Host susceptibility to MERS-CoV infection, a retrospective cohort study of the 2015 Korean MERS outbreak
Identifieur interne : 000713 ( Pmc/Corpus ); précédent : 000712; suivant : 000714Host susceptibility to MERS-CoV infection, a retrospective cohort study of the 2015 Korean MERS outbreak
Auteurs : Jae-Hoon Ko ; Hyeri Seok ; Ga Eun Park ; Ji Yeon Lee ; Ji Yong Lee ; Sun Young Cho ; Young Eun Ha ; Ji-Man Kang ; Yae-Jean Kim ; Cheol-In Kang ; Doo Ryeon Chung ; Jae-Hoon Song ; Kyong Ran PeckSource :
- Journal of Infection and Chemotherapy [ 1341-321X ] ; 2017.
Abstract
To evaluate host susceptibility factors to Middle East respiratory syndrome coronavirus (MERS-CoV) infection, we conducted a retrospective cohort study from the single largest exposure event of the 2015 Korean MERS outbreak. A total of 175 patients were closely exposed to a super-spreader, 26 of which were infected (14.9%). In a multivariate analysis, history of autologous stem cell transplantation (HR, 31.151; 95% CI, 5.447–178.145;
Url:
DOI: 10.1016/j.jiac.2017.09.008
PubMed: 29223614
PubMed Central: 7129617
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PMC:7129617Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Host susceptibility to MERS-CoV infection, a retrospective cohort study of the 2015 Korean MERS outbreak</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, 06531, Republic of Korea</nlm:aff></affiliation></author><author><name sortKey="Seok, Hyeri" sort="Seok, Hyeri" uniqKey="Seok H" first="Hyeri" last="Seok">Hyeri Seok</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, 06531, 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, 06531, 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, 06531, 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, 06531, 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, 06531, 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, 06531, 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="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, 06531, 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, 06531, 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, 06531, 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, 06531, Republic of Korea</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">29223614</idno><idno type="pmc">7129617</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7129617</idno><idno type="RBID">PMC:7129617</idno><idno type="doi">10.1016/j.jiac.2017.09.008</idno><date when="2017">2017</date><idno type="wicri:Area/Pmc/Corpus">000713</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000713</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Host susceptibility to MERS-CoV infection, a retrospective cohort study of the 2015 Korean MERS outbreak</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, 06531, Republic of Korea</nlm:aff></affiliation></author><author><name sortKey="Seok, Hyeri" sort="Seok, Hyeri" uniqKey="Seok H" first="Hyeri" last="Seok">Hyeri Seok</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, 06531, 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, 06531, 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, 06531, 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, 06531, 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, 06531, 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, 06531, 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="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, 06531, 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, 06531, 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, 06531, 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, 06531, Republic of Korea</nlm:aff></affiliation></author></analytic><series><title level="j">Journal of Infection and Chemotherapy</title><idno type="ISSN">1341-321X</idno><idno type="eISSN">1437-7780</idno><imprint><date when="2017">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>To evaluate host susceptibility factors to Middle East respiratory syndrome coronavirus (MERS-CoV) infection, we conducted a retrospective cohort study from the single largest exposure event of the 2015 Korean MERS outbreak. A total of 175 patients were closely exposed to a super-spreader, 26 of which were infected (14.9%). In a multivariate analysis, history of autologous stem cell transplantation (HR, 31.151; 95% CI, 5.447–178.145; <italic>P</italic> < 0.001) and tachypnea at ED (HR, 4.392; 95% CI, 1.402–13.761; <italic>P</italic> = 0.011) were significantly associated with MERS-CoV infection.