SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients
Identifieur interne : 000B26 ( Pmc/Corpus ); précédent : 000B25; suivant : 000B27SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients
Auteurs : Lirong ZouSource :
- The New England Journal of Medicine [ 0028-4793 ] ; 2020.
Url:
DOI: 10.1056/NEJMc2001737
PubMed: 32074444
PubMed Central: 7121626
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients</title><author><name sortKey="Zou, Lirong" sort="Zou, Lirong" uniqKey="Zou L" first="Lirong" last="Zou">Lirong Zou</name></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">32074444</idno><idno type="pmc">7121626</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7121626</idno><idno type="RBID">PMC:7121626</idno><idno type="doi">10.1056/NEJMc2001737</idno><date when="2020">2020</date><idno type="wicri:Area/Pmc/Corpus">000B26</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000B26</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients</title><author><name sortKey="Zou, Lirong" sort="Zou, Lirong" uniqKey="Zou L" first="Lirong" last="Zou">Lirong Zou</name></author></analytic><series><title level="j">The New England Journal of Medicine</title><idno type="ISSN">0028-4793</idno><idno type="eISSN">1533-4406</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></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">N Engl J Med</journal-id><journal-id journal-id-type="iso-abbrev">N. Engl. J. Med</journal-id><journal-id journal-id-type="publisher-id">nejm</journal-id><journal-title-group><journal-title>The New England Journal of Medicine</journal-title></journal-title-group><issn pub-type="ppub">0028-4793</issn><issn pub-type="epub">1533-4406</issn><publisher><publisher-name>Massachusetts Medical Society</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">32074444</article-id><article-id pub-id-type="pmc">7121626</article-id><article-id pub-id-type="doi">10.1056/NEJMc2001737</article-id><article-id pub-id-type="publisher-id">NJ202003193821219</article-id><article-categories><subj-group subj-group-type="heading"><subject>Correspondence</subject></subj-group></article-categories><title-group><article-title>SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Zou</surname><given-names>Lirong</given-names></name><degrees>M.Sc.</degrees></contrib><aff>Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, China</aff></contrib-group><contrib-group><contrib contrib-type="author"><name><surname>Ruan</surname><given-names>Feng</given-names></name><degrees>M.Med.</degrees></contrib><aff>Zhuhai Center for Disease Control and Prevention, Zhuhai, China</aff></contrib-group><contrib-group><contrib contrib-type="author"><name><surname>Huang</surname><given-names>Mingxing</given-names></name><degrees>Ph.D.</degrees></contrib><aff>Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China</aff></contrib-group><contrib-group><contrib contrib-type="author"><name><surname>Liang</surname><given-names>Lijun</given-names></name><degrees>Ph.D.</degrees></contrib><aff>Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, China</aff></contrib-group><contrib-group><contrib contrib-type="author"><name><surname>Huang</surname><given-names>Huitao</given-names></name><degrees>B.Sc.</degrees></contrib><aff>Zhuhai Center for Disease Control and Prevention, Zhuhai, China</aff></contrib-group><contrib-group><contrib contrib-type="author"><name><surname>Hong</surname><given-names>Zhongsi</given-names></name><degrees>M.D.</degrees></contrib><aff>Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China</aff></contrib-group><contrib-group><contrib contrib-type="author"><name><surname>Yu</surname><given-names>Jianxiang</given-names></name><degrees>B.Sc.</degrees></contrib><contrib contrib-type="author"><name><surname>Kang</surname><given-names>Min</given-names></name><degrees>M.Sc.</degrees></contrib><contrib contrib-type="author"><name><surname>Song</surname><given-names>Yingchao</given-names></name><degrees>B.Sc.</degrees></contrib><aff>Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, China</aff></contrib-group><contrib-group><contrib contrib-type="author"><name><surname>Xia</surname><given-names>Jinyu</given-names></name><degrees>M.D.</degrees></contrib><aff>Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China</aff></contrib-group><contrib-group><contrib contrib-type="author"><name><surname>Guo</surname><given-names>Qianfang</given-names></name><degrees>M.Sc.</degrees></contrib><contrib contrib-type="author"><name><surname>Song</surname><given-names>Tie</given-names></name><degrees>M.Sc.