Procalcitonin in patients with severe coronavirus disease 2019 (COVID-19): a meta-analysis
Identifieur interne : 000604 ( Pmc/Corpus ); précédent : 000603; suivant : 000605Procalcitonin in patients with severe coronavirus disease 2019 (COVID-19): a meta-analysis
Auteurs : Giuseppe Lippi ; Mario PlebaniSource :
- Clinica Chimica Acta; International Journal of Clinical Chemistry [ 0009-8981 ] ; 2020.
Url:
DOI: 10.1016/j.cca.2020.03.004
PubMed: 32145275
PubMed Central: 7094472
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Procalcitonin in patients with severe coronavirus disease 2019 (COVID-19): a meta-analysis</title><author><name sortKey="Lippi, Giuseppe" sort="Lippi, Giuseppe" uniqKey="Lippi G" first="Giuseppe" last="Lippi">Giuseppe Lippi</name><affiliation><nlm:aff id="af005">Section of Clinical Biochemistry, Department of Neuroscience, Biomedicine and Movement, University of Verona, Verona, Italy</nlm:aff></affiliation></author><author><name sortKey="Plebani, Mario" sort="Plebani, Mario" uniqKey="Plebani M" first="Mario" last="Plebani">Mario Plebani</name><affiliation><nlm:aff id="af010">Department of Laboratory Medicine, University Hospital of Padova, Padova, Italy</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">32145275</idno><idno type="pmc">7094472</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7094472</idno><idno type="RBID">PMC:7094472</idno><idno type="doi">10.1016/j.cca.2020.03.004</idno><date when="2020">2020</date><idno type="wicri:Area/Pmc/Corpus">000604</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000604</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Procalcitonin in patients with severe coronavirus disease 2019 (COVID-19): a meta-analysis</title><author><name sortKey="Lippi, Giuseppe" sort="Lippi, Giuseppe" uniqKey="Lippi G" first="Giuseppe" last="Lippi">Giuseppe Lippi</name><affiliation><nlm:aff id="af005">Section of Clinical Biochemistry, Department of Neuroscience, Biomedicine and Movement, University of Verona, Verona, Italy</nlm:aff></affiliation></author><author><name sortKey="Plebani, Mario" sort="Plebani, Mario" uniqKey="Plebani M" first="Mario" last="Plebani">Mario Plebani</name><affiliation><nlm:aff id="af010">Department of Laboratory Medicine, University Hospital of Padova, Padova, Italy</nlm:aff></affiliation></author></analytic><series><title level="j">Clinica Chimica Acta; International Journal of Clinical Chemistry</title><idno type="ISSN">0009-8981</idno><idno type="eISSN">1873-3492</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><analytic><author><name sortKey="Mattiuzzi, C" uniqKey="Mattiuzzi C">C. Mattiuzzi</name></author><author><name sortKey="Lippi, G" uniqKey="Lippi G">G. Lippi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cervellin, G" uniqKey="Cervellin G">G. Cervellin</name></author><author><name sortKey="Schuetz, P" uniqKey="Schuetz P">P. Schuetz</name></author><author><name sortKey="Lippi, G" uniqKey="Lippi G">G. Lippi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Schuetz, P" uniqKey="Schuetz P">P. Schuetz</name></author><author><name sortKey="Albrich, W" uniqKey="Albrich W">W. Albrich</name></author><author><name sortKey="Mueller, B" uniqKey="Mueller B">B. Mueller</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Guan, Wei Jie" uniqKey="Guan W">Wei-jie Guan</name></author><author><name sortKey="Ni, Zheng Yi" uniqKey="Ni Z">Zheng-yi Ni</name></author><author><name sortKey="Hu, Yu" uniqKey="Hu Y">Yu Hu</name></author><author><name sortKey="Liang, Wen Hua" uniqKey="Liang W">Wen-hua Liang</name></author><author><name sortKey="Ou, Chun Quan" uniqKey="Ou C">Chun-quan Ou</name></author><author><name sortKey="He, Jian Xing" uniqKey="He J">Jian-xing He</name></author><author><name sortKey="Liu, Lei" uniqKey="Liu L">Lei Liu</name></author><author><name sortKey="Shan, Hong" uniqKey="Shan H">Hong