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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Cytokine storm intervention in the early stages of COVID-19 pneumonia</title><author><name sortKey="Sun, Xinjuan" sort="Sun, Xinjuan" uniqKey="Sun X" first="Xinjuan" last="Sun">Xinjuan Sun</name><affiliation><nlm:aff id="aff0005">Department of Endocrinology, Air Force Hospital of Eastern Theater Command, Nanjing, Jiangsu, China</nlm:aff></affiliation></author><author><name sortKey="Wang, Tianyuan" sort="Wang, Tianyuan" uniqKey="Wang T" first="Tianyuan" last="Wang">Tianyuan Wang</name><affiliation><nlm:aff id="aff0005">Department of Endocrinology, Air Force Hospital of Eastern Theater Command, Nanjing, Jiangsu, China</nlm:aff></affiliation></author><author><name sortKey="Cai, Dayong" sort="Cai, Dayong" uniqKey="Cai D" first="Dayong" last="Cai">Dayong Cai</name><affiliation><nlm:aff id="aff0010">Department of Nephrology, Air Force Hospital of Eastern Theater Command, Nanjing, Jiangsu, China</nlm:aff></affiliation></author><author><name sortKey="Hu, Zhiwei" sort="Hu, Zhiwei" uniqKey="Hu Z" first="Zhiwei" last="Hu">Zhiwei Hu</name><affiliation><nlm:aff id="aff0005">Department of Endocrinology, Air Force Hospital of Eastern Theater Command, Nanjing, Jiangsu, China</nlm:aff></affiliation><affiliation><nlm:aff id="aff0010">Department of Nephrology, Air Force Hospital of Eastern Theater Command, Nanjing, Jiangsu, China</nlm:aff></affiliation><affiliation><nlm:aff id="aff0015">Department of Hematology, Air Force Hospital of Eastern Theater Command, Nanjing, Jiangsu, China</nlm:aff></affiliation><affiliation><nlm:aff id="aff0020">Translational Medicine Center, Air Force Hospital of Eastern Theater Command, Nanjing, Jiangsu, China</nlm:aff></affiliation><affiliation><nlm:aff id="aff0025">Department of Infectious Disease, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine. Nanjing, Jiangsu, China</nlm:aff></affiliation><affiliation><nlm:aff id="aff0030">Department of Pathology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China</nlm:aff></affiliation><affiliation><nlm:aff id="aff0035">Department of Respiratory Medicine, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China</nlm:aff></affiliation></author><author><name sortKey="Chen, Jin N" sort="Chen, Jin N" uniqKey="Chen J" first="Jin N" last="Chen">Jin N Chen</name><affiliation><nlm:aff id="aff0005">Department of Endocrinology, Air Force Hospital of Eastern Theater Command, Nanjing, Jiangsu, China</nlm:aff></affiliation><affiliation><nlm:aff id="aff0010">Department of Nephrology, Air Force Hospital of Eastern Theater Command, Nanjing, Jiangsu, China</nlm:aff></affiliation><affiliation><nlm:aff id="aff0015">Department of Hematology, Air Force Hospital of Eastern Theater Command, Nanjing, Jiangsu, China</nlm:aff></affiliation><affiliation><nlm:aff id="aff0020">Translational Medicine Center, Air Force Hospital of Eastern Theater Command, Nanjing, Jiangsu, China</nlm:aff></affiliation><affiliation><nlm:aff id="aff0025">Department of Infectious Disease, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine. Nanjing, Jiangsu, China</nlm:aff></affiliation><affiliation><nlm:aff id="aff0030">Department of Pathology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China</nlm:aff></affiliation><affiliation><nlm:aff id="aff0035">Department of Respiratory Medicine, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China</nlm:aff></affiliation></author><author><name sortKey="Liao, Hui" sort="Liao, Hui" uniqKey="Liao H" first="Hui" last="Liao">Hui Liao</name><affiliation><nlm:aff id="aff0015">Department of Hematology, Air Force Hospital of Eastern Theater Command, Nanjing, Jiangsu, China</nlm:aff></affiliation></author><author><name sortKey="Zhi, Liming" sort="Zhi, Liming" uniqKey="Zhi L" first="Liming" last="Zhi">Liming Zhi</name><affiliation><nlm:aff id="aff0020">Translational Medicine Center, Air Force Hospital of Eastern Theater Command, Nanjing, Jiangsu, China</nlm:aff></affiliation></author><author><name sortKey="Wei, Hongxia" sort="Wei, Hongxia" uniqKey="Wei H" first="Hongxia" last="Wei">Hongxia Wei</name><affiliation><nlm:aff id="aff0025">Department of Infectious Disease, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine. Nanjing, Jiangsu, China</nlm:aff></affiliation></author><author><name sortKey="Zhang, Zhihong" sort="Zhang, Zhihong" uniqKey="Zhang Z" first="Zhihong" last="Zhang">Zhihong Zhang</name><affiliation><nlm:aff id="aff0030">Department of Pathology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China</nlm:aff></affiliation></author><author><name sortKey="Qiu, Yuying" sort="Qiu, Yuying" uniqKey="Qiu Y" first="Yuying" last="Qiu">Yuying Qiu</name><affiliation><nlm:aff id="aff0035">Department of Respiratory Medicine, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China</nlm:aff></affiliation></author><author><name sortKey="Wang, Jing" sort="Wang, Jing" uniqKey="Wang J" first="Jing" last="Wang">Jing Wang</name><affiliation><nlm:aff id="aff0020">Translational Medicine Center, Air Force Hospital of Eastern Theater Command, Nanjing, Jiangsu, China</nlm:aff></affiliation></author><author><name sortKey="Wang, Aiping" sort="Wang, Aiping" uniqKey="Wang A" first="Aiping" last="Wang">Aiping Wang</name><affiliation><nlm:aff id="aff0005">Department of Endocrinology, Air Force Hospital of Eastern Theater Command, Nanjing, Jiangsu, China</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmc">7182527</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7182527</idno><idno type="RBID">PMC:7182527</idno><idno type="doi">10.1016/j.cytogfr.2020.04.002</idno><idno type="pmid">NONE</idno><date when="2020">2020</date><idno type="wicri:Area/Pmc/Corpus">000897</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000897</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Cytokine storm intervention in the early stages of COVID-19 pneumonia</title><author><name sortKey="Sun, Xinjuan" sort="Sun, Xinjuan" uniqKey="Sun X" first="Xinjuan" last="Sun">Xinjuan Sun</name><affiliation><nlm:aff id="aff0005">Department of Endocrinology, Air Force Hospital of Eastern Theater Command, Nanjing, Jiangsu, China</nlm:aff></affiliation></author><author><name sortKey="Wang, Tianyuan" sort="Wang, Tianyuan" uniqKey="Wang T" first="Tianyuan" last="Wang">Tianyuan Wang</name><affiliation><nlm:aff id="aff0005">Department of Endocrinology, Air Force Hospital of Eastern Theater Command, Nanjing, Jiangsu, China</nlm:aff></affiliation></author><author><name sortKey="Cai, Dayong" sort="Cai, Dayong" uniqKey="Cai D" first="Dayong" last="Cai">Dayong Cai</name><affiliation><nlm:aff id="aff0010">Department of Nephrology, Air Force Hospital of Eastern Theater Command, Nanjing, Jiangsu, China</nlm:aff></affiliation></author><author><name sortKey="Hu, Zhiwei" sort="Hu, Zhiwei" uniqKey="Hu Z" first="Zhiwei" last="Hu">Zhiwei Hu</name><affiliation><nlm:aff id="aff0005">Department of Endocrinology, Air Force Hospital of Eastern Theater Command, Nanjing, Jiangsu, China</nlm:aff></affiliation><affiliation><nlm:aff id="aff0010">Department of Nephrology, Air Force Hospital of Eastern Theater Command, Nanjing, Jiangsu, China</nlm:aff></affiliation><affiliation><nlm:aff id="aff0015">Department of Hematology, Air Force Hospital of Eastern Theater Command, Nanjing, Jiangsu, China</nlm:aff></affiliation><affiliation><nlm:aff id="aff0020">Translational Medicine Center, Air Force Hospital of Eastern Theater Command, Nanjing, Jiangsu, China</nlm:aff></affiliation><affiliation><nlm:aff id="aff0025">Department of Infectious Disease, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine. Nanjing, Jiangsu, China</nlm:aff></affiliation><affiliation><nlm:aff id="aff0030">Department of Pathology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China</nlm:aff></affiliation><affiliation><nlm:aff id="aff0035">Department of Respiratory Medicine, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China</nlm:aff></affiliation></author><author><name sortKey="Chen, Jin N" sort="Chen, Jin N" uniqKey="Chen J" first="Jin N" last="Chen">Jin N Chen</name><affiliation><nlm:aff id="aff0005">Department of Endocrinology, Air Force Hospital of Eastern Theater Command, Nanjing, Jiangsu, China</nlm:aff></affiliation><affiliation><nlm:aff id="aff0010">Department of Nephrology, Air Force Hospital of Eastern Theater Command, Nanjing, Jiangsu, China</nlm:aff></affiliation><affiliation><nlm:aff id="aff0015">Department of Hematology, Air Force Hospital of Eastern Theater Command, Nanjing, Jiangsu, China</nlm:aff></affiliation><affiliation><nlm:aff id="aff0020">Translational Medicine Center, Air Force Hospital of Eastern Theater Command, Nanjing, Jiangsu, China</nlm:aff></affiliation><affiliation><nlm:aff id="aff0025">Department of Infectious Disease, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine. Nanjing, Jiangsu, China</nlm:aff></affiliation><affiliation><nlm:aff