Host susceptibility to severe COVID-19 and establishment of a host risk score: findings of 487 cases outside Wuhan
Identifieur interne : 000123 ( Pmc/Corpus ); précédent : 000122; suivant : 000124Host susceptibility to severe COVID-19 and establishment of a host risk score: findings of 487 cases outside Wuhan
Auteurs : Yu Shi ; Xia Yu ; Hong Zhao ; Hao Wang ; Ruihong Zhao ; Jifang ShengSource :
- Critical Care [ 1364-8535 ] ; 2020.
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DOI: 10.1186/s13054-020-2833-7
PubMed: 32188484
PubMed Central: 7081524
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Host susceptibility to severe COVID-19 and establishment of a host risk score: findings of 487 cases outside Wuhan</title><author><name sortKey="Shi, Yu" sort="Shi, Yu" uniqKey="Shi Y" first="Yu" last="Shi">Yu Shi</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Yu, Xia" sort="Yu, Xia" uniqKey="Yu X" first="Xia" last="Yu">Xia Yu</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Zhao, Hong" sort="Zhao, Hong" uniqKey="Zhao H" first="Hong" last="Zhao">Hong Zhao</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Wang, Hao" sort="Wang, Hao" uniqKey="Wang H" first="Hao" last="Wang">Hao Wang</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Zhao, Ruihong" sort="Zhao, Ruihong" uniqKey="Zhao R" first="Ruihong" last="Zhao">Ruihong Zhao</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Sheng, Jifang" sort="Sheng, Jifang" uniqKey="Sheng J" first="Jifang" last="Sheng">Jifang Sheng</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">32188484</idno><idno type="pmc">7081524</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081524</idno><idno type="RBID">PMC:7081524</idno><idno type="doi">10.1186/s13054-020-2833-7</idno><date when="2020">2020</date><idno type="wicri:Area/Pmc/Corpus">000123</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000123</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Host susceptibility to severe COVID-19 and establishment of a host risk score: findings of 487 cases outside Wuhan</title><author><name sortKey="Shi, Yu" sort="Shi, Yu" uniqKey="Shi Y" first="Yu" last="Shi">Yu Shi</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Yu, Xia" sort="Yu, Xia" uniqKey="Yu X" first="Xia" last="Yu">Xia Yu</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Zhao, Hong" sort="Zhao, Hong" uniqKey="Zhao H" first="Hong" last="Zhao">Hong Zhao</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Wang, Hao" sort="Wang, Hao" uniqKey="Wang H" first="Hao" last="Wang">Hao Wang</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Zhao, Ruihong" sort="Zhao, Ruihong" uniqKey="Zhao R" first="Ruihong" last="Zhao">Ruihong Zhao</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Sheng, Jifang" sort="Sheng, Jifang" uniqKey="Sheng J" first="Jifang" last="Sheng">Jifang Sheng</name><affiliation><nlm:aff 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Y" uniqKey="Wang Y">Y Wang</name></author><author><name sortKey="Li, X" uniqKey="Li X">X Li</name></author><author><name sortKey="Ren, L" uniqKey="Ren L">L Ren</name></author><author><name sortKey="Zhao, J" uniqKey="Zhao J">J Zhao</name></author><author><name sortKey="Hu, Y" uniqKey="Hu Y">Y Hu</name></author><author><name sortKey="Zhang, L" uniqKey="Zhang L">L Zhang</name></author><author><name sortKey="Fan, G" uniqKey="Fan G">G Fan</name></author><author><name sortKey="Xu, J" uniqKey="Xu J">J Xu</name></author><author><name sortKey="Gu, X" uniqKey="Gu X">X Gu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Xu, X W" uniqKey="Xu X">X-W Xu</name></author><author><name sortKey="Wu, X X" uniqKey="Wu X">X-X Wu</name></author><author><name sortKey="Jiang, X G" uniqKey="Jiang X">X-G Jiang</name></author><author><name sortKey="Xu, K J" uniqKey="Xu