Shan</name></author><author><name sortKey="Lei, Chun Liang" uniqKey="Lei C">Chun-liang Lei</name></author><author><name sortKey="Hui, David S C" uniqKey="Hui D">David S.C. Hui</name></author><author><name sortKey="Du, Bin" uniqKey="Du B">Bin Du</name></author><author><name sortKey="Li, Lan Juan" uniqKey="Li L">Lan-juan Li</name></author><author><name sortKey="Zeng, Guang" uniqKey="Zeng G">Guang Zeng</name></author><author><name sortKey="Yuen, Kwok Yung" uniqKey="Yuen K">Kwok-Yung Yuen</name></author><author><name sortKey="Chen, Ru Chong" uniqKey="Chen R">Ru-chong Chen</name></author><author><name sortKey="Tang, Chun Li" uniqKey="Tang C">Chun-li Tang</name></author><author><name sortKey="Wang, Tao" uniqKey="Wang T">Tao Wang</name></author><author><name sortKey="Chen, Ping Yan" uniqKey="Chen P">Ping-yan Chen</name></author><author><name sortKey="Xiang, Jie" uniqKey="Xiang J">Jie Xiang</name></author><author><name sortKey="Li, Shi Yue" uniqKey="Li S">Shi-yue Li</name></author><author><name sortKey="Wang, Jin Lin" uniqKey="Wang J">Jin-lin Wang</name></author><author><name sortKey="Liang, Zi Jing" uniqKey="Liang Z">Zi-jing Liang</name></author><author><name sortKey="Peng, Yi Xiang" uniqKey="Peng Y">Yi-xiang Peng</name></author><author><name sortKey="Wei, Li" uniqKey="Wei L">Li Wei</name></author><author><name sortKey="Liu, Yong" uniqKey="Liu Y">Yong Liu</name></author><author><name sortKey="Hu, Ya Hua" uniqKey="Hu Y">Ya-hua Hu</name></author><author><name sortKey="Peng, Peng" uniqKey="Peng P">Peng Peng</name></author><author><name sortKey="Wang, Jian Ming" uniqKey="Wang J">Jian-ming Wang</name></author><author><name sortKey="Liu, Ji Yang" uniqKey="Liu J">Ji-yang Liu</name></author><author><name sortKey="Chen, Zhong" uniqKey="Chen Z">Zhong Chen</name></author><author><name sortKey="Li, Gang" uniqKey="Li G">Gang Li</name></author><author><name sortKey="Zheng, Zhi Jian" uniqKey="Zheng Z">Zhi-jian Zheng</name></author><author><name sortKey="Qiu, Shao Qin" uniqKey="Qiu S">Shao-qin Qiu</name></author><author><name sortKey="Luo, Jie" uniqKey="Luo J">Jie Luo</name></author><author><name sortKey="Ye, Chang Jiang" uniqKey="Ye C">Chang-jiang Ye</name></author><author><name sortKey="Zhu, Shao Yong" uniqKey="Zhu S">Shao-yong Zhu</name></author><author><name sortKey="Zhong, Nan Shan" uniqKey="Zhong N">Nan-shan Zhong</name></author></analytic></biblStruct><biblStruct></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><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></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, Dawei" uniqKey="Wang D">Dawei Wang</name></author><author><name sortKey="Hu, Bo" uniqKey="Hu B">Bo Hu</name></author><author><name sortKey="Hu, Chang" uniqKey="Hu C">Chang Hu</name></author><author><name sortKey="Zhu, Fangfang" uniqKey="Zhu F">Fangfang Zhu</name></author><author><name sortKey="Liu, Xing" uniqKey="Liu X">Xing Liu</name></author><author><name sortKey="Zhang, Jing" uniqKey="Zhang J">Jing Zhang</name></author><author><name sortKey="Wang, Binbin" uniqKey="Wang B">Binbin Wang</name></author><author><name sortKey="Xiang, Hui" uniqKey="Xiang H">Hui Xiang</name></author><author><name sortKey="Cheng, Zhenshun" uniqKey="Cheng Z">Zhenshun Cheng</name></author><author><name sortKey="Xiong, Yong" uniqKey="Xiong Y">Yong Xiong</name></author><author><name sortKey="Zhao, Yan" uniqKey="Zhao Y">Yan Zhao</name></author><author><name sortKey="Li, Yirong" uniqKey="Li Y">Yirong Li</name></author><author><name sortKey="Wang, Xinghuan" uniqKey="Wang X">Xinghuan Wang</name></author><author><name sortKey="Peng, Zhiyong" uniqKey="Peng Z">Zhiyong Peng</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Higgins, J P" uniqKey="Higgins J">J.P. Higgins</name></author><author><name sortKey="Thompson, S G" uniqKey="Thompson S">S.G. Thompson</name></author><author><name sortKey="Deeks, J J" uniqKey="Deeks