Clinical characteristics of severe acute respiratory syndrome coronavirus 2 reactivation
Identifieur interne : 001184 ( Pmc/Corpus ); précédent : 001183; suivant : 001185Clinical characteristics of severe acute respiratory syndrome coronavirus 2 reactivation
Auteurs : Guangming Ye ; Zhenyu Pan ; Yunbao Pan ; Qiaoling Deng ; Liangjun Chen ; Jin Li ; Yirong Li ; Xinghuan WangSource :
- The Journal of Infection [ 0163-4453 ] ; 2020.
Abstract
All reactivated patients presented normal aminotransferase levels. Throat swab samples from the reactivated patients indicated all positive for the virus. There might be no specific clinical characteristics to distinguish the reactivation of SARS-CoV-2.
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DOI: 10.1016/j.jinf.2020.03.001
PubMed: 32171867
PubMed Central: 7102560
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Clinical characteristics of severe acute respiratory syndrome coronavirus 2 reactivation</title><author><name sortKey="Ye, Guangming" sort="Ye, Guangming" uniqKey="Ye G" first="Guangming" last="Ye">Guangming Ye</name><affiliation><nlm:aff id="aff0001">Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, Hubei, China</nlm:aff></affiliation></author><author><name sortKey="Pan, Zhenyu" sort="Pan, Zhenyu" uniqKey="Pan Z" first="Zhenyu" last="Pan">Zhenyu Pan</name><affiliation><nlm:aff id="aff0002">Department of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, Hubei, China</nlm:aff></affiliation></author><author><name sortKey="Pan, Yunbao" sort="Pan, Yunbao" uniqKey="Pan Y" first="Yunbao" last="Pan">Yunbao Pan</name><affiliation><nlm:aff id="aff0001">Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, Hubei, China</nlm:aff></affiliation></author><author><name sortKey="Deng, Qiaoling" sort="Deng, Qiaoling" uniqKey="Deng Q" first="Qiaoling" last="Deng">Qiaoling Deng</name><affiliation><nlm:aff id="aff0001">Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, Hubei, China</nlm:aff></affiliation></author><author><name sortKey="Chen, Liangjun" sort="Chen, Liangjun" uniqKey="Chen L" first="Liangjun" last="Chen">Liangjun Chen</name><affiliation><nlm:aff id="aff0001">Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, Hubei, China</nlm:aff></affiliation></author><author><name sortKey="Li, Jin" sort="Li, Jin" uniqKey="Li J" first="Jin" last="Li">Jin Li</name><affiliation><nlm:aff id="aff0001">Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, Hubei, China</nlm:aff></affiliation></author><author><name sortKey="Li, Yirong" sort="Li, Yirong" uniqKey="Li Y" first="Yirong" last="Li">Yirong Li</name><affiliation><nlm:aff id="aff0001">Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, Hubei, China</nlm:aff></affiliation></author><author><name sortKey="Wang, Xinghuan" sort="Wang, Xinghuan" uniqKey="Wang X" first="Xinghuan" last="Wang">Xinghuan Wang</name><affiliation><nlm:aff id="aff0003">Center for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China</nlm:aff></affiliation><affiliation><nlm:aff id="aff0004">Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">32171867</idno><idno type="pmc">7102560</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102560</idno><idno type="RBID">PMC:7102560</idno><idno type="doi">10.1016/j.jinf.2020.03.001</idno><date when="2020">2020</date><idno type="wicri:Area/Pmc/Corpus">001184</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001184</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Clinical characteristics of severe acute respiratory syndrome coronavirus 2 reactivation</title><author><name sortKey="Ye, Guangming" sort="Ye, Guangming" uniqKey="Ye G" first="Guangming" last="Ye">Guangming Ye</name><affiliation><nlm:aff id="aff0001">Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, Hubei, China</nlm:aff></affiliation></author><author><name sortKey="Pan, Zhenyu" sort="Pan, Zhenyu" uniqKey="Pan Z" first="Zhenyu" last="Pan">Zhenyu Pan</name><affiliation><nlm:aff id="aff0002">Department