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MERS transmission and risk factors: a systematic review

Identifieur interne : 000212 ( Pmc/Corpus ); précédent : 000211; suivant : 000213

MERS transmission and risk factors: a systematic review

Auteurs : Ji-Eun Park ; Soyoung Jung ; Aeran Kim ; Ji-Eun Park

Source :

RBID : PMC:5930778

Abstract

Background

Since Middle East respiratory syndrome (MERS) infection was first reported in 2012, many studies have analysed its transmissibility and severity. However, the methodology and results of these studies have varied, and there has been no systematic review of MERS. This study reviews the characteristics and associated risk factors of MERS.

Method

We searched international (PubMed, ScienceDirect, Cochrane) and Korean databases (DBpia, KISS) for English- or Korean-language articles using the terms “MERS” and “Middle East respiratory syndrome”. Only human studies with > 20 participants were analysed to exclude studies with low representation. Epidemiologic studies with information on transmissibility and severity of MERS as well as studies containing MERS risk factors were included.

Result

A total of 59 studies were included. Most studies from Saudi Arabia reported higher mortality (22–69.2%) than those from South Korea (20.4%). While the R0 value in Saudi Arabia was < 1 in all but one study, in South Korea, the R0 value was 2.5–8.09 in the early stage and decreased to < 1 in the later stage. The incubation period was 4.5–5.2 days in Saudi Arabia and 6–7.8 days in South Korea. Duration from onset was 4–10 days to confirmation, 2.9–5.3 days to hospitalization, 11–17 days to death, and 14–20 days to discharge. Older age and concomitant disease were the most common factors related to MERS infection, severity, and mortality.

Conclusion

The transmissibility and severity of MERS differed by outbreak region and patient characteristics. Further studies assessing the risk of MERS should consider these factors.