J">J.J. Deeks</name></author><author><name sortKey="Altman, D G" uniqKey="Altman D">D.G. Altman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lippi, Giuseppe" uniqKey="Lippi G">Giuseppe Lippi</name></author><author><name sortKey="Plebani, Mario" uniqKey="Plebani M">Mario Plebani</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kotula, J J" uniqKey="Kotula J">J.J. Kotula</name></author><author><name sortKey="Moore, W S" uniqKey="Moore W">W.S. Moore</name></author><author><name sortKey="Chopra, A" uniqKey="Chopra A">A. Chopra</name></author><author><name sortKey="Cies, J J" uniqKey="Cies J">J.J. Cies</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">Clin Chim Acta</journal-id><journal-id journal-id-type="iso-abbrev">Clin. Chim. Acta</journal-id><journal-title-group><journal-title>Clinica Chimica Acta; International Journal of Clinical Chemistry</journal-title></journal-title-group><issn pub-type="ppub">0009-8981</issn><issn pub-type="epub">1873-3492</issn><publisher><publisher-name>Elsevier</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">32145275</article-id><article-id pub-id-type="pmc">7094472</article-id><article-id pub-id-type="publisher-id">S0009-8981(20)30106-6</article-id><article-id pub-id-type="doi">10.1016/j.cca.2020.03.004</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Procalcitonin in patients with severe coronavirus disease 2019 (COVID-19): a meta-analysis</article-title></title-group><contrib-group><contrib contrib-type="author" id="au005"><name><surname>Lippi</surname><given-names>Giuseppe</given-names></name><xref rid="af005" ref-type="aff">a</xref></contrib><contrib contrib-type="author" id="au010"><name><surname>Plebani</surname><given-names>Mario</given-names></name><email>mario.plebani@unipd.it</email><xref rid="af010" ref-type="aff">b</xref><xref rid="cor1" ref-type="corresp">⁎</xref></contrib></contrib-group><aff id="af005"><label>a</label>Section of Clinical Biochemistry, Department of Neuroscience, Biomedicine and Movement, University of Verona, Verona, Italy</aff><aff id="af010"><label>b</label>Department of Laboratory Medicine, University Hospital of Padova, Padova, Italy</aff><author-notes><corresp id="cor1"><label>⁎</label>Corresponding author at: Department of Laboratory Medicine, University-Hospital of Padova, Via Giustiniani 2, Padova 35128, Italy <email>mario.plebani@unipd.it</email></corresp></author-notes><pub-date pub-type="pmc-release"><day>4</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="epub"><day>4</day><month>3</month><year>2020</year></pub-date><elocation-id></elocation-id><history><date date-type="received"><day>3</day><month>3</month><year>2020</year></date><date date-type="accepted"><day>3</day><month>3</month><year>2020</year></date></history><permissions><copyright-statement>© 2020 Elsevier B.V. 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><kwd-group id="kg005"><title>Keywords</title><kwd>Coronavirus</kwd><kwd>COVID-19</kwd><kwd>procalcitonin</kwd><kwd>prognosis</kwd></kwd-group></article-meta></front><body><p id="p0075">Coronavirus disease 2019 (COVID-19), a new form of respiratory and systemic disorder sustained by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is now producing an outbreak of pandemic proportions, whereby nearly 90,000 people have already been infected around the world, 10-15% of whom with severe disease and over 2900 already died <xref rid="b0005" ref-type="bibr">[1]</xref>. A severe form of pneumonia, potentially evolving towards adult respiratory distress syndrome (ARDS) and occasionally associated with multiorgan failure, are the leading complications of this respiratory virus <xref rid="b0010" ref-type="bibr">[2]</xref>. Since laboratory medicine provides an essential contribution to the clinical decision making in this and many other infectious diseases <xref rid="b0015" ref-type="bibr">[3]</xref>, we aim to investigate here whether procalcitonin, whose values are not substantially modified in patients with viral infections <xref rid="b0020" ref-type="bibr">[4]</xref>, may play a role in distinguishing patients with or without severe COVID-19 (see <xref rid="t0005" ref-type="table">Tables 1</xref>and <xref rid="t0010" ref-type="table">2</xref>).