Comprehensive mapping of immune perturbations associated with severe COVID-19
Leticia Kuri-Cervantes, M Betina Pampena, Wenzhao Meng, Aaron M Rosenfeld, Caroline A G Ittner, Ariel R Weisman, Roseline S Agyekum, Divij Mathew, Amy E Baxter, Laura A Vella, Oliva Kuthuru, Sokratis A Apostolidis, Luanne Bershaw, Jeanette Dougherty, Allison R Greenplate, Ajinkya Pattekar, Justin Kim, Nicholas Han, Sigrid Gouma, Madison E Weirick, Claudia P Arevalo, Marcus J Bolton, Eileen C Goodwin, Elizabeth M Anderson, Scott E Hensley, Tiffanie K Jones, Nilam S Mangalmurti, Eline T Luning Prak, E John Wherry, Nuala J Meyer, Michael R Betts, Leticia Kuri-Cervantes, M Betina Pampena, Wenzhao Meng, Aaron M Rosenfeld, Caroline A G Ittner, Ariel R Weisman, Roseline S Agyekum, Divij Mathew, Amy E Baxter, Laura A Vella, Oliva Kuthuru, Sokratis A Apostolidis, Luanne Bershaw, Jeanette Dougherty, Allison R Greenplate, Ajinkya Pattekar, Justin Kim, Nicholas Han, Sigrid Gouma, Madison E Weirick, Claudia P Arevalo, Marcus J Bolton, Eileen C Goodwin, Elizabeth M Anderson, Scott E Hensley, Tiffanie K Jones, Nilam S Mangalmurti, Eline T Luning Prak, E John Wherry, Nuala J Meyer, Michael R Betts
Abstract
Although critical illness has been associated with SARS-CoV-2-induced hyperinflammation, the immune correlates of severe COVID-19 remain unclear. Here, we comprehensively analyzed peripheral blood immune perturbations in 42 SARS-CoV-2 infected and recovered individuals. We identified extensive induction and activation of multiple immune lineages, including T cell activation, oligoclonal plasmablast expansion, and Fc and trafficking receptor modulation on innate lymphocytes and granulocytes, that distinguished severe COVID-19 cases from healthy donors or SARS-CoV-2-recovered or moderate severity patients. We found the neutrophil to lymphocyte ratio to be a prognostic biomarker of disease severity and organ failure. Our findings demonstrate broad innate and adaptive leukocyte perturbations that distinguish dysregulated host responses in severe SARS-CoV-2 infection and warrant therapeutic investigation.
Copyright © 2020, American Association for the Advancement of Science.
Figures
References
- W. Novel-Coronavirus-2019 Reports. (World Health Organization, 2020), vol. 2020.
- Guan W. J., Ni Z. Y., Hu Y., Liang W. H., Ou C. Q., He J. X., Liu L., Shan H., Lei C. L., Hui D. S. C., Du B., Li L. J., Zeng G., Yuen K. Y., Chen R. C., Tang C. L., Wang T., Chen P. Y., Xiang J., Li S. Y., Wang J. L., Liang Z. J., Peng Y. X., Wei L., Liu Y., Hu Y. H., Peng P., Wang J. M., Liu J. Y., Chen Z., Li G., Zheng Z. J., Qiu S. Q., Luo J., Ye C. J., Zhu S. Y., Zhong N. S.; China Medical Treatment Expert Group for Covid-19 , Clinical Characteristics of Coronavirus Disease 2019 in China. N. Engl. J. Med. 382, 1708–1720 (2020). 10.1056/NEJMoa2002032
- Huang C., Wang Y., Li X., Ren L., Zhao J., Hu Y., Zhang L., Fan G., Xu J., Gu X., Cheng Z., Yu T., Xia J., Wei Y., Wu W., Xie X., Yin W., Li H., Liu M., Xiao Y., Gao H., Guo L., Xie J., Wang G., Jiang R., Gao Z., Jin Q., Wang J., Cao B., Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 395, 497–506 (2020). 10.1016/S0140-6736(20)30183-5