Url:
DOI: 10.1186/s12889-018-5484-8
PubMed: 29716568
PubMed Central: 5930778

Links to Exploration step

PMC:5930778

Le document en format XML

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<journal-id journal-id-type="nlm-ta">BMC Public Health</journal-id>
<journal-id journal-id-type="iso-abbrev">BMC Public Health</journal-id>
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<issn pub-type="epub">1471-2458</issn>
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<publisher-loc>London</publisher-loc>
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<article-meta>
<article-id pub-id-type="pmid">29716568</article-id>
<article-id pub-id-type="pmc">5930778</article-id>
<article-id pub-id-type="publisher-id">5484</article-id>
<article-id pub-id-type="doi">10.1186/s12889-018-5484-8</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Research Article</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>MERS transmission and risk factors: a systematic review</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">http://orcid.org/0000-0002-2932-5373</contrib-id>
<name>
<surname>Park</surname>
<given-names>Ji-Eun</given-names>
</name>
<address>
<email>janesky@kiom.re.kr</email>
</address>
<xref ref-type="aff" rid="Aff1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Jung</surname>
<given-names>Soyoung</given-names>
</name>
<address>
<email>syjung@kiom.re.kr</email>
</address>
<xref ref-type="aff" rid="Aff2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Kim</surname>
<given-names>Aeran</given-names>
</name>
<address>
<email>arkim@kiom.re.kr</email>
</address>
<xref ref-type="aff" rid="Aff2">2</xref>
</contrib>
<contrib contrib-type="author" corresp="yes">
<name>
<surname>Park</surname>
<given-names>Ji-Eun</given-names>
</name>
<address>
<phone>+82-42-868-9496</phone>
<email>jepark@kiom.re.kr</email>
</address>
<xref ref-type="aff" rid="Aff3">3</xref>
<xref ref-type="aff" rid="Aff4">4</xref>
</contrib>
<aff id="Aff1">
<label>1</label>
<institution-wrap>
<institution-id institution-id-type="ISNI">0000 0000 8749 5149</institution-id>
<institution-id institution-id-type="GRID">grid.418980.c</institution-id>
<institution>Research Center for Korean Medicine Policy,</institution>
<institution>Korea Institute of Oriental Medicine,</institution>
</institution-wrap>
Daejeon, Republic of Korea</aff>
<aff id="Aff2">
<label>2</label>
<institution-wrap>
<institution-id institution-id-type="ISNI">0000 0000 8749 5149</institution-id>
<institution-id institution-id-type="GRID">grid.418980.c</institution-id>
<institution>Clinical Research Division,</institution>
<institution>Korea Institute of Oriental Medicine,</institution>
</institution-wrap>
Daejeon, Republic of Korea</aff>
<aff id="Aff3">
<label>3</label>
<institution-wrap>
<institution-id institution-id-type="ISNI">0000 0000 8749 5149</institution-id>
<institution-id institution-id-type="GRID">grid.418980.c</institution-id>
<institution>Herbal Medicine Research Division,</institution>
<institution>Korea Institute of Oriental Medicine,</institution>
</institution-wrap>
Daejeon, Republic of Korea</aff>
<aff id="Aff4">
<label>4</label>
<institution-wrap>
<institution-id institution-id-type="ISNI">0000 0001 2296 8192</institution-id>
<institution-id institution-id-type="GRID">grid.29869.3c</institution-id>
<institution>Center for Convergent Research of Emerging Virus Infection,</institution>
<institution>Korea Research Institute of Chemical Technology,</institution>
</institution-wrap>
Daejeon, Republic of Korea</aff>
</contrib-group>
<pub-date pub-type="epub">
<day>2</day>
<month>5</month>
<year>2018</year>
</pub-date>
<pub-date pub-type="pmc-release">
<day>2</day>
<month>5</month>
<year>2018</year>
</pub-date>
<pub-date pub-type="collection">
<year>2018</year>
</pub-date>
<volume>18</volume>
<elocation-id>574</elocation-id>
<history>
<date date-type="received">
<day>21</day>
<month>11</month>
<year>2017</year>
</date>
<date date-type="accepted">
<day>19</day>
<month>4</month>
<year>2018</year>
</date>
</history>
<permissions>
<copyright-statement>© The Author(s). 2018</copyright-statement>
<license license-type="OpenAccess">
<license-p>
<bold>Open Access</bold>
This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (
<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>
), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (
<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/publicdomain/zero/1.0/">http://creativecommons.org/publicdomain/zero/1.0/</ext-link>
) applies to the data made available in this article, unless otherwise stated.</license-p>
</license>
</permissions>
<abstract id="Abs1">
<sec>
<title>Background</title>
<p id="Par1">Since Middle East respiratory syndrome (MERS) infection was first reported in 2012, many studies have analysed its transmissibility and severity. However, the methodology and results of these studies have varied, and there has been no systematic review of MERS. This study reviews the characteristics and associated risk factors of MERS.</p>
</sec>
<sec>
<title>Method</title>
<p id="Par2">We searched international (PubMed, ScienceDirect, Cochrane) and Korean databases (DBpia, KISS) for English- or Korean-language articles using the terms “MERS” and “Middle East respiratory syndrome”. Only human studies with > 20 participants were analysed to exclude studies with low representation. Epidemiologic studies with information on transmissibility and severity of MERS as well as studies containing MERS risk factors were included.</p>
</sec>
<sec>
<title>Result</title>
<p id="Par3">A total of 59 studies were included. Most studies from Saudi Arabia reported higher mortality (22–69.2%) than those from South Korea (20.4%). While the R
<sub>0</sub>
value in Saudi Arabia was < 1 in all but one study, in South Korea, the R
<sub>0</sub>
value was 2.5–8.09 in the early stage and decreased to < 1 in the later stage. The incubation period was 4.5–5.2 days in Saudi Arabia and 6–7.8 days in South Korea. Duration from onset was 4–10 days to confirmation, 2.9–5.3 days to hospitalization, 11–17 days to death, and 14–20 days to discharge. Older age and concomitant disease were the most common factors related to MERS infection, severity, and mortality.</p>
</sec>
<sec>
<title>Conclusion</title>
<p id="Par4">The transmissibility and severity of MERS differed by outbreak region and patient characteristics. Further studies assessing the risk of MERS should consider these factors.</p>
</sec>
</abstract>
<kwd-group xml:lang="en">
<title>Keywords</title>
<kwd>MERS</kwd>
<kwd>Middle East respiratory syndrome</kwd>
<kwd>Infectivity</kwd>
<kwd>Severity</kwd>
<kwd>Mortality</kwd>
</kwd-group>
<funding-group>
<award-group>
<funding-source>
<institution-wrap>
<institution-id institution-id-type="FundRef">http://dx.doi.org/10.13039/501100008783</institution-id>
<institution>National Research Council of Science and Technology</institution>
</institution-wrap>
</funding-source>
<award-id>CRC-16-01-KRICT</award-id>
<principal-award-recipient>
<name>
<surname>Park</surname>
<given-names>Ji-Eun</given-names>
</name>
</principal-award-recipient>
</award-group>
</funding-group>
<custom-meta-group>
<custom-meta>
<meta-name>issue-copyright-statement</meta-name>
<meta-value>© The Author(s) 2018</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
</front>
<body>
<sec id="Sec1">
<title>Background</title>
<p id="Par10">Middle East respiratory syndrome (MERS) was first reported in 2012 in Saudi Arabia [
<xref ref-type="bibr" rid="CR1">1</xref>
]. Although most patients are linked to the Arabian Peninsula geographically, MERS has been detected in many other parts of the world [
<xref ref-type="bibr" rid="CR2">2</xref>
]. A large MERS cluster was also observed in 2015 in South Korea [
<xref ref-type="bibr" rid="CR3">3</xref>
].</p>
<p id="Par11">MERS causes sporadic infection and intrafamilial and healthcare-associated infection. Its symptoms can vary from asymptomatic infection to death. Despite the infection’s association with high mortality, specified antiviral therapy is lacking, especially for patients with concomitant diseases [
<xref ref-type="bibr" rid="CR2">2</xref>
].</p>
<p id="Par12">Many previous studies have assessed the risks of MERS, such as factors dictating severity or an infection risk, yet the indices they present vary. For example, the case fatality rate was found to be 25.9% in the Middle East area, but 20.4% in South Korea [
<xref ref-type="bibr" rid="CR4">4</xref>
]. The incubation period was reported to be 6.83–7 days in South Korea [
<xref ref-type="bibr" rid="CR4">4</xref>
,
<xref ref-type="bibr" rid="CR5">5</xref>
], but 5.5 in a study using data from multiple areas [
<xref ref-type="bibr" rid="CR6">6</xref>
] and 5.2 in Saudi Arabia [
<xref ref-type="bibr" rid="CR7">7</xref>
]. Accurate assessment of the risk of MERS is essential for predicting and preventing infection.</p>