of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, Hubei, China</nlm:aff></affiliation></author><author><name sortKey="Pan, Yunbao" sort="Pan, Yunbao" uniqKey="Pan Y" first="Yunbao" last="Pan">Yunbao Pan</name><affiliation><nlm:aff id="aff0001">Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, Hubei, China</nlm:aff></affiliation></author><author><name sortKey="Deng, Qiaoling" sort="Deng, Qiaoling" uniqKey="Deng Q" first="Qiaoling" last="Deng">Qiaoling Deng</name><affiliation><nlm:aff id="aff0001">Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, Hubei, China</nlm:aff></affiliation></author><author><name sortKey="Chen, Liangjun" sort="Chen, Liangjun" uniqKey="Chen L" first="Liangjun" last="Chen">Liangjun Chen</name><affiliation><nlm:aff id="aff0001">Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, Hubei, China</nlm:aff></affiliation></author><author><name sortKey="Li, Jin" sort="Li, Jin" uniqKey="Li J" first="Jin" last="Li">Jin Li</name><affiliation><nlm:aff id="aff0001">Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, Hubei, China</nlm:aff></affiliation></author><author><name sortKey="Li, Yirong" sort="Li, Yirong" uniqKey="Li Y" first="Yirong" last="Li">Yirong Li</name><affiliation><nlm:aff id="aff0001">Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, Hubei, China</nlm:aff></affiliation></author><author><name sortKey="Wang, Xinghuan" sort="Wang, Xinghuan" uniqKey="Wang X" first="Xinghuan" last="Wang">Xinghuan Wang</name><affiliation><nlm:aff id="aff0003">Center for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China</nlm:aff></affiliation><affiliation><nlm:aff id="aff0004">Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China</nlm:aff></affiliation></author></analytic><series><title level="j">The Journal of Infection</title><idno type="ISSN">0163-4453</idno><idno type="eISSN">1532-2742</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Highlights</title><p><list list-type="simple" id="celist0001"><list-item id="celistitem0001"><label>•</label><p id="para0002">All reactivated patients presented normal aminotransferase levels.</p></list-item><list-item id="celistitem0002"><label>•</label><p id="para0003">Throat swab samples from the reactivated patients indicated all positive for the virus.</p></list-item><list-item id="celistitem0003"><label>•</label><p id="para0004">There might be no specific clinical characteristics to distinguish the reactivation of SARS-CoV-2.</p></list-item></list></p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Zhu, N" uniqKey="Zhu N">N. Zhu</name></author><author><name sortKey="Zhang, D" uniqKey="Zhang D">D. Zhang</name></author><author><name sortKey="Wang, W" uniqKey="Wang W">W. Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Huang, C" uniqKey="Huang C">C. Huang</name></author><author><name sortKey="Wang, Y" uniqKey="Wang Y">Y. Wang</name></author><author><name sortKey="Li, X" uniqKey="Li X">X. Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, N" uniqKey="Chen N">N. Chen</name></author><author><name sortKey="Zhou, M" uniqKey="Zhou M">M. Zhou</name></author><author><name sortKey="Dong, X" uniqKey="Dong X">X. Dong</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lu, R" uniqKey="Lu R">R. Lu</name></author><author><name sortKey="Zhao, X" uniqKey="Zhao X">X. Zhao</name></author><author><name sortKey="Li, J" uniqKey="Li J">J. Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhou, P" uniqKey="Zhou P">P. Zhou</name></author><author><name sortKey="Yang, X L" uniqKey="Yang X">X.L. Yang</name></author><author><name sortKey="Wang, X G" uniqKey="Wang X">X.G. Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Corman, V M" uniqKey="Corman V">V.M. Corman</name></author><author><name sortKey="Landt, O" uniqKey="Landt O">O. Landt</name></author><author><name sortKey="Kaiser, M" uniqKey="Kaiser M">M. Kaiser</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Zou, L" uniqKey="Zou L">L. Zou</name></author><author><name sortKey="Ruan, F" uniqKey="Ruan F">F. Ruan</name></author><author><name sortKey="Huang, M" uniqKey="Huang M">M. Huang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lowenberg, M" uniqKey="Lowenberg M">M. Lowenberg</name></author><author><name sortKey="Verhaar, A P" uniqKey="Verhaar A">A.P. Verhaar</name></author><author><name sortKey="Van Den Brink, G R" uniqKey="Van Den Brink G">G.R. van den Brink</name></author><author><name sortKey="Hommes, D W" uniqKey="Hommes D">D.W Hommes</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">J Infect</journal-id><journal-id journal-id-type="iso-abbrev">J. Infect</journal-id><journal-title-group><journal-title>The Journal of Infection</journal-title></journal-title-group><issn pub-type="ppub">0163-4453</issn><issn pub-type="epub">1532-2742</issn><publisher><publisher-name>The British Infection Association. Published by Elsevier Ltd.</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">32171867</article-id><article-id pub-id-type="pmc">7102560</article-id><article-id pub-id-type="publisher-id">S0163-4453(20)30114-6</article-id><article-id pub-id-type="doi">10.1016/j.jinf.2020.03.001</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Clinical characteristics of severe acute respiratory syndrome coronavirus 2 reactivation</article-title></title-group><contrib-group><contrib contrib-type="author" id="au0001"><name><surname>Ye</surname><given-names>Guangming</given-names></name><xref rid="aff0001" ref-type="aff">a</xref><xref rid="fn1" ref-type="fn">1</xref></contrib><contrib contrib-type="author" id="au0002"><name><surname>Pan</surname><given-names>Zhenyu</given-names></name><xref rid="aff0002" ref-type="aff">b</xref><xref rid="fn1" ref-type="fn">1</xref></contrib><contrib contrib-type="author" id="au0003"><name><surname>Pan</surname><given-names>Yunbao</given-names></name><xref rid="aff0001" ref-type="aff">a</xref><xref rid="fn1" ref-type="fn">1</xref></contrib><contrib contrib-type="author" id="au0004"><name><surname>Deng</surname><given-names>Qiaoling</given-names></name><xref rid="aff0001" ref-type="aff">a</xref></contrib><contrib contrib-type="author" id="au0005"><name><surname>Chen</surname><given-names>Liangjun</given-names></name><xref rid="aff0001" ref-type="aff">a</xref></contrib><contrib contrib-type="author" id="au0006"><name><surname>Li</surname><given-names>Jin</given-names></name><xref rid="aff0001" ref-type="aff">a</xref></contrib><contrib contrib-type="author" id="au0007"><name><surname>Li</surname><given-names>Yirong</given-names></name><email>liyirong838@163.com</email><xref rid="aff0001" ref-type="aff">a</xref><xref rid="cor0001" ref-type="corresp">⁎</xref></contrib><contrib contrib-type="author" id="au0008"><name><surname>Wang</surname><given-names>Xinghuan</given-names></name><email>wangxinghuan@whu.edu.cn</email><xref rid="aff0003" ref-type="aff">c</xref><xref rid="aff0004" ref-type="aff">d</xref><xref rid="cor0002" ref-type="corresp">⁎⁎</xref></contrib></contrib-group><aff id="aff0001"><label>a</label>Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, Hubei, China</aff><aff id="aff0002"><label>b</label>Department of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, Hubei, China</aff><aff id="aff0003"><label>c</label>Center for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China</aff><aff id="aff0004"><label>d</label>Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China</aff><author-notes><corresp id="cor0001"><label>⁎</label>Corresponding author at: Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China. <email>liyirong838@163.com</email></corresp><corresp id="cor0002"><label>⁎⁎</label>Corresponding author at: Center for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China. <email>wangxinghuan@whu.edu.cn</email></corresp><fn id="fn1"><label>1</label><p id="notep0001">Thease authors contributed equally.