>70.0</td><td>100</td><td>31.3</td><td>37.1</td><td>100</td></tr><tr><td>≥2</td><td>56.3</td><td>100</td><td>100</td><td>48.1</td><td>69.2</td><td>75.0</td><td>52.9</td><td>85.7</td></tr><tr><td>≥3</td><td>40.6</td><td>100</td><td>100</td><td>40.6</td><td>46.2</td><td>87.5</td><td>60.0</td><td>80.0</td></tr><tr><td>≥4</td><td>28.1</td><td>100</td><td>100</td><td>36.1</td><td>38.5</td><td>96.9</td><td>83.3</td><td>79.5</td></tr><tr><td>≥5</td><td>15.6</td><td>100</td><td>100</td><td>32.5</td><td>30.8</td><td>100</td><td>100</td><td>78.0</td></tr></tbody></table><table-wrap-foot><fn id="tspara0055"><p>Data are expressed as percentages.</p></fn><fn id="tspara0060"><p>Abbreviations: PPV, positive predictive value; NPV, negative predictive value; NA, not applicable.</p></fn></table-wrap-foot></table-wrap></p></sec></sec><sec id="sec4"><title>Discussion</title><p id="p0085">Initial rapid propagation of MERS-CoV during the Korean MERS outbreak was caused by three super-spreading events responsible for 73.1% of all transmissions.<xref rid="bib5" ref-type="bibr">5</xref>, <xref rid="bib7" ref-type="bibr">7</xref>, <xref rid="bib8" ref-type="bibr">8</xref> In addition to these super-spreaders, transmission of MERS-CoV despite application of personal protective equipment (PPE) occurred from patients with progressed pneumonia at our hospital.<xref rid="bib9" ref-type="bibr"><sup>9</sup></xref> In this regard, identifying the predictive factors for pneumonia development and progression is not only important in patient care, but also in infection control to prevent further in-hospital transmission.</p><p id="p0090">The present analysis of predictive factors for pneumonia development and progression to respiratory failure using variables obtained by day 3 of symptom onset could be conducted owing to the observation of entire clinical course of the disease from the exposure to MERS-CoV. Compared to MERS outbreaks in the Arabian Peninsula where community-acquired infections might simultaneously occur from animals, identifying epidemiologic links, exposure date, and symptom onset were relatively clear for each case.<xref rid="bib5" ref-type="bibr">5</xref>, <xref rid="bib19" ref-type="bibr">19</xref> In our observation, the clinical course of symptomatic MERS patients progressed serially and no one developed pneumonia before day 4 of symptom onset. This is the reason why we used clinical data obtained by day 3 of symptom onset. There is no other comparable data to which presented time interval from the symptom onset to the development of pneumonia. Although there were no ideal cut-off scores of predictive factors with good sensitivity and specificity, it should be noted that 100% of patients with ≥ two predictive factors for pneumonia actually progressed to pneumonia. Thus, careful and intensive management should be implemented for such patients including adequate isolation of patient in an airborne infection isolation room (AIIR), minimizing chance for exposure, application of PPE with hooded coverall, and consideration of experimental antiviral treatment.<xref rid="bib9" ref-type="bibr">9</xref>, <xref rid="bib21" ref-type="bibr">21</xref>, <xref rid="bib22" ref-type="bibr">22</xref>, <xref rid="bib23" ref-type="bibr">23</xref>, <xref rid="bib24" ref-type="bibr">24</xref> For patients with ≥ two predictive factors for respiratory failure, AIIRs in intensive care units should be prepared for early elective intubation. Although the time interval from symptom onset to MV support was much longer than in previous reports (median 12 days versus 7 days),<xref rid="bib1" ref-type="bibr"><sup>1</sup></xref> we also experienced rapid progression of pneumonia from the moment of desaturation: 73% of group 3 patients required MV within 2 days from desaturation (median 2, IQR 1–3 days). To avoid urgent situations which might break protection of healthcare workers, elective intubation should be considered when desaturation begins to progress. In addition, sensitivities of predictive values are relatively low with cut-off value of ≥ two factors, clinical course of patients with any predictive factors also should be carefully monitored.</p><p id="p0095">Of note, thrombocytopenia, lymphopenia, and increased CRP level were shared predictive factor for the pneumonia development and respiratory failure. They were observed in the very early course of the illness, indicating that inflammation had already been enhanced. Lymphopenia and thrombocytopenia presenting from the initial presentation of severe MERS-CoV infected patients were also observed in the recent report by Min et al.