<p id="Par13">A systematic review of the risk of MERS, as covered in previous studies, is potentially helpful for predicting this spread, and its future impact. This study aimed at reviewing the risk of MERS, focusing on indices related to infectivity and severity.</p>
</sec>
<sec id="Sec2">
<title>Methods</title>
<p id="Par14">We searched international (PubMed, ScienceDirect, Cochrane) and Korean databases (DBpia, KISS) using the term “MERS” or “Middle East respiratory syndrome”, encompassing articles published after 2000. The search process was conducted in October 2017. We also manually searched the reference lists of the included studies.</p>
<p id="Par15">Human studies were included, while animal studies and reviews were excluded. Only articles in English or Korean were included. Even if a study collected data on humans, such as collecting specimens from religious pilgrims, it was excluded if there were no MERS patients in the study sample. Additionally, case studies including fewer than 20 MERS patients were excluded as they were considered as having insufficient MERS patient numbers and representative information.</p>
<p id="Par16">The included studies were classified as epidemiologic studies and those covering risk factors of MERS. In the epidemiologic category, indices related to the risk of MERS were divided into two categories; related to infectivity and related to severity. The index related to infectivity included the reproduction number (R), attack rate, incubation period, serial interval, and days from onset to confirmation. The index related to severity included the case fatality rate (CFR), days from onset to hospitalization, days from onset to discharge, days from onset to death, and days from hospitalization to death.</p>
<p id="Par17">In the risk factor category, factors related to infection, transmission, severity, and mortality of MERS were analysed. Even if the included studies investigated factors that were related to mortality, when they did not analyse risk factors of severity or mortality using appropriate statistical methods (e.g., regression analysis, Cox proportional hazards model) or only compared prevalence factors, we excluded them from the risk factor category. In all categories, we extracted the study period, number of participants, and geographical region where the data were collected using a data extraction form confirmed after pilot assessment.</p>
</sec>
<sec id="Sec3">
<title>Results</title>
<p id="Par18">A total of 3009 studies were searched, and 2717 were reviewed, excluding 292 duplicate studies. After the title and abstract review, a further 1804 and 663 were excluded, respectively. Another four studies were included via a manual search, which left a total of 58 studies for analysis (Fig. 
<xref rid="Fig1" ref-type="fig">1</xref>
).
<fig id="Fig1">
<label>Fig. 1</label>
<caption>
<p>Flow of the systematic review in this study</p>
</caption>
<graphic xlink:href="12889_2018_5484_Fig1_HTML" id="MO1"></graphic>
</fig>
</p>
<sec id="Sec4">
<title>Epidemiologic studies</title>
<p id="Par19">The 38 of total 58 included studies were classified as epidemiologic studies (Table 
<xref rid="Tab1" ref-type="table">1</xref>
).
<table-wrap id="Tab1">
<label>Table 1</label>
<caption>
<p>Epidemiologic studies of MERS, 2012–2017</p>
</caption>
<table frame="hsides" rules="groups">
<tbody>
<tr>
<td>Author (year)</td>
<td>Country</td>
<td>Study period</td>
<td>
<p>No. of patients</p>
<p>(M/F)</p>
<p>Age of patients</p>
</td>
<td>Fatality rate</td>
<td>Contact/ comorbidity</td>
<td>Index related to infectivity</td>
<td>Index related to severity</td>
</tr>
<tr>
<td> Ahmed (2017) [
<xref ref-type="bibr" rid="CR31">31</xref>
]</td>
<td>Saudi Arabia</td>
<td>2015–2017</td>
<td>
<p>537 (370/167)</p>
<p>55 ± 17.9</p>
</td>
<td>218/537 (40.6%)</td>
<td>
<p>• Comorbidity: 73.9%</p>
<p>• Contacts</p>
<p>- Hospital-acquired: 38.7%</p>
<p>- Household: 9.9%</p>
<p>- Camel: 25.3%</p>
<p>- Unknown: 26.1%</p>
</td>
<td></td>
<td>• Onset to confirmation: 4 days (IQR: 2–7 days)</td>
</tr>
<tr>
<td> Alenazi (2017) [
<xref ref-type="bibr" rid="CR12">12</xref>
]</td>
<td>Saudi Arabia</td>
<td>2015</td>
<td>
<p>130 (66/64)</p>
<p>63.5 (community-acquired), 64.7 (healthcare-acquired), 40.1 (HCW)</p>
</td>
<td>51/130 (39.2%)</td>
<td>
<p>• Contacts</p>
<p>- Community-acquired: 20%</p>
<p>- Healthcare-acquired: 46.9%</p>
<p>- HCWs: 33.1%</p>
</td>
<td>
<p>• R</p>
<p>- Hospital-acquired: 0.98 for 2nd, 0.64 for 3rd, 0.23 for 4th generation</p>
</td>
<td></td>
</tr>
<tr>
<td> El- Bushra (2017) [
<xref ref-type="bibr" rid="CR21">21</xref>
]</td>
<td>Saudi Arabia</td>
<td>2015</td>
<td>
<p>87</p>
<p>n.r.</p>
</td>
<td>n.r.</td>
<td>
<p>• Contacts</p>
<p>- 20 primary, 39 first, 18 s, 7 third, 3 fourth generation</p>
</td>
<td>• Secondary attack rate/10,000: 42 (95% CI: 33–54)</td>
<td></td>
</tr>
<tr>
<td> Kim (2017)</td>
<td>South Korea</td>
<td>2015</td>
<td>
<p>186 (111/75)</p>
<p>55</p>
</td>
<td>
<p>38/186</p>
<p>(19.9%)</p>
</td>
<td>
<p>• Contacts</p>
<p>- Hospital (99.4%)</p>
<p>- Household (0.6%)</p>
<p>- Community (0%)</p>
<p>• Comorbidity</p>
<p>- 29/38 fatalities had underlying disease</p>
</td>
<td></td>
<td></td>
</tr>
<tr>
<td> Park (2017) [
<xref ref-type="bibr" rid="CR23">23</xref>
]</td>
<td>South Korea</td>
<td>2015</td>
<td>
<p>25 (13/12)</p>
<p>71
<sup>a</sup>
(IQR: 38–86)</p>
</td>
<td>25/11 (44.0%)</td>
<td></td>
<td>
<p>• Attack rate: 3.7%</p>
<p>• Incubation period: 6.1 days</p>
</td>
<td></td>
</tr>
<tr>
<td> Sha (2017) [
<xref ref-type="bibr" rid="CR29">29</xref>
]</td>
<td>
<p>Middle East area/</p>
<p>South Korea</p>
</td>
<td>2012–2016</td>
<td>
<p>683 (423/260)</p>
<p>50–60 (fatal), 38–46 (non-fatal)</p>
</td>
<td>
<p>182 (26.6%)</p>
<p>(Middle East: 25.9%,</p>
<p>South Korea: 13.8%)</p>
</td>
<td>
<p>• Comorbidity</p>
<p>- 67.9% in fatal, 22.2% in nonfatal cases</p>
</td>
<td>
<p>• Incubation period</p>
<p>- 4.5–5 days in Middle East area</p>
<p>- 6 days in South Korea</p>
</td>
<td>
<p>• Onset to confirmation</p>
<p>- 8 days in fatal, 4 days in nonfatal in Middle East area</p>
<p>- 4 days in fatal, 5 days nonfatal in South Korea</p>
<p>• Onset to death</p>
<p>- 11.5 days in Middle East area</p>
<p>- 11 days in South Korea</p>
<p>• Onset to discharge</p>
<p>- 14 days in Middle East area</p>
<p>- 17 days in South Korea</p>
</td>
</tr>
<tr>
<td> Sherbini (2017) [
<xref ref-type="bibr" rid="CR32">32</xref>
]</td>
<td>Saudi Arabia</td>
<td>2014</td>
<td>
<p>29 (20/9)</p>
<p>45 ± 12</p>
</td>
<td>10 (34%)</td>
<td>
<p>• Comorbidities</p>
<p>- Diabetes (31%)</p>
<p>- Chronic kidney disease (27%)</p>
</td>
<td></td>
<td>• Symptoms to hospitalization: 2.9–5 days</td>
</tr>
<tr>
<td> Assiri (2016) [
<xref ref-type="bibr" rid="CR36">36</xref>
]</td>
<td>Saudi Arabia</td>
<td>2014–2015</td>
<td>
<p>38 (28/10)</p>
<p>51 (range 17–84)</p>
</td>
<td>21/38 (55.3%)</td>
<td>
<p>• Contacts</p>
<p>- 13 HCWs</p>
<p>- 15 were associated with 1 dialysis unit</p>
</td>
<td></td>
<td>• Onset to death/discharge: 17 days (range 1.0–84.0)</td>
</tr>
<tr>
<td> Cho (2016) [
<xref ref-type="bibr" rid="CR5">5</xref>
]</td>
<td>South Korea</td>
<td>2015</td>
<td>
<p>82 (53/29)</p>
<p>57 (patients and visitors),</p>
<p>38 (HCW)</p>
</td>
<td>n.r.</td>
<td>
<p>• Contacts</p>
<p>- Patients: 40.2%</p>
<p>- Visitors: 50%</p>
<p>- HCWs: 9.8%</p>
<p>• Comorbidity</p>
<p>- 24 (29%) had underlying disease</p>
</td>
<td>
<p>• Incubation period: 7 days (range: 2–17, IQR: 5–10)</p>
<p>• Overall attack rate</p>
<p>- Patients in the emergency room: 4% (30/ 675)</p>
<p>- Visitors: 6% (38/683)</p>
</td>
<td></td>
</tr>
<tr>
<td> Halim (2016) [
<xref ref-type="bibr" rid="CR33">33</xref>
]</td>
<td>Saudi Arabia</td>
<td>2016</td>
<td>
<p>32 (20/12)</p>
<p>43.99 ± 13.03</p>
</td>
<td>14/32 (43.8%)</td>
<td></td>
<td></td>
<td>
<p>• From symptom to hospitalization</p>
<p>- 5.3 ± 3.3 days</p>
<p>• Total length of stay</p>
<p>- 15 ± 3.6 days</p>
</td>
</tr>
<tr>
<td> Liu (2016)</td>
<td>Taiwan</td>
<td>2012–2015</td>
<td>
<p>1368 (883/476)
<sup>a</sup>
</p>
<p>49 (range: 2–90)</p>
</td>
<td>
<p>35.6% (487/1368)</p>
<p>• CFR</p>
<p>7.03% for HCW</p>
<p>- 36.96% for non-HCW</p>
</td>
<td>
<p>• Contacts</p>
<p>- Patients: 46.2%</p>
<p>- Family members or visitors: 34.9%</p>
<p>- HCW: 18.9%</p>
</td>
<td></td>
<td>
<p>• Onset to death</p>
<p>- 13 (4–17) days for HCP</p>
<p>- 12 (1–52) days for non-HCW</p>
<p>• Onset to confirmation</p>
<p>- 6 (1–14) days for HCP</p>
<p>- 10 (1–21) days for non-HCW</p>
</td>
</tr>
<tr>
<td> Mohd (2016) [
<xref ref-type="bibr" rid="CR40">40</xref>
]</td>
<td>Saudi Arabia</td>
<td>2014–2015</td>
<td>
<p>80 (48/32)</p>
<p>40
<sup>a</sup>
</p>
</td>
<td>• 10% (8/80)</td>
<td>
<p>• Comorbidity</p>
<p>- Not different from non-MERS groups</p>
</td>
<td></td>
<td></td>
</tr>
<tr>
<td> Park (2016) [
<xref ref-type="bibr" rid="CR24">24</xref>
]</td>
<td>South Korea</td>
<td>2015</td>
<td>
<p>23 (13/10)</p>
<p>66
<sup>a</sup>
(range: 31–87) in hospital A;</p>
<p>74.5
<sup>a</sup>