<table-wrap position="float" id="t0005"><label>Table 1</label><caption><p>Main characteristics of the included studies. Laboratory data are reported as percent of patients with abnormalities defined according to the local reference ranges.</p></caption><table frame="hsides" rules="groups"><thead><tr><th>Characteristics</th><th>Zhang et al <xref rid="b0035" ref-type="bibr">[7]</xref></th><th>Huang et al <xref rid="b0040" ref-type="bibr">[8]</xref></th><th>Chen et al <xref rid="b0045" ref-type="bibr">[9]</xref></th><th>Xu et al <xref rid="b0050" ref-type="bibr">[10]</xref></th><th>Liu et al <xref rid="b0055" ref-type="bibr">[11]</xref></th><th>Wang et al. [12]</th><th>Chen et al [13]</th><th>Chen et al [14]</th></tr></thead><tbody><tr><td>Location</td><td>Wuhan, China</td><td>Wuhan, China</td><td>Wuhan, China</td><td>Zhejiang, China</td><td>Shenzhen, China</td><td>Shenzhen, China</td><td>Wuhan, China</td><td>Wuhan, China</td></tr><tr><td>N. cases</td><td>140 (58 severe)</td><td>41 (13 severe)</td><td>99 (17 severe)</td><td>62 (1 severe)</td><td>12 (6 severe)</td><td>34 children (no severe)</td><td>29 cases (14 severe)</td><td>9 pregnant</td></tr><tr><td>Age</td><td>57 years (median)</td><td>49 years (median)</td><td>56 years (mean)</td><td>41 years (median)</td><td>54 years (mean)</td><td>8 years (median)</td><td>56 years (median)</td><td>30 years (mean)</td></tr><tr><td>Women (%)</td><td>49%</td><td>27%</td><td>32%</td><td>44%</td><td>33%</td><td>59%</td><td>28%</td><td>100%</td></tr><tr><td>Setting</td><td>Hospitalized patients</td><td>Hospitalized patients</td><td>Hospitalized patients</td><td>Hospitalized patients</td><td>Hospitalized patients</td><td>Hospitalized patients</td><td>Hospitalized patients</td><td>Hospitalized patients</td></tr><tr><td>Laboratory data</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Leukocytes</td><td>↑12%; ↓20%</td><td>↑30%; ↓25%</td><td>↑24%; ↓9%</td><td>↑2%; ↓31%</td><td>↑8%</td><td>↑15%</td><td>↑21%; ↓21%</td><td>↑22%</td></tr><tr><td>Neutrophils</td><td>N/R</td><td>N/R</td><td>↑38%</td><td>N/R</td><td>↑17%</td><td>↑15%</td><td>N/R</td><td>N/R</td></tr><tr><td>Lymphocytes</td><td>↓75%</td><td>↓63%</td><td>↓35%</td><td>↑58%; ↓42%</td><td>↓55%</td><td>↓3%</td><td>↓69%</td><td>↓56%</td></tr><tr><td>Eosinophils</td><td>↓53%</td><td>N/R</td><td>N/R</td><td>N/R</td><td>N/R</td><td>N/R</td><td>N/R</td><td>N/R</td></tr><tr><td>Platelets</td><td>N/R</td><td>↓5%</td><td>N/R</td><td>↓5%</td><td>↓8%</td><td>N/R</td><td>↓17%</td><td>N/R</td></tr><tr><td>Hemoglobin</td><td>N/R</td><td>N/R</td><td>↓50%</td><td>N/R</td><td>N/R</td><td>N/R</td><td>↓41%</td><td>N/R</td></tr><tr><td>CRP</td><td>↑91%</td><td>N/R</td><td>↑86%</td><td>N/R</td><td>↑83%</td><td>↑3%</td><td>↑93%</td><td>↑75%</td></tr><tr><td>Procalcitonin</td><td>↑35%</td><td>↑8%</td><td>↑6%</td><td>↑11%</td><td>↑8%</td><td>↑3%</td><td>↑0%</td><td>N/R</td></tr><tr><td>ESR</td><td>N/R</td><td>N/R</td><td>↑85%</td><td>N/R</td><td>N/R</td><td>↑15%</td><td>N/R</td><td>N/R</td></tr><tr><td>Albumin</td><td>N/R</td><td>N/R</td><td>↓98%</td><td>N/R</td><td>↓50%</td><td>N/R</td><td>↓52%</td><td>N/R</td></tr><tr><td>ALT</td><td>N/R</td><td>N/R</td><td>↑28%</td><td>N/R</td><td>↑17%</td><td>N/R</td><td>↑17%</td><td>↑33%</td></tr><tr><td>AST</td><td>N/R</td><td>↑37%</td><td>↑35%</td><td>↑16%</td><td>↑8%</td><td>N/R</td><td>↑24%</td><td>↑33%</td></tr><tr><td>Bilirubin</td><td>N/R</td><td>N/R</td><td>↑18%</td><td>N/R</td><td>↑0%</td><td>N/R</td><td>↑3%</td><td>N/R</td></tr><tr><td>Creatinine</td><td>N/R</td><td>↑10%</td><td>↑3%</td><td>↑5%</td><td>↑17%</td><td>N/R</td><td>↑7%</td><td>N/R</td></tr><tr><td>CK</td><td>↑7%</td><td>↑33%</td><td>↑13%</td><td>N/R</td><td>↑17%</td><td>N/R</td><td>N/R</td><td>N/R</td></tr><tr><td>LDH</td><td>N/R</td><td>↑73%</td><td>↑76%</td><td>↑27%</td><td>↑92%</td><td>↑29%</td><td>↑69%</td><td>N/R</td></tr><tr><td>Myoglobin</td><td>N/R</td><td>N/R</td><td>↑15%</td><td>N/R</td><td>↑17%</td><td>N/R</td><td>N/R</td><td>N/R</td></tr><tr><td>Cardiac