</p></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><analytic><author><name sortKey="Drosten, C" uniqKey="Drosten C">C. Drosten</name></author><author><name sortKey="Muth, D" uniqKey="Muth D">D. Muth</name></author><author><name sortKey="Corman, V M" uniqKey="Corman V">V.M. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">J Infect Chemother</journal-id><journal-id journal-id-type="iso-abbrev">J. Infect. Chemother</journal-id><journal-title-group><journal-title>Journal of Infection and Chemotherapy</journal-title></journal-title-group><issn pub-type="ppub">1341-321X</issn><issn pub-type="epub">1437-7780</issn><publisher><publisher-name>Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd.</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">29223614</article-id><article-id pub-id-type="pmc">7129617</article-id><article-id pub-id-type="publisher-id">S1341-321X(17)30210-6</article-id><article-id pub-id-type="doi">10.1016/j.jiac.2017.09.008</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Host susceptibility to MERS-CoV infection, a retrospective cohort study of the 2015 Korean MERS outbreak</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><xref rid="fn1" ref-type="fn">1</xref><xref rid="fn2" ref-type="fn">2</xref></contrib><contrib contrib-type="author" id="au2"><name><surname>Seok</surname><given-names>Hyeri</given-names></name><xref rid="aff1" ref-type="aff">a</xref><xref rid="fn1" ref-type="fn">1</xref></contrib><contrib contrib-type="author" id="au3"><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="au4"><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="au5"><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="au6"><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="au7"><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="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>Kang</surname><given-names>Cheol-In</given-names></name><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author" id="au11"><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="au12"><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="au13"><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, 06531, 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><author-notes><corresp id="cor1"><label>∗</label>Corresponding author. Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81, Irwon-ro, Gangnam-gu, Seoul, 06531, Republic of Korea. <email>krpeck@skku.edu</email></corresp><fn id="fn1"><label>1</label><p id="ntpara0010">These authors contributed equally to this article.</p></fn><fn id="fn2"><label>2</label><p id="ntpara0015">Present address: Division of Infectious Diseases, Department of Internal Medicine, Armed Forces Capital Hospital, Seongnam, Korea.</p></fn></author-notes><pub-date pub-type="pmc-release"><day>6</day><month>12</month><year>2017</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>2</month><year>2018</year></pub-date><pub-date pub-type="epub"><day>6</day><month>12</month><year>2017</year></pub-date><volume>24</volume><issue>2</issue><fpage>150</fpage><lpage>152</lpage><history><date date-type="received"><day>31</day><month>5</month><year>2017</year></date><date date-type="rev-recd"><day>8</day><month>9</month><year>2017</year></date><date date-type="accepted"><day>15</day><month>9</month><year>2017</year></date></history><permissions><copyright-statement>© 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.