</p></fn></author-notes><pub-date pub-type="pmc-release"><day>20</day><month>3</month><year>2020</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>5</month><year>2020</year></pub-date><pub-date pub-type="epub"><day>20</day><month>3</month><year>2020</year></pub-date><volume>80</volume><issue>5</issue><fpage>e14</fpage><lpage>e17</lpage><history><date date-type="accepted"><day>5</day><month>3</month><year>2020</year></date></history><permissions><copyright-statement>© 2020 The British Infection Association. Published by Elsevier Ltd. All rights reserved.</copyright-statement><copyright-year>2020</copyright-year><copyright-holder></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 abstract-type="author-highlights" id="abs0001"><title>Highlights</title><p><list list-type="simple" id="celist0001"><list-item id="celistitem0001"><label>•</label><p id="para0002">All reactivated patients presented normal aminotransferase levels.</p></list-item><list-item id="celistitem0002"><label>•</label><p id="para0003">Throat swab samples from the reactivated patients indicated all positive for the virus.</p></list-item><list-item id="celistitem0003"><label>•</label><p id="para0004">There might be no specific clinical characteristics to distinguish the reactivation of SARS-CoV-2.</p></list-item></list></p></abstract><abstract id="abs0002"><title>Summary</title><sec><title>Objectives</title><p>Previous studies on the pneumonia outbreak caused by the 2019 novel coronavirus disease (COVID-19) were based on information from the general population. However, limited data was available for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reactivation. This study aimed to evaluate the clinical characteristics of the SARS-CoV-2 reactivation.</p></sec><sec><title>Methods</title><p>Clinical records, laboratory results, and chest CT scans were retrospectively reviewed for 55 patients with laboratory-confirmed COVID-19 pneumonia (i.e., with throat swab samples that were positive for SARS-CoV-2) who were admitted to Zhongnan Hospital of Wuhan University, Wuhan, China, from Jan. 8 to Feb. 10, 2020.</p></sec><sec><title>Results</title><p>All 55 patients had a history of epidemiological exposure to COVID-19, and 5 (9%) patients who discharged from hospital presented with SARS-CoV-2 reactivation. Among the 5 reactivated patients, other symptoms were also observed, including fever, cough, sore throat, and fatigue. One of the 5 patients had progressive lymphopenia (from 1.3 to 0.56 × 10<sup>9</sup> cells per L) and progressive neutrophilia (from 4.5 to 18.28 × 10<sup>9</sup> cells per L). All 5 reactivated patients presented normal aminotransferase levels. Throat swab samples from the 5 reactivated patients were tested for SARS-CoV-2, indicating all positive for the virus.</p></sec><sec><title>Conclusions</title><p>Findings from this small group of cases suggested that there was currently evidence for reactivation of SARS-CoV-2 and there might be no specific clinical characteristics to distinguish them.</p></sec></abstract><kwd-group id="keys0001"><title>Keywords</title><kwd>SARS-CoV-2</kwd><kwd>COVID-19</kwd><kwd>Laboratory medicine</kwd><kwd>CT scan</kwd></kwd-group></article-meta></front><body><sec id="sec0001"><title>Introduction</title><p id="para0009">A novel human coronavirus which is a new strain of RNA viruses was recognized in Wuhan, China, in Dec. 2019. The novel coronavirus is now officially named SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) by International Committee on Taxonomy of Viruses (ICTV). The pneumonia caused by SARS-CoV-2 has been recently identified as COVID-19 (coronavirus disease 2019). COVID-19 spread quickly across Hubei Province and other regions of China,<xref rid="bib0001" ref-type="bibr"><sup>1</sup></xref><sup>,</sup><xref rid="bib0002" ref-type="bibr"><sup>2</sup></xref> also the global alert for COVID-19 has been issued by the World Health Organization (WHO).<xref rid="bib0001" ref-type="bibr"><sup>1</sup></xref><sup>,</sup><xref rid="bib0002" ref-type="bibr"><sup>2</sup></xref> COVID-19 could induce symptoms including fever, dry cough, dyspnea, fatigue and lymphopenia in patients, and might result in severe acute respiratory syndrome (SARS) and even death in severe cases.