</degrees></contrib><contrib contrib-type="author"><name><surname>He</surname><given-names>Jianfeng</given-names></name><degrees>B.Sc.</degrees></contrib><aff>Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, China</aff></contrib-group><contrib-group><contrib contrib-type="author"><name><surname>Yen</surname><given-names>Hui-Ling</given-names></name><degrees>Ph.D.</degrees></contrib><contrib contrib-type="author"><name><surname>Peiris</surname><given-names>Malik</given-names></name><degrees>Ph.D.</degrees></contrib><aff>University of Hong Kong, Hong Kong, China</aff></contrib-group><contrib-group><contrib contrib-type="author" corresp="yes"><name><surname>Wu</surname><given-names>Jie</given-names></name><degrees>Ph.D.</degrees></contrib><aff>Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, China<email xlink:href="771276998@qq.com">771276998@qq.com</email></aff></contrib-group><pub-date pub-type="ppub"><day>19</day><month>3</month><year>2020</year></pub-date><volume>382</volume><issue>12</issue><fpage>1177</fpage><lpage>1179</lpage><permissions><copyright-statement>Copyright © 2020 Massachusetts Medical Society. All rights reserved.</copyright-statement><copyright-year>2020</copyright-year><copyright-holder>Massachusetts Medical Society</copyright-holder><license specific-use="PMC_Covid-19"><license-p>This article is made available via the PMC Open Access Subset for unrestricted re-use, except commercial resale, and analyses in any form or by any means with acknowledgment of the original source. These permissions are granted for the duration of the Covid-19 pandemic or until revoked in writing. Upon expiration of these permissions, PMC is granted a license to make this article available via PMC and Europe PMC, subject to existing copyright protections.</license-p></license></permissions><self-uri content-type="pdf" xlink:href="NEJMc2001737.pdf"></self-uri><kwd-group kwd-group-type="nejm-topics"><nested-kwd><compound-kwd><compound-kwd-part content-type="code">18</compound-kwd-part><compound-kwd-part content-type="keyword">Infectious Disease</compound-kwd-part></compound-kwd><nested-kwd><compound-kwd><compound-kwd-part content-type="code">18_1</compound-kwd-part><compound-kwd-part content-type="keyword">Infectious Disease General</compound-kwd-part></compound-kwd><compound-kwd><compound-kwd-part content-type="code">18_6</compound-kwd-part><compound-kwd-part content-type="keyword">Viral Infections</compound-kwd-part></compound-kwd><compound-kwd><compound-kwd-part content-type="code">18_9</compound-kwd-part><compound-kwd-part content-type="keyword">Global Health</compound-kwd-part></compound-kwd></nested-kwd></nested-kwd></kwd-group></article-meta></front><body><p><named-content content-type="salutation">To the Editor:</named-content> The 2019 novel coronavirus (SARS-CoV-2) epidemic, which was first reported in December 2019 in Wuhan, China, and has been declared a public health emergency of international concern by the World Health Organization, may progress to a pandemic associated with substantial morbidity and mortality. SARS-CoV-2 is genetically related to SARS-CoV, which caused a global epidemic with 8096 confirmed cases in more than 25 countries in 2002–2003.<sup><xref rid="r1" ref-type="bibr">1</xref></sup> The epidemic of SARS-CoV was successfully contained through public health interventions, including case detection and isolation. Transmission of SARS-CoV occurred mainly after days of illness<sup><xref rid="r2" ref-type="bibr">2</xref></sup> and was associated with modest viral loads in the respiratory tract early in the illness, with viral loads peaking approximately 10 days after symptom onset.<sup><xref rid="r3" ref-type="bibr">3</xref></sup> We monitored SARS-CoV-2 viral loads in upper respiratory specimens obtained from 18 patients (9 men and 9 women; median age, 59 years; range, 26 to 76) in Zhuhai, Guangdong, China, including 4 patients with secondary infections (1 of whom never had symptoms) within two family clusters (Table S1 in the <xref ref-type="app" rid="ap1">Supplementary Appendix</xref>, available with the full text of this letter at NEJM.org). The patient who never had symptoms was a close contact of a patient with a known case and was therefore monitored. A total of 72 nasal swabs (sampled from the mid-turbinate and nasopharynx) (<xref ref-type="fig" rid="f1">Figure 1A</xref>) and 72 throat swabs (<xref ref-type="fig" rid="f1">Figure 1B</xref>) were analyzed, with 1 to 9 sequential samples obtained from each patient. Polyester flock swabs were used for all the patients.