</copyright-statement><copyright-year>2017</copyright-year><copyright-holder>Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases</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"><p>To evaluate host susceptibility factors to Middle East respiratory syndrome coronavirus (MERS-CoV) infection, we conducted a retrospective cohort study from the single largest exposure event of the 2015 Korean MERS outbreak. A total of 175 patients were closely exposed to a super-spreader, 26 of which were infected (14.9%). In a multivariate analysis, history of autologous stem cell transplantation (HR, 31.151; 95% CI, 5.447–178.145; <italic>P</italic> < 0.001) and tachypnea at ED (HR, 4.392; 95% CI, 1.402–13.761; <italic>P</italic> = 0.011) were significantly associated with MERS-CoV infection.</p></abstract><kwd-group id="kwrds0010"><title>Keywords</title><kwd>Middle East respiratory syndrome coronavirus</kwd><kwd>Susceptibility</kwd><kwd>Stem cell transplantation</kwd><kwd>Tachypnea</kwd></kwd-group></article-meta></front><body><p id="p0010">Close exposure is a critical factor for human-to-human transmission of Middle East respiratory syndrome coronavirus (MERS-CoV), but clinical factors affecting host susceptibility to MERS-CoV have not been properly identified <xref rid="bib1" ref-type="bibr">[1]</xref>, <xref rid="bib2" ref-type="bibr">[2]</xref>, <xref rid="bib3" ref-type="bibr">[3]</xref>. To identify host susceptibility factors to MERS-CoV infection, we performed a retrospective cohort study from the largest exposure event during the 2015 Korean MERS outbreak <xref rid="bib3" ref-type="bibr">[3]</xref>, <xref rid="bib4" ref-type="bibr">[4]</xref>.</p><p id="p0015">A retrospective cohort study was performed to identify risk factors for increased host susceptibility to MERS-CoV. This exposure event was previously described in detail <xref rid="bib3" ref-type="bibr">[3]</xref>: While a severely-coughing MERS patient stayed at our emergency department (ED) for three days, 675 patients stayed at the ED and had chance to be exposed. After meticulous contact tracing, 175 closely exposed patients were identified and classified into two groups by exposure time and location: group A, patients who stayed in the same examination rooms at the same time with the index case (our ED is composed of zone I ∼ IV for adult patients, and the index case used zone II ∼ IV); and group B, patients who shared the same radiology room or registration area at the same time period (30 min before and 2 h after) with the index case. Exposure sites of group A were subdivided into the zone II, III, and IV, as attack rates of each zone were significantly different (23% (13/57), 32% (7/22), and 8% (3/38), respectively; <italic>P</italic> = 0.047) <xref rid="bib3" ref-type="bibr">[3]</xref>. Included patients were followed for 14 days, which is a previously determined incubation period of MERS-CoV <xref rid="bib1" ref-type="bibr">[1]</xref>. The Institutional Review Board of Samsung Medical Center approved this study. For simple comparison of clinical variables, Student's <italic>t</italic>-tests or Mann-Whitney U tests were used for continuous variables, and chi-square tests or Fisher's exact tests for categorical variables. The Cox proportional hazard model was used to examine the association of clinical variables with MERS-CoV infection. Variables with statistical significance in univariate analyses were included in the multivariate analysis. The effect of exposure intensity was adjusted by including exposure sites in the multivariate analysis. 