- Chen N., Zhou M., Dong X., Qu J., Gong F., Han Y., Qiu Y., Wang J., Liu Y., Wei Y., Xia J., Yu T., Zhang X., Zhang L., Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: A descriptive study. Lancet 395, 507–513 (2020). 10.1016/S0140-6736(20)30211-7
- 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. 46, 846–848 (2020). 10.1007/s00134-020-05991-x
- Yang X., Yu Y., Xu J., Shu H., Xia J., Liu H., Wu Y., Zhang L., Yu Z., Fang M., Yu T., Wang Y., Pan S., Zou X., Yuan S., Shang Y., Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: A single-centered, retrospective, observational study. Lancet Respir. Med. 8, 475–481 (2020). 10.1016/S2213-2600(20)30079-5
- Wang D., Hu B., Hu C., Zhu F., Liu X., Zhang J., Wang B., Xiang H., Cheng Z., Xiong Y., Zhao Y., Li Y., Wang X., Peng Z., Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA 323, 1061 (2020). 10.1001/jama.2020.1585
- Chen G., Wu D., Guo W., Cao Y., Huang D., Wang H., Wang T., Zhang X., Chen H., Yu H., Zhang X., Zhang M., Wu S., Song J., Chen T., Han M., Li S., Luo X., Zhao J., Ning Q., Clinical and immunological features of severe and moderate coronavirus disease 2019. J. Clin. Invest. 130, 2620–2629 (2020). 10.1172/JCI137244
- Wölfel R., Corman V. M., Guggemos W., Seilmaier M., Zange S., Müller M. A., Niemeyer D., Jones T. C., Vollmar P., Rothe C., Hoelscher M., Bleicker T., Brünink S., Schneider J., Ehmann R., Zwirglmaier K., Drosten C., Wendtner C., Virological assessment of hospitalized patients with COVID-2019. Nature 581, 465–469 (2020). 10.1038/s41586-020-2196-x
- Thevarajan I., Nguyen T. H. O., Koutsakos M., Druce J., Caly L., van de Sandt C. E., Jia X., Nicholson S., Catton M., Cowie B., Tong S. Y. C., Lewin S. R., Kedzierska K., Breadth of concomitant immune responses prior to patient recovery: A case report of non-severe COVID-19. Nat. Med. 26, 453–455 (2020). 10.1038/s41591-020-0819-2
- Wilk A. J., Rustagi A., Zhao N. Q., Roque J., Martínez-Colón G. J., McKechnie J. L., Ivison G. T., Ranganath T., Vergara R., Hollis T., Simpson L. J., Grant P., Subramanian A., Rogers A. J., Blish C. A., A single-cell atlas of the peripheral immune response in patients with severe COVID-19. Nat. Med. (2020). 10.1038/s41591-020-0944-y
- Wang W., Su B., Pang L., Qiao L., Feng Y., Ouyang Y., Guo X., Shi H., Wei F., Su X., Yin J., Jin R., Chen D., High-dimensional immune profiling by mass cytometry revealed immunosuppression and dysfunction of immunity in COVID-19 patients. Cell. Mol. Immunol. 17, 650–652 (2020). 10.1038/s41423-020-0447-2
- Zheng H.-Y., Zhang M., Yang C.-X., Zhang N., Wang X.-C., Yang X.-P., Dong X.-Q., Zheng Y.-T., Elevated exhaustion levels and reduced functional diversity of T cells in peripheral blood may predict severe progression in COVID-19 patients. Cell. Mol. Immunol. 17, 541–543 (2020). 10.1038/s41423-020-0401-3
- A. J. Wilk, A. Rustagi, N. Q. Zhao, J. Roque, G. J. Martinez-Colon, J. L. McKechnie, G. T. Ivison, T. Ranganath, R. Vergara, T. Hollis, L. J. Simpson, P. Grant, A. Subramanian, A. J. Rogers, C. A. Blish, A single-cell atlas of the peripheral immune response to severe COVID-19. medRxiv, 2020.2004.2017.20069930 (2020).