id="aff0030">Department of Pathology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China</nlm:aff></affiliation><affiliation><nlm:aff id="aff0035">Department of Respiratory Medicine, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China</nlm:aff></affiliation></author><author><name sortKey="Liao, Hui" sort="Liao, Hui" uniqKey="Liao H" first="Hui" last="Liao">Hui Liao</name><affiliation><nlm:aff id="aff0015">Department of Hematology, Air Force Hospital of Eastern Theater Command, Nanjing, Jiangsu, China</nlm:aff></affiliation></author><author><name sortKey="Zhi, Liming" sort="Zhi, Liming" uniqKey="Zhi L" first="Liming" last="Zhi">Liming Zhi</name><affiliation><nlm:aff id="aff0020">Translational Medicine Center, Air Force Hospital of Eastern Theater Command, Nanjing, Jiangsu, China</nlm:aff></affiliation></author><author><name sortKey="Wei, Hongxia" sort="Wei, Hongxia" uniqKey="Wei H" first="Hongxia" last="Wei">Hongxia Wei</name><affiliation><nlm:aff id="aff0025">Department of Infectious Disease, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine. Nanjing, Jiangsu, China</nlm:aff></affiliation></author><author><name sortKey="Zhang, Zhihong" sort="Zhang, Zhihong" uniqKey="Zhang Z" first="Zhihong" last="Zhang">Zhihong Zhang</name><affiliation><nlm:aff id="aff0030">Department of Pathology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China</nlm:aff></affiliation></author><author><name sortKey="Qiu, Yuying" sort="Qiu, Yuying" uniqKey="Qiu Y" first="Yuying" last="Qiu">Yuying Qiu</name><affiliation><nlm:aff id="aff0035">Department of Respiratory Medicine, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China</nlm:aff></affiliation></author><author><name sortKey="Wang, Jing" sort="Wang, Jing" uniqKey="Wang J" first="Jing" last="Wang">Jing Wang</name><affiliation><nlm:aff id="aff0020">Translational Medicine Center, Air Force Hospital of Eastern Theater Command, Nanjing, Jiangsu, China</nlm:aff></affiliation></author><author><name sortKey="Wang, Aiping" sort="Wang, Aiping" uniqKey="Wang A" first="Aiping" last="Wang">Aiping Wang</name><affiliation><nlm:aff id="aff0005">Department of Endocrinology, Air Force Hospital of Eastern Theater Command, Nanjing, Jiangsu, China</nlm:aff></affiliation></author></analytic><series><title level="j">Cytokine & Growth Factor Reviews</title><idno type="ISSN">1359-6101</idno><idno type="eISSN">1879-0305</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="lis0005"><list-item id="lsti0005"><label>•</label><p id="par0005">COVID-19 infection can lead to the development of systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome MODS within a few days of disease onset.</p></list-item><list-item id="lsti0010"><label>•</label><p id="par0010">A powerful cytokine storm accompanies COVID-19 pneumonia.</p></list-item><list-item id="lsti0015"><label>•</label><p id="par0015">The capacity to accurately predict and intervene in the cytokine storm during COVID-19 pneumonia, as well as the ability to design effective specific strategies to block excessive inflammation, is critical for patient survival.</p></list-item></list></p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Wu, J T" uniqKey="Wu J">J.T. Wu</name></author><author><name sortKey="Leung, K" uniqKey="Leung K">K. Leung</name></author><author><name sortKey="Leung, G M" uniqKey="Leung G">G.M. Leung</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="Jin, Y H" uniqKey="Jin Y">Y.H. Jin</name></author><author><name sortKey="Cai, L" uniqKey="Cai L">L. Cai</name></author><author><name sortKey="Cheng, Z S" uniqKey="Cheng Z">Z.S. Cheng</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shimabukuro Vornhagen, A" uniqKey="Shimabukuro Vornhagen A">A. Shimabukuro-Vornhagen</name></author><author><name sortKey="Godel, P" uniqKey="Godel P">P. Godel</name></author><author><name sortKey="Subklewe, M" uniqKey="Subklewe M">M. Subklewe</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tanaka, T" uniqKey="Tanaka T">T. Tanaka</name></author><author><name sortKey="Narazaki, M" uniqKey="Narazaki M">M. Narazaki</name></author><author><name sortKey="Kishimoto, T" uniqKey="Kishimoto T">T. Kishimoto</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hunter, C A" uniqKey="Hunter C">C.A. Hunter</name></author><author><name sortKey="Jones, S A" uniqKey="Jones S">S.A. Jones</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pathan, N" uniqKey="Pathan N">N. Pathan</name></author><author><name sortKey="Hemingway, C A" uniqKey="Hemingway C">C.A. Hemingway</name></author><author><name sortKey="Alizadeh, A A" uniqKey="Alizadeh A">A.A. Alizadeh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hay, K A" uniqKey="Hay K">K.A. Hay</name></author><author><name sortKey="Hanafi, L A" uniqKey="Hanafi L">L.A. Hanafi</name></author><author><name sortKey="Li, D" uniqKey="Li D">D. Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, D" uniqKey="Wang D">D. Wang</name></author><author><name sortKey="Hu, B" uniqKey="Hu B">B. Hu</name></author><author><name sortKey="Hu, C" uniqKey="Hu C">C. Hu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Osterholm, M T" uniqKey="Osterholm M">M.T. Osterholm</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Teijaro, J R" uniqKey="Teijaro J">J.R. Teijaro</name></author><author><name sortKey="Walsh, K B" uniqKey="Walsh K">K.B. Walsh</name></author><author><name sortKey="Rice, S" uniqKey="Rice S">S. Rice</name></author><author><name sortKey="Rosen, H" uniqKey="Rosen H">H. Rosen</name></author><author><name sortKey="Oldstone, M B" uniqKey="Oldstone M">M.B. Oldstone</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Reghunathan, R" uniqKey="Reghunathan R">R. Reghunathan</name></author><author><name sortKey="Jayapal, M" uniqKey="Jayapal M">M. Jayapal</name></author><author><name sortKey="Hsu, L Y" uniqKey="Hsu L">L.Y. Hsu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chien, J Y" uniqKey="Chien J">J.Y. Chien</name></author><author><name sortKey="Hsueh, P R" uniqKey="Hsueh P">P.R. Hsueh</name></author><author><name sortKey="Cheng, W C" uniqKey="Cheng W">W.C. Cheng</name></author><author><name sortKey="Yu, C J" uniqKey="Yu C">C.J. Yu</name></author><author><name sortKey="Yang, P C" uniqKey="Yang P">P.C. Yang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Min, C K" uniqKey="Min C">C.K. Min</name></author><author><name sortKey="Cheon, S" uniqKey="Cheon S">S. Cheon</name></author><author><name sortKey="Ha, N Y" uniqKey="Ha N">N.Y. Ha</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tsang, K" uniqKey="Tsang K">K. Tsang</name></author><author><name sortKey="Zhong, N S" uniqKey="Zhong N">N.S. Zhong</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Xu, Z" uniqKey="Xu Z">Z. Xu</name></author><author><name sortKey="Shi, L" uniqKey="Shi L">L. Shi</name></author><author><name sortKey="Wang, Y" uniqKey="Wang Y">Y. Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tian, S H" uniqKey="Tian S">S.H. Tian</name></author><author><name sortKey="Hu, W" uniqKey="Hu W">W. Hu</name></author><author><name sortKey="Niu, L" uniqKey="Niu L">L. Niu</name></author><author><name sortKey="Liu, H" uniqKey="Liu H">H. Liu</name></author><author><name sortKey="Xu, H" uniqKey="Xu H">H. Xu</name></author><author><name sortKey="Xiao, S" uniqKey="Xiao S">S. Xiao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bajema, K L" uniqKey="Bajema K">K.L. Bajema</name></author><author><name sortKey="Oster, A M" uniqKey="Oster A">A.M. Oster</name></author><author><name sortKey="Mcgovern, O L" uniqKey="Mcgovern O">O.L. McGovern</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Menachery, V D" uniqKey="Menachery V">V.D. Menachery</name></author><author><name sortKey="Schafer, A" uniqKey="Schafer A">A. Schafer</name></author><author><name sortKey="Burnum Johnson, K E" uniqKey="Burnum Johnson K">K.E. Burnum-Johnson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ho, J C" uniqKey="Ho J">J.C. Ho</name></author><author><name sortKey="Ooi, G C" uniqKey="Ooi G">G.C. Ooi</name></author><author><name sortKey="Mok, T Y" uniqKey="Mok T">T.Y. Mok</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yam, L Y" uniqKey="Yam L">L.Y. Yam</name></author><author><name sortKey="Lau, A C" uniqKey="Lau A">A.C. Lau</name></author><author><name sortKey="Lai, F Y" uniqKey="Lai F">F.Y. Lai</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Stockman, L J" uniqKey="Stockman L">L.J. Stockman</name></author><author><name sortKey="Bellamy, R" uniqKey="Bellamy R">R. Bellamy</name></author><author><name sortKey="Garner, P" uniqKey="Garner P">P. Garner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, D" uniqKey="Wang D">D. Wang</name></author><author><name sortKey="Hu, B" uniqKey="Hu B">B. Hu</name></author><author><name sortKey="Hu, C" uniqKey="Hu C">C. Hu</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="Xu, Z" uniqKey="Xu Z">Z. Xu</name></author><author><name sortKey="Shi, L" uniqKey="Shi L">L. Shi</name></author><author><name sortKey="Wang, Y" uniqKey="Wang Y">Y. Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Omrani, A S" uniqKey="Omrani A">A.S. Omrani</name></author><author><name sortKey="Saad, M M" uniqKey="Saad M">M.M. Saad</name></author><author><name sortKey="Baig, K" uniqKey="Baig K">K. Baig</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Channappanavar, R" uniqKey="Channappanavar R">R. Channappanavar</name></author><author><name sortKey="Fehr, A R" uniqKey="Fehr A">A.R. Fehr</name></author><author><name sortKey="Vijay, R" uniqKey="Vijay R">R. Vijay</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Imai, Y" uniqKey="Imai Y">Y. Imai</name></author><author><name sortKey="Kuba, K" uniqKey="Kuba K">K. Kuba</name></author><author><name sortKey="Neely, G G" uniqKey="Neely G">G.G. Neely</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shirey, K A" uniqKey="Shirey K">K.A. Shirey</name></author><author><name sortKey="Lai, W" uniqKey="Lai W">W. Lai</name></author><author><name sortKey="Scott, A J" uniqKey="Scott A">A.J. Scott</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Teijaro, J R" uniqKey="Teijaro J">J.R. Teijaro</name></author><author><name sortKey="Walsh, K B" uniqKey="Walsh K">K.B. Walsh</name></author><author><name sortKey="Cahalan, S" uniqKey="Cahalan S">S. Cahalan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mcqueen, J" uniqKey="Mcqueen J">J. McQueen</name></author><author><name sortKey="Jardine, A" uniqKey="Jardine A">A. Jardine</name></author><author><name sortKey="Kingdom, J" uniqKey="Kingdom J">J. Kingdom</name></author><author><name sortKey="Templeton, A" uniqKey="Templeton A">A. Templeton</name></author><author><name sortKey="Whittle, M J" uniqKey="Whittle M">M.J. Whittle</name></author><author><name sortKey="Connell, J M" uniqKey="Connell J">J.M. Connell</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Leuschner, F" uniqKey="Leuschner F">F. Leuschner</name></author><author><name sortKey="Dutta, P" uniqKey="Dutta P">P. Dutta</name></author><author><name sortKey="Gorbatov, R" uniqKey="Gorbatov R">R. Gorbatov</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Darwish, I" uniqKey="Darwish I">I. Darwish</name></author><author><name sortKey="Mubareka, S" uniqKey="Mubareka S">S. Mubareka</name></author><author><name sortKey="Liles, W C" uniqKey="Liles W">W.C. Liles</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mcdermott, J E" uniqKey="Mcdermott J">J.E. McDermott</name></author><author><name sortKey="Mitchell, H D" uniqKey="Mitchell H">H.D. Mitchell</name></author><author><name sortKey="Gralinski, L E" uniqKey="Gralinski L">L.E. Gralinski</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Silvester, W" uniqKey="Silvester W">W. Silvester</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="review-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Cytokine Growth Factor Rev</journal-id><journal-id journal-id-type="iso-abbrev">Cytokine Growth Factor Rev</journal-id><journal-title-group><journal-title>Cytokine & Growth Factor Reviews</journal-title></journal-title-group><issn pub-type="ppub">1359-6101</issn><issn pub-type="epub">1879-0305</issn><publisher><publisher-name>The Authors. Published by Elsevier Ltd.</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmc">7182527</article-id><article-id pub-id-type="publisher-id">S1359-6101(20)30048-4</article-id><article-id pub-id-type="doi">10.1016/j.cytogfr.2020.04.002</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Cytokine storm intervention in the early stages of COVID-19 pneumonia</article-title></title-group><contrib-group><contrib contrib-type="author" id="aut0005"><name><surname>Sun</surname><given-names>Xinjuan</given-names></name><xref rid="aff0005" ref-type="aff">a</xref><xref rid="fn0005" ref-type="fn">1</xref></contrib><contrib contrib-type="author" id="aut0010"><name><surname>Wang</surname><given-names>Tianyuan</given-names></name><xref rid="aff0005" ref-type="aff">a</xref><xref rid="fn0005" ref-type="fn">1</xref></contrib><contrib contrib-type="author" id="aut0015"><name><surname>Cai</surname><given-names>Dayong</given-names></name><xref rid="aff0010" ref-type="aff">b</xref></contrib><contrib contrib-type="author" id="aut0020"><name><surname>Hu</surname><given-names>Zhiwei</given-names></name><xref rid="aff0005" ref-type="aff">a</xref><xref rid="aff0010" ref-type="aff">b</xref><xref rid="aff0015" ref-type="aff">c</xref><xref rid="aff0020" ref-type="aff">d</xref><xref rid="aff0025" ref-type="aff">e</xref><xref rid="aff0030" ref-type="aff">f</xref><xref rid="aff0035" ref-type="aff">g</xref></contrib><contrib contrib-type="author" id="aut0025"><name><surname>Chen</surname><given-names>Jin’an</given-names></name><xref rid="aff0005" ref-type="aff">a</xref><xref rid="aff0010" ref-type="aff">b</xref><xref rid="aff0015" ref-type="aff">c</xref><xref rid="aff0020" ref-type="aff">d</xref><xref rid="aff0025" ref-type="aff">e</xref><xref rid="aff0030" ref-type="aff">f</xref><xref rid="aff0035" ref-type="aff">g</xref></contrib><contrib contrib-type="author" id="aut0030"><name><surname>Liao</surname><given-names>Hui</given-names></name><xref rid="aff0015" ref-type="aff">c</xref></contrib><contrib contrib-type="author" id="aut0035"><name><surname>Zhi</surname><given-names>Liming</given-names></name><xref rid="aff0020" ref-type="aff">d</xref></contrib><contrib contrib-type="author" id="aut0040"><name><surname>Wei</surname><given-names>Hongxia</given-names></name><xref rid="aff0025" ref-type="aff">e</xref></contrib><contrib contrib-type="author" id="aut0045"><name><surname>Zhang</surname><given-names>Zhihong</given-names></name><xref rid="aff0030" ref-type="aff">f</xref></contrib><contrib contrib-type="author" id="aut0050"><name><surname>Qiu</surname><given-names>Yuying</given-names></name><xref rid="aff0035" ref-type="aff">g</xref></contrib><contrib contrib-type="author" id="aut0055"><name><surname>Wang</surname><given-names>Jing</given-names></name><email>wj6373@hotmail.com</email><xref rid="aff0020" ref-type="aff">d</xref><xref rid="cor0005" ref-type="corresp">⁎</xref></contrib><contrib contrib-type="author" id="aut0060"><name><surname>Wang</surname><given-names>Aiping</given-names></name><email>wap454hospital@163.com</email><xref rid="aff0005" ref-type="aff">a</xref><xref rid="cor0005" ref-type="corresp">⁎</xref></contrib><aff id="aff0005"><label>a</label>Department of Endocrinology, Air Force Hospital of Eastern Theater Command, Nanjing, Jiangsu, China</aff><aff id="aff0010"><label>b</label>Department of Nephrology, Air Force Hospital of Eastern Theater Command, Nanjing, Jiangsu, China</aff><aff id="aff0015"><label>c</label>Department of Hematology, Air Force Hospital of Eastern Theater Command, Nanjing, Jiangsu, China</aff><aff id="aff0020"><label>d</label>Translational Medicine Center, Air Force Hospital of Eastern Theater Command, Nanjing, Jiangsu, China</aff><aff id="aff0025"><label>e</label>Department of Infectious Disease, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine. Nanjing, Jiangsu, China</aff><aff id="aff0030"><label>f</label>Department of Pathology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China</aff><aff id="aff0035"><label>g</label>Department of Respiratory Medicine, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China</aff></contrib-group><author-notes><corresp id="cor0005"><label>⁎</label>Corresponding authors. <email>wj6373@hotmail.com</email><email>wap454hospital@163.com</email></corresp><fn id="fn0005"><label>1</label><p id="npar0005">These authors contributed equally to this work.</p></fn></author-notes><pub-date pub-type="pmc-release"><day>25</day><month>4</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>25</day><month>4</month><year>2020</year></pub-date><history><date date-type="received"><day>12</day><month>3</month><year>2020</year></date><date date-type="rev-recd"><day>22</day><month>3</month><year>2020</year></date><date date-type="accepted"><day>9</day><month>4</month><year>2020</year></date></history><permissions><copyright-statement>© 2020 The Authors. Published by Elsevier Ltd.</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="abs0005"><title>Highlights</title><p><list list-type="simple" id="lis0005"><list-item id="lsti0005"><label>•</label><p id="par0005">COVID-19 infection can lead to the development of systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome MODS within a few days of disease onset.</p></list-item><list-item id="lsti0010"><label>•</label><p id="par0010">A powerful cytokine storm accompanies COVID-19 pneumonia.</p></list-item><list-item id="lsti0015"><label>•</label><p id="par0015">The capacity to accurately predict and intervene in the cytokine storm during COVID-19 pneumonia, as well as the ability to design effective specific strategies to block excessive inflammation, is critical for patient survival.