(range: 60–82) in hospital B</p>
</td>
<td>11/23 (47.8%)</td>
<td>
<p>• Generation</p>
<p>- 23 in 2nd; 3 in 3rd</p>
</td>
<td>
<p>• Incubation period</p>
<p>- 7.8 days (95% CI: 6.0–10.0)</p>
<p>• Serial interval</p>
<p>- 14.6 days (95% CI, 12.9–16.5)</p>
<p>• Secondary attack rate</p>
<p>- 15.8% in hospital A</p>
<p>- 14.3% in hospital B</p>
</td>
<td>
<p>• Time to death
<sup>c</sup>
</p>
<p>- 12.5 days (IQR: 5.5–19) in hospital A</p>
<p>- 11 days (IQR: 9–16) in hospital B</p>
</td>
</tr>
<tr>
<td> Virlogeux (2016) [
<xref ref-type="bibr" rid="CR25">25</xref>
]</td>
<td>South Korea</td>
<td>2015</td>
<td>
<p>170 (98/72)</p>
<p>54.6 ± 16.2</p>
</td>
<td>36/170 (21%)</td>
<td></td>
<td>Incubation period: 6.9 days (95% CI: 6.3–7.5)</td>
<td></td>
</tr>
<tr>
<td> Chowell (2015) [
<xref ref-type="bibr" rid="CR8">8</xref>
]</td>
<td>Saudi Arabia, South Korea</td>
<td>2013–2015</td>
<td>
<p>973 MERS and 7634 SARS cases</p>
<p>n.r.</p>
</td>
<td>n.r.</td>
<td>
<p>• Contacts</p>
<p>- 43.5–100% were linked to healthcare setting in MERS</p>
</td>
<td>
<p>R
<sub>0</sub>
(95% CI)</p>
<p>- MERS: 0.91 (0.36–1.44)</p>
<p>- SARS: 0.95 (0.67–1.23)</p>
<p>Infection rate of disease among HCWs:</p>
<p>- MERS: 13.4–13.5%</p>
<p>- SARS: 18.8–57.1%</p>
</td>
<td></td>
</tr>
<tr>
<td> Cowling (2015) [
<xref ref-type="bibr" rid="CR26">26</xref>
]</td>
<td>South Korea</td>
<td>2015</td>
<td>
<p>166 (101/65)</p>
<p>55.4 (range: 16–87)</p>
</td>
<td>24/166 (14.5%)</td>
<td>
<p>• Contacts</p>
<p>- 119 cases had contact with a confirmed case</p>
<p>- 30/166 (18%) were healthcare personnel</p>
</td>
<td>
<p>• Incubation period: 6.7 days</p>
<p>• Serial interval: 12.6 days.</p>
</td>
<td></td>
</tr>
<tr>
<td> KCDC (2015) [
<xref ref-type="bibr" rid="CR4">4</xref>
]</td>
<td>South Korea</td>
<td>2015</td>
<td>
<p>186 (111/75)</p>
<p>55
<sup>a</sup>
(IQR: 42–66)</p>
</td>
<td>36/186 (19.4%)</td>
<td>
<p>• Contacts</p>
<p>- 44.1% patients exposed in hospitals</p>
<p>- 32.8% caregivers</p>
<p>- 13.4% HCWs</p>
<p>• Comorbidities</p>
<p>- 45.2%</p>
</td>
<td>
<p>• Incubation period</p>
<p>- 6.83 days (95% CI: 6.31,7.36)</p>
</td>
<td></td>
</tr>
<tr>
<td> Ki (2015) [
<xref ref-type="bibr" rid="CR3">3</xref>
]</td>
<td>South Korea</td>
<td>2015</td>
<td>
<p>186 (111/75)</p>
<p>50s in men and 60s in women</p>
</td>
<td>36/186 (19.4%)</td>
<td>
<p>• Generation</p>
<p>- 28 in 1st (15.1%); 125 in 2nd (67.2%); 32 in 3rd (17.2%); 2 were not certain</p>
<p>• Contacts</p>
<p>- Same hospital: 82 (44%)</p>
<p>- Family/healthcare aides/visitors: 71 (38%)</p>
<p>- HCWs: 31 (17%)</p>
<p>• Comorbidities</p>
<p>- 77 (41%) had underlying diseases</p>
</td>
<td>• Incubation period: 6.5 days (2–16 days).</td>
<td>
<p>• From symptom onset to confirmation: 5 days (0–17 days)</p>
<p>• From symptom onset to discharge from the hospital: 20 days (8–41 days).</p>
<p>• From symptom onset to death: 13 days (1–41 days)</p>
</td>
</tr>
<tr>
<td> Ministry of Health, South Korea (2016) [
<xref ref-type="bibr" rid="CR27">27</xref>
]</td>
<td>South Korea</td>
<td>2015</td>
<td>
<p>186 (111/75)</p>
<p>50s (21.6%), 60s (19.9%)</p>
</td>
<td char="×" align="char">38/186 (20.4%)</td>
<td>
<p>• Generation</p>
<p>- 28 in 2nd, 120 in 3rd, 26 in 4th, 11 in unclear/</p>
<p>unknown</p>
<p>• Contacts</p>
<p>- 82 patients in hospital - 63 family members/</p>
<p>visitors</p>
<p>- 39 HCWs</p>
<p>- 2 others</p>
</td>
<td>
<p>• Incubation period</p>
<p>- 6.83 days (95% CI: 6.31–7.36)</p>
</td>
<td></td>
</tr>
<tr>
<td> Noorwali (2015) [
<xref ref-type="bibr" rid="CR37">37</xref>
]</td>
<td>Saudi Arabia</td>
<td>2014</td>
<td>
<p>261 (171/90)</p>
<p>n.r.</p>
</td>
<td>110/261 (42%)</td>
<td>
<p>• Contacts</p>
<p>- 84 HCWs</p>
<p>- 177 non-HCWs</p>
</td>
<td></td>
<td></td>
</tr>
<tr>
<td> Park (2015) [
<xref ref-type="bibr" rid="CR28">28</xref>
]</td>
<td>South Korea</td>
<td>2015</td>
<td>
<p>37 (21/16)</p>
<p>51.7 (range: 24–79)</p>
</td>
<td>6/37 (16.2%)</td>
<td>
<p>• Generation</p>
<p>- 1 in 1st, 25 in 2nd, 11 in 3rd</p>
<p>• Contacts</p>
<p>- 20 patients</p>
<p>- 12 relatives of patients</p>
<p>- 3 HCWs</p>
<p>- 1 unrelated visitors</p>
<p>• Comorbidities</p>
<p>- 5/6 in fatal, 3/31 in nonfatal</p>
</td>
<td>
<p>Incubation period</p>
<p>- 6 days (95% CI: 4–7 days)</p>
</td>
<td>
<p>• Symptom onset to confirmation</p>
<p>- 6.5 days (95% CI: 4–9) for all cases</p>
<p>- 9 days for second cases</p>
<p>- 4 days for third cases</p>
</td>
</tr>
<tr>
<td> Drosten (2014) [
<xref ref-type="bibr" rid="CR22">22</xref>
]</td>
<td>Saudi Arabia</td>
<td>2013</td>
<td>
<p>26 (17/9)</p>
<p>55
<sup>a</sup>
(range: 2–83)</p>
</td>
<td>18/26 (69.2%)</td>
<td>
<p>• Contacts</p>
<p>- 280 household contacts</p>
</td>
<td>• Secondary transmission: 4%</td>
<td></td>
</tr>
<tr>
<td> Assiri (2013) [
<xref ref-type="bibr" rid="CR7">7</xref>
]</td>
<td>Saudi Arabia</td>
<td>2012–2013</td>
<td>
<p>47 (36/11)</p>
<p>n.r.</p>
</td>
<td>28/47 (60%)</td>
<td>
<p>• Comorbidities</p>
<p>- 45 had underlying comorbid medical disorders (96%)</p>
</td>
<td>• Incubation period: 5.2 days</td>
<td></td>
</tr>
<tr>
<td> Breban (2013) [
<xref ref-type="bibr" rid="CR9">9</xref>
]</td>
<td>Multiple areas</td>
<td>2012–2013</td>
<td>
<p>64 (44/17)
<sup>b</sup>
</p>
<p>56
<sup>a</sup>
(IQR 41–68.5)</p>
</td>
<td>38/64 (59.4%)</td>
<td>n.r.</td>
<td>• R
<sub>0</sub>
: 0.69 (95% CI 0.50–0.92)</td>
<td></td>
</tr>
<tr>
<td> Oboho (2012) [
<xref ref-type="bibr" rid="CR38">38</xref>
]</td>
<td>Saudi Arabia</td>
<td>2014</td>
<td>
<p>255 (174/81)</p>
<p>45
<sup>a</sup>
(IQR:30–59)</p>
</td>
<td>93 (36.5%)</td>
<td>
<p>• Contacts</p>
<p>- 40 of 191 symptomatic were HCWs (20.9%)</p>
</td>
<td></td>
<td>n.r.</td>
</tr>
<tr>
<td> Penttinen (2013) [
<xref ref-type="bibr" rid="CR41">41</xref>
]</td>
<td>Multiple areas</td>
<td>2012–2013</td>
<td>
<p>133 (51/77)
<sup>b</sup>
</p>
<p>n.r.</p>
</td>
<td>45%</td>
<td>
<p>• Contacts</p>
<p>- 14 primary cases, 129 cases on transmission</p>
</td>
<td></td>
<td>
<p>• Proportion to ICU:</p>
<p>60 cases (45%)</p>
</td>
</tr>
<tr>
<td colspan="8">Estimating the index of infectivity and severity using secondary data</td>
</tr>
<tr>
<td>Author (year)</td>
<td>Country</td>
<td>Study period</td>
<td colspan="3">Indexes related to infectivity</td>
<td colspan="2">Index related to severity</td>
</tr>
<tr>
<td> Chang (2017) [
<xref ref-type="bibr" rid="CR18">18</xref>
]</td>
<td>South Korea</td>
<td>2015</td>
<td colspan="3">
<p>• R
<sub>0</sub>
</p>
<p>- 8.097</p>
</td>
<td colspan="2"></td>
</tr>
<tr>
<td> Choi (2017) [
<xref ref-type="bibr" rid="CR15">15</xref>
]</td>
<td>South Korea, Saudi Arabia</td>
<td>2015</td>
<td colspan="3">
<p>• R
<sub>0</sub>
</p>
<p>- 3.9 in South Korea</p>
<p>- 1.9–3.9 in Saudi Arabia (1.9 in Riyadh, 3.9 in Jeddah)</p>
</td>
<td colspan="2"></td>
</tr>
<tr>
<td> Eifan (2017) [
<xref ref-type="bibr" rid="CR13">13</xref>
]</td>
<td>Saudi Arabia</td>
<td>2013–2015</td>
<td colspan="3">
<p>• R</p>
<p>- 0.85–0.97</p>
</td>
<td colspan="2"></td>
</tr>
<tr>
<td> Zhang (2017) [
<xref ref-type="bibr" rid="CR17">17</xref>
]</td>
<td>South Korea</td>
<td>2015</td>
<td colspan="3">
<p>• R</p>
<p>- 2.5–7.2</p>
</td>
<td colspan="2"></td>
</tr>
<tr>
<td> Kim (2016) [
<xref ref-type="bibr" rid="CR16">16</xref>
]</td>
<td>South Korea</td>
<td>2015</td>
<td colspan="3">
<p>• R
<sub>0</sub>
</p>
<p>- 5.4 (95% CI: 4.61–6.19) in period 1</p>
<p>- 0.14 (95% CI: 0.04–0.26) in period 2</p>
<p>• Infectivity of hospitalized patients</p>
<p>- 22 (95% CI: 18.73–25.27) in period 1</p>
<p>- 1 (95% CI: 0.16–1.84) in period 2</p>
</td>
<td colspan="2"></td>
</tr>
<tr>
<td> Lessler (2016) [
<xref ref-type="bibr" rid="CR39">39</xref>
]</td>
<td>Saudi Arabia</td>
<td>2012–2014</td>
<td colspan="3"></td>
<td colspan="2">• CFR: 22% (95% CI: 18, 25)</td>
</tr>
<tr>
<td> Kucharski (2015) [
<xref ref-type="bibr" rid="CR10">10</xref>
]</td>
<td>Multiple areas</td>
<td>2012–2013</td>
<td colspan="3">• R
<sub>0</sub>
: 0.47 (95% CI: 0.29–0.80)</td>
<td colspan="2"></td>
</tr>
<tr>
<td> Mizumoto (2015) [
<xref ref-type="bibr" rid="CR35">35</xref>
]</td>
<td>South Korea</td>
<td>2015</td>
<td colspan="3"></td>
<td colspan="2">• CFR: 20.0% (95% CI): 14.6, 26.2).</td>
</tr>
<tr>
<td> Xia (2015) [
<xref ref-type="bibr" rid="CR19">19</xref>
]</td>
<td>South Korea</td>
<td>2015</td>
<td colspan="3">
<p>• R
<sub>0</sub>
</p>
<p>- 4.422 in early stage</p>
<p>- 0.385 with control</p>
</td>
<td colspan="2">from hospitalization to death: 15.16 (0–42) (mean, range)</td>
</tr>
<tr>
<td> Cauche-mez (2014) [
<xref ref-type="bibr" rid="CR6">6</xref>
]</td>
<td>Multiple areas</td>
<td>2012–2013</td>
<td colspan="3">
<p>• Incubation period</p>
<p>- 5.5 (95% CI: 3.6–10·2)</p>
<p>• R
<sub>0</sub>
: 0.8–1.3</p>
</td>
<td colspan="2">
<p>• CFR</p>
<p>- 74% (95% CI: 49–91) for first cases</p>
<p>- 21% (95% CI: 7–42) for second cases</p>
</td>
</tr>
<tr>
<td> Chowell (2014) [
<xref ref-type="bibr" rid="CR11">11</xref>
]</td>
<td>Saudi Arabia</td>
<td>2013</td>
<td colspan="3">