<xref rid="bib25" ref-type="bibr"><sup>25</sup></xref> Although time of measurements were not specifically described, these laboratory abnormalities were previously observed in severe MERS cases and other respiratory viral illnesses including severe acute respiratory syndrome (SARS) and influenza, which are caused by intense inflammatory response to the viruses.<xref rid="bib15" ref-type="bibr">15</xref>, <xref rid="bib26" ref-type="bibr">26</xref>, <xref rid="bib27" ref-type="bibr">27</xref>, <xref rid="bib28" ref-type="bibr">28</xref>, <xref rid="bib29" ref-type="bibr">29</xref>, <xref rid="bib30" ref-type="bibr">30</xref>, <xref rid="bib31" ref-type="bibr">31</xref>, <xref rid="bib32" ref-type="bibr">32</xref>, <xref rid="bib33" ref-type="bibr">33</xref> This is the first report that identified these laboratory findings as predictive factors for pneumonia development and progression to respiratory failure in MERS.</p><p id="p0100">Although other predictive factors for pneumonia development and respiratory failure were different due to discordance of statistical significance, they shared the same spectrum of etiology. Age increased according to pneumonia progression and was associated with both pneumonia and respiratory failure as a continuous variable (<italic>P</italic> = 0.015 and <italic>P</italic> = 0.036, respectively). These findings correlate with previous data suggesting that old age is associated with poor prognosis.<xref rid="bib11" ref-type="bibr">11</xref>, <xref rid="bib13" ref-type="bibr">13</xref>, <xref rid="bib14" ref-type="bibr">14</xref>, <xref rid="bib15" ref-type="bibr">15</xref>, <xref rid="bib34" ref-type="bibr">34</xref>, <xref rid="bib35" ref-type="bibr">35</xref> Similarly, the proportion of males increased according to disease severity, though male sex was only significant for predicting respiratory failure. Although the mean age of males was older than that of females (49.7 and 42.6 years, respectively), it was not statistically significant (<italic>P</italic> = 0.169). Previous data also reported that overall proportion of male was higher and was associated with severe infection.<xref rid="bib15" ref-type="bibr">15</xref>, <xref rid="bib34" ref-type="bibr">34</xref> It could be meaningful observation that the same finding was observed in the Republic of Korea where the social activity of females is not restricted, especially among healthcare workers. On the other hand, hypoalbuminemia and hypertension were predictive factors only for respiratory failure, while high viral load was predictive factor for the development of pneumonia. These factors were related with severe disease and poor prognosis of MERS in previous reports.<xref rid="bib1" ref-type="bibr">1</xref>, <xref rid="bib12" ref-type="bibr">12</xref>, <xref rid="bib13" ref-type="bibr">13</xref>, <xref rid="bib15" ref-type="bibr">15</xref>, <xref rid="bib16" ref-type="bibr">16</xref>, <xref rid="bib34" ref-type="bibr">34</xref>, <xref rid="bib35" ref-type="bibr">35</xref></p><p id="p0105">Our study has several strengths and limitations. Due to its retrospective nature, there may be a bias regarding collecting medical information in retrospective manner. However, as all electronic medical records were standardized to record symptoms and signs in the same way from the beginning of the outbreak, bias was minimized. Secondly, there were missing values when calculating the sensitivity and specificity of predictive factors, which is another limitation of retrospective study. Lastly, the present study did not perform multivariate analysis due to limited sample size and need to be validated. Prospective studies with sufficient number of patients are required for validation of the predictive factors identified in the present study. Despite these limitations, our data would be suitable for identifying predictive factors because we could observe entire course of the disease from exposure and apply homogenous management to patients.</p><p id="p0110">In conclusion, based on 45 cases from a single tertiary care hospital during the largest MERS outbreak outside of the Arabian Peninsula, we identified six predictive factors for the development of pneumonia and progression to respiratory failure, respectively. Thrombocytopenia, lymphopenia, and high CRP level were shared predictive factors. MERS-CoV infected patients with ≥ two predictive factors should be intensively managed from the initial presentation for successful control of MERS outbreak.