- Zhang J. J., Dong X., Cao Y. Y., Yuan Y. D., Yang Y. B., Yan Y. Q., Akdis C. A., Gao Y. D., Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan, China. Allergy all.14238 (2020). 10.1111/all.14238
- Levitt J. E., Calfee C. S., Goldstein B. A., Vojnik R., Matthay M. A., Early acute lung injury: Criteria for identifying lung injury prior to the need for positive pressure ventilation*. Crit. Care Med. 41, 1929–1937 (2013). 10.1097/CCM.0b013e31828a3d99
- Ziehr D. R., Alladina J., Petri C. R., Maley J. H., Moskowitz A., Medoff B. D., Hibbert K. A., Thompson B. T., Hardin C. C., Respiratory Pathophysiology of Mechanically Ventilated Patients with COVID-19: A Cohort Study. Am. J. Respir. Crit. Care Med. 201, 1560–1564 (2020). 10.1164/rccm.202004-1163LE
- Ranieri V. M., Rubenfeld G. D., Thompson B. T., Ferguson N. D., Caldwell E., Fan E., Camporota L., Slutsky A. S.; ARDS Definition Task Force , Acute respiratory distress syndrome: The Berlin Definition. JAMA 307, 2526–2533 (2012).
- Knaus W. A., Wagner D. P., Draper E. A., Zimmerman J. E., Bergner M., Bastos P. G., Sirio C. A., Murphy D. J., Lotring T., Damiano A., Harrell F. E. Jr., The APACHE III prognostic system. Risk prediction of hospital mortality for critically ill hospitalized adults. Chest 100, 1619–1636 (1991). 10.1378/chest.100.6.1619
- Merad M., Martin J. C., Pathological inflammation in patients with COVID-19: A key role for monocytes and macrophages. Nat. Rev. Immunol. 20, 355–362 (2020).
- Henry B. M., COVID-19, ECMO, and lymphopenia: A word of caution. Lancet Respir. Med. 8, e24 (2020). 10.1016/S2213-2600(20)30119-3
- 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. Signal Transduct. Target. Ther. 5, 33 (2020). 10.1038/s41392-020-0148-4
- J. Liu, Y. Liu, P. Xiang, L. Pu, H. Xiong, C. Li, M. Zhang, J. Tan, Y. Xu, R. Song, M. Song, L. Wang, W. Zhang, B. Han, L. Yang, X. Wang, G. Zhou, T. Zhang, B. Li, Y. Wang, Z. Chen, X. Wang, Neutrophil-to-Lymphocyte Ratio Predicts Severe Illness Patients with 2019 Novel Coronavirus in the Early Stage. medRxiv, 2020.2002.2010.20021584 (2020).
- Lau D., Lan L. Y., Andrews S. F., Henry C., Rojas K. T., Neu K. E., Huang M., Huang Y., DeKosky B., Palm A. E., Ippolito G. C., Georgiou G., Wilson P. C., Low CD21 expression defines a population of recent germinal center graduates primed for plasma cell differentiation. Sci. Immunol. 2, eaai8153 (2017). 10.1126/sciimmunol.aai8153
- Zhao J., Yuan Q., Wang H., Liu W., Liao X., Su Y., Wang X., Yuan J., Li T., Li J., Qian S., Hong C., Wang F., Liu Y., Wang Z., He Q., Li Z., He B., Zhang T., Fu Y., Ge S., Liu L., Zhang J., Xia N., Zhang Z., Antibody responses to SARS-CoV-2 in patients of novel coronavirus disease 2019. Clin. Infect. Dis. ciaa344 (2020). 10.1093/cid/ciaa344
- Marti G. E., Rawstron A. C., Ghia P., Hillmen P., Houlston R. S., Kay N., Schleinitz T. A., Caporaso N.; International Familial CLL Consortium , Diagnostic criteria for monoclonal B-cell lymphocytosis. Br. J. Haematol. 130, 325–332 (2005). 10.1111/j.1365-2141.2005.05550.x
- Tabibian-Keissar H., Hazanov L., Schiby G., Rosenthal N., Rakovsky A., Michaeli M., Shahaf G. L., Pickman Y., Rosenblatt K., Melamed D., Dunn-Walters D., Mehr R., Barshack I., Aging affects B-cell antigen receptor repertoire diversity in primary and secondary lymphoid tissues. Eur. J. Immunol. 46, 480–492 (2016). 10.1002/eji.201545586