<p>• R
<sub>overall</sub>
</p>
<p>- 0.45 (95% CI: 0.29, 0.61) under the surveillance-bias scenario</p>
<p>- 0.88 (95% CI: 0.58, 1.20) under the differential-transmissibility scenario</p>
</td>
<td colspan="2"></td>
</tr>
<tr>
<td> Poletto (2014) [
<xref ref-type="bibr" rid="CR14">14</xref>
]</td>
<td>Middle East area</td>
<td>2012–2013</td>
<td colspan="3">• R: 0.50 (95% CI: 0.30–0.77)</td>
<td colspan="2"></td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p>
<italic>CI</italic>
confidence interval,
<italic>ICU</italic>
intensive care unit,
<italic>IQR</italic>
interquartile range,
<italic>HCW</italic>
healthcare worker,
<italic>SARS</italic>
severe acute respiratory syndrome</p>
<p>
<sup>a</sup>
Median age, the others are mean age</p>
<p>
<sup>b</sup>
Information of several participants was missing</p>
<p>
<sup>c</sup>
Definition is not clear in this study</p>
</table-wrap-foot>
</table-wrap>
</p>
<sec id="Sec5">
<title>R value</title>
<p id="Par20">R value, representing the reproduction number, indicates the average number of secondary cases generated by infectious individuals. Thirteen studies reported R value of MERS. Four studies that used data from multiple areas had
<italic>R</italic>
 < 1.0 [
<xref ref-type="bibr" rid="CR6">6</xref>
,
<xref ref-type="bibr" rid="CR8">8</xref>
<xref ref-type="bibr" rid="CR10">10</xref>
]. Studies using Saudi Arabia or Middle East area data reported
<italic>R</italic>
 < 1, at 0.45–0.98 [
<xref ref-type="bibr" rid="CR11">11</xref>
<xref ref-type="bibr" rid="CR14">14</xref>
], though one reported 1.9–3.9 [
<xref ref-type="bibr" rid="CR15">15</xref>
]. Studies using South Korea data showed higher values, at 2.5–8.09 [
<xref ref-type="bibr" rid="CR16">16</xref>
<xref ref-type="bibr" rid="CR19">19</xref>
], in the early stage, and < 1 in the later period [
<xref ref-type="bibr" rid="CR20">20</xref>
] or with control intervention [
<xref ref-type="bibr" rid="CR19">19</xref>
].</p>
</sec>
<sec id="Sec6">
<title>Attack rate</title>
<p id="Par21">A total of eight studies reported the attack rate. Four reported the overall or secondary attack rate, and the other four reported the attack rate of specific participant groups. Two studies conducted in Saudi Arabia showed 0.42% [
<xref ref-type="bibr" rid="CR21">21</xref>
] and 4% [
<xref ref-type="bibr" rid="CR22">22</xref>
] secondary attack rates. Studies in South Korea showed secondary attack rates of 3.7% in one study [
<xref ref-type="bibr" rid="CR23">23</xref>
] and 14.3–15.8% in another [
<xref ref-type="bibr" rid="CR24">24</xref>
].</p>
<p id="Par22">Two studies reported the attack rate among healthcare workers (HCWs). One study in South Korea reported a MERS incidence of 1.5% among HCWs [
<xref ref-type="bibr" rid="CR20">20</xref>
], and another study using multiple area data reported a 13.4–13.5% infection rate among HCWs [
<xref ref-type="bibr" rid="CR8">8</xref>
]. The attack rate among hospital patients was 4% in one study [
<xref ref-type="bibr" rid="CR5">5</xref>
] and 22% in the early and 1% in the later period in another [
<xref ref-type="bibr" rid="CR16">16</xref>
].</p>
</sec>
<sec id="Sec7">
<title>Incubation period</title>
<p id="Par23">The incubation period is the period between infection and appearance of signs of a disease. A total of 12 studies reported the incubation period of MERS. Nine used data from South Korea and showed a 6–7.8 day incubation period [
<xref ref-type="bibr" rid="CR3">3</xref>
<xref ref-type="bibr" rid="CR5">5</xref>
,
<xref ref-type="bibr" rid="CR23">23</xref>
<xref ref-type="bibr" rid="CR28">28</xref>
]. One study using data from Saudi Arabia reported a 5.2 day incubation period [
<xref ref-type="bibr" rid="CR7">7</xref>
], and another using data from multiple areas reported a 5.5 day incubation period [
<xref ref-type="bibr" rid="CR6">6</xref>
]. Sha et al. compared the incubation periods between the Middle East area and South Korea and reported 4.5–5 and 6 days, respectively [
<xref ref-type="bibr" rid="CR29">29</xref>
].</p>
</sec>
<sec id="Sec8">
<title>Serial interval</title>
<p id="Par24">The serial interval of an infectious disease represents the duration between symptom onset of a primary case and of its secondary cases. Two studies used South Korea data, reporting serial intervals of MERS of 12.6 and 14.6 days, respectively [
<xref ref-type="bibr" rid="CR24">24</xref>
,
<xref ref-type="bibr" rid="CR26">26</xref>
].</p>
</sec>
<sec id="Sec9">
<title>Days from onset to confirmation</title>
<p id="Par25">Among five studies reporting days from onset to confirmation, three studies used data from South Korea. One study analysing all South Korea cases reported 5 days from onset to confirmation [
<xref ref-type="bibr" rid="CR3">3</xref>
]. Park et al. reported 6.5 days for all cases, 9 for second generation and 4 for third generation [
<xref ref-type="bibr" rid="CR28">28</xref>
]. One study from Taiwan reported 6 days for HCWs and 10 for non-HCWs [
<xref ref-type="bibr" rid="CR30">30</xref>
]. A study from Saudi Arabia reported 4 days from onset to confirmation [
<xref ref-type="bibr" rid="CR31">31</xref>
]. Sha et al. compared the data from Middle East and South Korea areas and reported 4–8 and 4–5 days, respectively [
<xref ref-type="bibr" rid="CR29">29</xref>
].</p>
</sec>
<sec id="Sec10">
<title>Days from onset to hospitalization</title>
<p id="Par26">Two studies from Saudi Arabia reported days from onset to hospitalization. One reported 2.9–5 days [
<xref ref-type="bibr" rid="CR32">32</xref>
], and the other reported 5.3 days [
<xref ref-type="bibr" rid="CR33">33</xref>
].</p>
</sec>
<sec id="Sec11">
<title>Mortality</title>
<p id="Par27">Twenty-six studies reported on MERS-related mortality. Ten reported the mortality rate in South Korea as 14.5–47.8% [
<xref ref-type="bibr" rid="CR3">3</xref>
,
<xref ref-type="bibr" rid="CR4">4</xref>
,
<xref ref-type="bibr" rid="CR23">23</xref>
<xref ref-type="bibr" rid="CR26">26</xref>
,
<xref ref-type="bibr" rid="CR28">28</xref>
,
<xref ref-type="bibr" rid="CR29">29</xref>
,
<xref ref-type="bibr" rid="CR34">34</xref>
,
<xref ref-type="bibr" rid="CR35">35</xref>
]; one of which, including all MERS patients in South Korea, reported a mortality rate of 20.4% [
<xref ref-type="bibr" rid="CR27">27</xref>
]. Ten studies analysing data from Saudi Arabia reported higher mortality rates, of 22–69.2% [
<xref ref-type="bibr" rid="CR7">7</xref>
,
<xref ref-type="bibr" rid="CR12">12</xref>
,
<xref ref-type="bibr" rid="CR22">22</xref>
,
<xref ref-type="bibr" rid="CR31">31</xref>
<xref ref-type="bibr" rid="CR33">33</xref>
,
<xref ref-type="bibr" rid="CR36">36</xref>
<xref ref-type="bibr" rid="CR39">39</xref>
], although others reported mortality rates 10% [
<xref ref-type="bibr" rid="CR40">40</xref>
] and 19.9% [
<xref ref-type="bibr" rid="CR21">21</xref>
]. A Taiwanese study reported a mortality rate of 35.6% [
<xref ref-type="bibr" rid="CR30">30</xref>
]. Studies using data from multiple areas reported mortality rates ranging from 26.6% [
<xref ref-type="bibr" rid="CR29">29</xref>
] to 59.4% [
<xref ref-type="bibr" rid="CR9">9</xref>
,
<xref ref-type="bibr" rid="CR41">41</xref>
].</p>
</sec>
<sec id="Sec12">
<title>Days from onset to discharge</title>
<p id="Par28">Three studies reported days from MERS onset to discharge. Sha et al. reported 14 days in the Middle East area and 17 in South Korea [
<xref ref-type="bibr" rid="CR29">29</xref>
]. One study from Saudi Arabia reported 17 days [
<xref ref-type="bibr" rid="CR36">36</xref>
], and another in South Korea reported 20 [
<xref ref-type="bibr" rid="CR3">3</xref>
].</p>
</sec>
<sec id="Sec13">
<title>Days from onset to death</title>
<p id="Par29">Two Korean studies reported similar periods of 11–13 days from onset to death: 11–12.5 in Park et al. [
<xref ref-type="bibr" rid="CR24">24</xref>
] and 13 in Ki et al. [
<xref ref-type="bibr" rid="CR3">3</xref>
]. Although one study from Saudi Arabia reported longer than 17 days from onset to death [
<xref ref-type="bibr" rid="CR36">36</xref>
], Sha et al., comparing data between the Middle East and South Korea, reported similar periods of 11.5 and 11 days, respectively [
<xref ref-type="bibr" rid="CR29">29</xref>
]. One Taiwanese study also reported a similar period of 12–13 days [
<xref ref-type="bibr" rid="CR30">30</xref>
].</p>
</sec>
<sec id="Sec14">
<title>Days from hospitalization to death</title>
<p id="Par30">Two studies reported a similar length of hospitalization: 15 [
<xref ref-type="bibr" rid="CR33">33</xref>
] and 15.2 days [
<xref ref-type="bibr" rid="CR19">19</xref>
].</p>
</sec>
</sec>
<sec id="Sec15">
<title>Risk factors related to mortality</title>
<p id="Par31">Of the 20 studies included in the risk factor category, four were duplicates of studies in the epidemiologic category as they had information regarding the epidemiologic index and risk factors (Table 
<xref rid="Tab2" ref-type="table">2</xref>
).
<table-wrap id="Tab2">
<label>Table 2</label>