<xref rid="bib0001" ref-type="bibr">1</xref>, <xref rid="bib0002" ref-type="bibr">2</xref>, <xref rid="bib0003" ref-type="bibr">3</xref></p><p id="para0010">SARS-CoV-2 belongs to the beta-coronavirus 2b lineage in the phylogenetic tree and shares ∼80% identity sequencing with the Bat SARS-like coronavirus and the original SARS epidemic virus.<xref rid="bib0004" ref-type="bibr"><sup>4</sup></xref><sup>,</sup><xref rid="bib0005" ref-type="bibr"><sup>5</sup></xref> Currently, it remains to be determined the origins and possible intermediate animal vectors of SARS-CoV-2, as well as the mechanism that this virus spread among humans. Despite many reports have characterized the clinical, epidemiological, laboratory, and radiological features, as well as treatment and clinical outcomes of patients with COVID-19 pneumonia, the information of the SARS-CoV-2 reactivation remains not reported. The curative and eradicative therapy for COVID-19 is not currently available. Urgent questions that need to be addressed promptly include whether patients with COVID-19 pneumonia will reactivate, and whether risk factors predict SARS-CoV-2 reactivation in patients. To prevent and control COVID-19 reactivation, we retrospectively collected and analyzed detailed clinical data from SARS-CoV-2 reactivated patients. In the study, we presented clinical features of SARS-CoV-2 reactivated patients and discussed the potential risk factors of SARS-CoV-2 reactivation.</p></sec><sec id="sec0002"><title>Material and methods</title><sec id="sec0003"><title>Study design and patients</title><p id="para0011">We retrospectively recruited 55 patients who were diagnosed as COVID-19 pneumonia at the Zhongnan Hospital of Wuhan University from Jan. 8, 2020 to Feb. 10, 2020. The patients comprised 19 males and 36 females with a median age of 37 (range 22–67 years). Diagnosis of COVID-19 pneumonia was based on the New Coronavirus Pneumonia Prevention and Control Program. All patients with COVID-19 pneumonia were tested positively for SARS-CoV-2 by use of quantitative RT-PCR on samples from the respiratory tract. This study was reviewed and approved by the Ethical Committee of Zhongnan Hospital of Wuhan University. Written informed consent was waived by the Ethics Commission for emerging infectious diseases.</p></sec><sec id="sec0004"><title>Data collection</title><p id="para0012">We reviewed clinical records, laboratory findings, and chest CT scans for all patients. Two study investigators independently reviewed the data. Throat swab samples were collected and tested for SARS-CoV-2, following WHO guidelines for qRT-PCR.<xref rid="bib0006" ref-type="bibr"><sup>6</sup></xref><sup>,</sup><xref rid="bib0007" ref-type="bibr"><sup>7</sup></xref></p></sec><sec id="sec0005"><title>Statistical analysis</title><p id="para0013">Statistical analysis was done with SPSS, version 22.0. Continuous variables were directly expressed as a range. Categorical variables were expressed as number (%).</p></sec></sec><sec id="sec0006"><title>Results</title><p id="para0014">At presentation, all 55 patients had a history of epidemiological exposure to COVID-19, and 5 (9%) patients who discharged from hospital presented SARS-CoV-2 reactivation. The age range of the SARS-CoV-2 reactivated patients was 27–42 years. None of the reactivated patients had underlying diseases such as diabetes, chronic hypertension, or cardiovascular disease. One patient, however, had history of tuberculosis in the mediastinal lymph node in 2009. Additionally, all the reactivated patients excluded influenza virus and H7 avian influenza virus infection upon admission to hospital.