Advanced search
Publication Cover
OncoImmunology Volume 9, 2020 - Issue 1
Submit an article Journal homepage
18,300
Views
95
CrossRef citations to date
0
Altmetric
Review

Immune responses during COVID-19 infection

Cléa Melenottea Immunology, Gustave Roussy, Villejuif, France;b Gustave Roussy, Université Paris-Saclay, Villejuif, France;c Infectious Diseases, Aix-Marseille Université, IRD, APHM, MEPHI, Marseille, France;d Infectious Diseases, IHU-Méditerranée Infection, Marseille, FranceCorrespondence[email protected]
View further author information
,
Aymeric Silvina Immunology, Gustave Roussy, Villejuif, FranceView further author information
,
Anne-Gaëlle Goubeta Immunology, Gustave Roussy, Villejuif, France;b Gustave Roussy, Université Paris-Saclay, Villejuif, France;e Immunology, Institut National de la Santé Et de la Recherche Médicale (INSERM), U1015 Equipe Labellisée—Ligue Nationale contre le Cancer, Villejuif, France;f Center of Clinical Investigations in Biotherapies of Cancer (CICBT) 1428, Villejuif, FranceView further author information
,
Imran Lahmara Immunology, Gustave Roussy, Villejuif, France;b Gustave Roussy, Université Paris-Saclay, Villejuif, France;e Immunology, Institut National de la Santé Et de la Recherche Médicale (INSERM), U1015 Equipe Labellisée—Ligue Nationale contre le Cancer, Villejuif, France;f Center of Clinical Investigations in Biotherapies of Cancer (CICBT) 1428, Villejuif, FranceView further author information
,
Agathe Dubuissona Immunology, Gustave Roussy, Villejuif, France;b Gustave Roussy, Université Paris-Saclay, Villejuif, France;e Immunology, Institut National de la Santé Et de la Recherche Médicale (INSERM), U1015 Equipe Labellisée—Ligue Nationale contre le Cancer, Villejuif, France;f Center of Clinical Investigations in Biotherapies of Cancer (CICBT) 1428, Villejuif, FranceView further author information
,
Alimuddin Zumlag Department of Infection, Division of Infection and Immunity, University College London, National Institute for Health Research Biomedical Research Centre, University College London Hospitals NHS Foundation Trust, London, UKView further author information
,
Didier Raoultb Gustave Roussy, Université Paris-Saclay, Villejuif, France;c Infectious Diseases, Aix-Marseille Université, IRD, APHM, MEPHI, Marseille, FranceView further author information
,
Mansouria Meradh Service de Urgences et de Permanence des Soins, Gustave Roussy Cancer Campus Grand Paris, Villejuif, FranceView further author information
,
Bertrand Gachota Immunology, Gustave Roussy, Villejuif, FranceView further author information
,
Clémence Hénona Immunology, Gustave Roussy, Villejuif, FranceView further author information
,
Eric Solarya Immunology, Gustave Roussy, Villejuif, FranceView further author information
,
Michaela Fontenayi INSERM U1016, Centre National Recherche Scientifique (CNRS) UMR8104, Institut Cochin, Université de Paris, Paris, FranceView further author information
,
Fabrice Andréa Immunology, Gustave Roussy, Villejuif, FranceView further author information
,
Markus Maeurerj Immunosurgery, Immunotherapy Unit, Champalimaud Centre for the Unknown, Lisbon, Portugal;k Med Clinic, University of Mainz, Mayence, GermanyView further author information
,
Giuseppe Ippolitol Dipartimento di Epidemiologia Ricerca Pre-Clinica e Diagnostica Avanzata, National Institute for Infectious Diseases “Lazzaro Spallanzani” I.R.C.C.S., Rome, ItalyView further author information
,
Mauro Piacentinim Department of Biology, University of Rome “Tor Vergata”, Rome, Italy;n Infectious Diseases Department, National Institute for Infectious Disease IRCCS “Lazzaro Spallanzani”, Rome, ItalyORCID Iconhttps://orcid.org/0000-0003-2919-1296View further author information
ORCID Icon,
Fu-Sheng Wango National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaView further author information
,
Florent Ginhouxp Singapore Immunology Network, Agency for Science, Technology and Research, Singapore;q Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China;r Translational Immunology Institute, SingHealth Duke-NUS Academic Medical Centre, SingaporeView further author information
,
Aurélien Marabellec Infectious Diseases, Aix-Marseille Université, IRD, APHM, MEPHI, Marseille, FranceView further author information
,
Guido Kroemers Centre de Recherche des Cordeliers, Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, Inserm U1138, Institut Universitaire de France, Paris, France;t Metabolomics and Cell Biology Platforms, Institut Gustave Roussy, Villejuif, France;u Pôle de Biologie,Pathologie – PUI – Hygiène, Hôpital Européen Georges Pompidou, AP-HP, Paris, France;v Karolinska Institute, Department of Women’s and Children’s Health, Karolinska University Hospital, Stockholm, Sweden;w Suzhou Institute for Systems Medicine, Chinese Academy of Medical Sciences, Suzhou, ChinaORCID Iconhttps://orcid.org/0000-0002-9334-4405View further author information
ORCID Icon,
Lisa Derosaa Immunology, Gustave Roussy, Villejuif, France;b Gustave Roussy, Université Paris-Saclay, Villejuif, France;e Immunology, Institut National de la Santé Et de la Recherche Médicale (INSERM), U1015 Equipe Labellisée—Ligue Nationale contre le Cancer, Villejuif, France;f Center of Clinical Investigations in Biotherapies of Cancer (CICBT) 1428, Villejuif, FranceView further author information
&
Laurence Zitvogela Immunology, Gustave Roussy, Villejuif, France;b Gustave Roussy, Université Paris-Saclay, Villejuif, France;e Immunology, Institut National de la Santé Et de la Recherche Médicale (INSERM), U1015 Equipe Labellisée—Ligue Nationale contre le Cancer, Villejuif, France;f Center of Clinical Investigations in Biotherapies of Cancer (CICBT) 1428, Villejuif, France;w Suzhou Institute for Systems Medicine, Chinese Academy of Medical Sciences, Suzhou, ChinaORCID Iconhttps://orcid.org/0000-0003-1596-0998View further author information
ORCID Icon show all
Article: 1807836 | Received 29 May 2020, Accepted 05 Aug 2020, Published online: 25 Aug 2020

References

  • Memish ZA, Perlman S, Van Kerkhove MD, Zumla A. Middle East respiratory syndrome. The Lancet. 2020;395(10229):1063–23. doi:10.1016/S0140-6736(19)33221-0.
  • Hui DSC, Zumla A. Severe Acute Respiratory Syndrome: Historical, Epidemiologic, and Clinical Features. Infect Dis Clin North Am. 2019;33(4):869–889. doi:10.1016/j.idc.2019.07.001.
  • Coronavirus disease (COVID-2019) situation reports. https://www.who.int/emergencies/diseases/novel-coronavirus-2019.
  • Institut de veille sanitaire france. https://www.santepubliquefrance.fr/dossiers/coronavirus-covid-19.
  • https://www.ecdc.europa.eu/en/covid-19-pandemic.
  • Lagier J-C, Million M, Gautret P, Colson P, Cortaredona S, Giraud-Gatineau A, Honoré S, Gaubert J-Y, Fournier P-E, Tissot-Dupont H, et al.. Outcomes of 3,737 COVID-19 patients treated with hydroxychloroquine/azithromycin and other regimens in Marseille, France: A retrospective analysis. Travel Med Infect Dis. 2020 Jun 25:101791. doi:10.1016/j.tmaid.2020.101791.
  • Chatterjee P, Anand T, Singh KJ, Rasaily R, Singh R, Das S, Singh H, Praharaj I, Gangakhedkar RR, Bhargava B, et al.. Healthcare workers & SARS-CoV-2 infection in India: a case-control investigation in the time of COVID-19. Indian J Med Res. 2020;151(5):459–467. doi:10.4103/ijmr.IJMR_2234_20.
  • Shittu MO, Afolami OI. Improving the efficacy of Chloroquine and Hydroxychloroquine against SARS-CoV-2 may require Zinc additives - a better synergy for future COVID-19 clinical trials. Infez Med. 2020;28:192–197.
  • Enzmann MO, Erickson MP, Grindeland CJ, Lopez SMC, Hoover SE, Leedahl DD. Treatment and preliminary outcomes of 150 acute care patients with COVID-19 in a rural health system in the Dakotas. Epidemiol Infect. 2020;148:e124. doi:10.1017/S0950268820001351.
  • Paar V, Wernly B, Zhou Z, Motloch LJ, Hoppe UC, Egle A, Lichtenauer M. Anti-coagulation for COVID-19 treatment: both anti-thrombotic and anti-inflammatory?. J Thromb Thrombolysis. 2020 Jul 6. doi: 10.1007/s11239-020-02212-6
  • Tay MZ, Poh CM, Rénia L, MacAry PA, Ng LFP. The trinity of COVID-19: immunity, inflammation and intervention. Nat Rev Immunol. 2020 Apr 28. doi: 10.1038/s41577-020-0311-8
  • Wang W, Xu Y, Gao R, Lu R, Han K, Wu G, Tan W. Detection of SARS-CoV-2 in Different Types of Clinical Specimens. JAMA. 2020 Mar 11. doi: 10.1001/jama.2020.3786
  • Su H, Yang M, Wan C, Yi L-X, Tang F, Zhu H-Y, Yi F, Yang H-C, Fogo AB, Nie X, et al.. Renal histopathological analysis of 26 postmortem findings of patients with COVID-19 in China. Kidney Int. 2020;98(1):219–227. doi:10.1016/j.kint.2020.04.003.
  • Tavazzi G, Pellegrini C, Maurelli M, Belliato M, Sciutti F, Bottazzi A, Sepe PA, Resasco T, Camporotondo R, Bruno R, et al.. Myocardial localization of coronavirus in COVID‐19 cardiogenic shock. Eur J Heart Fail. 2020;22(5):911–915. doi:10.1002/ejhf.1828.
  • Xiao F, Tang M, Zheng X, Liu Y, Li X, Shan H. Evidence for Gastrointestinal Infection of SARS-CoV-2. Gastroenterology. 2020;158(6):1831–1833.e3. doi:10.1053/j.gastro.2020.02.055.