</p></list-item></list></p></abstract><abstract id="abs0010"><p>Clinical intervention in patients with corona virus disease 2019 (COVID-19) has demonstrated a strong upregulation of cytokine production in patients who are critically ill with SARS-CoV2-induced pneumonia. In a retrospective study of 41 patients with COVID-19, most patients with SARS-CoV-2 infection developed mild symptoms, whereas some patients later developed aggravated disease symptoms, and eventually passed away because of multiple organ dysfunction syndrome (MODS), as a consequence of a severe cytokine storm. Guidelines for the diagnosis and treatment of SARS-CoV-2 infected pneumonia were first published January 30<sup>th</sup>, 2020; these guidelines recommended for the first time that cytokine monitoring should be applied in severely ill patients to reduce pneumonia related mortality. The cytokine storm observed in COVID-19 illness is also an important component of mortality in other viral diseases, including SARS, MERS and influenza. In view of the severe morbidity and mortality of COVID-19 pneumonia, we review the current understanding of treatment of human coronavirus infections from the perspective of a dysregulated cytokine and immune response.</p></abstract></article-meta></front><body><p id="par0020">The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), initially identified in Wuhan China in December 2019, has led to a global pandemic that has not been witnessed for more than a century. At the time of writing (April 9, 2020), the current estimate of global disease burden (Johns Hopkins University - <ext-link ext-link-type="uri" xlink:href="https://coronavirus.jhu.edu/map.html" id="intr0005">https://coronavirus.jhu.edu/map.html</ext-link>) is over 1.5 million infections and 85,000 deaths worldwide. Social distancing in cities and countries around the world remains the only means available to limit the impact of virus transmission. At the same time, an unprecedented response from the world’s biomedical research community seeks to identify treatments for COVID-19 that include antiviral drug and vaccine development.</p><p id="par0025">Current clinical observations indicate that SARS-CoV2 infection can range from an inapparent non-symptomatic infection, to a respiratory illness presenting with spiking fever and dry cough, accompanied by a high rate of human-human transmission. One of the most serious complications of Corona virus disease (COVID-2) is the development of an atypical upper respiratory tract pneumonia that poses a major challenge to clinicians in terms of disease management. An abnormal and uncontrolled production of cytokines has been observed in critically ill patients with COVID-19 pneumonia [<xref rid="bib0005" ref-type="bibr">1</xref>] and the ensuing uncontrolled cytokine storm in COVID-19 patients is centrally involved in the exacerbation of symptoms and disease development, and represents a major factor contributing to COVID-19 mortality. In this sense, COVID-19 disease shares similarities with other viral diseases such as SARS, MERS and influenza, where the development of a cytokine storm is a warning sign of disease escalation.</p><p id="par0030">In support of the above observations, a retrospective study of 41 patients with COVID-19 [<xref rid="bib0010" ref-type="bibr">2</xref>] showed that most SARS-CoV-2 infected patients present clinically with mild symptoms, while a minority of patients progressively declined from the infection and eventually died of acute respiratory distress syndrome (ARDS) and multiple organ dysfunction syndrome (MOD). Guidelines for the diagnosis and treatment of SARS-CoV-2 infected pneumonia were first published on January 30<sup>th</sup> 2020, and recommended for the first time that cytokine monitoring be applied to improve the curative rate and reduce mortality [<xref rid="bib0015" ref-type="bibr">3</xref>]. In view of the severe morbidity and mortality of COVID-19 pneumonia, here we review the current understanding of treatment of human coronavirus infections from the perspective of a dysregulated immune response.</p><sec id="sec0005"><label>1</label><title>The role of cytokine storm in the pathogenesis and progression of COVID-19 pneumonia</title><p id="par0035">The emerging and re-emerging viruses (Ebola, Zika, Chikungunya, H1N1, dengue, SARS, MERS) have led to numerous global public health crises in recent years and continue to threaten public health and security. Unfortunately, these viruses are often difficult to control due to the lack of approved antiviral drugs and vaccines. In addition to SARS-CoV2, two other novel coronaviruses have emerged as global health threats since 2002, namely severe acute respiratory syndrome coronavirus (SARS-CoV in 2002) that was transmitted to 37 countries, and the Middle East respiratory syndrome coronavirus (MERS-CoV in 2012) that was transmitted to 27 countries. Severe pneumonia caused by pathogenic human coronaviruses (HCoV) are often associated with induced hypercytokinemia, also termed cytokine storm, in immunocompetent individuals; uncontrolled overproduction of inflammatory cytokines contributes to acute lung injury and acute respiratory distress syndrome (ARDS).</p><p id="par0040">The secretion of multiple cytokines, also termed Cytokine Release Syndrome (CRS), is closely related to development of clinical symptoms; for example, IFN-γ can cause fever, chills, headaches, dizziness, and fatigue; TNF-α can cause flu-like symptoms similar to IFN-γ, with fever, general malaise, and fatigue, but can also cause vascular leakage, cardiomyopathy, lung injury, and acute-phase protein synthesis [<xref rid="bib0020" ref-type="bibr">4</xref>]. IL-6, which is an important target in CRS induced by adoptive cell therapy, can lead to vascular leakage, activation of complement and the coagulation cascade, leading to the characteristic symptoms of severe CRS, such as diffuse intravascular coagulation (DIC) [<xref rid="bib0025" ref-type="bibr">5</xref>,<xref rid="bib0030" ref-type="bibr">6</xref>]. It is noteworthy that IL-6 is likely to cause cardiomyopathy by promoting myocardial dysfunction, which is often observed in patients with CRS [<xref rid="bib0035" ref-type="bibr">7</xref>]. In addition, activation of endothelial cells may also be one of the hallmarks of severe CRS. Endothelial dysfunction can lead to capillary leakage, hypotension, and coagulopathy [<xref rid="bib0040" ref-type="bibr">8</xref>] (<xref rid="fig0005" ref-type="fig">Fig. 1</xref>). Taken together, these studies argue that the virus-induced immunopathological events play a crucial role in the fatal pneumonia observed after HCoV infections [<xref rid="bib0045" ref-type="bibr">9</xref>].<fig id="fig0005"><label>Fig. 1</label><caption><p>Schematic representation of clinical features versus pathogenic inflammatory cytokine response in SARS-CoV-2 infections.</p></caption><alt-text id="at0005">Fig. 1</alt-text><graphic xlink:href="gr1_lrg"></graphic></fig></p><p id="par0045">The development of a cytokine storm is a potentially fatal immune condition characterized by rapid proliferation and hyperactivation of T cells, macrophages, natural killer cells and the overproduction of more than 150 inflammatory cytokines and chemical mediators released by immune or nonimmune cells [<xref rid="bib0050" ref-type="bibr">10</xref>,<xref rid="bib0055" ref-type="bibr">11</xref>]. In viral infections, the aberrant release of pro-inflammatory factors leads to lung epithelial and endothelial cell apoptosis which damages the lung microvascular and alveolar epithelial cell barrier, leading to vascular leakage, alveolar edema and hypoxia. The uncontrolled production of pro-inflammatory factors, containing IL-6, IL-8, IL-1β, and GM-CSF, and chemokines such as CCL2, CCL-5, IP-10, and CCL3, together with reactive oxygen species cause ARDS leading to pulmonary fibrosis and death [<xref rid="bib0060" ref-type="bibr">12</xref>].</p><p id="par0050">In SARS-CoV infected patients, high levels of serum pro-inflammatory cytokines (IFN-γ, IL-1, IL-6, IL-12, and TGFβ) and chemokines (CCL2, CXCL10, CXCL9, and IL-8) were detected in cases of severe disease compared to patients with uncomplicated SARS [<xref rid="bib0065" ref-type="bibr">13</xref>]. In MERS infection, high levels of serum pro-inflammatory cytokines (IL-6 and IFN-α) and chemokines (IL-8, CXCL- 10, and CCL5) were likewise observed in severe disease, compared to mild or moderate disease [<xref rid="bib0070" ref-type="bibr">14</xref>]. In contrast to SARS and MERS, doctors in Wuhan Central South Hospital found that the levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1a and TNF α were significantly elevated in the blood of severely ill patients, compared to patients with mild illness [<xref rid="bib0010" ref-type="bibr">2</xref>]. The level of IL-6 in the blood of the severe group was 76 % higher than that of the mild group (30 %) [<xref rid="bib0075" ref-type="bibr">15</xref>]. Furthermore, histological examination and biopsy samples obtained from a patient who died from severe SARS-CoV-2 infection showed an increased concentration of highly proinflammatory CCR4+CCR6+ Th17+ CD4 T cells, suggesting that T cell hyperactivation contributesdin part to the severe immune injury in this patient [<xref rid="bib0080" ref-type="bibr">16</xref>]. Pulmonary examination in other patients with early phase SARS-COV-2 pneumonia also revealed patchy inflammatory cell infiltration; however, the pathological results in early stage of SARS-COV2 pneumonia require further confirmation [<xref rid="bib0085" ref-type="bibr">17</xref>]. In short, aberrant release of multiple cytokines appears to trigger a cytokine storm that produces immunopathogenic damage to tissues and organs, even while the immune response seeks to suppress and eradicate the virus (<xref rid="fig0005" ref-type="fig">Fig. 1</xref>).