- DeWitt W. S., Lindau P., Snyder T. M., Sherwood A. M., Vignali M., Carlson C. S., Greenberg P. D., Duerkopp N., Emerson R. O., Robins H. S., A Public Database of Memory and Naive B-Cell Receptor Sequences. PLOS ONE 11, e0160853 (2016). 10.1371/journal.pone.0160853
- Kurioka A., Cosgrove C., Simoni Y., van Wilgenburg B., Geremia A., Björkander S., Sverremark-Ekström E., Thurnheer C., Günthard H. F., Khanna N., Walker L. J., Arancibia-Cárcamo C. V., Newell E. W., Willberg C. B., Klenerman P.; Swiss HIV Cohort Study; Oxford IBD Cohort Investigators , CD161 Defines a Functionally Distinct Subset of Pro-Inflammatory Natural Killer Cells. Front. Immunol. 9, 486 (2018). 10.3389/fimmu.2018.00486
- Poggi A., Rubartelli A., Moretta L., Zocchi M. R., Expression and function of NKRP1A molecule on human monocytes and dendritic cells. Eur. J. Immunol. 27, 2965–2970 (1997). 10.1002/eji.1830271132
- Goodier M. R., Lusa C., Sherratt S., Rodriguez-Galan A., Behrens R., Riley E. M., Sustained Immune Complex-Mediated Reduction in CD16 Expression after Vaccination Regulates NK Cell Function. Front. Immunol. 7, 384 (2016). 10.3389/fimmu.2016.00384
- Giamarellos-Bourboulis E. J., Netea M. G., Rovina N., Akinosoglou K., Antoniadou A., Antonakos N., Damoraki G., Gkavogianni T., Adami M. E., Katsaounou P., Ntaganou M., Kyriakopoulou M., Dimopoulos G., Koutsodimitropoulos I., Velissaris D., Koufargyris P., Karageorgos A., Katrini K., Lekakis V., Lupse M., Kotsaki A., Renieris G., Theodoulou D., Panou V., Koukaki E., Koulouris N., Gogos C., Koutsoukou A., Complex Immune Dysregulation in COVID-19 Patients with Severe Respiratory Failure. Cell Host Microbe 27, 992–1000.e3 (2020). 10.1016/j.chom.2020.04.009
- McElroy A. K., Akondy R. S., Davis C. W., Ellebedy A. H., Mehta A. K., Kraft C. S., Lyon G. M., Ribner B. S., Varkey J., Sidney J., Sette A., Campbell S., Ströher U., Damon I., Nichol S. T., Spiropoulou C. F., Ahmed R., Human Ebola virus infection results in substantial immune activation. Proc. Natl. Acad. Sci. U.S.A. 112, 4719–4724 (2015). 10.1073/pnas.1502619112
- Wang Z., Zhu L., Nguyen T. H. O., Wan Y., Sant S., Quiñones-Parra S. M., Crawford J. C., Eltahla A. A., Rizzetto S., Bull R. A., Qiu C., Koutsakos M., Clemens E. B., Loh L., Chen T., Liu L., Cao P., Ren Y., Kedzierski L., Kotsimbos T., McCaw J. M., La Gruta N. L., Turner S. J., Cheng A. C., Luciani F., Zhang X., Doherty P. C., Thomas P. G., Xu J., Kedzierska K., Clonally diverse CD38+HLA-DR+CD8+ T cells persist during fatal H7N9 disease. Nat. Commun. 9, 824 (2018). 10.1038/s41467-018-03243-7
- D. Mathew, J. R. Giles, A. E. Baxter, A. R. Greenplate, J. E. Wu, C. Alanio, D. A. Oldridge, L. Kuri-Cervantes, M. B. Pampena, K. D’Andrea, S. Manne, Z. Chen, Y. J. Huang, J. P. Reilly, A. R. Weisman, C. A. G. Ittner, O. Kuthuru, J. Dougherty, K. Nzingha, N. Han, J. Kim, A. Pattekar, E. C. Goodwin, E. M. Anderson, M. E. Weirick, S. Gouma, C. P. Arevalo, M. J. Bolton, F. Chen, S. F. Lacey, S. E. Hensley, S. Apostolidis, A. C. Huang, L. A. Vella, M. R. Betts, N. J. Meyer, E. J. Wherry, Deep immune profiling of COVID-19 patients reveals patient heterogeneity and distinct immunotypes with implications for therapeutic interventions. bioRxiv, 2020.2005.2020.106401 (2020).