  • Qi F, Qian S, Zhang S, Zhang Z. Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses. Biochem Biophys Res Commun. 2020;526(1):135–140. doi:10.1016/j.bbrc.2020.03.044.
  • Pan X, Xu D, Zhang H, Zhou W, Wang L, Cui X. Identification of a potential mechanism of acute kidney injury during the COVID-19 outbreak: a study based on single-cell transcriptome analysis. Intensive Care Med. 2020;46(6):1114–1116. doi:10.1007/s00134-020-06026-1.
  • Ziegler CGK, Allon SJ, Nyquist SK, Mbano IM, Miao VN, Tzouanas CN, Cao Y, Yousif AS, Bals J, Hauser BM, et al.. SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues. Cell. 2020 Apr 27. doi:10.1016/j.cell.2020.04.035.
  • Puelles VG, Lütgehetmann M, Lindenmeyer MT, Sperhake JP, Wong MN, Allweiss L, Chilla S, Heinemann A, Wanner N, Liu S, et al.. Multiorgan and Renal Tropism of SARS-CoV-2. N Engl J Med. 2020 May 13. doi:10.1056/NEJMc2011400.
  • Zhang Y, Cao W, Jiang W, Xiao M, Li Y, Tang N, Liu Z, Yan X, Zhao Y, Li T, et al.. Profile of natural anticoagulant, coagulant factor and anti-phospholipid antibody in critically ill COVID-19 patients. J Thromb Thrombolysis. 2020 Jul 9. doi:10.1007/s11239-020-02182-9.
  • Xiao M, Zhang Y, Zhang S, Qin X, Xia P, Cao W, Jiang W, Chen H, Ding X, Zhao H, et al.. Brief Report: Anti-phospholipid antibodies in critically ill patients with Coronavirus Disease 2019 (COVID-19). Arthritis Rheumatol. 2020 Jun 30. doi:10.1002/art.41425.
  • Bertin D, Brodovitch A, Beziane A, Hug S, Bouamri A, Mege JL, Bardin N. Anti-cardiolipin IgG autoantibodies are an independent risk factor of COVID-19 severity. Arthritis Rheumatol. 2020 Jun 21. doi: 10.1002/art.41409
  • Pineton de Chambrun M, Frere C, Miyara M, Amoura Z, Martin-Toutain I, Mathian A, Hekimian G, Combes A. High frequency of antiphospholipid antibodies in critically ill COVID-19 patients: a link with hypercoagulability?. J Intern Med. 2020 Jun 12. doi: 10.1111/joim.13126
  • Zayet S, Klopfenstein T, Kovẚcs R, Stancescu S, Hagenkötter B. Acute Cerebral Stroke with Multiple Infarctions and COVID-19, France, 2020. Emerg Infect Dis. 2020;26(9). doi:10.3201/eid2609.201791.
  • Zhang Y, Xiao M, Zhang S, Xia P, Cao W, Jiang W, Chen H, Ding X, Zhao H, Zhang H, et al.. Coagulopathy and Antiphospholipid Antibodies in Patients with Covid-19. N Engl J Med. 2020 Apr;8:e38. doi:10.1056/NEJMc2007575.
  • Patil NR, Herc ES, Girgis M. Cold agglutinin disease and autoimmune hemolytic anemia with pulmonary embolism as a presentation of COVID-19 infection. Hematol Oncol Stem Cell Ther. 2020 Jul 6. doi: 10.1016/j.hemonc.2020.06.005
  • Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA, Somasundaran M, Sullivan JL, Luzuriaga K, Greenough TC, et al.. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature. 2003;426(6965):450–454. doi:10.1038/nature02145.
  • Shulla A, Heald-Sargent T, Subramanya G, Zhao J, Perlman S, Gallagher T. A transmembrane serine protease is linked to the severe acute respiratory syndrome coronavirus receptor and activates virus entry. J Virol. 2011;85(2):873–882. doi:10.1128/JVI.02062-10.
  • Engelmann B, Massberg S. Thrombosis as an intravascular effector of innate immunity. Nat Rev Immunol. 2013;13(1):34–45. doi:10.1038/nri3345.
  • Josephine M, Lew L, Jeong-ho L. A third of coronavirus cases may be ‘silent carriers’, classified Chinese data suggests. South China Morning Post. 2020 Mar; Hong Kong, China.
  • Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S, Huang H, Zhang L, Zhou X, Du C, et al.. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med. 2020 Mar 13. doi:10.1001/jamainternmed.2020.0994.
  • Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ. COVID-19: consider cytokine storm syndromes and immunosuppression. The Lancet. 2020 Mar;S0140673620306280. doi:10.1016/S0140-6736(20)30628-0.
  • Tan L, Wang Q, Zhang D, Ding J, Huang Q, Tang Y-Q, Wang Q, Miao H. Lymphopenia predicts disease severity of COVID-19: a descriptive and predictive study. Sig Transduct Target Ther. 2020;5(1):33. doi:10.1038/s41392-020-0148-4.
  • Lavin Y, Winter D, Blecher-Gonen R, David E, Keren-Shaul H, Merad M, Jung S, Amit I. Tissue-resident macrophage enhancer landscapes are shaped by the local microenvironment. Cell. 2014;159(6):1312–1326. doi:10.1016/j.cell.2014.11.018.
  • Chakarov S, Lim HY, Tan L, Lim SY, See P, Lum J, Zhang X-M, Foo S, Nakamizo S, Duan K, et al.. Two distinct interstitial macrophage populations coexist across tissues in specific subtissular niches. Science. 2019;363(6432):eaau0964. doi:10.1126/science.aau0964.
  • Gibbings SL, Thomas SM, Atif SM, McCubbrey AL, Desch AN, Danhorn T, Leach SM, Bratton DL, Henson PM, Janssen WJ, et al.. Three unique interstitial macrophages in the murine lung at steady state. Am J Respir Cell Mol Biol. 2017;57(1):66–76. doi:10.1165/rcmb.2016-0361OC.
  • Schyns J, Bai Q, Ruscitti C, Radermecker C, De Schepper S, Chakarov S, Farnir F, Pirottin D, Ginhoux F, Boeckxstaens G, et al.. Non-classical tissue monocytes and two functionally distinct populations of interstitial macrophages populate the mouse lung. Nat Commun. 2019;10(1):3964. doi:10.1038/s41467-019-11843-0.
  • Ural BB, Yeung ST, Damani-Yokota P, Devlin JC, de Vries M, Vera-Licona P, Samji T, Sawai CM, Jang G, Perez OA, et al.. Identification of a nerve-associated, lung-resident interstitial macrophage subset with distinct localization and immunoregulatory properties. Sci Immunol. 2020;5(45):eaax8756. doi:10.1126/sciimmunol.aax8756.
  • Liao M, Liu Y, Yuan J, Wen Y, Xu G, Zhao J, Cheng L, Li J, Wang X, Wang F, et al.. Single-cell landscape of bronchoalveolar immune cells in patients with COVID-19. Nat Med. 2020;26(6):842–844. doi:10.1038/s41591-020-0901-9.
  • Byrne AJ, Powell JE, O’Sullivan BJ, Ogger PP, Hoffland A, Cook J, Bonner KL, Hewitt RJ, Wolf S, Ghai P, et al.. Dynamics of human monocytes and airway macrophages during healthy aging and after transplant. J Exp Med. 2020;217(3):e20191236. doi:10.1084/jem.20191236.
  • Goplen NP, Huang S, Zhu B, Cheon IS, Son YM, Wang Z, Li C, Dai Q, Jiang L, Sun J. Tissue-Resident Macrophages Limit Pulmonary CD8 Resident Memory T Cell Establishment. Front Immunol. 2019;10:2332. doi:10.3389/fimmu.2019.02332.
  • Wu T, Hu Y, Lee Y-T, Bouchard KR, Benechet A, Khanna K, Cauley LS. Lung-resident memory CD8 T cells (TRM) are indispensable for optimal cross-protection against pulmonary virus infection. J Leukoc Biol. 2014;95(2):215–224. doi:10.1189/jlb.0313180.
  • Wakim LM, Smith J, Caminschi I, Lahoud MH, Villadangos JA. Antibody-targeted vaccination to lung dendritic cells generates tissue-resident memory CD8 T cells that are highly protective against influenza virus infection. Mucosal Immunol. 2015;8(5):1060–1071. doi:10.1038/mi.2014.133.
  • Pizzolla A, Nguyen TH, Sant S, Jaffar J, Loudovaris T, Mannering SI, Thomas PG, Westall GP, Kedzierska K, Wakim LM. Influenza-specific lung-resident memory T cells are proliferative and polyfunctional and maintain diverse TCR profiles. J Clin Invest. 2018;128(2):721–733. doi:10.1172/JCI96957.
  • McMaster SR, Wein AN, Dunbar PR, Hayward SL, Cartwright EK, Denning TL, Kohlmeier JE. Pulmonary antigen encounter regulates the establishment of tissue-resident CD8 memory T cells in the lung airways and parenchyma. Mucosal Immunol. 2018;11(4):1071–1078. doi:10.1038/s41385-018-0003-x.
  • Zhao J, Zhao J, Mangalam AK, Channappanavar R, Fett C, Meyerholz DK, Agnihothram S, Baric RS, David CS, Perlman S. Airway memory CD4(+) T cells mediate protective immunity against emerging respiratory coronaviruses. Immunity. 2016;44(6):1379–1391. doi:10.1016/j.immuni.2016.05.006.
  • Duerr CU, CDA M, Mindt BC, Rubio M, Meli AP, Pothlichet J, Eva MM, Gauchat J-F, Qureshi ST, Mazer BD, et al.. Type I interferon restricts type 2 immunopathology through the regulation of group 2 innate lymphoid cells. Nat Immunol. 2016;17(1):65–75. doi:10.1038/ni.3308.
  • Moro K, Kabata H, Tanabe M, Koga S, Takeno N, Mochizuki M, Fukunaga K, Asano K, Betsuyaku T, Koyasu S. Interferon and IL-27 antagonize the function of group 2 innate lymphoid cells and type 2 innate immune responses. Nat Immunol. 2016;17(1):76–86. doi:10.1038/ni.3309.