</p></sec><sec id="sec0010"><label>2</label><title>Treatment of the cytokine storm in COVID-19 pneumonia</title><sec id="sec0015"><label>2.1</label><title>Current management strategies for COVID-19</title><p id="par0055">In view of the above observations, therapeutic strategies to treat the cytokine storm in the pathogenesis of severe COVID-19 pneumonia deserve special attention. In accordance with current WHO guidance [<xref rid="bib0090" ref-type="bibr">18</xref>], supportive therapy remains the most important management strategy for this pneumonia, including supplemental oxygen therapy, conservative fluid management and empiric antimicrobial application in the time of need. It is noteworthy that the use of glucocorticoids remains controversial. Current WHO guidance recommends that corticosteroids should not be used in SARS-CoV2-induced lung injury or shock, except in the setting of a clinical trial. However, in clinical settings, front-line physicians in China tend to use corticosteroids prudently at a low to moderate dosage in patients with SARS-CoV2 infection [<xref rid="bib0095" ref-type="bibr">19</xref>].</p><p id="par0060">In the period of SARS epidemic (2002–2003), corticosteroids were generally used by clinicians for immunomodulatory treatment, and according to clinical feedback, could bring early beneficial changes including a decline in fever, resolution of radiographic lung infiltrates, and the improvement of oxygenation [<xref rid="bib0100" ref-type="bibr">20</xref>,<xref rid="bib0105" ref-type="bibr">21</xref>]. However, further studies indicated opposite clinical outcomes and a systematic review in SARS, MERS and influenza infections indicated no survival benefit and possible harm (avascular necrosis, psychosis, diabetes, delayed viral clearance and secondary infections) with corticosteroids [<xref rid="bib0110" ref-type="bibr">22</xref>]. In our opinion, the use of corticosteroids is not recommended for patients with HCoV infections, although corticosteroids may be used prudently in critically ill patients.</p></sec><sec id="sec0020"><label>2.2</label><title>Immunotherapeutic strategies in COVID-19 pneumonia</title><p id="par0065">In the treatment of patients with SARS-CoV-2 infection, clinicians should pay close attention to the impact immune inflammatory factor release, and several effective cytokine storm blockers and therapeutic methods have been reported. In the clinical process of COVID-19 pneumonia, there is window period between the diagnosis and the occurrence of MODS (about 5–7 days). After this window, the majority of patients tend to improve (∼80 %), whereas ∼20 % of the patients progress to severe pneumonia, with ∼ 2 % mortality [<xref rid="bib0115" ref-type="bibr">23</xref>,<xref rid="bib0120" ref-type="bibr">24</xref>,<xref rid="bib0010" ref-type="bibr">2</xref>]. To improve the prognosis, we suggest that patients with COVID-19 pneumonia be given immunotherapy treatment at the time of diagnosis, in order to block the possibility of a subsequent cytokine storm. The early use of immunological intervention in the evaluation of patients with MODS may reduce mortality in the most severe patients (<xref rid="fig0010" ref-type="fig">Fig. 2</xref>, position 2).<fig id="fig0010"><label>Fig. 2</label><caption><p>A summary of the process of onset SARS-CoV2 pathogenesis with potential treatment options against the virus-induced cytokine storm.</p></caption><alt-text id="at0010">Fig. 2</alt-text><graphic xlink:href="gr2_lrg"></graphic></fig></p><sec id="sec0025"><label>2.2.1</label><title>Neutralizing antibodies</title><p id="par0070">One strategy that has received considerable attention in the face of COVID-19 is the use of convalescent plasma, also called passive antibody therapy, to treat patients with advanced disease. The treatment uses plasma from a patient who has survived COVID-19 infection to provide neutralizing antibodies against the virus; the antibodies are available and active immediately, but only for a limited time. As an example of one study, five patients critically ill with COVID-19 and on mechanical ventilation received convalescent plasma 10–22 days after being admitted to a hospital in Shenzhen, China. All patients improved; three were discharged after 50 days in hospital, while the other two patients were in stable condition. Well controlled clinical evaluation of this strategy is currently ongoing in light of such positive anecdotal responses.</p><p id="par0075">Another potential treatment involves the use of anti-IL-6 monoclonal antibody (SILTUXIMAB) (Johnson & Johnson) which was used previously to treat the consequences of cytokine storm following by CAR-T cell therapy for cancer. Interleukin-6 (IL-6) has become a key point in some CRS. Originally described as B-cell differentiation factor-2 (BSF-2) and macrophage and granulocyte induction factor-2 (MGI-2), IL-6 has significant pro-inflammatory and pyrogenic properties, and given chronic overproduction in COVID-19 patients, anti-IL-6 monoclonal antibody may be beneficial in controlling cytokine release. Also IL-17 inhibitor (Secukinumab) (Novartis) was used as specific treatment for severe patients with COVID-19 pneumonia [<xref rid="bib0125" ref-type="bibr">25</xref>] to control Th17 cell activation. An additional observation indicated that the expression levels of CD4<sup>+</sup> T and CD8<sup>+</sup> T were low, while IL-6 levels were high in patients with severe pneumonia, suggesting that T cell subsets and cytokine levels could be used as one predictor of the transition from mild to severe pneumonia [<xref rid="bib0075" ref-type="bibr">15</xref>].</p></sec><sec id="sec0030"><label>2.2.2</label><title>Interferons</title><p id="par0080">Pegylated and non-pegylated interferons (IFN) have been under intensive study for some time. However, in the case of HCoV infection, the results of IFN therapy were mixed, as predicted by animal and human HCoV infection models. Early application of IFN was slightly beneficial to reduce viral load and improve clinical outcome. However, delayed IFN administration was of no benefitscompared with the placebo group. Early application of IFN and ribavirin moderately improved disease severity without affecting mortality [<xref rid="bib0130" ref-type="bibr">26</xref>]. The use of Sifalimumab monoclonal antibody, produced against multiple IFN subtypes (MedImmune) has not been examined clinically but could hold promise in situations of constitutive IFN production.</p></sec><sec id="sec0035"><label>2.2.3</label><title>IFN-αβ inhibitors and IFN-λ</title><p id="par0085">The early use of IFN had some beneficial effects in SARS-CoV-infected animal model, although the timing of IFN treatment was crucial in determining the course of disease. The use of IFN-αβ receptor inhibitors or antagonists could be considered as an approach to avoid excessive inflammatory reactions in late stage severe HCoV infection [<xref rid="bib0135" ref-type="bibr">27</xref>]. Since SARS-CoV and MERS-CoV infect mainly airway epithelial cells and IFN-λ stimulates antiviral gene expression in these cells without over-stimulating the immune system, IFN-λ might be a option in the therapy of HCoV infection.</p></sec><sec id="sec0040"><label>2.2.4</label><title>Inhibition of oxidized phospholipids</title><p id="par0090">Oxidized phospholipids (OxPL) have been demonstrated to promote acute lung injury by increasing the production of cytokines/chemokines from lung macrophages via TLR4-TRIF signaling in influenza A virus (IAV)-infected mice [<xref rid="bib0140" ref-type="bibr">28</xref>]. In a recent study, therapeutic administration of the TLR4 antagonist Eritoran protected mice from lethal IAV infection by decreasing the levels of OxPL and inflammatory cytokines/chemokines [<xref rid="bib0145" ref-type="bibr">29</xref>]. Because pathogenic human coronaviruses can cause acute lung injury and promote the production of OxPL in the lungs, the strategies of OxPL suppression by using Eritoran (BOC Sciences) or other similar compounds may have value in controlling HCoV induced inflammation.