- Y. Jouan, A. Guillon, L. Gonzalez, Y. Perez, S. Ehrmann, M. Ferreira, T. Daix, R. Jeannet, B. Francois, P.-F. Dequin, M. Si-Tahar, T. Baranek, C. Paget, Functional alteration of innate T cells in critically ill Covid-19 patients. medRxiv, 2020.2005.2003.20089300 (2020).
- Seebach J. D., Morant R., Rüegg R., Seifert B., Fehr J., The diagnostic value of the neutrophil left shift in predicting inflammatory and infectious disease. Am. J. Clin. Pathol. 107, 582–591 (1997). 10.1093/ajcp/107.5.582
- Zuo Y., Yalavarthi S., Shi H., Gockman K., Zuo M., Madison J. A., Blair C., Weber A., Barnes B. J., Egeblad M., Woods R. J., Kanthi Y., Knight J. S., Neutrophil extracellular traps in COVID-19. JCI Insight 5, 138999 (2020). 10.1172/jci.insight.138999
- Victor A. R., Weigel C., Scoville S. D., Chan W. K., Chatman K., Nemer M. M., Mao C., Young K. A., Zhang J., Yu J., Freud A. G., Oakes C. C., Caligiuri M. A., Epigenetic and Posttranscriptional Regulation of CD16 Expression during Human NK Cell Development. J. Immunol. 200, 565–572 (2018). 10.4049/jimmunol.1701128
- Srpan K., Ambrose A., Karampatzakis A., Saeed M., Cartwright A. N. R., Guldevall K., De Matos G. D. S. C., Önfelt B., Davis D. M., Shedding of CD16 disassembles the NK cell immune synapse and boosts serial engagement of target cells. J. Cell Biol. 217, 3267–3283 (2018). 10.1083/jcb.201712085
- Mare T. A., Treacher D. F., Shankar-Hari M., Beale R., Lewis S. M., Chambers D. J., Brown K. A., The diagnostic and prognostic significance of monitoring blood levels of immature neutrophils in patients with systemic inflammation. Crit. Care 19, 57 (2015). 10.1186/s13054-015-0778-z
- Nierhaus A., Klatte S., Linssen J., Eismann N. M., Wichmann D., Hedke J., Braune S. A., Kluge S., Revisiting the white blood cell count: Immature granulocytes count as a diagnostic marker to discriminate between SIRS and sepsis—a prospective, observational study. BMC Immunol. 14, 8 (2013). 10.1186/1471-2172-14-8
- Balakrishnan T., Bela-Ong D. B., Toh Y. X., Flamand M., Devi S., Koh M. B., Hibberd M. L., Ooi E. E., Low J. G., Leo Y. S., Gu F., Fink K., Dengue virus activates polyreactive, natural IgG B cells after primary and secondary infection. PLOS ONE 6, e29430 (2011). 10.1371/journal.pone.0029430
- Wrammert J., Onlamoon N., Akondy R. S., Perng G. C., Polsrila K., Chandele A., Kwissa M., Pulendran B., Wilson P. C., Wittawatmongkol O., Yoksan S., Angkasekwinai N., Pattanapanyasat K., Chokephaibulkit K., Ahmed R., Rapid and massive virus-specific plasmablast responses during acute dengue virus infection in humans. J. Virol. 86, 2911–2918 (2012). 10.1128/JVI.06075-11
- M. Woodruff, R. Ramonell, K. Cashman, D. Nguyen, A. Ley, S. Kyu, A. Saini, N. Haddad, W. Chen, J. C. Howell, T. Ozturk, S. Lee, J. Estrada, A. Morrison-Porter, A. Derrico, F. Anam, H. Wu, S. Le, S. Jenks, W. Hu, F. E.-H. Lee, I. Sanz, Critically ill SARS-CoV-2 patients display lupus-like hallmarks of extrafollicular B cell activation. medRxiv, 2020.2004.2029.20083717 (2020).