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><p id="p0020">During the study period, a total of 175 patients were closely exposed to the index case, 26 of whom (14.9%) were infected with MERS-CoV (3 patients at radiology rooms or registration area, 13 at zone II, 7 at zone III, and 3 at zone IV) <xref rid="bib3" ref-type="bibr">[3]</xref>. Baseline characteristics and clinical presentation of the study population at the time of ED visit are presented in <xref rid="tbl1" ref-type="table">Table 1</xref>. There was no statistical difference in age, sex, body mass index, and immunosuppressive conditions. Patients exposed at zone II and III showed higher attack rates as previously described <xref rid="bib3" ref-type="bibr">[3]</xref>. Among underlying diseases, hypertension and cardiovascular diseases were significantly different between infected and non-infected patients (all <italic>P</italic> < 0.05). Significantly higher proportion of MERS-infected patients presented with tachypnea (respiratory rate > 24/min) at ED visit, compared to non-infected patients (15.4% (4/26) and 2.7% (4/149), respectively; <italic>P</italic> = 0.018). The proportion of concomitant infections and laboratory test results were not statistically different between the two groups.<table-wrap position="float" id="tbl1"><label>Table 1</label><caption><p>Baseline characteristics and clinical presentation of the study population at ED visit.</p></caption><alt-text id="alttext0010">Table 1</alt-text><table frame="hsides" rules="groups"><thead><tr><th>Variables</th><th>Infected with MERS (n = 26)</th><th>Not infected with MERS (n = 149)</th><th><italic>P</italic> value</th></tr></thead><tbody><tr><td colspan="4">Demographics</td></tr><tr><td> Age, years (mean ± SD)</td><td>56.5 ± 16.8</td><td>52.2 ± 19.9</td><td>0.306</td></tr><tr><td> Male sex</td><td>13 (50%)</td><td>61 (40.9%)</td><td>0.388</td></tr><tr><td> BMI (kg/m<sup>2</sup>, median, IQR)</td><td>22.0 (19.8–24.4)</td><td>22.1 (19.8–24.1)</td><td>0.992</td></tr><tr><td colspan="4">Exposure sites</td></tr><tr><td> Radiology or registration</td><td>3 (11.5%)</td><td>55 (36.9%)</td><td>0.011</td></tr><tr><td> Zone II</td><td>13 (50.0%)</td><td>44 (29.5%)</td><td>0.040</td></tr><tr><td> Zone III</td><td>7 (26.9%)</td><td>15 (10.1%)</td><td>0.026</td></tr><tr><td> Zone IV</td><td>3 (11.5%)</td><td>35 (23.5%)</td><td>0.173</td></tr><tr><td colspan="4">Immunosuppressive therapies</td></tr><tr><td> Chemotherapy</td><td>3 (11.5%)</td><td>36 (24.2%)</td><td>0.154</td></tr><tr><td> Radiotherapy</td><td>1 (3.8%)</td><td>9 (6.0%)</td><td>1.000</td></tr><tr><td> Steroid use</td><td>1 (3.8%)</td><td>2 (1.3%)</td><td>0.385</td></tr><tr><td colspan="4">Underlying diseases</td></tr><tr><td> Hypertension</td><td>12 (46.2%)</td><td>38 (25.5%)</td><td>0.031</td></tr><tr><td> Diabetes mellitus</td><td>4 (15.4%)</td><td>25 (16.8%)</td><td>1.000</td></tr><tr><td> Cardiovascular diseases</td><td>9 (34.6%)</td><td>21 (14.1%)</td><td>0.020</td></tr><tr><td> Pulmonary diseases</td><td>1 (3.8%)</td><td>4 (2.7%)</td><td>0.557</td></tr><tr><td> Liver diseases</td><td>1 (3.8%)</td><td>6 (4.0%)</td><td>1.000</td></tr><tr><td> Renal diseases</td><td>2 (7.7%)</td><td>3 (2.0%)</td><td>0.160</td></tr><tr><td> Solid cancers</td><td>9 (34.6%)</td><td>58 (38.9%)</td><td>0.676</td></tr><tr><td> Hematologic diseases</td><td>3 (11.5%)</td><td>9 (6.0%)</td><td>0.391</td></tr><tr><td> Autologous SCT</td><td>2 (7.7%)</td><td>1 (0.7%)</td><td>0.058</td></tr><tr><td> Solid organ transplantation</td><td>0 (0.0%)</td><td>3 (2.0%)</td><td>1.000</td></tr><tr><td> Charlson's WIC (median, IQR)</td><td>2 (1–6)</td><td>2 (0–6)</td><td>0.444</td></tr><tr><td colspan="4">Vital signs (median, IQR)</td></tr><tr><td> Fever (>38 °C)</td><td>6 (23.1%)</td><td>20 (13.4%)</td><td>0.231</td></tr><tr><td> Hypotension (MAP < 65)</td><td>0 (0.0%)</td><td>7 (4.7%)</td><td>0.596</td></tr><tr><td> Tachycardia (HR > 90)</td><td>11 (42.3%)</td><td>44 (29.5%)</td><td>0.195</td></tr><tr><td> Tachypnea (RR > 24)</td><td>4 (15.4%)</td><td>4 (2.7%)</td><td>0.018</td></tr><tr><td> SIRS</td><td>7 (26.9%)</td><td>36 (24.2%)</td><td>0.763</td></tr><tr><td>Concomitant infections</td><td>10 (38.5%)</td><td>45 (32.8%)</td><td>0.652</td></tr><tr><td> Bacterial</td><td>8 (30.8%)</td><td>53 (35.8%)</td><td>0.795</td></tr><tr><td> Tuberculosis</td><td>1 (3.8%)</td><td>1 (0.7%)</td><td>0.276</td></tr><tr><td> Viral</td><td>1 (3.8%)</td><td>7 (4.7%)</td><td>1.000</td></tr></tbody></table><table-wrap-foot><fn id="tspara0015"><p>Data are expressed as the number (%) of patients, unless indicated otherwise.