</p></sec><sec id="sec5"><title>Potential conflicts of interest</title><p id="p0115">There are no potential conflicts of interest relevant to this article to report.</p></sec><sec id="sec6"><title>Funding</title><p id="p0120">This work was supported by the <funding-source id="gs1">Samsung Biomedical Research Institute (SBRI)</funding-source> grant [#SMX1161321].</p></sec></body><back><ref-list id="cebib0010"><title>References</title><ref id="bib1"><label>1</label><element-citation publication-type="journal" id="sref1"><person-group person-group-type="author"><name><surname>Zumla</surname><given-names>A.</given-names></name><name><surname>Hui</surname><given-names>D.S.</given-names></name><name><surname>Perlman</surname><given-names>S.</given-names></name></person-group><article-title>Middle East respiratory syndrome</article-title><source>Lancet</source><volume>386</volume><year>2015</year><fpage>995</fpage><lpage>1007</lpage><pub-id pub-id-type="pmid">26049252</pub-id></element-citation></ref><ref id="bib2"><label>2</label><element-citation publication-type="book" id="sref2"><chapter-title>Summary of current situation, Literature Update and Risk Assessment</chapter-title><year>2015 July 7</year><publisher-name>World Health Organization</publisher-name><ext-link ext-link-type="uri" xlink:href="http://www.who.int/csr/disease/coronavirus_infections/risk-assessment-7july2015/en" id="interref0010">http://www.who.int/csr/disease/coronavirus_infections/risk-assessment-7july2015/en</ext-link></element-citation></ref><ref id="bib3"><label>3</label><element-citation publication-type="book" id="sref3"><chapter-title>Middle east respiratory syndrome coronavirus (MERS-CoV) – Republic of Korea</chapter-title><year>2015 July 10</year><publisher-name>World Health Organization</publisher-name><ext-link ext-link-type="uri" xlink:href="http://www.who.int/csr/don/10-july-2015-mers-korea/en" id="interref0015">http://www.who.int/csr/don/10-july-2015-mers-korea/en</ext-link></element-citation></ref><ref id="bib4"><label>4</label><element-citation publication-type="journal" id="sref4"><article-title>An unexpected outbreak of Middle East respiratory syndrome coronavirus infection in the Republic of Korea, 2015</article-title><source>Infect Chemother</source><volume>47</volume><year>2015</year><fpage>120</fpage><lpage>122</lpage><pub-id pub-id-type="pmid">26157591</pub-id></element-citation></ref><ref id="bib5"><label>5</label><element-citation publication-type="journal" id="sref5"><person-group person-group-type="author"><name><surname>Kim</surname><given-names>Y.</given-names></name><name><surname>Lee</surname><given-names>S.</given-names></name><name><surname>Chu</surname><given-names>C.</given-names></name><name><surname>Choe</surname><given-names>S.</given-names></name><name><surname>Hong</surname><given-names>S.</given-names></name><name><surname>Shin</surname><given-names>Y.</given-names></name></person-group><article-title>The characteristics of middle eastern respiratory syndrome coronavirus transmission dynamics in South Korea</article-title><source>Osong Public Health Res Perspect</source><volume>7</volume><year>2016</year><fpage>49</fpage><lpage>55</lpage><pub-id pub-id-type="pmid">26981343</pub-id></element-citation></ref><ref id="bib6"><label>6</label><element-citation publication-type="journal" id="sref6"><person-group person-group-type="author"><name><surname>Cowling</surname><given-names>B.J.</given-names></name><name><surname>Park</surname><given-names>M.</given-names></name><name><surname>Fang</surname><given-names>V.J.</given-names></name><name><surname>Wu</surname><given-names>P.</given-names></name><name><surname>Leung</surname><given-names>G.M.</given-names></name><name><surname>Wu</surname><given-names>J.T.</given-names></name></person-group><article-title>Preliminary epidemiological assessment of MERS-CoV outbreak in South Korea, May to June 2015</article-title><source>Euro Surveill</source><volume>20</volume><year>2015</year></element-citation></ref><ref id="bib7"><label>7</label><element-citation publication-type="journal" id="sref7"><person-group person-group-type="author"><name><surname>Nishiura</surname><given-names>H.</given-names></name><name><surname>Endo</surname><given-names>A.</given-names></name><name><surname>Saitoh</surname><given-names>M.</given-names></name><name><surname>Kinoshita</surname><given-names>R.