- Martin V., Bryan Wu Y. C., Kipling D., Dunn-Walters D., Ageing of the B-cell repertoire. Philos. Trans. R. Soc. Lond. B Biol. Sci. 370, 20140237 (2015). 10.1098/rstb.2014.0237
- Muggen A. F., de Jong M., Wolvers-Tettero I. L. M., Kallemeijn M. J., Teodósio C., Darzentas N., Stadhouders R., IJspeert H., van der Burg M., van IJcken W. F. J., Verhaar J. A. N., Abdulahad W. H., Brouwer E., Boots A. M. H., Hendriks R. W., van Dongen J. J. M., Langerak A. W., The presence of CLL-associated stereotypic B cell receptors in the normal BCR repertoire from healthy individuals increases with age. Immun. Ageing 16, 22 (2019). 10.1186/s12979-019-0163-x
- Rodriguez-Zhurbenko N., Quach T. D., Hopkins T. J., Rothstein T. L., Hernandez A. M., Human B-1 Cells and B-1 Cell Antibodies Change With Advancing Age. Front. Immunol. 10, 483 (2019). 10.3389/fimmu.2019.00483
- W. Wen, W. Su, H. Tang, W. Le, X. Zhang, Y. Zheng, X. Liu, L. Xie, J. Li, J. Ye, X. Cui, Y. Miao, D. Wang, J. Dong, C.-L. Xiao, W. Chen, H. Wang, Immune Cell Profiling of COVID-19 Patients in the Recovery Stage by Single-Cell Sequencing. medRxiv, 2020.2003.2023.20039362 (2020).
- Di Niro R., Lee S. J., Vander Heiden J. A., Elsner R. A., Trivedi N., Bannock J. M., Gupta N. T., Kleinstein S. H., Vigneault F., Gilbert T. J., Meffre E., McSorley S. J., Shlomchik M. J., Salmonella Infection Drives Promiscuous B Cell Activation Followed by Extrafollicular Affinity Maturation. Immunity 43, 120–131 (2015). 10.1016/j.immuni.2015.06.013
- Jenks S. A., Cashman K. S., Zumaquero E., Marigorta U. M., Patel A. V., Wang X., Tomar D., Woodruff M. C., Simon Z., Bugrovsky R., Blalock E. L., Scharer C. D., Tipton C. M., Wei C., Lim S. S., Petri M., Niewold T. B., Anolik J. H., Gibson G., Eun-Hyung Lee F., Boss J. M., Lund F. E., Sanz I., Distinct Effector B Cells Induced by Unregulated Toll-like Receptor 7 Contribute to Pathogenic Responses in Systemic Lupus Erythematosus. Immunity 52, 203 (2020). 10.1016/j.immuni.2019.12.005
- Wardemann H., Yurasov S., Schaefer A., Young J. W., Meffre E., Nussenzweig M. C., Predominant autoantibody production by early human B cell precursors. Science 301, 1374–1377 (2003). 10.1126/science.1086907
- Cardoso R. M., Zwick M. B., Stanfield R. L., Kunert R., Binley J. M., Katinger H., Burton D. R., Wilson I. A., Broadly neutralizing anti-HIV antibody 4E10 recognizes a helical conformation of a highly conserved fusion-associated motif in gp41. Immunity 22, 163–173 (2005). 10.1016/j.immuni.2004.12.011
- Fenalti G., Hampe C. S., O’connor K., Banga J. P., Mackay I. R., Rowley M. J., El-Kabbani O., Molecular characterization of a disease associated conformational epitope on GAD65 recognised by a human monoclonal antibody b96.11. Mol. Immunol. 44, 1178–1189 (2007). 10.1016/j.molimm.2006.06.025
- Haynes B. F., Fleming J., St Clair E. W., Katinger H., Stiegler G., Kunert R., Robinson J., Scearce R. M., Plonk K., Staats H. F., Ortel T. L., Liao H. X., Alam S. M., Cardiolipin polyspecific autoreactivity in two broadly neutralizing HIV-1 antibodies. Science 308, 1906–1908 (2005). 10.1126/science.1111781
- Ofek G., Tang M., Sambor A., Katinger H., Mascola J. R., Wyatt R., Kwong P. D., Structure and mechanistic analysis of the anti-human immunodeficiency virus type 1 antibody 2F5 in complex with its gp41 epitope. J. Virol. 78, 10724–10737 (2004). 10.1128/JVI.78.19.10724-10737.2004