  • Seo S-U, Kuffa P, Kitamoto S, Nagao-Kitamoto H, Rousseau J, Kim Y-G, Núñez G, Kamada N. Intestinal macrophages arising from CCR2(+) monocytes control pathogen infection by activating innate lymphoid cells. Nat Commun. 2015;6:8010. doi:10.1038/ncomms9010.
  • Wallace M, Malkovsky M, Carding SR. Gamma/delta T lymphocytes in viral infections. J Leukoc Biol. 1995;58(3):277–283. doi:10.1002/jlb.58.3.277.
  • Poccia F, Agrati C, Castilletti C, Bordi L, Gioia C, Horejsh D, Ippolito G, Chan PKS, Hui DSC, Sung JJY, et al.. Anti-severe acute respiratory syndrome coronavirus immune responses: the role played by V gamma 9V delta 2 T cells. J Infect Dis. 2006;193(9):1244–1249. doi:10.1086/502975.
  • Wang Z, Wan Y, Qiu C, Quiñones-Parra S, Zhu Z, Loh L, Tian D, Ren Y, Hu Y, Zhang X, et al.. Recovery from severe H7N9 disease is associated with diverse response mechanisms dominated by CD8+ T cells. Nat Commun. 2015;6:6833. doi:10.1038/ncomms7833.
  • Zhou P, Yang X-L, Wang X-G, Hu B, Zhang L, Zhang W, Si H-R, Zhu Y, Li B, Huang C-L, et al.. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579(7798):270–273. doi:10.1038/s41586-020-2012-7.
  • Ahn M, Anderson DE, Zhang Q, Tan CW, Lim BL, Luko K, Wen M, Chia WN, Mani S, Wang LC, et al.. Dampened NLRP3-mediated inflammation in bats and implications for a special viral reservoir host. Nat Microbiol. 2019;4(5):789–799. doi:10.1038/s41564-019-0371-3.
  • Zhou P, Chionh YT, Irac SE, Ahn M, Ng JH J, Fossum E, Bogen B, Ginhoux F, Irving AT, Dutertre C-A, et al.. Unlocking bat immunology: establishment of Pteropus alecto bone marrow-derived dendritic cells and macrophages. Sci Rep. 2016;6(1):38597. doi:10.1038/srep38597.
  • Guilliams M, Ginhoux F, Jakubzick C, Naik SH, Onai N, Schraml BU, Segura E, Tussiwand R, Yona S. Dendritic cells, monocytes and macrophages: a unified nomenclature based on ontogeny. Nat Rev Immunol. 2014;14(8):571–578. doi:10.1038/nri3712.
  • Zhang Z, Xu D, Li Y, Jin L, Shi M, Wang M, Zhou X, Wu H, Gao GF, Wang F-S. Longitudinal alteration of circulating dendritic cell subsets and its correlation with steroid treatment in patients with severe acute respiratory syndrome. Clin Immunol. 2005;116(3):225–235. doi:10.1016/j.clim.2005.04.015.
  • Yoshikawa T, Hill T, Li K, Peters CJ, Tseng C-TK. Severe acute respiratory syndrome (SARS) coronavirus-induced lung epithelial cytokines exacerbate SARS pathogenesis by modulating intrinsic functions of monocyte-derived macrophages and dendritic cells. J Virol. 2009;83(7):3039–3048. doi:10.1128/JVI.01792-08.
  • Zhao J, Zhao J, Legge K, Perlman S. Age-related increases in PGD(2) expression impair respiratory DC migration, resulting in diminished T cell responses upon respiratory virus infection in mice. J Clin Invest. 2011;121(12):4921–4930. doi:10.1172/JCI59777.
  • Silvin A, Yu CI, Lahaye X, Imperatore F, Brault J-B, Cardinaud S, Becker C, Kwan W-H, Conrad C, Maurin M, et al.. Constitutive resistance to viral infection in human CD141 + dendritic cells. Sci Immunol. 2017;2(13):eaai8071. doi:10.1126/sciimmunol.aai8071.
  • See P, Dutertre C-A, Chen J, Günther P, McGovern N, Irac SE, Gunawan M, Beyer M, Händler K, Duan K, et al.. Mapping the human DC lineage through the integration of high-dimensional techniques. Science. 2017;356(6342). doi:10.1126/science.aag3009
  • Ruffin N, Gea-Mallorquí E, Brouiller F, Jouve M, Silvin A, See P, Dutertre C-A, Ginhoux F, Benaroch P. Constitutive Siglec-1 expression confers susceptibility to HIV-1 infection of human dendritic cell precursors. Proc Natl Acad Sci U S A. 2019;116(43):21685–21693. doi:10.1073/pnas.1911007116.
  • Cervantes-Barragan L, Züst R, Weber F, Spiegel M, Lang KS, Akira S, Thiel V, Ludewig B. Control of coronavirus infection through plasmacytoid dendritic-cell–derived type I interferon. Blood. 2007;109(3):1131–1137. doi:10.1182/blood-2006-05-023770.
  • Liu S-Y, Sanchez DJ, Aliyari R, Lu S, Cheng G. Systematic identification of type I and type II interferon-induced antiviral factors. Proc Nat Acad Sci. 2012;109(11):4239–4244. doi:10.1073/pnas.1114981109.
  • Hadjadj J, Yatim N, Barnabei L, Corneau A, Boussier J, Smith N, Péré H, Charbit B, Bondet V, Chenevier-Gobeaux Cet al. Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients. Science. 2020 Jul 13:eabc6027. doi:10.1126/science.abc6027.
  • Chen X, Yang X, Zheng Y, Yang Y, Xing Y, Chen Z. SARS coronavirus papain-like protease inhibits the type I interferon signaling pathway through interaction with the STING-TRAF3-TBK1 complex. Protein Cell. 2014;5(5):369–381. doi:10.1007/s13238-014-0026-3.
  • Lui P-Y, Wong L-YR, Fung C-L, Siu K-L, Yeung M-L, Yuen K-S, Chan C-P, Woo PC-Y, Yuen K-Y, Jin D-Y. Middle East respiratory syndrome coronavirus M protein suppresses type I interferon expression through the inhibition of TBK1-dependent phosphorylation of IRF3. Emerg Microbes Infect. 2016;5:e39. doi:10.1038/emi.2016.33.
  • Honce R, Karlsson EA, Wohlgemuth N, Estrada LD, Meliopoulos VA, Yao J, Schultz-Cherry S. Obesity-Related Microenvironment Promotes Emergence of Virulent Influenza Virus Strains. mBio. 2020;11(2). doi:10.1128/mBio.03341-19.
  • Terán-Cabanillas E, Hernández J. Role of leptin and SOCS3 in inhibiting the type I interferon response during obesity. Inflammation. 2017;40(1):58–67. doi:10.1007/s10753-016-0452-x.
  • Ciancanelli MJ, Huang SXL, Luthra P, Garner H, Itan Y, Volpi S, Lafaille FG, Trouillet C, Schmolke M, Albrecht RA, et al.. Infectious disease. Life-threatening influenza and impaired interferon amplification in human IRF7 deficiency. Science. 2015;348(6233):448–453. doi:10.1126/science.aaa1578.
  • Hernandez N, Melki I, Jing H, Habib T, Huang SSY, Danielson J, Kula T, Drutman S, Belkaya S, Rattina V, et al.. Life-threatening influenza pneumonitis in a child with inherited IRF9 deficiency. J Exp Med. 2018;215(10):2567–2585. doi:10.1084/jem.20180628.
  • Sallard E, Lescure F-X, Yazdanpanah Y, Mentre F, Peiffer-Smadja N. Type 1 interferons as a potential treatment against COVID-19. Antiviral Res. 2020;178:104791. doi:10.1016/j.antiviral.2020.104791.
  • Zhou Q, Chen V, Shannon CP, Wei X-S, Xiang X, Wang X, Wang Z-H, Tebbutt SJ, Kollmann TR, Fish EN. Interferon-α2b treatment for COVID-19. Front. Immunol. 2020;11:1061. doi:10.3389/fimmu.2020.01061.
  • DeDiego ML, Nieto-Torres JL, Jimenez-Guardeño JM, Regla-Nava JA, Castaño-Rodriguez C, Fernandez-Delgado R, Usera F, Enjuanes L. Coronavirus virulence genes with main focus on SARS-CoV envelope gene. Virus Res. 2014;194:124–137. doi:10.1016/j.virusres.2014.07.024.
  • Angelini MM, Akhlaghpour M, Neuman BW, Buchmeier MJ. Severe acute respiratory syndrome coronavirus nonstructural proteins 3, 4, and 6 induce double-membrane vesicles moscona A, editor. mBio. 2013;4(4):e00524–13. doi:10.1128/mBio.00524-13.
  • Totura AL, Whitmore A, Agnihothram S, Schäfer A, Katze MG, Heise MT, Baric RS. Toll-like receptor 3 signaling via TRIF contributes to a protective innate immune response to severe acute respiratory syndrome coronavirus infection. mBio. 2015;6(3):e00638–00615. doi:10.1128/mBio.00638-15.
  • Wong HH, Fung TS, Fang S, Huang M, Le MT, Liu DX. Accessory proteins 8b and 8ab of severe acute respiratory syndrome coronavirus suppress the interferon signaling pathway by mediating ubiquitin-dependent rapid degradation of interferon regulatory factor 3. Virology. 2018;515:165–175. doi:10.1016/j.virol.2017.12.028.
  • Yang Y, Zhang L, Geng H, Deng Y, Huang B, Guo Y, Zhao Z, Tan W. The structural and accessory proteins M, ORF 4a, ORF 4b, and ORF 5 of Middle East respiratory syndrome coronavirus (MERS-CoV) are potent interferon antagonists. Protein Cell. 2013;4(12):951–961. doi:10.1007/s13238-013-3096-8.
  • Selinger M. Towards formal representation and evaluation of arguments. Argumentation. 2014;28(3):379–393. doi:10.1007/s10503-014-9325-3.
  • Channappanavar R, Fehr AR, Vijay R, Mack M, Zhao J, Meyerholz DK, Perlman S. Dysregulated type I interferon and inflammatory monocyte-macrophage responses cause lethal pneumonia in SARS-CoV-infected mice. Cell Host Microbe. 2016;19(2):181–193. doi:10.1016/j.chom.2016.01.007.