K">K-J Xu</name></author><author><name sortKey="Ying, L J" uniqKey="Ying L">L-J Ying</name></author><author><name sortKey="Ma, C L" uniqKey="Ma C">C-L Ma</name></author><author><name sortKey="Li, S B" uniqKey="Li S">S-B Li</name></author><author><name sortKey="Wang, H Y" uniqKey="Wang H">H-Y Wang</name></author><author><name sortKey="Zhang, S" uniqKey="Zhang S">S Zhang</name></author><author><name sortKey="Gao, H N" uniqKey="Gao H">H-N Gao</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="letter"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Crit Care</journal-id><journal-title-group><journal-title>Critical Care</journal-title></journal-title-group><issn pub-type="ppub">1364-8535</issn><issn pub-type="epub">1466-609X</issn><publisher><publisher-name>BioMed Central</publisher-name><publisher-loc>London</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">32188484</article-id><article-id pub-id-type="pmc">7081524</article-id><article-id pub-id-type="publisher-id">2833</article-id><article-id pub-id-type="doi">10.1186/s13054-020-2833-7</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Letter</subject></subj-group></article-categories><title-group><article-title>Host susceptibility to severe COVID-19 and establishment of a host risk score: findings of 487 cases outside Wuhan</article-title></title-group><contrib-group><contrib contrib-type="author" equal-contrib="yes"><name><surname>Shi</surname><given-names>Yu</given-names></name><xref ref-type="aff" rid="Aff1"></xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Yu</surname><given-names>Xia</given-names></name><xref ref-type="aff" rid="Aff1"></xref></contrib><contrib contrib-type="author"><name><surname>Zhao</surname><given-names>Hong</given-names></name><xref ref-type="aff" rid="Aff1"></xref></contrib><contrib contrib-type="author"><name><surname>Wang</surname><given-names>Hao</given-names></name><xref ref-type="aff" rid="Aff1"></xref></contrib><contrib contrib-type="author"><name><surname>Zhao</surname><given-names>Ruihong</given-names></name><xref ref-type="aff" rid="Aff1"></xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Sheng</surname><given-names>Jifang</given-names></name><address><email>jifang_sheng@zju.edu.cn</email></address><xref ref-type="aff" rid="Aff1"></xref></contrib><aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1803 6319</institution-id><institution-id institution-id-type="GRID">grid.452661.2</institution-id><institution>State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases,</institution><institution>The First Affiliated Hospital, College of Medicine, Zhejiang University,</institution></institution-wrap>Qingchun Road, No. 79, Hangzhou, 310003 China</aff></contrib-group><pub-date pub-type="epub"><day>18</day><month>3</month><year>2020</year></pub-date><pub-date pub-type="pmc-release"><day>18</day><month>3</month><year>2020</year></pub-date><pub-date pub-type="collection"><year>2020</year></pub-date><volume>24</volume><elocation-id>108</elocation-id><history><date date-type="received"><day>5</day><month>3</month><year>2020</year></date><date date-type="accepted"><day>13</day><month>3</month><year>2020</year></date></history><permissions><copyright-statement>© The Author(s). 2020</copyright-statement><license license-type="OpenAccess"><license-p><bold>Open Access</bold>This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>. 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 in a credit line to the data.