</given-names></name><name><surname>Ueno</surname><given-names>R.</given-names></name><name><surname>Nakaoka</surname><given-names>S.</given-names></name></person-group><article-title>Identifying determinants of heterogeneous transmission dynamics of the Middle East respiratory syndrome (MERS) outbreak in the Republic of Korea, 2015: a retrospective epidemiological analysis</article-title><source>BMJ Open</source><volume>6</volume><year>2016</year><fpage>e009936</fpage></element-citation></ref><ref id="bib8"><label>8</label><element-citation publication-type="journal" id="sref8"><person-group person-group-type="author"><name><surname>Chowell</surname><given-names>G.</given-names></name><name><surname>Abdirizak</surname><given-names>F.</given-names></name><name><surname>Lee</surname><given-names>S.</given-names></name><name><surname>Lee</surname><given-names>J.</given-names></name><name><surname>Jung</surname><given-names>E.</given-names></name><name><surname>Nishiura</surname><given-names>H.</given-names></name></person-group><article-title>Transmission characteristics of MERS and SARS in the healthcare setting: a comparative study</article-title><source>BMC Med</source><volume>13</volume><year>2015</year><fpage>210</fpage><pub-id pub-id-type="pmid">26336062</pub-id></element-citation></ref><ref id="bib9"><label>9</label><element-citation publication-type="journal" id="sref9"><person-group person-group-type="author"><name><surname>Park</surname><given-names>G.E.</given-names></name><name><surname>Ko</surname><given-names>J.H.</given-names></name><name><surname>Peck</surname><given-names>K.R.</given-names></name><name><surname>Lee</surname><given-names>J.Y.</given-names></name><name><surname>Lee</surname><given-names>J.Y.</given-names></name><name><surname>Cho</surname><given-names>S.Y.</given-names></name></person-group><article-title>Control of an outbreak of Middle East respiratory syndrome in a tertiary hospital in Korea</article-title><source>Ann Intern Med</source><volume>165</volume><year>2016</year><fpage>87</fpage><lpage>93</lpage><pub-id pub-id-type="pmid">27272273</pub-id></element-citation></ref><ref id="bib10"><label>10</label><element-citation publication-type="journal" id="sref10"><person-group person-group-type="author"><name><surname>Cho</surname><given-names>S.Y.</given-names></name><name><surname>Kang</surname><given-names>J.M.</given-names></name><name><surname>Ha</surname><given-names>Y.E.</given-names></name><name><surname>Park</surname><given-names>G.E.</given-names></name><name><surname>Lee</surname><given-names>J.Y.</given-names></name><name><surname>Ko</surname><given-names>J.H.</given-names></name></person-group><article-title>MERS-CoV outbreak following a single patient exposure in an emergency room in South Korea: an epidemiological outbreak study</article-title><source>Lancet</source><year>2016 Jul 8</year><comment>pii: S0140-6736(16)30623-7. [Epub ahead of print]</comment></element-citation></ref><ref id="bib11"><label>11</label><element-citation publication-type="journal" id="sref11"><person-group person-group-type="author"><name><surname>Mizumoto</surname><given-names>K.</given-names></name><name><surname>Endo</surname><given-names>A.</given-names></name><name><surname>Chowell</surname><given-names>G.</given-names></name><name><surname>Miyamatsu</surname><given-names>Y.</given-names></name><name><surname>Saitoh</surname><given-names>M.</given-names></name><name><surname>Nishiura</surname><given-names>H.</given-names></name></person-group><article-title>Real-time characterization of risks of death associated with the Middle East respiratory syndrome (MERS) in the Republic of Korea, 2015</article-title><source>BMC Med</source><volume>13</volume><year>2015</year><fpage>228</fpage><pub-id pub-id-type="pmid">26420593</pub-id></element-citation></ref><ref id="bib12"><label>12</label><element-citation publication-type="journal" id="sref12"><person-group person-group-type="author"><name><surname>Corman</surname><given-names>V.M.</given-names></name><name><surname>Albarrak</surname><given-names>A.M.</given-names></name><name><surname>Omrani</surname><given-names>A.S.</given-names></name><name><surname>Albarrak</surname><given-names>M.M.</given-names></name><name><surname>Farah</surname><given-names>M.E.</given-names></name><name><surname>Almasri</surname><given-names>M.