  • Cameron MJ, Ran L, Xu L, Danesh A, Bermejo-Martin JF, Cameron CM, Muller MP, Gold WL, Richardson SE, Poutanen SM, et al.. Interferon-mediated immunopathological events are associated with atypical innate and adaptive immune responses in patients with severe acute respiratory syndrome. J Virol. 2007;81(16):8692–8706. doi:10.1128/JVI.00527-07.
  • Zhang H, Hu Q, Zhang M, Yang F, Peng C, Zhang Z, Huang C. Bach2 deficiency leads to spontaneous expansion of IL-4-producing T follicular helper cells and autoimmunity. Front Immunol. 2019;10:2050. doi:10.3389/fimmu.2019.02050.
  • Scheuplein VA, Seifried J, Malczyk AH, Miller L, Höcker L, Vergara-Alert J, Dolnik O, Zielecki F, Becker B, Spreitzer I, et al.. High secretion of interferons by human plasmacytoid dendritic cells upon recognition of middle east respiratory syndrome coronavirus perlman S, editor. J Virol. 2015;89(7):3859–3869. doi:10.1128/JVI.03607-14.
  • Zhao J, Wohlford-Lenane C, Zhao J, Fleming E, Lane TE, McCray PB, Perlman S. Intranasal treatment with Poly(I{middle dot}C) protects aged mice from lethal respiratory virus infections. J Virol. 2012;86(21):11416–11424. doi:10.1128/JVI.01410-12.
  • Pérez-Girón JV, Belicha-Villanueva A, Hassan E, Gómez-Medina S, Cruz JLG, Lüdtke A, Ruibal P, Albrecht RA, García-Sastre A, Muñoz-Fontela C. Mucosal polyinosinic-polycytidylic acid improves protection elicited by replicating influenza vaccines via enhanced dendritic cell function and T cell immunity. J Immunol. 2014;193(3):1324–1332. doi:10.4049/jimmunol.1400222.
  • Sheahan T, Morrison TE, Funkhouser W, Uematsu S, Akira S, Baric RS, Heise MT. MyD88 is required for protection from lethal infection with a mouse-adapted SARS-CoV Subbarao K, editor. PLoS Pathog. 2008;4(12):e1000240. doi:10.1371/journal.ppat.1000240.
  • Kulcsar KA, Coleman CM, Beck SE, Frieman MB. Comorbid diabetes results in immune dysregulation and enhanced disease severity following MERS-CoV infection. JCI Insight. 2019;4(20):e131774. doi:10.1172/jci.insight.131774.
  • Chen Y, Li L. SARS-CoV-2: virus dynamics and host response. Lancet Infect Dis. 2020 Mar;S1473309920302358. doi:10.1016/S1473-3099(20)30235-8.
  • Poon LLM, Chan KH, Wong OK, Cheung TKW, Ng I, Zheng B, Seto WH, Yuen KY, Guan Y, Peiris JSM. Detection of SARS coronavirus in patients with severe acute respiratory syndrome by conventional and real-time quantitative reverse transcription-PCR assays. Clin Chem. 2004;50(1):67–72. doi:10.1373/clinchem.2003.023663.
  • Imai Y, Kuba K, Neely GG, Yaghubian-Malhami R, Perkmann T, van Loo G, Ermolaeva M, Veldhuizen R, Leung YHC, Wang H, et al.. Identification of oxidative stress and Toll-like receptor 4 signaling as a key pathway of acute lung injury. Cell. 2008;133(2):235–249. doi:10.1016/j.cell.2008.02.043.
  • Martínez Gómez JM, Periasamy P, Dutertre C-A, Irving AT, Ng JHJ, Crameri G, Baker ML, Ginhoux F, Wang L-F, Alonso S. Phenotypic and functional characterization of the major lymphocyte populations in the fruit-eating bat Pteropus alecto. Sci Rep. 2016;6:37796. doi:10.1038/srep37796.
  • Channappanavar R, Zhao J, Perlman S. T cell-mediated immune response to respiratory coronaviruses. Immunol Res. 2014;59(1–3):118–128. doi:10.1007/s12026-014-8534-z.
  • Chu H, Zhou J, Wong BH-Y, Li C, Chan JF-W, Cheng Z-S, Yang D, Wang D, Lee AC-Y, Li C, et al.. Middle east respiratory syndrome coronavirus efficiently infects human primary T lymphocytes and activates the extrinsic and intrinsic apoptosis pathways. J Infect Dis. 2016;213(6):904–914. doi:10.1093/infdis/jiv380.
  • Zhao J, Zhao J, Van Rooijen N, Perlman S. Evasion by stealth: inefficient immune activation underlies poor T cell response and severe disease in SARS-CoV-infected mice. PLoS Pathog. 2009;5(10):e1000636. doi:10.1371/journal.ppat.1000636.
  • Bahl K, Kim S-K, Calcagno C, Ghersi D, Puzone R, Celada F, Selin LK, Welsh RM. IFN-induced attrition of CD8 T cells in the presence or absence of cognate antigen during the early stages of viral infections. J Immunol. 2006;176(7):4284–4295. doi:10.4049/jimmunol.176.7.4284.
  • Qin C, Zhou L, Hu Z, Zhang S, Yang S, Tao Y, Xie C, Ma K, Shang K, Wang W, et al.. Dysregulation of immune response in patients with COVID-19 in Wuhan, China. Clin Infect Dis. 2020 Mar 12. doi:10.1093/cid/ciaa248.
  • Liu Z, Long W, Tu M, Chen S, Huang Y, Wang S, Zhou W, Chen D, Zhou L, Wang M, et al.. Lymphocyte subset (CD4+, CD8+) counts reflect the severity of infection and predict the clinical outcomes in patients with COVID-19. J Infect. 2020 Apr:S0163445320301821. doi:10.1016/j.jinf.2020.03.054.
  • Zhao J, Zhao J, Perlman S. T cell responses are required for protection from clinical disease and for virus clearance in severe acute respiratory syndrome coronavirus-infected mice. JVI. 2010;84(18):9318–9325. doi:10.1128/JVI.01049-10.
  • Pope M, Chung SW, Mosmann T, Leibowitz JL, Gorczynski RM, Levy GA. Resistance of naive mice to murine hepatitis virus strain 3 requires development of a Th1, but not a Th2, response, whereas pre-existing antibody partially protects against primary infection. J Immunol. 1996;156:3342–3349.
  • Turner DL, Farber DL. Mucosal resident memory CD4 T cells in protection and immunopathology. Front Immunol. 2014;5:331. doi:10.3389/fimmu.2014.00331.
  • Swain SL, McKinstry KK, Strutt TM. Expanding roles for CD4+ T cells in immunity to viruses. Nat Rev Immunol. 2012;12(2):136–148. doi:10.1038/nri3152.
  • Teijaro JR, Turner D, Pham Q, Wherry EJ, Lefrançois L, Farber DL. Cutting edge: tissue-retentive lung memory CD4 T cells mediate optimal protection to respiratory virus infection. J I. 2011;187(11):5510–5514. doi:10.4049/jimmunol.1102243.
  • Xu X, Gao X. Immunological responses against SARS-coronavirus infection in humans. Cell Mol Immunol. 2004;1:119–122.
  • Wang Y-D, Sin W-YF, Xu G-B, Yang -H-H, Wong T, Pang X-W, He X-Y, Zhang H-G, Ng JNL, Cheng C-S-S, et al.. T-cell epitopes in severe acute respiratory syndrome (SARS) coronavirus spike protein elicit a specific T-cell immune response in patients who recover from SARS. J Virol. 2004;78(11):5612–5618. doi:10.1128/JVI.78.11.5612-5618.2004.
  • Yang L-T, Peng H, Zhu Z-L, Li G, Huang Z-T, Zhao Z-X, Koup RA, Bailer RT, Wu C-Y. Long-lived effector/central memory T-cell responses to severe acute respiratory syndrome coronavirus (SARS-CoV) S antigen in recovered SARS patients. Clin Immunol. 2006;120(2):171–178. doi:10.1016/j.clim.2006.05.002.
  • Peng H, Yang L, Wang L, Li J, Huang J, Lu Z, Koup RA, Bailer RT, Wu C. Long-lived memory T lymphocyte responses against SARS coronavirus nucleocapsid protein in SARS-recovered patients. Virology. 2006;351(2):466–475. doi:10.1016/j.virol.2006.03.036.
  • Oh H-LJ, Chia A, Chang CXL, Leong HN, Ling KL, Grotenbreg GM, Gehring AJ, Tan YJ, Bertoletti A. Engineering T cells specific for a dominant severe acute respiratory syndrome coronavirus CD8 T cell epitope. J Virol. 2011;85(20):10464–10471. doi:10.1128/JVI.05039-11.
  • Wang Z, Zhu L, Nguyen THO, Wan Y, Sant S, Quiñones-Parra SM, Crawford JC, Eltahla AA, Rizzetto S, Bull RA, et al.. Clonally diverse CD38+HLA-DR+CD8+ T cells persist during fatal H7N9 disease. Nat Commun. 2018;9(1):824. doi:10.1038/s41467-018-03243-7.
  • Everitt AR, Clare S, Pertel T, John SP, Wash RS, Smith SE, Chin CR, Feeley EM, Sims JS, Adams DJ, et al.. IFITM3 restricts the morbidity and mortality associated with influenza. Nature. 2012;484(7395):519–523. doi:10.1038/nature10921.
  • Wang Z, Zhang A, Wan Y, Liu X, Qiu C, Xi X, Ren Y, Wang J, Dong Y, Bao M, et al.. Early hypercytokinemia is associated with interferon-induced transmembrane protein-3 dysfunction and predictive of fatal H7N9 infection. Proc Natl Acad Sci U S A. 2014;111(2):769–774. doi:10.1073/pnas.1321748111.
  • Baize S, Leroy EM, Georges-Courbot MC, Capron M, Lansoud-Soukate J, Debré P, Fisher-Hoch SP, McCormick JB, Georges AJ. Defective humoral responses and extensive intravascular apoptosis are associated with fatal outcome in Ebola virus-infected patients. Nat Med. 1999;5(4):423–426. doi:10.1038/7422.
  • Wauquier N, Becquart P, Padilla C, Baize S, Leroy EM. Human fatal zaire ebola virus infection is associated with an aberrant innate immunity and with massive lymphocyte apoptosis. PLoS Negl Trop Dis. 2010;4(10). doi:10.1371/journal.pntd.0000837.