</p></fn><fn id="tspara0020"><p>Abbreviations: MERS, Middle East respiratory syndrome; SD, standard deviation; BMI, body mass index; IQR, interquartile range; SCT, stem cell transplantation; WIC, weighted index of comorbidity.</p></fn></table-wrap-foot></table-wrap></p><p id="p0025">To identify possible risk factors for increased host susceptibility to MERS-CoV, all the obtained clinical variables and exposure sites were evaluated. History of autologous stem cell transplantation (SCT), underlying hypertension and cardiovascular disease, tachypnea at ED visit, and exposure sties of zone II and III were statistically significantly associated with MERS-CoV infection in univariate analyses (<xref rid="appsec1" ref-type="sec">Supplementary Table 1</xref>). In the multivariate analysis, history of autologous SCT (HR, 31.151; 95% CI, 5.447–178.145; <italic>P</italic> < 0.001) and tachypnea at ED visit (HR, 4.392; 95% CI, 1.402–13.761; <italic>P</italic> = 0.011) were identified as risk factors for increased host susceptibility to MERS-CoV (<xref rid="tbl2" ref-type="table">Table 2</xref>). Significant association of exposure sties of zone II and III was relevant with the previous analysis <xref rid="bib3" ref-type="bibr">[3]</xref>.<table-wrap position="float" id="tbl2"><label>Table 2</label><caption><p>Multivariate analysis for host susceptibility factors to MERS-CoV infection.</p></caption><alt-text id="alttext0015">Table 2</alt-text><table frame="hsides" rules="groups"><thead><tr><th rowspan="2">Variables</th><th colspan="2">Univariate analysis<hr></hr></th><th colspan="2">Multivariate analysis<hr></hr></th></tr><tr><th>HR (95% CI)</th><th><italic>P</italic> value</th><th>HR (95% CI)</th><th><italic>P</italic> value</th></tr></thead><tbody><tr><td colspan="5">Exposure sites</td></tr><tr><td> Radiology or registration area</td><td>1</td><td></td><td>1</td><td></td></tr><tr><td> Zone II</td><td>4.711 (1.342–16.535)</td><td>0.016</td><td>5.990 (1.503–23.867)</td><td>0.011</td></tr><tr><td> Zone III</td><td>7.413 (1.916–28.686)</td><td>0.004</td><td>5.520 (1.199–25.411)</td><td>0.028</td></tr><tr><td> Zone IV</td><td>1.531 (0.309–7.587)</td><td>0.602</td><td>1.313 (0.263–6.550)</td><td>0.740</td></tr><tr><td>Autologous SCT</td><td>6.181 (1.458–26.200)</td><td>0.013</td><td>31.151 (5.447–178.145)</td><td><0.001</td></tr><tr><td>Tachypnea</td><td>6.535 (2.243–19.037)</td><td>0.001</td><td>4.392 (1.402–13.761)</td><td>0.011</td></tr><tr><td>Hypertension</td><td>2.283 (1.056–4.937)</td><td>0.036</td><td>1.872 (0.746–4.698)</td><td>0.181</td></tr><tr><td>Cardiovascular diseases</td><td>2.788 (1.242–6.257)</td><td>0.013</td><td>2.004 (0.762–5.270)</td><td>0.159</td></tr></tbody></table><table-wrap-foot><fn><p>Abbreviations: MERS-CoV, Middle East respiratory syndrome coronavirus; SCT, stem cell transplantation.</p></fn></table-wrap-foot></table-wrap></p><p id="p0030">Although many studies have reported poor prognosis factors of MERS-CoV infection since the discovery of MERS-CoV in 2012, little has been determined about host susceptibility to the virus <xref rid="bib1" ref-type="bibr">[1]</xref>. Evaluating an exposure cohort for host susceptibility is often not feasible as enough number, medical records, contact tracing, and follow-up of the exposed patients is required. We experienced a unique situation in that discrete population of patients was exposed to the single index case in the defined space of ED, which made it possible to conduct the first cohort study to evaluate host susceptibility to MERS-CoV. Of note, previously reported poor prognostic factors, including old age, male sex, concomitant infection, low albumin concentrations, lymphopenia, diabetes, and multiple comorbidities <xref rid="bib3" ref-type="bibr">[3]</xref>, <xref