</given-names></name></person-group><article-title>Viral shedding and antibody response in 37 patients with Middle East respiratory syndrome coronavirus infection</article-title><source>Clin Infect Dis</source><volume>62</volume><year>2016</year><fpage>477</fpage><lpage>483</lpage><pub-id pub-id-type="pmid">26565003</pub-id></element-citation></ref><ref id="bib13"><label>13</label><element-citation publication-type="journal" id="sref13"><person-group person-group-type="author"><name><surname>Feikin</surname><given-names>D.R.</given-names></name><name><surname>Alraddadi</surname><given-names>B.</given-names></name><name><surname>Qutub</surname><given-names>M.</given-names></name><name><surname>Shabouni</surname><given-names>O.</given-names></name><name><surname>Curns</surname><given-names>A.</given-names></name><name><surname>Oboho</surname><given-names>I.K.</given-names></name></person-group><article-title>Association of higher MERS-CoV virus load with severe disease and death, Saudi Arabia, 2014</article-title><source>Emerg Infect Dis</source><volume>21</volume><year>2015</year><fpage>2029</fpage><lpage>2035</lpage><pub-id pub-id-type="pmid">26488195</pub-id></element-citation></ref><ref id="bib14"><label>14</label><element-citation publication-type="journal" id="sref14"><person-group person-group-type="author"><name><surname>Majumder</surname><given-names>M.S.</given-names></name><name><surname>Kluberg</surname><given-names>S.A.</given-names></name><name><surname>Mekaru</surname><given-names>S.R.</given-names></name><name><surname>Brownstein</surname><given-names>J.S.</given-names></name></person-group><article-title>Mortality risk factors for Middle East respiratory syndrome outbreak, South Korea, 2015</article-title><source>Emerg Infect Dis</source><volume>21</volume><year>2015</year><fpage>2088</fpage><lpage>2090</lpage><pub-id pub-id-type="pmid">26488869</pub-id></element-citation></ref><ref id="bib15"><label>15</label><element-citation publication-type="journal" id="sref15"><person-group person-group-type="author"><name><surname>Saad</surname><given-names>M.</given-names></name><name><surname>Omrani</surname><given-names>A.S.</given-names></name><name><surname>Baig</surname><given-names>K.</given-names></name><name><surname>Bahloul</surname><given-names>A.</given-names></name><name><surname>Elzein</surname><given-names>F.</given-names></name><name><surname>Matin</surname><given-names>M.A.</given-names></name></person-group><article-title>Clinical aspects and outcomes of 70 patients with Middle East respiratory syndrome coronavirus infection: a single-center experience in Saudi Arabia</article-title><source>Int J Infect Dis</source><volume>29</volume><year>2014</year><fpage>301</fpage><lpage>306</lpage><pub-id pub-id-type="pmid">25303830</pub-id></element-citation></ref><ref id="bib16"><label>16</label><element-citation publication-type="journal" id="sref16"><person-group person-group-type="author"><name><surname>Banik</surname><given-names>G.R.</given-names></name><name><surname>Alqahtani</surname><given-names>A.S.</given-names></name><name><surname>Booy</surname><given-names>R.</given-names></name><name><surname>Rashid</surname><given-names>H.</given-names></name></person-group><article-title>Risk factors for severity and mortality in patients with MERS-CoV: analysis of publicly available data from Saudi Arabia</article-title><source>Virol Sin</source><volume>31</volume><year>2016</year><fpage>81</fpage><lpage>84</lpage><pub-id pub-id-type="pmid">26826080</pub-id></element-citation></ref><ref id="bib17"><label>17</label><element-citation publication-type="book" id="sref17"><source>Management of asymptomatic persons who are RTPCR positive for Middle East respiratory syndrome coronavirus (MERS-CoV), Interim Guidance</source><year>July 27, 2015</year><publisher-name>World Health Organization</publisher-name><ext-link ext-link-type="uri" xlink:href="http://www.who.int/csr/disease/coronavirus_infections/management_of_asymptomatic_patients/en/" id="intref0010">http://www.who.int/csr/disease/coronavirus_infections/management_of_asymptomatic_patients/en/</ext-link><comment>[Accessed 27.05.16]</comment></element-citation></ref><ref id="bib18"><label>18</label><element-citation publication-type="journal" id="sref18"><person-group person-group-type="author"><name><surname>Madani</surname><given-names>T.A.</given-names></name></person-group><article-title>Case definition and management of patients with MERS coronavirus in Saudi Arabia</article-title><source>Lancet Infect Dis</source><volume>14</volume><year>2014</year><fpage>911</fpage><lpage>913</lpage><pub-id pub-id-type="pmid">25253396</pub-id></element-citation></ref><ref id="bib19"><label>19</label><element-citation publication-type="journal" id="sref19"><person-group person-group-type="author"><name><surname>Oboho</surname><given-names>I.K.