  • McElroy AK, Akondy RS, Davis CW, Ellebedy AH, Mehta AK, Kraft CS, Lyon GM, Ribner BS, Varkey J, Sidney J, et al.. Human Ebola virus infection results in substantial immune activation. Proc Natl Acad Sci USA. 2015;112(15):4719–4724. doi:10.1073/pnas.1502619112.
  • Grifoni A, Weiskopf D, Ramirez SI, Mateus J, Dan JM, Moderbacher CR, Rawlings SA, Sutherland A, Premkumar L, Jadi RS, et al.. Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals. Cell. 2020;181(7):1489–1501.e15. doi:10.1016/j.cell.2020.05.015.
  • Diao B, Wang C, Tan Y, Chen X, Liu Y, Ning L, Chen L, Li M, Liu Y, Wang G, et al. Reduction and Functional Exhaustion of T Cells in Patients with Coronavirus Disease 2019 (COVID-19). Infect. Dis. (except HIV/AIDS). 2020.
  • Zhang X, Tan Y, Ling Y, Lu G, Liu F, Yi Z, Jia X, Wu M, Shi B, Xu S, et al.. Viral and host factors related to the clinical outcome of COVID-19. Nature. 2020 May 20. doi:10.1038/s41586-020-2355-0.
  • Liu Y, Pang Y, Hu Z, Wu M, Wang C, Feng Z, Mao C, Tan Y, Liu Y, Chen L, et al.. Thymosin alpha 1 (Tα1) reduces the mortality of severe COVID-19 by restoration of lymphocytopenia and reversion of exhausted T cells. Clin Infect Dis. 2020 May 22. doi:10.1093/cid/ciaa630.
  • Mathew D, Giles JR, Baxter AE, Oldridge DA, Greenplate AR, Wu JE, Alanio C, Kuri-Cervantes L, Pampena MB, D’Andrea K, et al.. Deep immune profiling of COVID-19 patients reveals distinct immunotypes with therapeutic implications. Science. 2020 Jul 15:eabc8511. doi:10.1126/science.abc8511.
  • Lv H, Wu NC, Tak-Yin Tsang O, Yuan M, Perera RAPM, Leung WS, So RTY, Chun Chan JM, Yip GK, Hong Chik TS, et al.. Cross-reactive antibody response between SARS-CoV-2 and SARS-CoV infections. Cell Rep. 2020 May;18:107725. doi:10.1016/j.celrep.2020.107725.
  • Grifoni A, Sidney J, Zhang Y, Scheuermann RH, Peters B, Sette A. A sequence homology and bioinformatic approach can predict candidate targets for immune responses to SARS-CoV-2. Cell Host Microbe. 2020;27(4):671–680.e2. doi:10.1016/j.chom.2020.03.002.
  • Mateus J, Grifoni A, Tarke A, Sidney J, Ramirez SI, Dan JM, Burger ZC, Rawlings SA, Smith DM, Phillips E, et al. Selective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans. Science. 2020 Aug 4:eabd3871. doi:10.1126/science.abd3871.
  • Le Bert N, Tan AT, Kunasegaran K, Tham CYL, Hafezi M, Chia A, Chng MHY, Lin M, Tan N, Linster M, et al.. SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls. Nature. 2020 Jul 15. doi:10.1038/s41586-020-2550-z.
  • Escobar LE, Molina-Cruz A, Barillas-Mury C. BCG vaccine protection from severe coronavirus disease 2019 (COVID-19). Proc Natl Acad Sci U S A. 2020 Jul 9. doi: 10.1073/pnas.2008410117
  • Klinger D, Blass I, Rappoport N, Linial M. Significantly improved COVID-19 outcomes in countries with higher BCG vaccination coverage: a multivariable analysis. Vaccines (Basel). 2020;8:3. doi:10.3390/vaccines8030378.
  • Miller A, Reandelar MJ, Fasciglione K, Roumenova V, Li Y, Otazu GH. Correlation between universal BCG vaccination policy and reduced morbidity and mortality for COVID-19: an epidemiological study. 2020. doi:10.1101/2020.03.24.20042937.
  • Berg MK, Yu Q, Salvador CE, Melani I, Kitayama S. Mandated Bacillus Calmette-Guérin (BCG) vaccination predicts flattened curves for the spread of COVID-19. Sci. Adv. 2020;6(32):eabc1463. doi:10.1126/sciadv.abc1463.
  • M-G H-D, Stuart EA, Black RE. Acute lower respiratory infection among bacille calmette-guérin (BCG)–vaccinated children. Pediatrics. 2014;133(1):e73–e81. doi:10.1542/peds.2013-2218.
  • Leentjens J, Kox M, Stokman R, Gerretsen J, Diavatopoulos DA, van Crevel R, Rimmelzwaan GF, Pickkers P, Netea MG. BCG vaccination enhances the immunogenicity of subsequent influenza vaccination in healthy volunteers: a randomized, placebo-controlled pilot study. J Infect Dis. 2015;212(12):1930–1938. doi:10.1093/infdis/jiv332.
  • Hamiel U, Kozer E, Youngster I. SARS-CoV-2 rates in BCG-vaccinated and unvaccinated young adults. JAMA. 2020 May 13. doi: 10.1001/jama.2020.8189
  • Mulder WJM, Ochando J, Joosten LAB, Fayad ZA, Netea MG. Therapeutic targeting of trained immunity. Nat Rev Drug Discov. 2019;18(7):553–566. doi:10.1038/s41573-019-0025-4.
  • Huang J, Cao Y, Du J, Bu X, Ma R, Wu C. Priming with SARS CoV S DNA and boosting with SARS CoV S epitopes specific for CD4+ and CD8+ T cells promote cellular immune responses. Vaccine. 2007;25(39–40):6981–6991. doi:10.1016/j.vaccine.2007.06.047.
  • Gutierrez L, Beckford J, Alachkar H. Deciphering the TCR repertoire to solve the COVID-19 Mystery. Trends Pharmacol Sci. 2020;41(8):518–530. doi:10.1016/j.tips.2020.06.001.
  • Wu H, Zhu H, Yuan C, Yao C, Luo W, Shen X, Wang J, Shao J, Xiang Y. Clinical and immune features of hospitalized pediatric patients with coronavirus disease 2019 (COVID-19) in Wuhan, China. JAMA Netw Open. 2020;3(6):e2010895. doi:10.1001/jamanetworkopen.2020.10895.
  • Ni M, Tian F-B, Xiang -D-D, Yu B. Characteristics of inflammatory factors and lymphocyte subsets in patients with severe COVID-19. J Med Virol. 2020 May 29. doi: 10.1002/jmv.26070
  • Woodruff M, Ramonell R, Cashman K, Nguyen D, Ley A, Kyu S, Saini A, Haddad N, Chen W, Howell JC, et al.. Critically ill SARS-CoV-2 patients display lupus-like hallmarks of extrafollicular B cell activation. medRxiv. 2020 May 3. doi:10.1101/2020.04.29.20083717.
  • Aziz M, Brenner M, Wang P. Therapeutic Potential of B-1a Cells in COVID-19. Shock. 2020 Jun 26. doi: 10.1097/SHK.0000000000001610
  • Wilk AJ, Rustagi A, Zhao NQ, Roque J, Martinez-Colon GJ, McKechnie JL, Ivison GT, Ranganath T, Vergara R, Hollis T, et al.. A single-cell atlas of the peripheral immune response to severe COVID-19. medRxiv. 2020 Apr 23. doi:10.1101/2020.04.17.20069930.
  • Schultheiß C, Paschold L, Simnica D, Mohme M, Willscher E, von Wenserski L, Scholz R, Wieters I, Dahlke C, Tolosa E, et al.. Next-generation sequencing of T and B cell receptor repertoires from COVID-19 patients showed signatures associated with severity of disease. Immunity. 2020 Jun 30. doi:10.1016/j.immuni.2020.06.024.
  • Huang Q, Hu J, Tang J, Xu L, Ye L. Molecular basis of the differentiation and function of virus specific follicular helper CD4+ T Cells. Front Immunol. 2019;10:249. doi:10.3389/fimmu.2019.00249.
  • Deenick EK, Ma CS. The regulation and role of T follicular helper cells in immunity. Immunology. 2011;134(4):361–367. doi:10.1111/j.1365-2567.2011.03487.x.
  • Locci M, Havenar-Daughton C, Landais E, Wu J, Kroenke MA, Arlehamn CL, Su LF, Cubas R, Davis MM, Sette A, et al.. Human circulating PD-1+CXCR3-CXCR5+ memory Tfh cells are highly functional and correlate with broadly neutralizing HIV antibody responses. Immunity. 2013;39(4):758–769. doi:10.1016/j.immuni.2013.08.031.
  • Thevarajan I, Nguyen THO, Koutsakos M, Druce J, Caly L, van de Sandt CE, Jia X, Nicholson S, Catton M, Cowie B, et al.. Breadth of concomitant immune responses prior to patient recovery: a case report of non-severe COVID-19. Nat Med. 2020 Mar 16. doi:10.1038/s41591-020-0819-2.
  • Mesin L, Ersching J, Victora GD. Germinal center B Cell dynamics. Immunity. 2016;45(3):471–482. doi:10.1016/j.immuni.2016.09.001.
  • Ksiazek TG, Rollin PE, Williams AJ, Bressler DS, Martin ML, Swanepoel R, Burt FJ, Leman PA, Khan AS, Rowe AK, et al.. Clinical virology of ebola hemorrhagic fever (EHF): virus, virus antigen, and IgG and IgM antibody findings among Ehf patients in KikWit, democratic republic of the congo, 1995. J Infect Dis. 1999;179(s1):S177–S187. doi:10.1086/514321.
  • Rowe AK, Bertolli J, Khan AS, Mukunu R, Muyembe-Tamfum JJ, Bressler D, Williams AJ, Peters CJ, Rodriguez L, Feldmann H, et al.. Clinical, virologic, and immunologic follow-up of convalescent Ebola hemorrhagic fever patients and their household contacts, Kikwit, Democratic Republic of the Congo. Commission de Lutte contre les Epidémies à Kikwit. J Infect Dis. 1999;179(Suppl 1):S28–35. doi:10.1086/514318.