</license-p></license></permissions><kwd-group xml:lang="en"><title>Keywords</title><kwd>COVID-2019</kwd><kwd>Disease severity</kwd><kwd>Risk factors</kwd><kwd>Host susceptibility</kwd></kwd-group><funding-group><award-group><funding-source><institution-wrap><institution-id institution-id-type="FundRef">http://dx.doi.org/10.13039/501100001809</institution-id><institution>National Natural Science Foundation of China</institution></institution-wrap></funding-source><award-id>81670567</award-id><award-id>81870425</award-id><principal-award-recipient><name><surname>Shi</surname><given-names>Yu</given-names></name></principal-award-recipient></award-group></funding-group><funding-group><award-group><funding-source><institution-wrap><institution-id institution-id-type="FundRef">http://dx.doi.org/10.13039/501100012226</institution-id><institution>Fundamental Research Funds for the Central Universities</institution></institution-wrap></funding-source></award-group></funding-group><custom-meta-group><custom-meta><meta-name>issue-copyright-statement</meta-name><meta-value>© The Author(s) 2020</meta-value></custom-meta></custom-meta-group></article-meta></front><body><p id="Par1">The recent outbreak of coronavirus disease 2019 (COVID-19), caused by a new zoonotic coronary virus, SARS-CoV-2 [<xref ref-type="bibr" rid="CR1">1</xref>], is being a great threat to public health. Up to February 11, 2020, it is reported that over 70,000 persons have been infected with SARS-CoV-2 in China [<xref ref-type="bibr" rid="CR2">2</xref>]. The COVID-19 caused by SARS-CoV-2 infection represents a spectrum of clinical severity [<xref ref-type="bibr" rid="CR3">3</xref>–<xref ref-type="bibr" rid="CR5">5</xref>]. Some patients are asymptomatic or have merely mild upper respiratory tract symptoms. However, SARS-CoV-2 causes pneumonia that can be severe and characterized by fever, cough, dyspnea, bilateral pulmonary infiltrates, and acute respiratory injury. It is estimated that approximately 20% of patients are developing severe respiratory illness, with the overall mortality around 2.3% [<xref ref-type="bibr" rid="CR2">2</xref>]. Thereby, it is critical to identify individuals who confer intrinsic susceptibility to become severe or even critically ill upon infection, for the purposes of prevention and treatment, especially when there is no drug directly targeting at SARS-CoV-2 that has been proven to be clinically effective. In the study, we explored potential host risk factors associated with severe cases at admission in a retrospective cohort of 487 patients in Zhejiang Province of China and attempt to establish a score system to identify high-risk individuals. We reviewed medical records, laboratory findings, and pulmonary CT scan of each patient with COVID-19, provided by the local health authority and inputted into a pre-specified electronic data collection form. Clinical outcomes were followed up to February 17, 2020. The primary endpoint was occurrence of death and severe cases.</p><p id="Par2">A total of 487 COVID-19 patients were included for analysis, with 49 (10.1%) severe cases at admission. As shown in Table <xref rid="Tab1" ref-type="table">1</xref>, severe cases are elderly (56 (17) vs. 45 (19), <italic>P</italic> < 0.001), with more male (73.5% vs. 50.9%, <italic>P</italic> = 0.003). They have a higher incidence of hypertension (53.1% vs. 16.7%, <italic>P</italic> < 0.001), diabetes (14.3% vs. 5.0%, <italic>P</italic> = 0.009), cardiovascular diseases (8.2% vs. 1.6%, <italic>P</italic> = 0.003), and malignancy (4.1% vs. 0.7%, <italic>P</italic> = 0.025), and less exposure to epidemic area (49.0% vs. 65.1%, <italic>P</italic> = 0.027), but more infected family members (<italic>P</italic> = 0.031). On multivariate analysis, elder age (OR 1.06 [95% CI 1.03–1.08], <italic>P</italic> < 0.001), male (OR 3.68 [95% CI 1.75–7.75], <italic>P</italic> = 0.001), and presence of hypertension (OR 2.71 [95% CI 1.32–5.59], <italic>P</italic> = 0.007) are independently associated with severe disease at admission, irrespective of adjustment of time to admission.