</given-names></name><name><surname>Tomczyk</surname><given-names>S.M.</given-names></name><name><surname>Al-Asmari</surname><given-names>A.M.</given-names></name><name><surname>Banjar</surname><given-names>A.A.</given-names></name><name><surname>Al-Mugti</surname><given-names>H.</given-names></name><name><surname>Aloraini</surname><given-names>M.S.</given-names></name></person-group><article-title>2014 MERS-CoV outbreak in Jeddah – a link to health care facilities</article-title><source>N Engl J Med</source><volume>372</volume><year>2015</year><fpage>846</fpage><lpage>854</lpage><pub-id pub-id-type="pmid">25714162</pub-id></element-citation></ref><ref id="bib20"><label>20</label><element-citation publication-type="journal" id="sref20"><person-group person-group-type="author"><name><surname>Woolf</surname><given-names>B.</given-names></name></person-group><article-title>On estimating the relation between blood group and disease</article-title><source>Ann Hum Genet</source><volume>19</volume><year>1955</year><fpage>251</fpage><lpage>253</lpage><pub-id pub-id-type="pmid">14388528</pub-id></element-citation></ref><ref id="bib21"><label>21</label><element-citation publication-type="journal" id="sref21"><person-group person-group-type="author"><name><surname>Al Ghamdi</surname><given-names>M.</given-names></name><name><surname>Alghamdi</surname><given-names>K.M.</given-names></name><name><surname>Ghandoora</surname><given-names>Y.</given-names></name><name><surname>Alzahrani</surname><given-names>A.</given-names></name><name><surname>Salah</surname><given-names>F.</given-names></name><name><surname>Alsulami</surname><given-names>A.</given-names></name></person-group><article-title>Treatment outcomes for patients with Middle Eastern respiratory syndrome coronavirus (MERS CoV) infection at a coronavirus referral center in the Kingdom of Saudi Arabia</article-title><source>BMC Infect Dis</source><volume>16</volume><year>2016</year><fpage>174</fpage><pub-id pub-id-type="pmid">27097824</pub-id></element-citation></ref><ref id="bib22"><label>22</label><element-citation publication-type="journal" id="sref22"><person-group person-group-type="author"><name><surname>Modjarrad</surname><given-names>K.</given-names></name></person-group><article-title>Treatment strategies for Middle East respiratory syndrome coronavirus</article-title><source>J Virus Erad</source><volume>2</volume><year>2016</year><fpage>1</fpage><lpage>4</lpage></element-citation></ref><ref id="bib23"><label>23</label><element-citation publication-type="journal" id="sref23"><person-group person-group-type="author"><name><surname>Chan</surname><given-names>J.F.</given-names></name><name><surname>Yao</surname><given-names>Y.</given-names></name><name><surname>Yeung</surname><given-names>M.L.</given-names></name><name><surname>Deng</surname><given-names>W.</given-names></name><name><surname>Bao</surname><given-names>L.</given-names></name><name><surname>Jia</surname><given-names>L.</given-names></name></person-group><article-title>Treatment with lopinavir/ritonavir or interferon-beta1b improves outcome of MERS-CoV infection in a nonhuman primate model of common marmoset</article-title><source>J Infect Dis</source><volume>212</volume><year>2015</year><fpage>1904</fpage><lpage>1913</lpage><pub-id pub-id-type="pmid">26198719</pub-id></element-citation></ref><ref id="bib24"><label>24</label><element-citation publication-type="book" id="sref24"><source>Interim infection prevention and control recommendations for hospitalized patients with Middle East respiratory syndrome coronavirus (MERS-CoV), US CDC</source><year>June 2015</year><ext-link ext-link-type="uri" xlink:href="http://www.cdc.gov/coronavirus/mers/infection-prevention-control.html" id="intref0015">http://www.cdc.gov/coronavirus/mers/infection-prevention-control.html</ext-link><comment>[Accessed 27.05.16]</comment></element-citation></ref><ref id="bib25"><label>25</label><element-citation publication-type="journal" id="sref25"><person-group person-group-type="author"><name><surname>Min</surname><given-names>C.K.</given-names></name><name><surname>Cheon</surname><given-names>S.</given-names></name><name><surname>Ha</surname><given-names>N.Y.</given-names></name><name><surname>Sohn</surname><given-names>K.M.