</p><p id="para0015">Four of the 5 patients presented with a fever without chills, one had a high fever (39.3 °C). Patients’ body temperatures fluctuated within a range from 36.2 to 39.3 °C. One patient showed normal body temperature. Other symptoms of an upper respiratory tract infection were also observed: one patient had cough, one had sore throat, all patients reported fatigue (<xref rid="tbl0001" ref-type="table">Table 1</xref>). Additionally, one patient showed constipation. However, none of the 5 patients developed severe pneumonia, requiring mechanical ventilation, or died of COVID-19 pneumonia, as of Feb. 24, 2020.<table-wrap position="float" id="tbl0001"><label>Table 1</label><caption><p>Clinical and laboratory characteristics.</p></caption><alt-text id="alt0002">Table 1</alt-text><table frame="hsides" rules="groups"><thead><tr><th valign="top">Clinical characteristics</th><th valign="top">Patient 1</th><th valign="top">Patient 2</th><th valign="top">Patient 3</th><th valign="top">Patient 4</th><th valign="top">Patient 5</th></tr></thead><tbody><tr><td valign="top">Date of admission</td><td valign="top">Jan. 3</td><td valign="top">Jan. 13</td><td valign="top">Jan. 27</td><td valign="top">Jan. 22</td><td valign="top">Jan. 20</td></tr><tr><td valign="top">Sex</td><td valign="top">Male</td><td valign="top">Male</td><td valign="top">Female</td><td valign="top">Female</td><td valign="top">Female</td></tr><tr><td valign="top">Age (years)</td><td valign="top">30</td><td valign="top">42</td><td valign="top">32</td><td valign="top">27</td><td valign="top">31</td></tr><tr><td valign="top">Epidemiological history</td><td valign="top">Yes</td><td valign="top">Yes</td><td valign="top">Yes</td><td valign="top">Yes</td><td valign="top">Yes</td></tr><tr><td valign="top">SARS-CoV-2 negative to positive (days)</td><td valign="top">4</td><td valign="top">8</td><td valign="top">17</td><td valign="top">15</td><td valign="top">9</td></tr><tr><td valign="top">Complications</td><td valign="top">None</td><td valign="top">None</td><td valign="top">None</td><td valign="top">None</td><td valign="top">None</td></tr><tr><td valign="top">Signs and symptoms</td><td valign="top"></td><td valign="top"></td><td valign="top"></td><td valign="top"></td><td valign="top"></td></tr><tr><td valign="top">Fever on admission</td><td valign="top">Yes</td><td valign="top">Yes</td><td valign="top">Yes</td><td valign="top">No</td><td valign="top">Yes</td></tr><tr><td valign="top">Cough</td><td valign="top">No</td><td valign="top">Yes</td><td valign="top">No</td><td valign="top">No</td><td valign="top">No</td></tr><tr><td valign="top">Dyspnoea</td><td valign="top">No</td><td valign="top">No</td><td valign="top">No</td><td valign="top">No</td><td valign="top">No</td></tr><tr><td valign="top">Sore throat</td><td valign="top">No</td><td valign="top">No</td><td valign="top">Yes</td><td valign="top">No</td><td valign="top">No</td></tr><tr><td valign="top">Fatigue</td><td valign="top">Yes</td><td valign="top">Yes</td><td valign="top">Yes</td><td valign="top">Yes</td><td valign="top">Yes</td></tr><tr><td valign="top">Laboratory characteristics</td><td valign="top"></td><td valign="top"></td><td valign="top"></td><td valign="top"></td><td valign="top"></td></tr><tr><td valign="top">White blood cell count (× 10<sup>9</sup> cells per L)</td><td valign="top">5.9</td><td valign="top">7.1</td><td valign="top">4.4</td><td valign="top">6.5</td><td valign="top">4.5</td></tr><tr><td valign="top">Neutrophil count (× 10<sup>9</sup> cells per L)</td><td valign="top">3.5</td><td valign="top">4.5</td><td valign="top">1.8</td><td valign="top">4.1</td><td valign="top">2.6</td></tr><tr><td valign="top">Lymphocyte count (× 10<sup>9</sup> cells per L)</td><td valign="top">1.7</td><td valign="top">1.3</td><td valign="top">1.7</td><td valign="top">1.7</td><td valign="top">1.4</td></tr><tr><td valign="top">Monocyte count (× 10<sup>9</sup> cells per L)</td><td valign="top">0.63</td><td valign="top">1.24</td><td valign="top">0.75</td><td valign="top">0.58</td><td valign="top">0.4</td></tr><tr><td valign="top">Eosinophil count (× 10<sup>9</sup> cells per L)</td><td valign="top">0.13</td><td valign="top">0.05</td><td valign="top">0.02</td><td valign="top">0.09</td><td valign="top">0</td></tr><tr><td