</p></sec><sec id="sec0045"><label>2.2.5</label><title>Sphingosine-1-phosphate receptor 1 agonist therapy</title><p id="par0095">Signal transduction by the sphingosine-1-phosphate receptor 1 (S1P1) in mouse endothelial cells nfected with influenza A virus has been shown to contribute to the pathogenesis of inflammation responses [<xref rid="bib0150" ref-type="bibr">30</xref>]. Targeted S1P1 antagonism inhibited the recruitment of inflammatory cells, limited pro-inflammatory cytokine/chemokine release, and reduced mortality and morbidity induced by influenza A virus [<xref rid="bib0155" ref-type="bibr">31</xref>]. S1P1 antagonism may be considered a potential therapy in HCoV-infected individuals to limit cytokine responses.</p></sec><sec id="sec0050"><label>2.2.6</label><title>Inhibitors of monocyte recruitment and function</title><p id="par0100">The results of studies in animal models have borne out claims that IMMs paly pathogenic roles in the process of fatal HCoV infections. In the mice cardiac inflammation model, the systemic administration of optimized lipid nanoparticles including CCR2-silenced small interfering RNA (siRNA) can effectively degrade CCR2 mRNA and destroy the IMM recruitment in the inflammatory site, thus improving the outcome of the disease [<xref rid="bib0160" ref-type="bibr">32</xref>]. Because HCoVs are single-chain RNA viruses and TLR7 agonist R837 (a synthetic single-chain RNA analog) stimulates IMMs which causes exuberant inflammatory response. Therefore, IMM specific TLR-7 signal may promote the excessive inflammatory response caused by HCoV infection. Therefore, a TLR7 antagonist targeted approach to alleviate inflammation reaction could be useful.</p></sec><sec id="sec0055"><label>2.2.7</label><title>Continuous renal replacement therapy</title><p id="par0105">Continuous renal replacement therapy (CRRT) may benefit severe patients by removing potentially harmful components and maintaining haemodynamic and metabolic status. In addition to the conventional aim of maintaining renal function, CRRT can be used to regulate the immune response of patients with sepsis, with the goal to regulate circulating levels of inflammatory cytokine mediators, as shown in studies demonstrating removal of inflammatory mediators containing cytokines and complement (TNFα, IL-1β, IL-6, IL-8, complement factors C3a, C5a, and D) by CRRT [<xref rid="bib0175" ref-type="bibr">35</xref>]. At present, there is a need for well-designed clinical trial to evaluate the efficacy of such a treatment regimen.</p></sec></sec></sec><sec id="sec0060"><label>3</label><title>Conclusion</title><p id="par0110">After COVID-19 infection, some patients develop systemic inflammatory response syndrome (SIRS) and MODS characterized by the uncontrolled release of inflammatory mediators, giving rise to a cytokine storm that contributes to increased mortality in ARDS. In summary, further experimentations is required to understand the changes in the immune response of patients with COVID-19 infection and the mechanisms of abnormal cytokine expression in COVID-19 pneumonia. Accurate prediction and targeted intervention during the course of COVID-19 pneumonia will be essential to improve patient survival (<xref rid="fig0010" ref-type="fig">Fig. 2</xref>).</p></sec><sec id="sec0065"><title>Conflict of interest</title><p id="par0115">There are no financial or other interests with regard to the paper that represent a conflict of interest.</p></sec><sec id="sec0070"><title>Uncited references</title><p id="par0120">[<xref rid="bib0165" ref-type="bibr">33</xref>,<xref rid="bib0170" ref-type="bibr">34</xref>].</p></sec></body><back><ref-list id="bibl0005"><title>References</title><ref id="bib0005"><label>1</label><element-citation publication-type="journal" id="sbref0005"><person-group person-group-type="author"><name><surname>Wu</surname><given-names>J.T.</given-names></name><name><surname>Leung</surname><given-names>K.</given-names></name><name><surname>Leung</surname><given-names>G.M.</given-names></name></person-group><article-title>Nowcasting and forecasting the potential domestic and international spread of the 2019-nCoV outbreak originating in Wuhan, China: a modelling study</article-title><source>Lancet</source><year>2020</year></element-citation></ref><ref id="bib0010"><label>2</label><element-citation publication-type="journal" id="sbref0010"><person-group person-group-type="author"><name><surname>Huang</surname><given-names>C.</given-names></name><name><surname>Wang</surname><given-names>Y.</given-names></name><name><surname>Li</surname><given-names>X.</given-names></name></person-group><article-title>Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China</article-title><source>Lancet</source><volume>395</volume><issue>10223</issue><year>2020</year><fpage>497</fpage><lpage>506</lpage><pub-id pub-id-type="pmid">31986264</pub-id></element-citation></ref><ref id="bib0015"><label>3</label><element-citation publication-type="journal" id="sbref0015"><person-group person-group-type="author"><name><surname>Jin</surname><given-names>Y.H.</given-names></name><name><surname>Cai</surname><given-names>L.</given-names></name><name><surname>Cheng</surname><given-names>Z.S.</given-names></name></person-group><article-title>A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)</article-title><source>Mil. Med. Res.</source><volume>7</volume><issue>1</issue><year>2020</year><fpage>4</fpage><pub-id pub-id-type="pmid">32029004</pub-id></element-citation></ref><ref id="bib0020"><label>4</label><element-citation publication-type="journal" id="sbref0020"><person-group person-group-type="author"><name><surname>Shimabukuro-Vornhagen</surname><given-names>A.</given-names></name><name><surname>Godel</surname><given-names>P.</given-names></name><name><surname>Subklewe</surname><given-names>M.</given-names></name></person-group><article-title>Cytokine release syndrome</article-title><source>J. Immunother. Cancer</source><volume>6</volume><issue>1</issue><year>2018</year><fpage>56</fpage><pub-id pub-id-type="pmid">29907163</pub-id></element-citation></ref><ref id="bib0025"><label>5</label><element-citation publication-type="journal" id="sbref0025"><person-group person-group-type="author"><name><surname>Tanaka</surname><given-names>T.</given-names></name><name><surname>Narazaki</surname><given-names>M.</given-names></name><name><surname>Kishimoto</surname><given-names>T.</given-names></name></person-group><article-title>Immunotherapeutic implications of IL-6 blockade for cytokine storm</article-title><source>Immunotherapy</source><volume>8</volume><issue>8</issue><year>2016</year><fpage>959</fpage><lpage>970</lpage><pub-id pub-id-type="pmid">27381687</pub-id></element-citation></ref><ref id="bib0030"><label>6</label><element-citation publication-type="journal" id="sbref0030"><person-group person-group-type="author"><name><surname>Hunter</surname><given-names>C.A.</given-names></name><name><surname>Jones</surname><given-names>S.A.</given-names></name></person-group><article-title>IL-6 as a keystone cytokine in health and disease</article-title><source>Nat. Immunol.</source><volume>16</volume><issue>5</issue><year>2015</year><fpage>448</fpage><lpage>457</lpage><pub-id pub-id-type="pmid">25898198</pub-id></element-citation></ref><ref id="bib0035"><label>7</label><element-citation publication-type="journal" id="sbref0035"><person-group person-group-type="author"><name><surname>Pathan</surname><given-names>N.</given-names></name><name><surname>Hemingway</surname><given-names>C.A.</given-names></name><name><surname>Alizadeh</surname><given-names>A.A.</given-names></name></person-group><article-title>Role of interleukin 6 in myocardial dysfunction of meningococcal septic shock</article-title><source>Lancet</source><volume>363</volume><issue>9404</issue><year>2004</year><fpage>203</fpage><lpage>209</lpage><pub-id pub-id-type="pmid">14738793</pub-id></element-citation></ref><ref id="bib0040"><label>8</label><element-citation publication-type="journal" id="sbref0040"><person-group person-group-type="author"><name><surname>Hay</surname><given-names>K.A.</given-names></name><name><surname>Hanafi</surname><given-names>L.A.</given-names></name><name><surname>Li</surname><given-names>D.</given-names></name></person-group><article-title>Kinetics and biomarkers of severe cytokine release syndrome after CD19 chimeric antigen receptor-modified T-cell therapy</article-title><source>Blood</source><volume>130</volume><issue>21</issue><year>2017</year><fpage>2295</fpage><lpage>2306</lpage><pub-id pub-id-type="pmid">28924019</pub-id></element-citation></ref><ref id="bib0045"><label>9</label><element-citation publication-type="journal" id="sbref0045"><person-group person-group-type="author"><name><surname>Wang</surname><given-names>D.