</given-names></name><name><surname>Kim</surname><given-names>Y.</given-names></name><name><surname>Aigerim</surname><given-names>A.</given-names></name></person-group><article-title>Comparative and kinetic analysis of viral shedding and immunological responses in MERS patients representing a broad spectrum of disease severity</article-title><source>Sci Rep</source><volume>6</volume><year>2016</year><fpage>25359</fpage><pub-id pub-id-type="pmid">27146253</pub-id></element-citation></ref><ref id="bib26"><label>26</label><element-citation publication-type="journal" id="sref26"><person-group person-group-type="author"><name><surname>Arabi</surname><given-names>Y.M.</given-names></name><name><surname>Arifi</surname><given-names>A.A.</given-names></name><name><surname>Balkhy</surname><given-names>H.H.</given-names></name><name><surname>Najm</surname><given-names>H.</given-names></name><name><surname>Aldawood</surname><given-names>A.S.</given-names></name><name><surname>Ghabashi</surname><given-names>A.</given-names></name></person-group><article-title>Clinical course and outcomes of critically ill patients with Middle East respiratory syndrome coronavirus infection</article-title><source>Ann Intern Med</source><volume>160</volume><year>2014</year><fpage>389</fpage><lpage>397</lpage><pub-id pub-id-type="pmid">24474051</pub-id></element-citation></ref><ref id="bib27"><label>27</label><element-citation publication-type="journal" id="sref27"><person-group person-group-type="author"><name><surname>Guery</surname><given-names>B.</given-names></name><name><surname>Poissy</surname><given-names>J.</given-names></name><name><surname>el Mansouf</surname><given-names>L.</given-names></name><name><surname>Sejourne</surname><given-names>C.</given-names></name><name><surname>Ettahar</surname><given-names>N.</given-names></name><name><surname>Lemaire</surname><given-names>X.</given-names></name></person-group><article-title>Clinical features and viral diagnosis of two cases of infection with Middle East respiratory syndrome coronavirus: a report of nosocomial transmission</article-title><source>Lancet</source><volume>381</volume><year>2013</year><fpage>2265</fpage><lpage>2272</lpage><pub-id pub-id-type="pmid">23727167</pub-id></element-citation></ref><ref id="bib28"><label>28</label><element-citation publication-type="journal" id="sref28"><person-group person-group-type="author"><name><surname>Choi</surname><given-names>K.W.</given-names></name><name><surname>Chau</surname><given-names>T.N.</given-names></name><name><surname>Tsang</surname><given-names>O.</given-names></name><name><surname>Tso</surname><given-names>E.</given-names></name><name><surname>Chiu</surname><given-names>M.C.</given-names></name><name><surname>Tong</surname><given-names>W.L.</given-names></name></person-group><article-title>Outcomes and prognostic factors in 267 patients with severe acute respiratory syndrome in Hong Kong</article-title><source>Ann Intern Med</source><volume>139</volume><year>2003</year><fpage>715</fpage><lpage>723</lpage><pub-id pub-id-type="pmid">14597455</pub-id></element-citation></ref><ref id="bib29"><label>29</label><element-citation publication-type="journal" id="sref29"><person-group person-group-type="author"><name><surname>Lupovitch</surname><given-names>A.</given-names></name></person-group><article-title>White cell differential count and influenza A</article-title><source>Am J Med</source><volume>118</volume><year>2005</year><fpage>1306</fpage><lpage>1307</lpage><comment>author reply 7–9</comment><pub-id pub-id-type="pmid">16271935</pub-id></element-citation></ref><ref id="bib30"><label>30</label><element-citation publication-type="journal" id="sref30"><person-group person-group-type="author"><name><surname>Yang</surname><given-names>M.</given-names></name><name><surname>Ng</surname><given-names>M.H.</given-names></name><name><surname>Li</surname><given-names>C.K.</given-names></name></person-group><article-title>Thrombocytopenia in patients with severe acute respiratory syndrome (review)</article-title><source>Hematology</source><volume>10</volume><year>2005</year><fpage>101</fpage><lpage>105</lpage><pub-id pub-id-type="pmid">16019455</pub-id></element-citation></ref><ref id="bib31"><label>31</label><element-citation publication-type="journal" id="sref31"><person-group person-group-type="author"><name><surname>Le</surname><given-names>V.B.</given-names></name><name><surname>Schneider</surname><given-names>J.G.</given-names></name><name><surname>Boergeling</surname><given-names>Y.