valign="top">Basophile count (× 10<sup>9</sup> cells per L)</td><td valign="top">0.02</td><td valign="top">0.04</td><td valign="top">0.03</td><td valign="top">0.02</td><td valign="top">0.02</td></tr><tr><td valign="top">C-reactive protein (mg/L)</td><td valign="top">18.7</td><td valign="top">23.7</td><td valign="top">NA</td><td valign="top"><0.50</td><td valign="top">NA</td></tr><tr><td valign="top">Elevated ALT (>45 U/L) or AST (>35 U/L)</td><td valign="top">No</td><td valign="top">No</td><td valign="top">No</td><td valign="top">No</td><td valign="top">No</td></tr><tr><td valign="top">ALT (U/L)</td><td valign="top">40</td><td valign="top">16</td><td valign="top">11</td><td valign="top">9</td><td valign="top">10</td></tr><tr><td valign="top">AST(U/L)</td><td valign="top">32</td><td valign="top">19</td><td valign="top">20</td><td valign="top">13</td><td valign="top">22</td></tr><tr><td valign="top">Confirmatory test (SARS-CoV-2 PCR)</td><td valign="top">Yes</td><td valign="top">Yes</td><td valign="top">Yes</td><td valign="top">Yes</td><td valign="top">Yes</td></tr><tr><td valign="top">CT evidence of pneumonia</td><td valign="top"></td><td valign="top"></td><td valign="top"></td><td valign="top"></td><td valign="top"></td></tr><tr><td valign="top">Typical signs of viral infection</td><td valign="top">Yes</td><td valign="top">Yes</td><td valign="top">Yes</td><td valign="top">Yes</td><td valign="top">Yes</td></tr><tr><td valign="top">Treatment</td><td valign="top"></td><td valign="top"></td><td valign="top"></td><td valign="top"></td><td valign="top"></td></tr><tr><td valign="top">Antiviral therapy</td><td valign="top">Yes</td><td valign="top">Yes</td><td valign="top">Yes</td><td valign="top">Yes</td><td valign="top">Yes</td></tr><tr><td valign="top">Antibiotic therapy</td><td valign="top">Yes</td><td valign="top">Yes</td><td valign="top">Yes</td><td valign="top">Yes</td><td valign="top">Yes</td></tr><tr><td valign="top">Use of corticosteroid</td><td valign="top">Yes</td><td valign="top">Yes</td><td valign="top">No</td><td valign="top">No</td><td valign="top">Yes</td></tr></tbody></table><table-wrap-foot><fn><p>NA=not applicable. ALT=alanine transaminase. AST=aspartate transaminase.</p></fn></table-wrap-foot></table-wrap></p><p id="para0016">All the 5 reactivated patients were given empirical antibiotic treatment and were administered antiviral therapy (<xref rid="tbl0001" ref-type="table">Table 1</xref>). Data from laboratory tests showed that one patient had progressive lymphopenia (from 1.3 to 0.56 × 10<sup>9</sup> cells per L) and progressive elevated neutrophilia (from 4.5 to 18.28 × 10<sup>9</sup> cells per L). Two patients had elevated concentrations of C-reactive protein (> 18 mg/L). All the 5 patients had normal alanine aminotransferase (ALT) and aspartate aminotransferase (AST). All 5 patients had chest CT scan. All patients showed typical findings of chest CT images-multiple patchy ground-glass shadows in lungs (<xref rid="fig0001" ref-type="fig">Fig. 1</xref>).<fig id="fig0001"><label>Fig. 1</label><caption><p>Chest CT scans of the 5 patients.</p></caption><alt-text id="alt0001">Fig 1</alt-text><graphic xlink:href="gr1_lrg"></graphic></fig></p></sec><sec id="sec0007"><title>Discussion</title><p id="para0017">We confirmed that in a significantly proportion of COVID-19 patients, SARS-CoV-2 reactivation developed after discharging from hospital (9%). We reported clinical data from 5 patients with SARS-CoV-2 reactivation. The clinical characteristics of these patients with SARS-CoV-2 reactivation were similar to those of non-reactivated patients with COVID-19 infection. None of the 5 patients developed severe pneumonia or died, as of Feb. 24, 2020. Notably, based on our findings in these 5 patients, there is currently evidence to suggest that a proportion of recovered COVID-19 patients could reactivate.