</given-names></name><name><surname>Hu</surname><given-names>B.</given-names></name><name><surname>Hu</surname><given-names>C.</given-names></name></person-group><article-title>Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China</article-title><source>JAMA</source><year>2020</year></element-citation></ref><ref id="bib0050"><label>10</label><element-citation publication-type="journal" id="sbref0050"><person-group person-group-type="author"><name><surname>Osterholm</surname><given-names>M.T.</given-names></name></person-group><article-title>Preparing for the next pandemic</article-title><source>N. Engl. J. Med.</source><volume>352</volume><issue>18</issue><year>2005</year><fpage>1839</fpage><lpage>1842</lpage><pub-id pub-id-type="pmid">15872196</pub-id></element-citation></ref><ref id="bib0055"><label>11</label><element-citation publication-type="journal" id="sbref0055"><person-group person-group-type="author"><name><surname>Teijaro</surname><given-names>J.R.</given-names></name><name><surname>Walsh</surname><given-names>K.B.</given-names></name><name><surname>Rice</surname><given-names>S.</given-names></name><name><surname>Rosen</surname><given-names>H.</given-names></name><name><surname>Oldstone</surname><given-names>M.B.</given-names></name></person-group><article-title>Mapping the innate signaling cascade essential for cytokine storm during influenza virus infection</article-title><source>Proc. Natl. Acad. Sci. U. S. A.</source><volume>111</volume><issue>10</issue><year>2014</year><fpage>3799</fpage><lpage>3804</lpage><pub-id pub-id-type="pmid">24572573</pub-id></element-citation></ref><ref id="bib0060"><label>12</label><element-citation publication-type="journal" id="sbref0060"><person-group person-group-type="author"><name><surname>Reghunathan</surname><given-names>R.</given-names></name><name><surname>Jayapal</surname><given-names>M.</given-names></name><name><surname>Hsu</surname><given-names>L.Y.</given-names></name></person-group><article-title>Expression profile of immune response genes in patients with Severe Acute Respiratory Syndrome</article-title><source>BMC Immunol.</source><volume>6</volume><year>2005</year><fpage>2</fpage><pub-id pub-id-type="pmid">15655079</pub-id></element-citation></ref><ref id="bib0065"><label>13</label><element-citation publication-type="journal" id="sbref0065"><person-group person-group-type="author"><name><surname>Chien</surname><given-names>J.Y.</given-names></name><name><surname>Hsueh</surname><given-names>P.R.</given-names></name><name><surname>Cheng</surname><given-names>W.C.</given-names></name><name><surname>Yu</surname><given-names>C.J.</given-names></name><name><surname>Yang</surname><given-names>P.C.</given-names></name></person-group><article-title>Temporal changes in cytokine/chemokine profiles and pulmonary involvement in severe acute respiratory syndrome</article-title><source>Respirology</source><volume>11</volume><issue>6</issue><year>2006</year><fpage>715</fpage><lpage>722</lpage><pub-id pub-id-type="pmid">17052299</pub-id></element-citation></ref><ref id="bib0070"><label>14</label><element-citation publication-type="journal" id="sbref0070"><person-group person-group-type="author"><name><surname>Min</surname><given-names>C.K.</given-names></name><name><surname>Cheon</surname><given-names>S.</given-names></name><name><surname>Ha</surname><given-names>N.Y.</given-names></name></person-group><article-title>Comparative and kinetic analysis of viral shedding and immunological responses in MERS patients representing a broad spectrum of disease severity</article-title><source>Sci. Rep.</source><volume>6</volume><year>2016</year><fpage>25359</fpage><pub-id pub-id-type="pmid">27146253</pub-id></element-citation></ref><ref id="bib0075"><label>15</label><element-citation publication-type="journal" id="sbref0075"><person-group person-group-type="author"><name><surname>Tsang</surname><given-names>K.</given-names></name><name><surname>Zhong</surname><given-names>N.S.</given-names></name></person-group><article-title>SARS: pharmacotherapy</article-title><source>Respirology</source><volume>8</volume><issue>Suppl</issue><year>2003</year><fpage>S25</fpage><lpage>S30</lpage><pub-id pub-id-type="pmid">15018130</pub-id></element-citation></ref><ref id="bib0080"><label>16</label><element-citation publication-type="journal" id="sbref0080"><person-group person-group-type="author"><name><surname>Xu</surname><given-names>Z.</given-names></name><name><surname>Shi</surname><given-names>L.</given-names></name><name><surname>Wang</surname><given-names>Y.</given-names></name></person-group><article-title>Pathological findings of COVID-19 associated with acute respiratory distress syndrome</article-title><source>Lancet Respir. Med.</source><year>2020</year></element-citation></ref><ref id="bib0085"><label>17</label><element-citation publication-type="journal" id="sbref0085"><person-group person-group-type="author"><name><surname>Tian</surname><given-names>S.H.</given-names></name><name><surname>Hu</surname><given-names>W.</given-names></name><name><surname>Niu</surname><given-names>L.</given-names></name><name><surname>Liu</surname><given-names>H.</given-names></name><name><surname>Xu</surname><given-names>H.</given-names></name><name><surname>Xiao</surname><given-names>S.</given-names></name></person-group><article-title>Pulmonary pathology of early phase SARS-COV-2 pneumonia</article-title><source>Preprints</source><year>2020</year></element-citation></ref><ref id="bib0090"><label>18</label><element-citation publication-type="journal" id="sbref0090"><person-group person-group-type="author"><name><surname>Bajema</surname><given-names>K.L.</given-names></name><name><surname>Oster</surname><given-names>A.M.</given-names></name><name><surname>McGovern</surname><given-names>O.L.</given-names></name></person-group><article-title>Persons evaluated for 2019 novel coronavirus - United States, January 2020</article-title><source>MMWR Morb. Mortal. Wkly. Rep.</source><volume>69</volume><issue>6</issue><year>2020</year><fpage>166</fpage><lpage>170</lpage><pub-id pub-id-type="pmid">32053579</pub-id></element-citation></ref><ref id="bib0095"><label>19</label><element-citation publication-type="journal" id="sbref0095"><person-group person-group-type="author"><name><surname>Menachery</surname><given-names>V.D.</given-names></name><name><surname>Schafer</surname><given-names>A.</given-names></name><name><surname>Burnum-Johnson</surname><given-names>K.E.</given-names></name></person-group><article-title>MERS-CoV and H5N1 influenza virus antagonize antigen presentation by altering the epigenetic landscape</article-title><source>Proc. Natl. Acad. Sci. U. S. A.</source><volume>115</volume><issue>5</issue><year>2018</year><comment>E1012-E21</comment></element-citation></ref><ref id="bib0100"><label>20</label><element-citation publication-type="journal" id="sbref0100"><person-group person-group-type="author"><name><surname>Ho</surname><given-names>J.C.</given-names></name><name><surname>Ooi</surname><given-names>G.C.</given-names></name><name><surname>Mok</surname><given-names>T.Y.</given-names></name></person-group><article-title>High-dose pulse versus nonpulse corticosteroid regimens in severe acute respiratory syndrome</article-title><source>Am. J. Respir. Crit. Care Med.</source><volume>168</volume><issue>12</issue><year>2003</year><fpage>1449</fpage><lpage>1456</lpage><pub-id pub-id-type="pmid">12947028</pub-id></element-citation></ref><ref id="bib0105"><label>21</label><element-citation publication-type="journal" id="sbref0105"><person-group person-group-type="author"><name><surname>Yam</surname><given-names>L.Y.</given-names></name><name><surname>Lau</surname><given-names>A.C.</given-names></name><name><surname>Lai</surname><given-names>F.Y.</given-names></name></person-group><article-title>Corticosteroid treatment of severe acute respiratory syndrome in Hong Kong</article-title><source>J. Infect.</source><volume>54</volume><issue>1</issue><year>2007</year><fpage>28</fpage><lpage>39</lpage><pub-id pub-id-type="pmid">16542729</pub-id></element-citation></ref><ref id="bib0110"><label>22</label><element-citation publication-type="journal" id="sbref0110"><person-group person-group-type="author"><name><surname>Stockman</surname><given-names>L.J.</given-names></name><name><surname>Bellamy</surname><given-names>R.</given-names></name><name><surname>Garner</surname><given-names>P.</given-names></name></person-group><article-title>SARS: systematic review of treatment effects</article-title><source>PLoS Med.</source><volume>3</volume><issue>9</issue><year>2006</year><fpage>e343</fpage><pub-id pub-id-type="pmid">16968120</pub-id></element-citation></ref><ref id="bib0115"><label>23</label><element-citation publication-type="journal" id="sbref0115"><person-group person-group-type="author"><name><surname>Wang</surname><given-names>D.