<caption>
<p>Factors related to infection, transmission, severity, and mortality of MERS</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th>Author (year)</th>
<th>Study period</th>
<th>No. of participants
<break></break>
(Total/death)</th>
<th>Country</th>
<th>Predictors</th>
<th>Significant factors</th>
</tr>
</thead>
<tbody>
<tr>
<td colspan="6">
<italic>Risk factors of infection</italic>
</td>
</tr>
<tr>
<td> Alraddadi (2016) [
<xref ref-type="bibr" rid="CR42">42</xref>
]</td>
<td>2014</td>
<td>146 (30 cases, 116 controls)</td>
<td>Saudi Arabia</td>
<td>Travel history, animal-related exposure, food exposure, underlying health conditions and behaviors</td>
<td>Direct dromedary exposure in 2 weeks, concomitant with diabetes or heart disease, currently smoking tobacco</td>
</tr>
<tr>
<td> Hastings (2016) [
<xref ref-type="bibr" rid="CR43">43</xref>
]</td>
<td>2014</td>
<td>78</td>
<td>Saudi Arabia</td>
<td>Nationality, sex, age group, hospital setting, outbreak week</td>
<td>Older age, outbreak week, nationality</td>
</tr>
<tr>
<td colspan="6">
<italic>Risk factors of transmission (spreader)</italic>
</td>
</tr>
<tr>
<td> Kang (2017) [
<xref ref-type="bibr" rid="CR44">44</xref>
]</td>
<td>2015</td>
<td>186</td>
<td>South Korea</td>
<td>Age, sex, comorbidity, symptoms, laboratory test, clinical outcome, phase in transmission, incubation period, symptom onset to isolation, non-isolated in-hospital days, symptom onset to diagnosis</td>
<td>Fever, chest X-ray abnormality in > 3 lung zones, more non-isolated in-hospital days</td>
</tr>
<tr>
<td> Kim (2017) [
<xref ref-type="bibr" rid="CR34">34</xref>
]</td>
<td>2015</td>
<td>186</td>
<td>South Korea</td>
<td>Underlying respiratory disease, cycle threshold value, symptom onset to diagnosis, no. of contacts, hospitalization or emergency room before isolation</td>
<td>Lower cycle threshold value, hospitalization or emergency room visit before isolation</td>
</tr>
<tr>
<td> Majumder (2017) [
<xref ref-type="bibr" rid="CR45">45</xref>
]</td>
<td>2015</td>
<td>186</td>
<td>South Korea</td>
<td>Sex, age, comorbidity, case class (HCW, visitor, patient), case outcome (recovered/deceased)</td>
<td>Deceased case outcome</td>
</tr>
<tr>
<td colspan="6">
<italic>Risk factors of severity</italic>
</td>
</tr>
<tr>
<td> Zhao (2017) [
<xref ref-type="bibr" rid="CR46">46</xref>
]</td>
<td>2014–2015</td>
<td>21</td>
<td>Saudi Arabia</td>
<td>CD4 T cell, CD8 T cell, PRNT
<sub>50</sub>
</td>
<td>Higher PRNT
<sub>50</sub>
, higher CD4 T cell response</td>
</tr>
<tr>
<td> Ko (2016) [
<xref ref-type="bibr" rid="CR48">48</xref>
]</td>
<td>2015</td>
<td>45</td>
<td>South Korea</td>
<td>Demographics (age, sex, BMI, underlying disease), symptoms (fever, myalgia, cough, sputum, diarrhea), laboratory test (white blood cell, hemoglobin, thrombocytopenia, lymphopenia, albumin, bilirubin, aspartate transaminase, alanine transaminase, blood urea nitrogen, creatinine, C-reactive protein, lactate dehydrogenase, threshold cycle value of PCR)</td>
<td>
<p>• Pneumonia development: older age, fever, thrombocytopenia, lymphopenia, C-reactive protein ≥2 mg/dL, lower threshold cycle value of PCR < 28</p>
<p>• Respiratory failure: male, hypertension, low albumin concentration, thrombocytopenia, lymphopenia, C-reactive protein</p>
</td>
</tr>
<tr>
<td> Feikin (2015) [
<xref ref-type="bibr" rid="CR47">47</xref>
]</td>
<td>2014</td>
<td>102</td>
<td>Saudi Arabia</td>
<td>Age, sex, underlying illness, week of specimen collection, MERS-CoV virus load</td>
<td>
<p>• Severity: older age, underlying illness, high MERS-CoV virus load</p>
<p>• Mortality: older age, underlying illness, high MERS-CoV virus load</p>
</td>
</tr>
<tr>
<td> Saad (2014) [
<xref ref-type="bibr" rid="CR49">49</xref>
]</td>
<td>2012–2014</td>
<td>70</td>
<td>Saudi Arabia</td>
<td>Age, gender, occupation, acquisition of infection, comorbidity, radiological findings, concomitant infections, laboratory abnormalities</td>
<td>
<p>• ICU care: concomitant infection, decreased albumin</p>
<p>• Mortality: older age</p>
</td>
</tr>
<tr>
<td colspan="6">
<italic>Risk factors of mortality</italic>
</td>
</tr>
<tr>
<td> Adegboye (2017) [
<xref ref-type="bibr" rid="CR50">50</xref>
]</td>
<td>2012–2015</td>
<td>959/317 (33%)</td>
<td>Saudi Arabia</td>
<td>Sex, age, comorbidity, animal contact, camel contact, HCW, secondary contact, clinical experience</td>
<td>Older age, comorbidity, non-HCW, fatal clinical experience</td>
</tr>
<tr>
<td> Ahmed (2017) [
<xref ref-type="bibr" rid="CR51">51</xref>
]</td>
<td>2014–2016</td>
<td>660/197 (29.8%)</td>
<td>Saudi Arabia</td>
<td>Age, sex, nationality, symptomatic, HCW, severity, source of infection, regions</td>
<td>
<p>• 3-day mortality: older age, non-HCW, hospital-acquired infection</p>
<p>• 30-day mortality: older age, non-HCW, pre-existing illness, severity, hospital-acquired infection</p>
</td>
</tr>
<tr>
<td> Sha (2017) [
<xref ref-type="bibr" rid="CR29">29</xref>
]</td>
<td>2012–2016</td>
<td>216/56 (25.9%) in Middle East area, 174/24 (13.8%) in South Korea</td>
<td>Middle East Area/South Korea</td>
<td>Age, sex, exposure to camel or other animals, comorbidity, disease progress (days)</td>
<td>Older age (Middle East, South Korea), high comorbidity (Middle East, South Korea), longer days from onset to confirmation of infection (Middle East), longer hospitalized days (Middle East)</td>
</tr>
<tr>
<td> Sherbini (2017) [
<xref ref-type="bibr" rid="CR32">32</xref>
]</td>
<td>2014</td>
<td>29/10 (34.5%)</td>
<td>Saudi Arabia</td>
<td>Sex, symptoms, history of chronic disease, duration of disease before hospitalization, vital signs, temperature, blood pressure</td>
<td>Older age, gastrointestinal symptoms, longer duration of symptoms prior to hospitalization, diabetes mellitus, chronic kidney disease, smokers, lower blood pressure</td>
</tr>
<tr>
<td> Nam (2017) [
<xref ref-type="bibr" rid="CR56">56</xref>
]</td>
<td>2015</td>
<td>25/11 (44%)</td>
<td>South Korea</td>
<td>
<p>- Epidemiologic (age, sex, hospital, inpatient, staying in the same room as the index case, smoking, preexisting pneumonia, chronic lung disease, incubation period)</p>
<p>- Clinical symptom</p>
<p>- Laboratory examinations</p>
</td>
<td>Male, pre-existing pneumonia, smoking history, incubation period of less than 5 days, leukocytosis, abnormal renal function at diagnosis, respiratory symptoms.</td>
</tr>
<tr>
<td> Yang (2017) [
<xref ref-type="bibr" rid="CR52">52</xref>
]</td>
<td>2012–2016</td>
<td>1743/559 (32.1%)</td>
<td>Multiple area</td>
<td>Age, sex, comorbidity, epidemic period, contact pattern, country</td>
<td>Older age, comorbidity, epidemic later period</td>
</tr>
<tr>
<td> Almekhlafi (2016) [
<xref ref-type="bibr" rid="CR57">57</xref>
]</td>
<td>2012–2014</td>
<td>31/23 (74.2%)</td>
<td>Saudi Arabia</td>
<td>Age, comorbidity, initial manifestations, procedures (non-invasive ventilation, invasive ventilation, continuous renal replacement therapy), need for vasopressor</td>
<td>Need for vasopressors</td>
</tr>
<tr>
<td> Alsahafi (2016) [
<xref ref-type="bibr" rid="CR53">53</xref>
]</td>
<td>2012–2015</td>
<td>924/ 425 (46%)</td>
<td>Saudi Arabia</td>
<td>Age, sex, comorbidities, location of acquisition (household, inpatient, HCW)</td>
<td>Older age, cardiac disease, cancer, household patients, HCW</td>
</tr>
<tr>
<td> Virlogeux (2016) [
<xref ref-type="bibr" rid="CR25">25</xref>
]</td>
<td>2015</td>
<td>170/36 (21%)</td>
<td>South Korea</td>
<td>Age, sex, incubation period</td>
<td>Older age, shorter incubation period</td>
</tr>
<tr>
<td> Cha (2015)</td>
<td>2015</td>
<td>30/5 (16.7%)</td>
<td>South Korea</td>
<td>Age, sex, chronic kidney disease, diabetes, hypertension, comorbidity, estimated glomerular filtration rate, mechanical ventilator</td>
<td>None</td>
</tr>
<tr>
<td> Majumder (2015) [
<xref ref-type="bibr" rid="CR54">54</xref>
]</td>
<td>2015</td>
<td>159/35 (22%)</td>
<td>South Korea</td>
<td>Five potential covariates were analyzed: sex, age, concurrent health condition status, health care worker status, time from onset to diagnosis</td>
<td>Older age, pre-existing concurrent health conditions</td>
</tr>
<tr>
<td> KCDC (2015) [
<xref ref-type="bibr" rid="CR4">4</xref>
]</td>
<td>2015</td>
<td>186/36 (19.4%)</td>
<td>South Korea</td>
<td>Sex, age, case classification, respiratory disease, diabetes, cardiac disease, chronic kidney disease, malignancy</td>
<td>Older age, underlying respiratory disease</td>
</tr>
<tr>
<td> Das (2015) [
<xref ref-type="bibr" rid="CR58">58</xref>
]</td>
<td>2014</td>
<td>55/19 (35%)</td>
<td>Saudi Arabia</td>
<td>Age, chest radiographic score, absolute lymphocyte count, no. of comorbidities, congestive heart failure, hypertension, diabetes</td>
<td>Chest radiographic score</td>
</tr>
<tr>
<td> Al Ghamdi (2016) [
<xref ref-type="bibr" rid="CR59">59</xref>
]</td>
<td>2014</td>
<td>51/19 (37%)</td>
<td>Saudi Arabia</td>
<td>Beta interferon, alpha interferon, hydrocortisone, Ribavirin, APACHE score</td>