rid="bib5" ref-type="bibr">[5]</xref>, <xref rid="bib6" ref-type="bibr">[6]</xref>, were not statistically significant in the multivariate analysis. These factors were evaluated in the present cohort with sufficient numbers, and the analysis indicated that they did not play critical roles in host susceptibility to MERS-CoV infection. This finding suggests that risk factors associated with poor prognosis and host susceptibility need to be separately considered. Meticulous surveillance of MERS-CoV exposed patients should be conducted regardless of presence of poor prognosis factors.</p><p id="p0035">On the other hand, history of autologous SCT showed statistical significance in the multivariate analysis. Although susceptibility of autologous SCT recipients to viral infections after engraftment has not been well evaluated, two of three autologous SCT recipients (66.7%) in the present cohort were infected with MERS-CoV despite relatively low exposure intensity (at radiology room and zone IV). Because all the autologous SCT recipients in this cohort had underlying lymphoma and had multiple chemotherapy before SCT, whether autologous SCT per se or heavily-treated aggressive lymphoma would be a risk for increased host susceptibility for MERS-CoV infection is not conclusive. Also, immunocompromising conditions generally associated with viral infections including hematologic malignancies other than lymphoma, allogeneic SCT, and corticosteroid use were scarcely included in this cohort <xref rid="bib7" ref-type="bibr">[7]</xref>, <xref rid="bib8" ref-type="bibr">[8]</xref>. Therefore, it would be more relevant to interpret the present data that severely immunocompromised hosts could be more vulnerable to MERS-CoV infection and need special caution when exposed to the virus.</p><p id="p0040">Interestingly, tachypnea at ED (HR, 4.392; 95% CI, 1.402–13.761; <italic>P</italic> = 0.011) was associated with MERS-CoV infection. Although association between respiratory rate and increased susceptibility to a certain respiratory virus has not been evaluated, theoretically patients with tachypnea may inhale more virus-containing droplets or aerosols. A recent study reported isolation of MERS-CoV from the air in MERS outbreak units, suggesting possibility of air-borne transmission <xref rid="bib9" ref-type="bibr">[9]</xref>. Although this association needs to be further evaluated, patients with tachypnea at the time of exposure should to be monitored with caution, especially when the exposure occurs from severely-coughing MERS patients at a restricted space.</p><p id="p0045">Our study has several limitations. Although we could not identify entire routes of exposed patients, we adjusted the exposure intensity by specific exposure sites. Sizes, structure, crowdedness, exposure time from the index case were different between each site, which resulted in significantly different attack rates by exposure site <xref rid="bib3" ref-type="bibr">[3]</xref>. In addition, we only evaluated a single exposure cohort, which could be biased by some special situation.</p><p id="p0050">In conclusion, in a cohort study from the single largest exposure event, history of autologous SCT and tachypnea at ED were identified as host susceptibility factors to MERS-CoV infection. 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article:<supplementary-material content-type="local-data" id="ec1"><media xlink:href="mmc1.docx"></media></supplementary-material></p></sec><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><fn-group><fn id="appsec2" fn-type="supplementary-material"><label>Appendix A</label><p id="p0075">Supplementary data related to this article can be found at <ext-link ext-link-type="doi" xlink:href="10.1016/j.jiac.2017.09.008" id="intref0010">https://doi.org/10.1016/j.jiac.2017.09.008</ext-link>.</p></fn></fn-group></back></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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