  • Woo PCY, Lau SKP, Wong BHL, Chan K-H, Hui W-T, Kwan GSW, Peiris JSM, Couch RB, Yuen K-Y. False-positive results in a recombinant severe acute respiratory syndrome-associated coronavirus (SARS-CoV) nucleocapsid enzyme-linked immunosorbent assay due to HCoV-OC43 and HCoV-229E rectified by Western blotting with recombinant SARS-CoV spike polypeptide. J Clin Microbiol. 2004;42(12):5885–5888. doi:10.1128/JCM.42.12.5885-5888.2004.
  • Agnihothram S, Gopal R, Yount BL, Donaldson EF, Menachery VD, Graham RL, Scobey TD, Gralinski LE, Denison MR, Zambon M, et al.. Evaluation of serologic and antigenic relationships between middle eastern respiratory syndrome coronavirus and other coronaviruses to develop vaccine platforms for the rapid response to emerging coronaviruses. J Infect Dis. 2014;209(7):995–1006. doi:10.1093/infdis/jit609.
  • Sui J, Li W, Roberts A, Matthews LJ, Murakami A, Vogel L, Wong SK, Subbarao K, Farzan M, Marasco WA. Evaluation of human monoclonal antibody 80R for immunoprophylaxis of severe acute respiratory syndrome by an animal study, epitope mapping, and analysis of spike variants. J Virol. 2005;79(10):5900–5906. doi:10.1128/JVI.79.10.5900-5906.2005.
  • Muth D, Corman VM, Meyer B, Assiri A, Al-Masri M, Farah M, Steinhagen K, Lattwein E, Al-Tawfiq JA, Albarrak A, et al.. Infectious Middle East respiratory syndrome coronavirus excretion and serotype variability based on live virus isolates from patients in Saudi Arabia. J Clin Microbiol. 2015;53(9):2951–2955. doi:10.1128/JCM.01368-15.
  • Channappanavar R, Fett C, Zhao J, Meyerholz DK, Perlman S. Virus-specific memory CD8 T cells provide substantial protection from lethal severe acute respiratory syndrome coronavirus infection. J Virol. 2014;88(19):11034–11044. doi:10.1128/JVI.01505-14.
  • Peiris JSM, Chu CM, Cheng VCC, Chan KS, Hung IFN, Poon LLM, Law KI, Tang BSF, Hon TYW, Chan CS, et al.. Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study. Lancet. 2003;361(9371):1767–1772. doi:10.1016/s0140-6736(03)13412-5.
  • Guo L, Ren L, Yang S, Xiao M, Chang D, Yang F, Dela Cruz CS, Wang Y, Wu C, Xiao Y, et al.. Profiling early humoral response to diagnose novel coronavirus disease (COVID-19). Clin Infect Dis. 2020 Mar 21. doi:10.1093/cid/ciaa310.
  • Liu W, Liu L, Kou G, Zheng Y, Ding Y, Ni W, Wang Q, Tan L, Wu W, Tang S, et al.. Evaluation of nucleocapsid and spike protein-based ELISAs for detecting antibodies against SARS-CoV-2. J Clin Microbiol. 2020 Mar 30. doi:10.1128/JCM.00461-20.
  • Wölfel R, Corman VM, Guggemos W, Seilmaier M, Zange S, Müller MA, Niemeyer D, Jones TC, Vollmar P, Rothe C, et al.. Virological assessment of hospitalized patients with COVID-2019. Nature. 2020 Apr 1. doi:10.1038/s41586-020-2196-x.
  • Lou B, Li T-D, Zheng S-F, Su -Y-Y, Li Z-Y, W L, Yu F, Ge S-X, Zou Q-D, Q Y, et al.. Serology characteristics of SARS-CoV-2 infection since exposure and post symptom onset. Eur Respir J. 2020 May 19. doi:10.1183/13993003.00763-2020.
  • Edouard S, Colson P, Melenotte C, La Scola B, Tissot-Dupont H. Evaluating serological status of COVID-19 patients using an indirect immunofluorescent assay, France. Eur J Clin Microbiol Infect Dis. 2020.
  • Okba NMA, Müller MA, Li W, Wang C, GeurtsvanKessel CH, Corman VM, Lamers MM, Sikkema RS, de Bruin E, Chandler FD, et al.. Severe acute respiratory syndrome coronavirus 2-specific antibody responses in coronavirus disease 2019 patients. Emerg Infect Dis. 2020;26(7). doi:10.3201/eid2607.200841
  • Yongchen Z, Shen H, Wang X, Shi X, Li Y, Yan J, Chen Y, Gu B. Different longitudinal patterns of nucleic acid and serology testing results based on disease severity of COVID-19 patients. Emerg Microbes Infect. 2020 Apr;20:1–14. doi:10.1080/22221751.2020.1756699.
  • Liu L, Wei Q, Lin Q, Fang J, Wang H, Kwok H, Tang H, Nishiura K, Peng J, Tan Z, et al.. Anti-spike IgG causes severe acute lung injury by skewing macrophage responses during acute SARS-CoV infection. JCI Insight. 2019;4(4). doi:10.1172/jci.insight.123158
  • Walls AC, Park Y-J, Tortorici MA, Wall A, McGuire AT, Veesler D. Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell. 2020;181(2):281–292.e6. doi:10.1016/j.cell.2020.02.058.
  • Amanat F, Stadlbauer D, Strohmeier S, Nguyen THO, Chromikova V, McMahon M, Jiang K, Arunkumar GA, Jurczyszak D, Polanco J, et al. A serological assay to detect SARS-CoV-2 seroconversion in humans. Nat Med. 2020;26(7):1033–1036. doi:10.1038/s41591-020-0913-5
  • Robbiani DF, Gaebler C, Muecksch F, Lorenzi JCC, Wang Z, Cho A, Agudelo M, Barnes CO, Gazumyan A, Finkin S, et al.. Convergent antibody responses to SARS-CoV-2 in convalescent individuals. Nature. 2020 Jun 18. doi:10.1038/s41586-020-2456-9.
  • Shen C, Wang Z, Zhao F, Yang Y, Li J, Yuan J, Wang F, Li D, Yang M, Xing L, et al.. Treatment of 5 critically ill patients with COVID-19 with convalescent plasma. JAMA. 2020 Mar 27. doi:10.1001/jama.2020.4783.
  • Cheng Y, Wong R, Soo YOY, Wong WS, Lee CK, Ng MHL, Chan P, Wong KC, Leung CB, Cheng G. Use of convalescent plasma therapy in SARS patients in Hong Kong. Eur J Clin Microbiol Infect Dis. 2005;24(1):44–46. doi:10.1007/s10096-004-1271-9.
  • Hung IF, To KK, Lee C-K, Lee K-L, Chan K, Yan -W-W, Liu R, Watt C-L, Chan W-M, Lai K-Y, et al.. Convalescent Plasma Treatment Reduced Mortality in Patients With Severe Pandemic Influenza A (H1N1) 2009 Virus Infection. Clin Infect Diseases. 2011;52(4):447–456. doi:10.1093/cid/ciq106.
  • Zhou B, Zhong N, Guan Y. Treatment with convalescent plasma for influenza A (H5N1) infection. N Engl J Med. 2007;357(14):1450–1451. doi:10.1056/NEJMc070359.
  • Ko J-H, Seok H, Cho SY, Ha YE, Baek JY, Kim SH, Kim Y-J, Park JK, Chung CR, Kang E-S, et al.. Challenges of convalescent plasma infusion therapy in Middle East respiratory coronavirus infection: a single centre experience. Antivir Ther. 2018;23(7):617–622. doi:10.3851/IMP3243.
  • van Griensven J, Edwards T, de Lamballerie X, Semple MG, Gallian P, Baize S, Horby PW, Raoul H, Magassouba N, Antierens A, et al.. Evaluation of convalescent plasma for ebola virus disease in guinea. N Engl J Med. 2016;374(1):33–42. doi:10.1056/NEJMoa1511812.
  • Florescu DF, Kalil AC, Hewlett AL, Schuh AJ, Stroher U, Uyeki TM, Smith PW. Administration of brincidofovir and convalescent plasma in a patient with ebola virus disease. Clin Infect Dis. 2015;61(6):969–973. doi:10.1093/cid/civ395.
  • Duan K, Liu B, Li C, Zhang H, Yu T, Qu J, Zhou M, Chen L, Meng S, Hu Y, et al.. Effectiveness of convalescent plasma therapy in severe COVID-19 patients. Proc Natl Acad Sci USA. 2020 Apr 6:202004168. doi:10.1073/pnas.2004168117.
  • Case JB, Rothlauf PW, Chen RE, Kafai NM, Fox JM, Shrihari S, McCune BT, Harvey IB, Smith B, Keeler SP, et al.. Replication-competent vesicular stomatitis virus vaccine vector protects against SARS-CoV-2-mediated pathogenesis. bioRxiv. 2020 Jul 10. doi:10.1101/2020.07.09.196386.
  • Zhu F-C, Li Y-H, Guan X-H, Hou L-H, Wang W-J, Li J-X, Wu S-P, Wang B-S, Wang Z, Wang L, et al.. Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomised, first-in-human trial. Lancet. 2020;395(10240):1845–1854. doi:10.1016/S0140-6736(20)31208-3.
  • Rathnasinghe R, Strohmeier S, Amanat F, Gillespie VL, Krammer F, García-Sastre A, Coughlan L, Schotsaert M, Uccellini M. Comparison of Transgenic and Adenovirus hACE2 Mouse Models for SARS-CoV-2 Infection. bioRxiv. 2020 Jul 6. doi:10.1101/2020.07.06.190066.
  • Jackson LA, Anderson EJ, Rouphael NG, Roberts PC, Makhene M, Coler RN, McCullough MP, Chappell JD, Denison MR, Stevens LJ, et al.. An mRNA vaccine against SARS-CoV-2 — preliminary report. N Engl J Med. 2020 Jul 14:NEJMoa2022483. doi:10.1056/NEJMoa2022483.
  • NIH clinical trial of investigational vaccine for COVID-19 begins. 2020 Mar 16.