<td>APACHE score</td>
</tr>
<tr>
<td> Choi (2016) [
<xref ref-type="bibr" rid="CR55">55</xref>
]</td>
<td>2016</td>
<td>186/33 (17.7%)</td>
<td>South Korea</td>
<td>Age, sex, HCW, coexisting medical condition, symptoms at admission, vital signs at admission, laboratory abnormalities at admission, treatment</td>
<td>Age ≥ 55 years, occurrence of dyspnea during the disease course, presence of concomitant medical conditions including diabetes or chronic lung disease, systolic blood pressure < 90 mmHg at admission, leukocytosis at admission, use of mechanical ventilation</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p>
<italic>APACHE</italic>
acute physiologic and chronic health evaluation,
<italic>ICD</italic>
intensive care unit,
<italic>HCW</italic>
healthcare worker,
<italic>PCR</italic>
polymerase chain reaction,
<italic>PRNT</italic>
plaque reduction neutralization test</p>
</table-wrap-foot>
</table-wrap>
</p>
<sec id="Sec16">
<title>Factors related to MERS infection</title>
<p id="Par32">Two studies reported on the risk factors of MERS infection. Alraddadi et al. [
<xref ref-type="bibr" rid="CR42">42</xref>
] analysed the effect of non-human contact, including travel history, animal-related exposure, food exposure, health condition, and behaviour and reported direct dromedary exposure, diabetes or heart disease, and smoking as risk factors of MERS infection. Another study reported older age, outbreak week, and nationality as risk factors [
<xref ref-type="bibr" rid="CR43">43</xref>
].</p>
</sec>
<sec id="Sec17">
<title>Factors related to MERS transmission</title>
<p id="Par33">Three studies analysed factors associated with spreaders. Non-isolated in-hospital days, hospitalization or emergency room visits before isolation, deceased patients, and clinical symptoms, including fever, chest X-ray abnormality in more than three lung zones, and the cycle threshold value, were related to spreaders [
<xref ref-type="bibr" rid="CR34">34</xref>
,
<xref ref-type="bibr" rid="CR44">44</xref>
,
<xref ref-type="bibr" rid="CR45">45</xref>
].</p>
</sec>
<sec id="Sec18">
<title>Factors related to MERS severity</title>
<p id="Par34">Four studies reported risk factors of MERS severity. The included studies showed that the PRNT
<sub>50</sub>
and CD4 T cell response [
<xref ref-type="bibr" rid="CR46">46</xref>
] as well as a high MERS virus load [
<xref ref-type="bibr" rid="CR47">47</xref>
] were associated with the severity of MERS. Additionally, male sex; older age; concomitant disease, including hypertension; and symptoms, including fever, thrombocytopenia, lymphopenia, and low albumin concentration, were related to MERS severity or secondary disease [
<xref ref-type="bibr" rid="CR47">47</xref>
<xref ref-type="bibr" rid="CR49">49</xref>
].</p>
</sec>
<sec id="Sec19">
<title>Factors related to MERS mortality</title>
<p id="Par35">Fifteen studies reported risk factors of mortality in MERS patients. Older age [
<xref ref-type="bibr" rid="CR4">4</xref>
,
<xref ref-type="bibr" rid="CR25">25</xref>
,
<xref ref-type="bibr" rid="CR32">32</xref>
,
<xref ref-type="bibr" rid="CR49">49</xref>
<xref ref-type="bibr" rid="CR55">55</xref>
] and comorbidity [
<xref ref-type="bibr" rid="CR29">29</xref>
,
<xref ref-type="bibr" rid="CR50">50</xref>
<xref ref-type="bibr" rid="CR52">52</xref>
,
<xref ref-type="bibr" rid="CR54">54</xref>
], including diabetes [
<xref ref-type="bibr" rid="CR32">32</xref>
,
<xref ref-type="bibr" rid="CR55">55</xref>
], chronic kidney disease [
<xref ref-type="bibr" rid="CR32">32</xref>
], respiratory disease [
<xref ref-type="bibr" rid="CR4">4</xref>
,
<xref ref-type="bibr" rid="CR55">55</xref>
], pneumonia [
<xref ref-type="bibr" rid="CR56">56</xref>
], cardiac disease, and cancer [
<xref ref-type="bibr" rid="CR53">53</xref>
], were the most prevalent in the included studies. Male sex was reported as a risk factor in one study [
<xref ref-type="bibr" rid="CR56">56</xref>
]. Smoking [
<xref ref-type="bibr" rid="CR32">32</xref>
,
<xref ref-type="bibr" rid="CR56">56</xref>
] and location of acquisition [
<xref ref-type="bibr" rid="CR51">51</xref>
,
<xref ref-type="bibr" rid="CR53">53</xref>
] were also reported. While one study noted that HCW, as a profession, was associated with mortality [
<xref ref-type="bibr" rid="CR53">53</xref>
], non-HCWs were reported to be related to mortality in two other studies [
<xref ref-type="bibr" rid="CR50">50</xref>
,
<xref ref-type="bibr" rid="CR51">51</xref>
].</p>
<p id="Par36">Additionally, a shorter incubation period [
<xref ref-type="bibr" rid="CR25">25</xref>
,
<xref ref-type="bibr" rid="CR56">56</xref>
], longer duration of symptoms [
<xref ref-type="bibr" rid="CR32">32</xref>
], more days from onset to confirmation [
<xref ref-type="bibr" rid="CR29">29</xref>
], later epidemic period [
<xref ref-type="bibr" rid="CR52">52</xref>
], and longer hospitalized days [
<xref ref-type="bibr" rid="CR29">29</xref>
] were reported as mortality risk factors.</p>
<p id="Par37">Symptoms at diagnosis, including abnormal renal function [
<xref ref-type="bibr" rid="CR56">56</xref>
], respiratory symptoms [
<xref ref-type="bibr" rid="CR56">56</xref>
], gastrointestinal symptoms [
<xref ref-type="bibr" rid="CR32">32</xref>
], lower blood pressure [
<xref ref-type="bibr" rid="CR32">32</xref>
,
<xref ref-type="bibr" rid="CR55">55</xref>
], and leucocytosis [
<xref ref-type="bibr" rid="CR55">55</xref>
,
<xref ref-type="bibr" rid="CR56">56</xref>
], were also found to be associated with mortality in MERS patients.</p>
<p id="Par38">Severity of illness, [
<xref ref-type="bibr" rid="CR50">50</xref>
,
<xref ref-type="bibr" rid="CR51">51</xref>
] such as need for vasopressors [
<xref ref-type="bibr" rid="CR57">57</xref>
], chest radiographic score [
<xref ref-type="bibr" rid="CR58">58</xref>
], health condition [
<xref ref-type="bibr" rid="CR59">59</xref>
], use of mechanical ventilation [
<xref ref-type="bibr" rid="CR55">55</xref>
], and occurrence of dyspnoea [
<xref ref-type="bibr" rid="CR55">55</xref>
] were also found to increase the mortality risk.</p>
</sec>
<sec id="Sec20">
<title>Epidemiological index of MERS between the Middle East area and South Korea</title>
<p id="Par39">The characteristics of MERS differ between South Korea and the Middle East area. The R value of MERS was reported to be below 1 in the Middle East area, except in one study [
<xref ref-type="bibr" rid="CR15">15</xref>
], but was from 2.5–8.1 in South Korea [
<xref ref-type="bibr" rid="CR15">15</xref>
<xref ref-type="bibr" rid="CR19">19</xref>
]. Although studies using data from the Middle East area reported 0.42–4% secondary attack rates, studies in South Korea reported 4–6% secondary attack rates for patients or hospital visitors [
<xref ref-type="bibr" rid="CR5">5</xref>
], and 3.7–15.8% for the overall attack rate [
<xref ref-type="bibr" rid="CR23">23</xref>
,
<xref ref-type="bibr" rid="CR24">24</xref>
]. The MERS incubation period was reported to be 4.5–5.2 days in the Middle East area [
<xref ref-type="bibr" rid="CR7">7</xref>
,
<xref ref-type="bibr" rid="CR29">29</xref>
], but this period was found to be slightly longer in South Korea [
<xref ref-type="bibr" rid="CR3">3</xref>
<xref ref-type="bibr" rid="CR5">5</xref>
,
<xref ref-type="bibr" rid="CR23">23</xref>
<xref ref-type="bibr" rid="CR28">28</xref>
].</p>
<p id="Par40">The severity of MERS also differed between the Middle East area and South Korea. Mortality of MERS patients was found to be 20.4% in South Korea based on a report including all cases [
<xref ref-type="bibr" rid="CR27">27</xref>
], but most studies from Saudi Arabia reported higher rates, from 22 to 69.2% [
<xref ref-type="bibr" rid="CR7">7</xref>
,
<xref ref-type="bibr" rid="CR22">22</xref>
,
<xref ref-type="bibr" rid="CR33">33</xref>
,
<xref ref-type="bibr" rid="CR37">37</xref>
<xref ref-type="bibr" rid="CR39">39</xref>
]. Days from onset to confirmation were similar, 4–8 days in the Middle East area [
<xref ref-type="bibr" rid="CR29">29</xref>
,
<xref ref-type="bibr" rid="CR31">31</xref>
] and 4–6.5 days in South Korea [
<xref ref-type="bibr" rid="CR3">3</xref>
,
<xref ref-type="bibr" rid="CR28">28</xref>
,
<xref ref-type="bibr" rid="CR29">29</xref>
]. Days from onset to discharge were slightly longer in South Korea, 14–17 days in the Middle East area [
<xref ref-type="bibr" rid="CR29">29</xref>
,
<xref ref-type="bibr" rid="CR36">36</xref>
] and 17–20 days in South Korea [
<xref ref-type="bibr" rid="CR3">3</xref>
,
<xref ref-type="bibr" rid="CR29">29</xref>
] (Table 
<xref rid="Tab3" ref-type="table">3</xref>
).
<table-wrap id="Tab3">
<label>Table 3</label>
<caption>
<p>Epidemiologic index of MERS between the Middle East area and South Korea</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th>Index</th>
<th>Saudi Arabia/Middle East area</th>
<th>South Korea
<break></break>
(Study including all Korean cases)</th>
</tr>
</thead>
<tbody>
<tr>
<td>Mortality</td>
<td>
<p>22–69.2%</p>