</given-names></name><name><surname>Hu</surname><given-names>B.</given-names></name><name><surname>Hu</surname><given-names>C.</given-names></name></person-group><article-title>Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China</article-title><source>JAMA</source><year>2020</year></element-citation></ref><ref id="bib0120"><label>24</label><element-citation publication-type="journal" id="sbref0120"><person-group person-group-type="author"><name><surname>Chen</surname><given-names>N.</given-names></name><name><surname>Zhou</surname><given-names>M.</given-names></name><name><surname>Dong</surname><given-names>X.</given-names></name></person-group><article-title>Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study</article-title><source>Lancet</source><volume>395</volume><issue>10223</issue><year>2020</year><fpage>507</fpage><lpage>513</lpage><pub-id pub-id-type="pmid">32007143</pub-id></element-citation></ref><ref id="bib0125"><label>25</label><element-citation publication-type="journal" id="sbref0125"><person-group person-group-type="author"><name><surname>Xu</surname><given-names>Z.</given-names></name><name><surname>Shi</surname><given-names>L.</given-names></name><name><surname>Wang</surname><given-names>Y.</given-names></name></person-group><article-title>Pathological findings of COVID-19 associated with acute respiratory distress syndrome</article-title><source>Lancet Respir. Med.</source><year>2020</year></element-citation></ref><ref id="bib0130"><label>26</label><element-citation publication-type="journal" id="sbref0130"><person-group person-group-type="author"><name><surname>Omrani</surname><given-names>A.S.</given-names></name><name><surname>Saad</surname><given-names>M.M.</given-names></name><name><surname>Baig</surname><given-names>K.</given-names></name></person-group><article-title>Ribavirin and interferon alfa-2a for severe Middle East respiratory syndrome coronavirus infection: a retrospective cohort study</article-title><source>Lancet Infect. Dis.</source><volume>14</volume><issue>11</issue><year>2014</year><fpage>1090</fpage><lpage>1095</lpage><pub-id pub-id-type="pmid">25278221</pub-id></element-citation></ref><ref id="bib0135"><label>27</label><element-citation publication-type="journal" id="sbref0135"><person-group person-group-type="author"><name><surname>Channappanavar</surname><given-names>R.</given-names></name><name><surname>Fehr</surname><given-names>A.R.</given-names></name><name><surname>Vijay</surname><given-names>R.</given-names></name></person-group><article-title>Dysregulated type I interferon and inflammatory monocyte-macrophage responses cause lethal pneumonia in SARS-CoV-infected mice</article-title><source>Cell Host Microbe</source><volume>19</volume><issue>2</issue><year>2016</year><fpage>181</fpage><lpage>193</lpage><pub-id pub-id-type="pmid">26867177</pub-id></element-citation></ref><ref id="bib0140"><label>28</label><element-citation publication-type="journal" id="sbref0140"><person-group person-group-type="author"><name><surname>Imai</surname><given-names>Y.</given-names></name><name><surname>Kuba</surname><given-names>K.</given-names></name><name><surname>Neely</surname><given-names>G.G.</given-names></name></person-group><article-title>Identification of oxidative stress and Toll-like receptor 4 signaling as a key pathway of acute lung injury</article-title><source>Cell</source><volume>133</volume><issue>2</issue><year>2008</year><fpage>235</fpage><lpage>249</lpage><pub-id pub-id-type="pmid">18423196</pub-id></element-citation></ref><ref id="bib0145"><label>29</label><element-citation publication-type="journal" id="sbref0145"><person-group person-group-type="author"><name><surname>Shirey</surname><given-names>K.A.</given-names></name><name><surname>Lai</surname><given-names>W.</given-names></name><name><surname>Scott</surname><given-names>A.J.</given-names></name></person-group><article-title>The TLR4 antagonist Eritoran protects mice from lethal influenza infection</article-title><source>Nature</source><volume>497</volume><issue>7450</issue><year>2013</year><fpage>498</fpage><lpage>502</lpage><pub-id pub-id-type="pmid">23636320</pub-id></element-citation></ref><ref id="bib0150"><label>30</label><element-citation publication-type="journal" id="sbref0150"><person-group person-group-type="author"><name><surname>Teijaro</surname><given-names>J.R.</given-names></name><name><surname>Walsh</surname><given-names>K.B.</given-names></name><name><surname>Cahalan</surname><given-names>S.</given-names></name></person-group><article-title>Endothelial cells are central orchestrators of cytokine amplification during influenza virus infection</article-title><source>Cell</source><volume>146</volume><issue>6</issue><year>2011</year><fpage>980</fpage><lpage>991</lpage><pub-id pub-id-type="pmid">21925319</pub-id></element-citation></ref><ref id="bib0155"><label>31</label><element-citation publication-type="journal" id="sbref0155"><person-group person-group-type="author"><name><surname>McQueen</surname><given-names>J.</given-names></name><name><surname>Jardine</surname><given-names>A.</given-names></name><name><surname>Kingdom</surname><given-names>J.</given-names></name><name><surname>Templeton</surname><given-names>A.</given-names></name><name><surname>Whittle</surname><given-names>M.J.</given-names></name><name><surname>Connell</surname><given-names>J.M.</given-names></name></person-group><article-title>Interaction of angiotensin II and atrial natriuretic peptide in the human fetoplacental unit</article-title><source>Am. J. Hypertens.</source><volume>3</volume><issue>8 Pt 1</issue><year>1990</year><fpage>641</fpage><lpage>644</lpage><pub-id pub-id-type="pmid">2171565</pub-id></element-citation></ref><ref id="bib0160"><label>32</label><element-citation publication-type="journal" id="sbref0160"><person-group person-group-type="author"><name><surname>Leuschner</surname><given-names>F.</given-names></name><name><surname>Dutta</surname><given-names>P.</given-names></name><name><surname>Gorbatov</surname><given-names>R.</given-names></name></person-group><article-title>Therapeutic siRNA silencing in inflammatory monocytes in mice</article-title><source>Nat. Biotechnol.</source><volume>29</volume><issue>11</issue><year>2011</year><fpage>1005</fpage><lpage>1010</lpage><pub-id pub-id-type="pmid">21983520</pub-id></element-citation></ref><ref id="bib0165"><label>33</label><element-citation publication-type="journal" id="sbref0165"><person-group person-group-type="author"><name><surname>Darwish</surname><given-names>I.</given-names></name><name><surname>Mubareka</surname><given-names>S.</given-names></name><name><surname>Liles</surname><given-names>W.C.</given-names></name></person-group><article-title>Immunomodulatory therapy for severe influenza</article-title><source>Expert Rev. Anti. Ther.</source><volume>9</volume><issue>7</issue><year>2011</year><fpage>807</fpage><lpage>822</lpage></element-citation></ref><ref id="bib0170"><label>34</label><element-citation publication-type="journal" id="sbref0170"><person-group person-group-type="author"><name><surname>McDermott</surname><given-names>J.E.</given-names></name><name><surname>Mitchell</surname><given-names>H.D.</given-names></name><name><surname>Gralinski</surname><given-names>L.E.</given-names></name></person-group><article-title>The effect of inhibition of PP1 and TNFalpha signaling on pathogenesis of SARS coronavirus</article-title><source>BMC Syst. Biol.</source><volume>10</volume><issue>1</issue><year>2016</year><fpage>93</fpage><pub-id pub-id-type="pmid">27663205</pub-id></element-citation></ref><ref id="bib0175"><label>35</label><element-citation publication-type="journal" id="sbref0175"><person-group person-group-type="author"><name><surname>Silvester</surname><given-names>W.</given-names></name></person-group><article-title>Mediator removal with CRRT: complement and cytokines</article-title><source>Am. J. Kidney Dis.</source><volume>30</volume><issue>5 Suppl. 4</issue><year>1997</year><fpage>S38</fpage><lpage>S43</lpage><pub-id pub-id-type="pmid">9372978</pub-id></element-citation></ref></ref-list><sec id="sec0080" sec-type="supplementary-material"><label>Appendix A</label><title>Supplementary data</title><p id="par0130">The following are Supplementary data to this article:<supplementary-material content-type="local-data" id="upi0005"><media xlink:href="mmc1.zip"></media></supplementary-material></p></sec><fn-group><fn id="sec0075" fn-type="supplementary-material"><label>Appendix A</label><p id="par0125">Supplementary material related to this article can be found, in the online version, at doi:<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1016/j.cytogfr.2020.04.002" id="intr0010">https://doi.org/10.1016/j.cytogfr.2020.04.002</ext-link>.</p></fn></fn-group></back></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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