troponins</td><td>N/R</td><td>↑12%</td><td>N/R</td><td>N/R</td><td>↑8%</td><td>N/R</td><td>N/R</td><td>N/R</td></tr><tr><td>Ferritin</td><td>N/R</td><td>N/R</td><td>↑63%</td><td>N/R</td><td>N/R</td><td>N/R</td><td>N/R</td><td>N/R</td></tr><tr><td>Glucose</td><td>N/R</td><td>N/R</td><td>↑52%</td><td>N/R</td><td>N/R</td><td>N/R</td><td>N/R</td><td>N/R</td></tr><tr><td>D-dimer</td><td>↑43%</td><td>N/R</td><td>↑36%</td><td>N/R</td><td>N/R</td><td>↑9%</td><td>N/R</td><td>N/R</td></tr></tbody></table><table-wrap-foot><fn><p>ALT, Alanine aminotransferase; AST, Aspartate aminotransferase; CK, Creatine Kinase; CRP, C reactive Protein; ESR, Erythrocyte sedimentation rate; LDH, Lactate dehydrogenase; N/R Not (clearly) reported.</p></fn></table-wrap-foot></table-wrap><table-wrap position="float" id="t0010"><label>Table 2</label><caption><p>Main laboratory abnormalities in patients with unfavorable progression of Coronavirus disease 2019 (COVID-19).</p></caption><table frame="hsides" rules="groups"><tbody><tr><td><list list-type="simple" id="l0005"><list-item id="o0005"><label>•</label><p id="p0005">Increased white blood cell count</p></list-item></list></td></tr><tr><td><list list-type="simple" id="l0010"><list-item id="o0010"><label>•</label><p id="p0010">Increased neutrophil count</p></list-item></list></td></tr><tr><td><list list-type="simple" id="l0015"><list-item id="o0015"><label>•</label><p id="p0015">Decreased lymphocyte count</p></list-item></list></td></tr><tr><td><list list-type="simple" id="l0020"><list-item id="o0020"><label>•</label><p id="p0020">Decreased albumin</p></list-item></list></td></tr><tr><td><list list-type="simple" id="l0025"><list-item id="o0025"><label>•</label><p id="p0025">Increased lactate dehydrogenase (LDH)</p></list-item></list></td></tr><tr><td><list list-type="simple" id="l0030"><list-item id="o0030"><label>•</label><p id="p0030">Increased alanine aminotransferase (AST)</p></list-item></list></td></tr><tr><td><list list-type="simple" id="l0035"><list-item id="o0035"><label>•</label><p id="p0035">Increased aspartate aminotransferase (AST)</p></list-item></list></td></tr><tr><td><list list-type="simple" id="l0040"><list-item id="o0040"><label>•</label><p id="p0040">Increased total bilirubin</p></list-item></list></td></tr><tr><td><list list-type="simple" id="l0045"><list-item id="o0045"><label>•</label><p id="p0045">Increased creatinine</p></list-item></list></td></tr><tr><td><list list-type="simple" id="l0050"><list-item id="o0050"><label>•</label><p id="p0050">Increased cardiac troponin</p></list-item></list></td></tr><tr><td><list list-type="simple" id="l0055"><list-item id="o0055"><label>•</label><p id="p0055">Increased D-dimer</p></list-item></list></td></tr><tr><td><list list-type="simple" id="l0060"><list-item id="o0060"><label>•</label><p id="p0060">Increased prothrombin time (PT)</p></list-item></list></td></tr><tr><td><list list-type="simple" id="l0065"><list-item id="o0065"><label>•</label><p id="p0065">Increased procalcitonin</p></list-item></list></td></tr><tr><td><list list-type="simple" id="l0070"><list-item id="o0070"><label>•</label><p id="p0070">Increased C reactive protein (CRP)</p></list-item></list></td></tr></tbody></table></table-wrap></p><p id="p0080">We carried out an electronic search in Medline (PubMed