<p>(Two of ten studies reported lower mortality than 20%)</p>
</td>
<td>14.5–47.8% (20.4%)</td>
</tr>
<tr>
<td>R-value</td>
<td>
<p>0.45–0.98</p>
<p>(Only one study</p>
<p>reported 1.9–3.9)</p>
</td>
<td>
<p>• 2.5–8.1</p>
<p>• Less than 1 in later period or with control intervention</p>
</td>
</tr>
<tr>
<td>Attack rate</td>
<td>0.42–4%</td>
<td>3.7–15.8%</td>
</tr>
<tr>
<td>Incubation period</td>
<td>4.5–5.2 days</td>
<td>6–7.8 days (6.83 days)</td>
</tr>
<tr>
<td>Serial interval</td>
<td></td>
<td>12.6–14.6 days</td>
</tr>
<tr>
<td>Days from onset to confirmation</td>
<td>4–8 days</td>
<td>4–6.5 days (5 days)</td>
</tr>
<tr>
<td>Days from onset to hospitalization</td>
<td>2.9–5.3 days</td>
<td></td>
</tr>
<tr>
<td>Days from onset to discharge</td>
<td>14–17 days</td>
<td>17–20 days</td>
</tr>
<tr>
<td>Days from onset to death</td>
<td>11.5–17 days</td>
<td>11–13 days</td>
</tr>
</tbody>
</table>
</table-wrap>
</p>
</sec>
</sec>
</sec>
<sec id="Sec21">
<title>Discussion</title>
<p id="Par41">The transmissibility and severity of MERS were different by outbreak countries, especially between the Middle East area and South Korea. The virus, host, and environmental factors may be the causes of the MERS outbreak-related differences between the two regions. From the standpoint of viral factors, there was a mutation of the MERS coronavirus (MERS-CoV) in the South Korea outbreak. Kim et al. [
<xref ref-type="bibr" rid="CR60">60</xref>
] reported a point mutation in the receptor-binding domain of the viral spike protein in MERS-CoV, and another study showed that MERS-CoV in South Korea had higher genetic variability and mutation rates [
<xref ref-type="bibr" rid="CR61">61</xref>
]. Individual characteristics can also affect MERS transmission. As previous studies showed, there is an association between older age and MERS infection [
<xref ref-type="bibr" rid="CR43">43</xref>
], severity [
<xref ref-type="bibr" rid="CR48">48</xref>
], and mortality [
<xref ref-type="bibr" rid="CR4">4</xref>
,
<xref ref-type="bibr" rid="CR50">50</xref>
], and the population structure may be related to transmission and severity. Additionally, individuals aware of MERS were found to be more likely to practice preventive behaviour [
<xref ref-type="bibr" rid="CR62">62</xref>
], which differed by demographic characteristics [
<xref ref-type="bibr" rid="CR63">63</xref>
,
<xref ref-type="bibr" rid="CR64">64</xref>
]. The transmission environment may also contribute to the difference. While many MERS cases were contracted through exposure to camels in Saudi Arabia [
<xref ref-type="bibr" rid="CR42">42</xref>
], the South Korea outbreak involved multiple generations of secondary infections caused by intra-hospital and hospital-to-hospital transmission [
<xref ref-type="bibr" rid="CR3">3</xref>
,
<xref ref-type="bibr" rid="CR65">65</xref>
]. Strategies considering various factors are therefore needed to assess the impact of MERS and to better control its spread.</p>
<p id="Par42">Although several studies have reported the overall R value [
<xref ref-type="bibr" rid="CR9">9</xref>
,
<xref ref-type="bibr" rid="CR10">10</xref>
,
<xref ref-type="bibr" rid="CR14">14</xref>
,
<xref ref-type="bibr" rid="CR19">19</xref>
], others have shown that this value this can be variable based on the generation or a control intervention [
<xref ref-type="bibr" rid="CR11">11</xref>
,
<xref ref-type="bibr" rid="CR16">16</xref>
,
<xref ref-type="bibr" rid="CR19">19</xref>
]. Especially in the South Korea epidemic, the R value was particularly high in the early stage or first generation, at 4.42–5.4, though it later decreased to 0.14–0.39 [
<xref ref-type="bibr" rid="CR16">16</xref>
,
<xref ref-type="bibr" rid="CR19">19</xref>
]. Further studies should consider and analyse the variation of the R value depending on the period or control intervention.</p>
<p id="Par43">While earlier studies on infectious diseases assumed a homogeneous infection ability of a population, recent studies have shown the existence of so-called super spreaders, individuals with a high potential to infect others in many infectious diseases, including Ebola and severe acute respiratory syndrome (SARS) [
<xref ref-type="bibr" rid="CR66">66</xref>
]. The role of the super spreader is also important in the spread of MERS. In South Korea, 83.2% of MERS patients were associated with five super-spreading events [
<xref ref-type="bibr" rid="CR27">27</xref>
]. Stein et al. [
<xref ref-type="bibr" rid="CR67">67</xref>
] asserted that super spreaders were related with the host, pathogen, and environmental factors, and Wong et al. [
<xref ref-type="bibr" rid="CR66">66</xref>
] reported that individual behaviours could also contribute to disease spread.</p>
<p id="Par44">There are variations in the mortality and attack rates among studies using South Korea data. For example, Park et al. [
<xref ref-type="bibr" rid="CR24">24</xref>
] reported a 47.8% MERS mortality, while reports from the Korean Ministry of Health and Welfare showed 20.4% MERS mortality. This disparity may, in part, be due to small sample sizes. Park et al. [
<xref ref-type="bibr" rid="CR24">24</xref>
] included only 23 patients because the study was conducted in an early phase of a MERS outbreak. We excluded studies that included cases with < 20 subjects, which were mostly case series, to reduce those types of biases.</p>
<p id="Par45">The present review found that older age and concomitant disease were risk factors of MERS infection and mortality. These results are consistent with a recent systematic review that reported older age, male, and an underlying medical condition as predictors of death related to MERS [
<xref ref-type="bibr" rid="CR68">68</xref>
]; therefore, these factors should be prioritized in protection and treatment procedures.</p>
<p id="Par46">One limitation of this study was the possibility of subject duplication. Especially in South Korea, the Korean government publishes MERS reports that include all patients. The epidemiologic index in other studies might be biased since they included partial Korean patients and were analysed in the middle of an outbreak. However, we included those studies because they showed the characteristics of MERS in different situations and different stages.</p>
<p id="Par47">We did not conduct a meta-analysis because of the small number of studies for each index, which might be another limitation of this study. Although this study reviewed the risk factors of MERS and their impact, assessing the effect size of each risk factor is important. More studies investigating the effect of risk factors on MERS need to be constantly conducted.</p>
</sec>
<sec id="Sec22">
<title>Conclusion</title>
<p id="Par48">Most studies on the transmissibility and severity of MERS have originated from Saudi Arabia and South Korea. Even though the R
<sub>0</sub>
value in South Korea was higher than that in Saudi Arabia, mortality was higher in Saudi Arabia. The most common factors behind MERS infection and mortality were older age and concomitant disease. Future studies should consider the risk of MERS based on the outbreak region and patient characteristics. The results of the present study are valuable for informing further studies and health policy in preparation for MERS outbreaks.</p>
</sec>
</body>
<back>
<glossary>
<title>Abbreviations</title>
<def-list>
<def-item>
<term>CD4</term>
<def>
<p id="Par5">Cluster of differentiation 4</p>
</def>
</def-item>
<def-item>
<term>CFR</term>
<def>
<p id="Par6">Case fatality rate</p>
</def>
</def-item>
<def-item>
<term>MERS</term>
<def>
<p id="Par7">Middle East respiratory syndrome</p>
</def>
</def-item>
<def-item>
<term>PRNT</term>
<def>
<p id="Par8">Plaque reduction neutralization test</p>
</def>
</def-item>
<def-item>
<term>SARS</term>
<def>
<p id="Par9">Severe acute respiratory syndrome</p>
</def>
</def-item>
</def-list>
</glossary>
<ack>
<title>Funding</title>
<p>This work was supported by the National Research Council of Science & Technology (NST) grant by the Korea government (MSIP) (No. CRC-16-01-KRICT) and Korea Institute of Oriental Medicine (G17273).</p>
</ack>
<notes notes-type="author-contribution">
<title>Authors’ contributions</title>
<p>JEP (corresponding author) designed the study, and conducted the data search and the analysis with JEP (1st author). SYJ and ARK participated in the data review. JEP (corresponding) drafted the manuscript, and JEP (1st), SYJ, and ARK revised it. All authors read and approved the final manuscript.</p>
</notes>
<notes>
<title>Ethics approval and consent to participate</title>
<p id="Par49">Not applicable.</p>
</notes>
<notes notes-type="COI-statement">
<title>Competing interests</title>
<p id="Par50">The authors declare that they have no competing interests.</p>
</notes>
<notes>
<title>Publisher’s Note</title>
<p id="Par51">Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.</p>
</notes>
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