<table-wrap id="Tab1"><label>Table 1</label><caption><p>Demographic, epidermiological characteristics, and underlying comorbidities of patients with confirmed 2019-nCoV infection</p></caption><table frame="hsides" rules="groups"><thead><tr><th>Variables</th><th>Total (<italic>N</italic> = 487)</th><th>Mild (<italic>N</italic> = 438)</th><th>Severe (<italic>N</italic> = 49)</th><th><italic>P</italic> value</th></tr></thead><tbody><tr><td>Age (years)</td><td>46 (19)</td><td>45 (19)</td><td>56 (17)</td><td>< 0.001</td></tr><tr><td colspan="5">Sex</td></tr><tr><td> Male</td><td>259 (53.2%)</td><td>223 (50.9%)</td><td>36 (73.5%)</td><td></td></tr><tr><td> Female</td><td>228 (46.8%)</td><td>215 (49.1%)</td><td>13 (26.5%)</td><td>0.003</td></tr><tr><td colspan="5">Occupation</td></tr><tr><td> Agricultural worker</td><td>140 (28.7%)</td><td>122 (27.9%)</td><td>18 (36.7%)</td><td></td></tr><tr><td> Self-employed</td><td>219 (45.0%)</td><td>203 (46.3%)</td><td>16 (32.7%)</td><td></td></tr><tr><td> Employee</td><td>82 (16.8%)</td><td>79 (18.0%)</td><td>3 (6.1%)</td><td></td></tr><tr><td> Retired</td><td>38 (7.8%)</td><td>26 (5.9%)</td><td>12 (24.5%)</td><td></td></tr><tr><td> Student</td><td>8 (1.6%)</td><td>8 (1.8%)</td><td>0 (0%)</td><td>< 0.001</td></tr><tr><td colspan="5">Smoking history</td></tr><tr><td> Yes</td><td>40 (8.2%)</td><td>34 (7.8%)</td><td>6 (12.2%)</td><td></td></tr><tr><td> No</td><td>434 (89.1%)</td><td>391 (89.3%)</td><td>43 (87.8%)</td><td></td></tr><tr><td> Unknown</td><td>13 (2.7%)</td><td>13 (2.7%)</td><td>0 (0%)</td><td>0.331</td></tr><tr><td colspan="5">Comorbidities</td></tr><tr><td> Hypertension</td><td>99 (20.3%)</td><td>73 (16.7%)</td><td>26 (53.1%)</td><td>< 0.001</td></tr><tr><td> Diabetes</td><td>29 (6.0%)</td><td>22 (5.0%)</td><td>7 (14.3%)</td><td>0.009</td></tr><tr><td> Cardiovascular disease</td><td>11 (2.3%)</td><td>7 (1.6%)</td><td>4 (8.2%)</td><td>0.003</td></tr><tr><td> Malignancy</td><td>5 (1%)</td><td>3 (0.7%)</td><td>2 (4.1%)</td><td>0.025</td></tr><tr><td> Chronic liver diseases</td><td>22 (4.5%)</td><td>20 (4.6%)</td><td>2 (4.1%)</td><td>0.877</td></tr><tr><td> Chronic renal diseases</td><td>7 (1.4%)</td><td>5 (1.1%)</td><td>2 (4.1%)</td><td>0.101</td></tr><tr><td> Others</td><td>32 (6.6%)</td><td>27 (6.1%)</td><td>5 (10.2%)</td><td>0.279</td></tr><tr><td>Exposure to confirmed cases</td><td>186 (38.2%)</td><td>173 (39.5%)</td><td>13 (26.5%)</td><td>0.077</td></tr><tr><td colspan="5">Family cluster</td></tr><tr><td> 0</td><td>392 (80.5%)</td><td>352 (80.4%)</td><td>40 (81.6%)</td><td></td></tr><tr><td> 1</td><td>67 (13.8%)</td><td>63 (14.4%)</td><td>4 (8.2%)</td><td></td></tr><tr><td> 2</td><td>12 (2.5%)</td><td>12 (2.7%)</td><td>0 (0%)</td><td></td></tr><tr><td> ≥ 3</td><td>16 (3.3%)</td><td>11 (2.5%)</td><td>5 (10.2%)</td><td>0.031</td></tr><tr><td>Recent travel or residence to/in epidemic area</td><td>309 (63.4%)</td><td>285 (65.1%)</td><td>24 (49.0%)</td><td>0.027</td></tr><tr><td>Time from onset of symptom to admission</td><td>2 (3)</td><td>2 (3)</td><td>3 (5)</td><td>0.10</td></tr></tbody></table><table-wrap-foot><p>Data are expressed as mean ± standard deviation (SD), median (interquartile range), or number (percent). Comparisons between mild and severe cases were performed by the Mann-Whitney <italic>U</italic> test or a chi-square test</p></table-wrap-foot></table-wrap></p><p id="Par3">Then, we defined a host risk score on the basis of the three risk factors, to assess the intrinsic host susceptibility to develop severe cases of COVID-19 (Fig. <xref rid="Fig1" ref-type="fig">1</xref>a). As shown in Fig. <xref rid="Fig1" ref-type="fig">1</xref>b, a step-wise