</p><p>From January 7 through January 26, 2020, a total of 14 patients who had recently returned from Wuhan and had fever (≥37.3°C) received a diagnosis of Covid-19 (the illness caused by SARS-CoV-2) by means of reverse-transcriptase–polymerase-chain-reaction assay with primers and probes targeting the N and Orf1b genes of SARS-CoV-2; the assay was developed by the Chinese Center for Disease Control and Prevention. Samples were tested at the Guangdong Provincial Center for Disease Control and Prevention. Thirteen of 14 patients with imported cases had evidence of pneumonia on computed tomography (CT). None of them had visited the Huanan Seafood Wholesale Market in Wuhan within 14 days before symptom onset. Patients E, I, and P required admission to intensive care units, whereas the others had mild-to-moderate illness. Secondary infections were detected in close contacts of Patients E, I, and P. Patient E worked in Wuhan and visited his wife (Patient L), mother (Patient D), and a friend (Patient Z) in Zhuhai on January 17. Symptoms developed in Patients L and D on January 20 and January 22, respectively, with viral RNA detected in their nasal and throat swabs soon after symptom onset. Patient Z reported no clinical symptoms, but his nasal swabs (cycle threshold [Ct] values, 22 to 28) and throat swabs (Ct values, 30 to 32) tested positive on days 7, 10, and 11 after contact. A CT scan of Patient Z that was obtained on February 6 was unremarkable. Patients I and P lived in Wuhan and visited their daughter (Patient H) in Zhuhai on January 11 when their symptoms first developed. Fever developed in Patient H on January 17, with viral RNA detected in nasal and throat swabs on day 1 after symptom onset.</p><p>We analyzed the viral load in nasal and throat swabs obtained from the 17 symptomatic patients in relation to day of onset of any symptoms (<xref ref-type="fig" rid="f1">Figure 1C</xref>). Higher viral loads (inversely related to Ct value) were detected soon after symptom onset, with higher viral loads detected in the nose than in the throat. Our analysis suggests that the viral nucleic acid shedding pattern of patients infected with SARS-CoV-2 resembles that of patients with influenza<sup><xref rid="r4" ref-type="bibr">4</xref></sup> and appears different from that seen in patients infected with SARS-CoV.<sup><xref rid="r3" ref-type="bibr">3</xref></sup> The viral load that was detected in the asymptomatic patient was similar to that in the symptomatic patients, which suggests the transmission potential of asymptomatic or minimally symptomatic patients. These findings are in concordance with reports that transmission may occur early in the course of infection<sup><xref rid="r5" ref-type="bibr">5</xref></sup> and suggest that case detection and isolation may require strategies different from those required for the control of SARS-CoV. How SARS-CoV-2 viral load correlates with culturable virus needs to be determined. Identification of patients with few or no symptoms and with modest levels of detectable viral RNA in the oropharynx for at least 5 days suggests that we need better data to determine transmission dynamics and inform our screening practices.</p></body><back><fn-group><fn fn-type="financial-disclosure"><p><xref ref-type="app" rid="ap2">Disclosure forms</xref> provided by the authors are available with the full text of this letter at NEJM.org.</p></fn></fn-group><notes><p content-type="published/updated">This letter was published on February 19, 2020, and updated on February 20, 2020, at NEJM.org.</p><p content-type="other">Ms. Zou, Mr. Ruan, and Dr. Huang contributed equally to this letter.</p></notes><app-group><app content-type="supplementary-appendix" id="ap1"><title>Supplementary Appendix</title><supplementary-material content-type="local-data"><media xlink:href="NEJMc2001737_appendix.pdf"><caption><p>Click here for additional data file.</p></caption></media></supplementary-material></app><app content-type="disclosures" id="ap2"><title>Disclosure Forms</title><supplementary-material content-type="local-data"><media xlink:href="NEJMc2001737_disclosures.pdf"><caption><p>Click here for additional data file.</p></caption></media></supplementary-material></app></app-group><ref-list><title>References</title><ref id="r1"><label>1</label><mixed-citation publication-type="eref">Summary of probable SARS cases with onset of illness from 1 November 2002 to 31 July 2003. Geneva: World Health Organization, 2004 (<uri xlink:href="https://www.who.int/csr/sars/country/table2004_04_21/en/">https://www.who.int/csr/sars/country/table2004_04_21/en/</uri>).