</given-names></name><name><surname>Berri</surname><given-names>F.</given-names></name><name><surname>Ducatez</surname><given-names>M.</given-names></name><name><surname>Guerin</surname><given-names>J.L.</given-names></name></person-group><article-title>Platelet activation and aggregation promote lung inflammation and influenza virus pathogenesis</article-title><source>Am J Respir Crit Care Med</source><volume>191</volume><year>2015</year><fpage>804</fpage><lpage>819</lpage><pub-id pub-id-type="pmid">25664391</pub-id></element-citation></ref><ref id="bib32"><label>32</label><element-citation publication-type="journal" id="sref32"><person-group person-group-type="author"><name><surname>Ying</surname><given-names>T.</given-names></name><name><surname>Li</surname><given-names>W.</given-names></name><name><surname>Dimitrov</surname><given-names>D.S.</given-names></name></person-group><article-title>Discovery of T cell infection and apoptosis by MERS Coronavirus</article-title><source>J Infect Dis</source><volume>213</volume><year>2016</year><fpage>877</fpage><lpage>879</lpage><pub-id pub-id-type="pmid">26203059</pub-id></element-citation></ref><ref id="bib33"><label>33</label><element-citation publication-type="journal" id="sref33"><person-group person-group-type="author"><name><surname>Chu</surname><given-names>H.</given-names></name><name><surname>Zhou</surname><given-names>J.</given-names></name><name><surname>Wong</surname><given-names>B.H.</given-names></name><name><surname>Li</surname><given-names>C.</given-names></name><name><surname>Chan</surname><given-names>J.F.</given-names></name><name><surname>Cheng</surname><given-names>Z.S.</given-names></name></person-group><article-title>Middle East Respiratory syndrome coronavirus efficiently infects human primary T lymphocytes and activates both the extrinsic and intrinsic apoptosis pathways</article-title><source>J Infect Dis</source><volume>213</volume><year>2016</year><fpage>904</fpage><lpage>914</lpage><pub-id pub-id-type="pmid">26203058</pub-id></element-citation></ref><ref id="bib34"><label>34</label><element-citation publication-type="journal" id="sref34"><person-group person-group-type="author"><name><surname>Assiri</surname><given-names>A.</given-names></name><name><surname>Al-Tawfiq</surname><given-names>J.A.</given-names></name><name><surname>Al-Rabeeah</surname><given-names>A.A.</given-names></name><name><surname>Al-Rabiah</surname><given-names>F.A.</given-names></name><name><surname>Al-Hajjar</surname><given-names>S.</given-names></name><name><surname>Al-Barrak</surname><given-names>A.</given-names></name></person-group><article-title>Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study</article-title><source>Lancet Infect Dis</source><volume>13</volume><year>2013</year><fpage>752</fpage><lpage>761</lpage><pub-id pub-id-type="pmid">23891402</pub-id></element-citation></ref><ref id="bib35"><label>35</label><element-citation publication-type="journal" id="sref35"><person-group person-group-type="author"><name><surname>Chan</surname><given-names>J.F.</given-names></name><name><surname>Lau</surname><given-names>S.K.</given-names></name><name><surname>To</surname><given-names>K.K.</given-names></name><name><surname>Cheng</surname><given-names>V.C.</given-names></name><name><surname>Woo</surname><given-names>P.C.</given-names></name><name><surname>Yuen</surname><given-names>K.Y.</given-names></name></person-group><article-title>Middle East respiratory syndrome coronavirus: another zoonotic betacoronavirus causing SARS-like disease</article-title><source>Clin Microbiol Rev</source><volume>28</volume><year>2015</year><fpage>465</fpage><lpage>522</lpage><pub-id pub-id-type="pmid">25810418</pub-id></element-citation></ref></ref-list><ack id="ack0010"><title>Acknowledgements</title><p>We would like to express our sincerest condolences to the patients and families who suffered from the MERS outbreak. We also greatly appreciate the health care personnel and staff members at Samsung Medical Center and all other hospitals who worked together to overcome the MERS outbreak.</p></ack></back></pmc></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/MersV1/Data/Pmc/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000E65 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd -nk 000E65 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= MersV1
|flux= Pmc
|étape= Corpus
|type= RBID
|clé=
|texte=
}}
| This area was generated with Dilib version V0.6.33. |  |