  • Tang J, Zhang N, Tao X, Zhao G, Guo Y, Tseng C-TK, Jiang S, Du L, Zhou Y. Optimization of antigen dose for a receptor-binding domain-based subunit vaccine against MERS coronavirus. Hum Vaccin Immunother. 2015;11(5):1244–1250. doi:10.1080/21645515.2015.1021527.
  • Enjuanes L, Dediego ML, Alvarez E, Deming D, Sheahan T, Baric R. Vaccines to prevent severe acute respiratory syndrome coronavirus-induced disease. Virus Res. 2008;133(1):45–62. doi:10.1016/j.virusres.2007.01.021.
  • Zhang ZH, Jhaveri DJ, Marshall VM, Bauer DC, Edson J, Narayanan RK, Robinson GJ, Lundberg AE, Bartlett PF, Wray NR, et al.. A comparative study of techniques for differential expression analysis on RNA-Seq data provero P, editor. PLoS ONE. 2014;9(8):e103207. doi:10.1371/journal.pone.0103207.
  • Papaneri AB, Johnson RF, Wada J, Bollinger L, Jahrling PB, Kuhn JH. Middle East respiratory syndrome: obstacles and prospects for vaccine development. Expert Rev Vaccines. 2015;14(7):949–962. doi:10.1586/14760584.2015.1036033.
  • Enjuanes L, Zuñiga S, Castaño-Rodriguez C, Gutierrez-Alvarez J, Canton J, Sola I. Sola Basis of Coronavirus Virulence and Vaccine Development. Adv. Virus Res. 2016;96:245–286. doi:10.1016/bs.aivir.2016.08.003.
  • Wang C, Li W, Drabek D, Okba NMA, van Haperen R, Osterhaus ADME, van Kuppeveld FJM, Haagmans BL, Grosveld F, Bosch B-J. A human monoclonal antibody blocking SARS-CoV-2 infection. Nat Commun. 2020;11(1):2251. doi:10.1038/s41467-020-16256-y.
  • Tian X, Li C, Huang A, Xia S, Lu S, Shi Z, Lu L, Jiang S, Yang Z, Wu Y, et al.. Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus-specific human monoclonal antibody. Emerg Microbes Infect. 2020;9(1):382–385. doi:10.1080/22221751.2020.1729069.
  • Pinto D, Park Y-J, Beltramello M, Walls AC, Tortorici MA, Bianchi S, Jaconi S, Culap K, Zatta F, De Marco A, et al.. Structural and functional analysis of a potent sarbecovirus neutralizing antibody. bioRxiv. 2020 Apr 9. doi:10.1101/2020.04.07.023903.
  • Dogan M, Kozhaya L, Placek L, Gunter C, Yigit M, Hardy R, Plassmeyer M, Coatney P, Lillard K, Bukhari Z, et al.. Novel SARS-CoV-2 specific antibody and neutralization assays reveal wide range of humoral immune response during COVID-19. medRxiv. 2020 Jul 8. doi:10.1101/2020.07.07.20148106.
  • Kreer C, Zehner M, Weber T, Ercanoglu MS, Gieselmann L, Rohde C, Halwe S, Korenkov M, Schommers P, Vanshylla K, et al.. Longitudinal Isolation of Potent Near-Germline SARS-CoV-2-Neutralizing Antibodies from COVID-19 Patients. Cell. 2020 Jul 13. doi:10.1016/j.cell.2020.06.044.
  • Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, Liu S, Zhao P, Liu H, Zhu L, et al.. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020 Feb 18. doi:10.1016/S2213-2600(20)30076-X.
  • Ding Y, Wang H, Shen H, Li Z, Geng J, Han H, Cai J, Li X, Kang W, Weng D, et al.. The clinical pathology of severe acute respiratory syndrome (SARS): a report from China. J Pathol. 2003;200(3):282–289. doi:10.1002/path.1440.
  • Ng DL, Al Hosani F, Keating MK, Gerber SI, Jones TL, Metcalfe MG, Tong S, Tao Y, Alami NN, Haynes LM, et al.. Clinicopathologic, immunohistochemical, and ultrastructural findings of a fatal case of Middle East respiratory syndrome coronavirus infection in the united arab emirates, April 2014. Am J Pathol. 2016;186(3):652–658. doi:10.1016/j.ajpath.2015.10.024.
  • Khanolkar A, Kirschmann DA, Caparelli EA, Wilks JD, Cerullo JM, Bergerson JRE, Jennings LJ, Fuleihan RL. CD4 T cell–restricted IL-2 signaling defect in a patient with a novel IFNGR1 deficiency. J Allergy Clin Immunol. 2018;141(1):435–439.e7. doi:10.1016/j.jaci.2017.08.018.
  • Wu GF, Dandekar AA, Pewe L, Perlman S. CD4 and CD8 T cells have redundant but not identical roles in virus-induced demyelination. J Immunol. 2000;165(4):2278–2286. doi:10.4049/jimmunol.165.4.2278.
  • Trandem K, Zhao J, Fleming E, Perlman S. Highly activated cytotoxic CD8 T cells express protective IL-10 at the peak of coronavirus-induced encephalitis. J Immunol. 2011;186(6):3642–3652. doi:10.4049/jimmunol.1003292.
  • Sun J, Madan R, Karp CL, Braciale TJ. Effector T cells control lung inflammation during acute influenza virus infection by producing IL-10. Nat Med. 2009;15(3):277–284. doi:10.1038/nm.1929.
  • Cecere TE, Todd SM, Leroith T. Regulatory T cells in arterivirus and coronavirus infections: do they protect against disease or enhance it?. Viruses. 2012;4(5):833–846. doi:10.3390/v4050833.
  • de Lang A, Osterhaus ADME, Haagmans BL. Interferon-gamma and interleukin-4 downregulate expression of the SARS coronavirus receptor ACE2 in Vero E6 cells. Virology. 2006;353(2):474–481. doi:10.1016/j.virol.2006.06.011.
  • Silva-Filho JL, Caruso-Neves C, Pinheiro AAS. Angiotensin II type-1 receptor (AT1R) regulates expansion, differentiation, and functional capacity of antigen-specific CD8+ T cells. Sci Rep. 2016;6(1):35997. doi:10.1038/srep35997.
  • Zheng M, Gao Y, Wang G, Song G, Liu S, Sun D, Xu Y, Tian Z. Functional exhaustion of antiviral lymphocytes in COVID-19 patients. Cell Mol Immunol. 2020 Mar 19. doi: 10.1038/s41423-020-0402-2
  • Liu P, Pan X, Chen C, Niu T, Shuai X, Wang J, Chen X, Liu J, Guo Y, Xie L, et al.. Nivolumab treatment of relapsed/refractory Epstein-Barr virus–associated hemophagocytic lymphohistiocytosis in adults. Blood. 2020;135(11):826–833. doi:10.1182/blood.2019003886.
  • Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020 Mar 3. doi: 10.1007/s00134-020-05991-x
  • Liu T, Zhang J, Yang Y, Ma H, Li Z, Zhang J, Cheng J, Zhang X, Zhao Y, Xia Z, et al. The role of interleukin-6 in monitoring severe case of coronavirus disease 2019. EMBO Mol Med. 2020;12(7):e12421. doi:10.15252/emmm.202012421.
  • yongwen C, Feng Z, Diao B, Wang R, Wang G, Wang C, Tan Y, Liu L, Wang C, Liu Y, et al.. The Novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Directly Decimates Human Spleens and Lymph Nodes.doi:10.1101/2020.03.27.20045427.
  • Li S, Jiang L, Li X, Lin F, Wang Y, Li B, Jiang T, An W, Liu S, Liu H, et al.. Clinical and pathological investigation of severe COVID-19 patients. JCI Insight. 2020 May 19. doi:10.1172/jci.insight.138070.
  • Zhou H, Chen W, Li Z, Yang B, Zhou Q, Wang P, Zhu J, Chen X, Yang P. Delayed-Phase Thrombocytopenia in Patients of Coronavirus Disease 2019 (COVID-19). Br J Haematol. 2020 Jul;190(2):179–184. doi:10.1111/bjh.16885.
  • Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020;18(4):844–847. doi:10.1111/jth.14768.
  • Allegra A, Innao V, Allegra AG, Musolino C. Coagulopathy and thromboembolic events in patients with SARS-CoV-2 infection: pathogenesis and management strategies. Ann Hematol. 2020 Jul 15. doi: 10.1007/s00277-020-04182-4
  • Shaigany S, Gnirke M, Guttmann A, Chong H, Meehan S, Raabe V, Louie E, Solitar B, Femia A. An adult with Kawasaki-like multisystem inflammatory syndrome associated with COVID-19. Lancet. 2020 Jul 10. doi: 10.1016/S0140-6736(20)31526-9
  • Ahmed S, Zimba O, Gasparyan AY. Thrombosis in Coronavirus disease 2019 (COVID-19) through the prism of Virchow’s triad. Clin Rheumatol. 2020 Jul 11. doi: 10.1007/s10067-020-05275-1
  • Wichmann D, Sperhake J-P, Lütgehetmann M, Steurer S, Edler C, Heinemann A, Heinrich F, Mushumba H, Kniep I, Schröder AS, et al.. Autopsy Findings and Venous Thromboembolism in Patients With COVID-19. Ann Intern Med. 2020 May 6. doi:10.7326/M20-2003.
  • Middleton EA, He X-Y, Denorme F, Campbell RA, Ng D, Salvatore SP, Mostyka M, Baxter-Stoltzfus A, Borczuk AC, Loda M, et al.. Neutrophil Extracellular Traps (NETs) contribute to immunothrombosis in COVID-19 acute respiratory distress syndrome. Blood. 2020 Jun 29. doi:10.1182/blood.2020007008.
  • Dupont V, Kanagaratnam L, Goury A, Poitevin G, Bard M, Julien G, Bonnivard M, Champenois V, Noel V, Mourvillier B, et al.. Excess soluble fms-like tyrosine kinase 1 correlates with endothelial dysfunction and organ failure in critically ill COVID-19 patients. Clin Infect Dis. 2020 Jul 16. doi:10.1093/cid/ciaa1007.
  • Lippi G, Favaloro EJ. D-dimer is associated with severity of coronavirus disease 2019: a Pooled Analysis. Thromb Haemost. 2020;120(5):876–878. doi:10.1055/s-0040-1709650.