</mixed-citation></ref><ref id="r2"><label>2</label><mixed-citation publication-type="journal"><string-name><surname>Lipsitch</surname><given-names>M</given-names></string-name>, <string-name><surname>Cohen</surname><given-names>T</given-names></string-name>, <string-name><surname>Cooper</surname><given-names>B</given-names></string-name>, <etal>et al.</etal><article-title>Transmission dynamics and control of severe acute respiratory syndrome.</article-title><source>Science</source><year>2003</year>;<volume>300</volume>:<fpage>1966</fpage>-<lpage>1970</lpage>.<pub-id pub-id-type="pmid">12766207</pub-id></mixed-citation></ref><ref id="r3"><label>3</label><mixed-citation publication-type="journal"><string-name><surname>Peiris</surname><given-names>JSM</given-names></string-name>, <string-name><surname>Chu</surname><given-names>CM</given-names></string-name>, <string-name><surname>Cheng</surname><given-names>VCC</given-names></string-name>, <etal>et al.</etal><article-title>Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study.</article-title><source>Lancet</source><year>2003</year>;<volume>361</volume>:<fpage>1767</fpage>-<lpage>1772</lpage>.<pub-id pub-id-type="pmid">12781535</pub-id></mixed-citation></ref><ref id="r4"><label>4</label><mixed-citation publication-type="journal"><string-name><surname>Tsang</surname><given-names>TK</given-names></string-name>, <string-name><surname>Cowling</surname><given-names>BJ</given-names></string-name>, <string-name><surname>Fang</surname><given-names>VJ</given-names></string-name>, <etal>et al.</etal><article-title>Influenza A virus shedding and infectivity in households.</article-title><source>J Infect Dis</source><year>2015</year>;<volume>212</volume>:<fpage>1420</fpage>-<lpage>1428</lpage>.<pub-id pub-id-type="pmid">25883385</pub-id></mixed-citation></ref><ref id="r5"><label>5</label><mixed-citation publication-type="journal"><string-name><surname>Rothe</surname><given-names>C</given-names></string-name>, <string-name><surname>Schunk</surname><given-names>M</given-names></string-name>, <string-name><surname>Sothmann</surname><given-names>P</given-names></string-name>, <etal>et al.</etal><article-title>Transmission of 2019-nCoV infection from an asymptomatic contact in Germany.</article-title><source>N Engl J Med</source><year>2020</year>;<volume>382</volume>:<fpage>970</fpage>-<lpage>971</lpage>.
<pub-id pub-id-type="pmid">32003551</pub-id></mixed-citation></ref></ref-list></back><floats-group><fig id="f1" orientation="portrait" position="float"><label>Figure 1</label><caption><title>Viral Load Detected in Nasal and Throat Swabs Obtained from Patients Infected with SARS-CoV-2.</title><p>Panel A shows cycle threshold (Ct) values of Orf1b on reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assay that were detected in nasal swabs obtained from 14 patients with imported cases and 3 patients with secondary cases, and Panel B shows the Ct values in throat swabs. Patient Z did not have clinical symptoms and is not included in the figure. Patients with imported cases who had severe illness (Patients E, I, and P) are labeled in red, patients with imported cases who had mild-to-moderate illness are labeled in black, and patients with secondary cases (Patients D, H, and L) are labeled in blue. A linear mixed-effects model was used to test the Ct values from nasal and throat swabs among severe as compared with mild-to-moderate imported cases, which allowed for within-patient correlation and a time trend of Ct change. The mean Ct values in nasal and throat swabs obtained from patients with severe cases were lower by 2.8 (95% confidence interval [CI], −2.4 to 8.0) and 2.5 (95% CI, −0.8 to 5.7), respectively, than the values in swabs obtained from patients with mild-to-moderate cases. Panel C shows the aggregated Ct values of Orf1b on RT-PCR assay in 14 patients with imported cases and 3 patients with secondary cases, according to day after symptom onset. Ct values are inversely related to viral RNA copy number, with Ct values of 30.76, 27.67, 24.56, and 21.48 corresponding to 1.5×10<sup>4</sup>, 1.5×10<sup>5</sup>, 1.5×10<sup>6</sup>, and 1.5×10<sup>7</sup> copies per milliliter. Negative samples are denoted with a Ct of 40, which was the limit of detection.</p></caption><graphic xlink:href="NEJMc2001737_f1"></graphic></fig></floats-group></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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