</p><p id="para0018">The reactivated patients included 1 asymptomatic patient and 4 symptomatic patients, which suggests the reactivation potential of asymptomatic or minimally symptomatic patients. The time from SARS-CoV-2 negative to positive ranged from 4 to 17 days, suggesting that recovered patients still may be virus carriers and require additional round of viral detection and isolation.</p><p id="para0019">We need better data to determine risk factors and mechanisms that cause SARS-CoV-2 reactivation. The timing of onset of SARS-CoV-2 reactivation can be variable depending upon the host factors, underlying disease and the type of immunosuppressive therapies. In our study, the recovered patients had positive RT-PCR test results 4–17 days later. The key risk factors for reactivation would include 3 categories: (1) host status, (2) virologic factors and (3) type and degree of immunosuppression. Host factors may include sex, older age, type of disease needing immunosuppression. Although we could not identify risk factors for these host factors in the current study, the potential requires further large cohort confirmation. The virologic factors associated with increased risk of reactivation include high baseline SARS-CoV-2 load and variable genotype. SARS-CoV-2 viral load would also linked to treatment response, disease severity and progression.<xref rid="bib0008" ref-type="bibr"><sup>8</sup></xref> The association of SARS-CoV-2 genotypes and viral load with SARS-CoV-2 reactivation will be an important question to address. In our study, all the patients received antiviral therapy (Oseltamivir or Arbidol). These cases suggest that SARS-CoV-2 reactivation may occur whatever the antiviral therapy used. These host and virologic factors are important considerations that may further increase the likelihood of SARS-CoV-2 reactivation. Therefore, the assessment of host as well as virologic risk factors should be important caveats to help decide whether to initiate prophylactic therapy and immunosuppression. Immunosuppressive therapies are the commonly used causative agents. These agents have a general mechanism that inhibits many immune functions. For example, steroid inhibits cell-mediated immunity by suppressing interleukins production which is important for T and B cell proliferation.<xref rid="bib0009" ref-type="bibr"><sup>9</sup></xref> It is thus not surprising that these general immunosuppressive effects result in broad immune dysfunctions and potential SARS-CoV-2 reactivation.</p><p id="para0020">SARS-CoV-2 reactivation will be a vexing and persistent problem. Considering numerous patients infected or previously exposed to the virus, such a problem poses a major public health burden in terms of global morbidity and possibly mortality. Currently, we did not find reliable markers in predicting the risk of SARS-CoV-2 reactivation, nor there are any validated tests to determine whether a particular drug or therapy is associated with SARS-CoV-2 reactivation. The latter point was often determined by our empirical experience. Although decades of the experiences helped us to identify important drugs and to manage these situations appropriately, we could not accurately evaluate the risk of the drugs prior to its clinical application.</p><p id="para0021">Considering the significance of this ongoing global public health emergency, although our conclusions are limited by the small sample size, we believe that the findings are important to understand the clinical characteristics and SARS-CoV-2 reactivation potential in COVID-19 patients.</p></sec><sec id="sec0008"><title>Funding/support</title><p id="para0022">This study was supported in part by grants from Medical Science Advancement Program (Clinical Medicine) of Wuhan University (TFLC2018002).</p></sec><sec id="sec0009"><title>Role of the funders/sponsors</title><p id="para0023">The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.</p></sec><sec id="sec0010"><title>Statement of patient consent</title><p id="para0024">All patients provided written informed consent. 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