  • Ackermann M, Verleden SE, Kuehnel M, Haverich A, Welte T, Laenger F, Vanstapel A, Werlein C, Stark H, Tzankov A, et al.. Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19. N Engl J Med. 2020;383(2):120–128. doi:10.1056/NEJMoa2015432.
  • Varga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R, Zinkernagel AS, Mehra MR, Schuepbach RA, Ruschitzka F, Moch H. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020;395(10234):1417–1418. doi:10.1016/S0140-6736(20)30937-5.
  • Goshua G, Pine AB, Meizlish ML, Chang C-H, Zhang H, Bahel P, Baluha A, Bar N, Bona RD, Burns AJ, et al.. Endotheliopathy in COVID-19-associated coagulopathy: evidence from a single-centre, cross-sectional study. Lancet Haematol. 2020 Jun 30. doi:10.1016/S2352-3026(20)30216-7.
  • Huisman A, Beun R, Sikma M, Westerink J, Kusadasi N. Involvement of ADAMTS13 and von Willebrand factor in thromboembolic events in patients infected with SARS-CoV-2. Int J Lab Hematol. 2020 May 22. doi: 10.1111/ijlh.13244
  • Panigada M, Bottino N, Tagliabue P, Grasselli G, Novembrino C, Chantarangkul V, Pesenti A, Peyvandi F, Tripodi A. Hypercoagulability of COVID-19 patients in intensive care unit: a report of thromboelastography findings and other parameters of hemostasis. J Thromb Haemost. 2020;18(7):1738–1742. doi:10.1111/jth.14850.
  • McGonagle D, Sharif K, O’Regan A, Bridgewood C. The role of cytokines including Interleukin-6 in COVID-19 induced pneumonia and macrophage activation syndrome-like disease. Autoimmun Rev. 2020;19(6):102537. doi:10.1016/j.autrev.2020.102537.
  • Teuwen L-A, Geldhof V, Pasut A, Carmeliet P. COVID-19: the vasculature unleashed. Nat Rev Immunol. 2020;20(7):389–391. doi:10.1038/s41577-020-0343-0.
  • Schulte-Schrepping J, Reusch N, Paclik D, Baßler K, Schlickeiser S, Zhang B, Krämer B, Krammer T, Brumhard S, Bonaguro L, et al.. Suppressive myeloid cells are a hallmark of severe COVID-199, Cell, 2020.doi:10.1016/j.cell.2020.08.001.
  • Guérin E, Orabona M, Raquil M-A, Giraudeau B, Bellier R, Gibot S, M-C B, Lacombe F, Droin N, Solary E, et al.. Circulating immature granulocytes with T-cell killing functions predict sepsis deterioration*. Crit Care Med. 2014;42(9):2007–2018. doi:10.1097/CCM.0000000000000344.
  • Katahira Y, Higuchi H, Matsushita H, Yahata T, Yamamoto Y, Koike R, Ando K, Sato K, Imadome K-I, Kotani A. Increased granulopoiesis in the bone marrow following Epstein-Barr virus infection. Sci Rep. 2019;9(1):13445. doi:10.1038/s41598-019-49937-w.
  • Rubio I, Osuchowski MF, Shankar-Hari M, Skirecki T, Winkler MS, Lachmann G, La Rosée P, Monneret G, Venet F, Bauer M, et al.. Current gaps in sepsis immunology: new opportunities for translational research. Lancet Infect Dis. 2019;19(12):e422–e436. doi:10.1016/S1473-3099(19)30567-5.
  • Jiang Y, Zhao G, Song N, Li P, Chen Y, Guo Y, Li J, Du L, Jiang S, Guo R, et al.. Blockade of the C5a-C5aR axis alleviates lung damage in hDPP4-transgenic mice infected with MERS-CoV. Emerg Microbes Infect. 2018;7(1):77. doi:10.1038/s41426-018-0063-8.
  • Gralinski LE, Sheahan TP, Morrison TE, Menachery VD, Jensen K, Leist SR, Whitmore A, Heise MT, Baric RS. Complement Activation Contributes to Severe Acute Respiratory Syndrome Coronavirus Pathogenesis Subbarao K, editor. mBio. 2018;9(5):e01753-18,/mbio/9/5/mBio.01753-18.atom. doi:10.1128/mBio.01753-18.
  • Ren R, Wu S, Cai J, Yang Y, Ren X, Feng Y, Chen L, Qin B, Xu C, Yang H, et al.. The H7N9 influenza A virus infection results in lethal inflammation in the mammalian host via the NLRP3-caspase-1 inflammasome. Sci Rep. 2017;7(1):7625. doi:10.1038/s41598-017-07384-5.
  • Caudrillier A, Kessenbrock K, Gilliss BM, Nguyen JX, Marques MB, Monestier M, Toy P, Werb Z, Looney MR. Platelets induce neutrophil extracellular traps in transfusion-related acute lung injury. J Clin Invest. 2012;122(7):2661–2671. doi:10.1172/JCI61303.
  • Clark SR, Ma AC, Tavener SA, McDonald B, Goodarzi Z, Kelly MM, Patel KD, Chakrabarti S, McAvoy E, Sinclair GD, et al.. Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood. Nat Med. 2007;13(4):463–469. doi:10.1038/nm1565.
  • Fuchs TA, Brill A, Duerschmied D, Schatzberg D, Monestier M, Myers DD, Wrobleski SK, Wakefield TW, Hartwig JH, Wagner DD. Extracellular DNA traps promote thrombosis. Proc Nat Acad Sci. 2010;107(36):15880–15885. doi:10.1073/pnas.1005743107.
  • Massberg S, Grahl L, von Bruehl M-L, Manukyan D, Pfeiler S, Goosmann C, Brinkmann V, Lorenz M, Bidzhekov K, Khandagale AB, et al.. Reciprocal coupling of coagulation and innate immunity via neutrophil serine proteases. Nat Med. 2010;16(8):887–896. doi:10.1038/nm.2184.
  • Sreeramkumar V, Adrover JM, Ballesteros I, Cuartero MI, Rossaint J, Bilbao I, Nácher M, Pitaval C, Radovanovic I, Fukui Y, et al.. Neutrophils scan for activated platelets to initiate inflammation. Science. 2014;346(6214):1234–1238. doi:10.1126/science.1256478.
  • von Brühl M-L, Stark K, Steinhart A, Chandraratne S, Konrad I, Lorenz M, Khandoga A, Tirniceriu A, Coletti R, Köllnberger M, et al.. Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivo. J Exp Med. 2012;209(4):819–835. doi:10.1084/jem.20112322.
  • Yago T, Liu Z, Ahamed J, McEver RP. Cooperative PSGL-1 and CXCR2 signaling in neutrophils promotes deep vein thrombosis in mice. Blood. 2018;132(13):1426–1437. doi:10.1182/blood-2018-05-850859.
  • Guo C, Li B, Ma H, Wang X, Cai P, Yu Q, Zhu L, Jin L, Jiang C, Fang J, et al. Single-cell analysis of two severe COVID-19 patients reveals a monocyte-associated and tocilizumab-responding cytokine storm. Nat Commun. 2020;11(1):3924. doi:10.1038/s41467-020-17834-w
  • Moots RJ, Sebba A, Rigby W, Ostor A, Porter-Brown B, Donaldson F, Dimonaco S, Rubbert-Roth A, van Vollenhoven R, Genovese MC. Effect of tocilizumab on neutrophils in adult patients with rheumatoid arthritis: pooled analysis of data from phase 3 and 4 clinical trials. Rheumatology (Oxford). 2017;56(4):541–549. doi:10.1093/rheumatology/kew370.
  • Michot J-M, Albiges L, Chaput N, Saada V, Pommeret F, Griscelli F, Balleyguier C, Besse B, Marabelle A, Netzer F, et al.. Tocilizumab, an anti-IL6 receptor antibody, to treat Covid-19-related respiratory failure: a case report. Ann Oncol. 2020 Apr 2. doi:10.1016/j.annonc.2020.03.300.
  • De Luna G, Habibi A, Deux J-F, Colard M, Pham Hung d’Alexandry d’Orengiani A-L, Schlemmer F, Joher N, Kassasseya C, Pawlotsky JM, Ourghanlian C, et al.. Rapid and severe Covid-19 pneumonia with severe acute chest syndrome in a sickle cell patient successfully treated with tocilizumab. Am J Hematol. 2020 Apr 13. doi:10.1002/ajh.25833.
  • Luo P, Y L, Qiu L, X L, D L, Li J. Tocilizumab treatment in COVID-19: A single center experience. J Med Virol. 2020 Apr 6. doi: 10.1002/jmv.25801
  • Toniati P, Piva S, Cattalini M, Garrafa E, Regola F, Castelli F, Franceschini F, Focà E, Andreoli L, Latronico N, et al.. Tocilizumab for the treatment of severe COVID-19 pneumonia with hyperinflammatory syndrome and acute respiratory failure: A single center study of 100 patients in Brescia, Italy. Autoimmun Rev. 2020 May 3;102568. doi:10.1016/j.autrev.2020.102568
  • Duan K, Liu B, Li C, Zhang H, Yu T, Qu J, Zhou M, Chen L, Meng S, Hu Y, et al. Effectiveness of convalescent plasma therapy in severe COVID-19 patients. Proc Natl Acad Sci USA. 2020 Apr 6:202004168. doi:10.1073/pnas.2004168117
  • Radbel J, Narayanan N, Bhatt PJ. Use of tocilizumab for COVID-19-induced cytokine release syndrome: a cautionary case report. Chest. 2020 Apr 25. doi: 10.1016/j.chest.2020.04.024
  • Rojo M, Cano-Valderrama O, Picazo S, Saez C, Gómez L, Sánchez C, Sanz-Ortega G, Torres AJ. Gastrointestinal perforation after treatment with tocilizumab : an unexpected consequence of COVID-19 pandemic. Am Surg. 2020;86(6):565–566. doi:10.1177/0003134820926481.
  • Chu H, Chan JF-W, Wang Y, Yuen -T-T-T, Chai Y, Hou Y, Shuai H, Yang D, Hu B, Huang X, et al.. Comparative replication and immune activation profiles of SARS-CoV-2 and SARS-CoV in human lungs: an ex vivo study with implications for the pathogenesis of COVID-19. Clin Infect Dis. 2020 Apr 9. doi:10.1093/cid/ciaa410.

Related research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.