increase in the incidence of severe COVID-19 at admission was observed with the increment of the host risk score (<italic>P</italic> < 0.001). The performance of the score was also validated in 66 patients who presented mild at admission and were under follow-up during hospital stay. Fifteen patients progressed to severe COVID-19 within a median follow-up time of 15 days. No death was reported by the end of follow-up. A similar trend to the above was confirmed when analyzing the correlation between host risk score and occurrence of severe COVID-19 (<italic>P</italic> = 0.014) (see Fig. <xref rid="Fig1" ref-type="fig">1</xref>c).
<fig id="Fig1"><label>Fig. 1</label><caption><p>Definition of host risk factor score and incidences of severe cases by host risk score. The host risk factor score was calculated by the sum of three variables (<bold>a</bold>). The incidences of severe cases at admission (<bold>b</bold>) or developing during hospitalization (<bold>c</bold>) were compared across the different score groups by a linear-by-linear association test</p></caption><graphic xlink:href="13054_2020_2833_Fig1_HTML" id="MO1"></graphic></fig></p><p id="Par4">In summary, by identifying host risk factors associated with severe COVID-19, this study shed light on the underlying mechanisms of disease progression. In particular, the major finding that hypertension is a host risk factor for severe COVID-19 may underscore the involvement of renin-angiotensin system (RAS) in the pathogenesis of this disease. Additionally, the host risk score provides a useful tool to identify high-risk individuals, which is helpful for designing specific strategies for prevention and treatment of this disease. But further studies, particularly those enrolling Wuhan patients, are needed to validate the findings.</p></body><back><fn-group><fn><p><bold>Publisher’s Note</bold></p><p>Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.</p></fn><fn><p>Yu Shi and Xia Yu contributed equally to this work.</p></fn></fn-group><ack><title>Acknowledgements</title><p>Not applicable.</p></ack><notes notes-type="author-contribution"><title>Authors’ contributions</title><p>JS and YS conceptualized the idea and designed the study. YS and XY drafted the manuscript, and JS revised it. XY, HZ, HW, and RZ participated in the data collection, analysis, and interpretation. All authors read and approved the final manuscript.</p></notes><notes notes-type="funding-information"><title>Funding</title><p>This work was supported by grants from the Chinese National Natural Science Foundation (nos. 81670567 and 81870425) and the Fundamental Research Funds for the Central Universities.</p></notes><notes notes-type="data-availability"><title>Availability of data and materials</title><p>The datasets and materials used and/or analyzed during the current study are available from the corresponding author on reasonable request.</p></notes><notes><title>Ethics approval and consent to participate</title><p id="Par5">The ethics committee of the First Affiliated Hospital of Zhejiang University reviewed and approved this study. Written consent was obtained from each patient or his/her authorized representatives following a full explanation of the study.</p></notes><notes><title>Consent for publication</title><p id="Par6">Not applicable.</p></notes><notes notes-type="COI-statement"><title>Competing interests</title><p id="Par7">The authors declare that they have no competing interests.</p></notes><ref-list id="Bib1"><title>References</title><ref id="CR1"><label>1.</label><element-citation publication-type="journal"><person-group 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