interface), Scopus and Web of Science, using the keywords “procalcitonin” AND “2019 novel coronavirus” OR “2019-nCoV” OR “COVID-19” without date (i.e., up to March 3, 2020) and language restrictions. The title, abstract and full text of all documents identified according to these search criteria were scrutinized by the authors, and those reporting data in COVID-19 patients with or without severe disease (defined as needing admission to intensive care unit or use of mechanical ventilation), were finally included in our meta-analysis. The reference list of each article was reviewed (forward and backward citation tracking) for identifying other potentially eligible documents. A meta-analysis was then carried out for calculating the individual and pooled odds ratios (OR) with their relative 95% confidence interval (95% CI), using MetaXL software Version 5.3 (EpiGear International Pty Ltd., Sunrise Beach, Australia). Procalcitonin values were entered as dichotomous variable, i.e., below or above the locally defined reference range (typically ≥0.50 ng/mL). Since the heterogeneity (I<sup>2</sup> statistics) did not exceed 50%, a fixed effects model was finally used.</p><p id="p0085">Overall, 27 articles could be originally identified using our search criteria, 24 of which were excluded after title, abstract or full text reading, because they did not report procalcitonin values in patients with or without severe COVID-19. An additional document could be identified from the reference list of one of selected articles. Overall, 4 studies were finally included in our meta-analysis <xref rid="b0025" ref-type="bibr">[5]</xref>, <xref rid="b0030" ref-type="bibr">[6]</xref>, <xref rid="b0035" ref-type="bibr">[7]</xref>, <xref rid="b0040" ref-type="bibr">[8]</xref>. The pooled OR of these studies is summarized in <xref rid="f0005" ref-type="fig">Fig. 1</xref>, which shows that increased procalcitonin values are associated with a nearly 5-fold higher risk of severe SARS-CoV-2 infection (OR, 4.76; 95% CI, 2.74-8.29). The heterogeneity among the different studies was found to be modest (i.e., 34%) <xref rid="b0045" ref-type="bibr">[9]</xref>.<fig id="f0005"><label>Fig. 1</label><caption><p>Odds ratio (OR) and 95% confidence interval (95% CI) of procalcitonin values above the normal reference range for predicting severe coronavirus disease 2019 (COVID-19).</p></caption><graphic xlink:href="gr1_lrg"></graphic></fig></p><p id="p0090">Although the overall number of COVID-19 patients with increased procalcitonin values seems limited, as highlighted in a recent article <xref rid="b0050" ref-type="bibr">[10]</xref>, the results of this concise meta-analysis of the literature would suggest that serial procalcitonin measurement may play a role for predicting evolution towards a more severe form of disease. There is a plausible explanation for this evidence. The production and release into the circulation of procalcitonin from extrathyroidal sources is enormously amplified during bacterial infections, actively sustained by enhanced concentrations of interleukin (IL)-1β, tumor necrosis factor (TNF)-α and IL-6 <xref rid="b0045" ref-type="bibr">[9]</xref>. Nevertheless, the synthesis of this biomarker is inhibited by interferon (INF)-γ, whose concentration increases during viral infections <xref rid="b0045" ref-type="bibr">[9]</xref>. It is hence not surprising that the procalcitonin value would remain within the reference range in several patients with non-complicated SARS-CoV-2 infection, whereby its substantial increase would reflect bacterial coinfection in those developing severe form of disease, thus contributing to complicate the clinical picture, as recently shown in children with viral lower respiratory tract infections <xref rid="b0055" ref-type="bibr">[11]</xref>. 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