- Haveri A., Smura T., Kuivanen S., Österlund P., Hepojoki J., Ikonen N., Pitkäpaasi M., Blomqvist S., Rönkkö E., Kantele A., Strandin T., Kallio-Kokko H., Mannonen L., Lappalainen M., Broas M., Jiang M., Siira L., Salminen M., Puumalainen T., Sane J., Melin M., Vapalahti O., Savolainen-Kopra C., Serological and molecular findings during SARS-CoV-2 infection: The first case study in Finland, January to February 2020. Euro Surveill. 25, 2000266 (2020). 10.2807/1560-7917.ES.2020.25.11.2000266
- Ni L., Ye F., Cheng M. L., Feng Y., Deng Y. Q., Zhao H., Wei P., Ge J., Gou M., Li X., Sun L., Cao T., Wang P., Zhou C., Zhang R., Liang P., Guo H., Wang X., Qin C. F., Chen F., Dong C., Detection of SARS-CoV-2-Specific Humoral and Cellular Immunity in COVID-19 Convalescent Individuals. Immunity 52, 971–977.e3 (2020). 10.1016/j.immuni.2020.04.023
- Okba N. M. A., Müller M. A., Li W., Wang C., GeurtsvanKessel C. H., Corman V. M., Lamers M. M., Sikkema R. S., de Bruin E., Chandler F. D., Yazdanpanah Y., Le Hingrat Q., Descamps D., Houhou-Fidouh N., Reusken C. B. E. M., Bosch B.-J., Drosten C., Koopmans M. P. G., Haagmans B. L., Severe Acute Respiratory Syndrome Coronavirus 2-Specific Antibody Responses in Coronavirus Disease Patients. Emerg. Infect. Dis. 26, 1478–1488 (2020). 10.3201/eid2607.200841
- Seydoux E., Homad L. J., MacCamy A. J., Parks K. R., Hurlburt N. K., Jennewein M. F., Akins N. R., Stuart A. B., Wan Y.-H., Feng J., Whaley R. E., Singh S., Boeckh M., Cohen K. W., McElrath M. J., Englund J. A., Chu H. Y., Pancera M., McGuire A. T., Stamatatos L., Analysis of a SARS-CoV-2-infected individual reveals development of potent neutralizing antibodies to distinct epitopes with limited somatic mutation. Immunity (2020). 10.1016/j.immuni.2020.06.001
- Amanat F., Stadlbauer D., Strohmeier S., Nguyen T. H. O., Chromikova V., McMahon M., Jiang K., Arunkumar G. A., Jurczyszak D., Polanco J., Bermudez-Gonzalez M., Kleiner G., Aydillo T., Miorin L., Fierer D. S., Lugo L. A., Kojic E. M., Stoever J., Liu S. T. H., Cunningham-Rundles C., Felgner P. L., Moran T., García-Sastre A., Caplivski D., Cheng A. C., Kedzierska K., Vapalahti O., Hepojoki J. M., Simon V., Krammer F., A serological assay to detect SARS-CoV-2 seroconversion in humans. Nat. Med. (2020). 10.1038/s41591-020-0913-5
- Doi H., Tanoue S., Kaplan D. E., Peripheral CD27-CD21- B-cells represent an exhausted lymphocyte population in hepatitis C cirrhosis. Clin. Immunol. 150, 184–191 (2014). 10.1016/j.clim.2013.12.001
- Moir S., Malaspina A., Ogwaro K. M., Donoghue E. T., Hallahan C. W., Ehler L. A., Liu S., Adelsberger J., Lapointe R., Hwu P., Baseler M., Orenstein J. M., Chun T. W., Mican J. A., Fauci A. S., HIV-1 induces phenotypic and functional perturbations of B cells in chronically infected individuals. Proc. Natl. Acad. Sci. U.S.A. 98, 10362–10367 (2001). 10.1073/pnas.181347898
- Sciaranghella G., Tong N., Mahan A. E., Suscovich T. J., Alter G., Decoupling activation and exhaustion of B cells in spontaneous controllers of HIV infection. AIDS 27, 175–180 (2013). 10.1097/QAD.0b013e32835bd1f0
- Fearon D. T., The CD19-CR2-TAPA-1 complex, CD45 and signaling by the antigen receptor of B lymphocytes. Curr. Opin. Immunol. 5, 341–348 (1993). 10.1016/0952-7915(93)90051-S
- Fearon D. T., Carter R. H., The CD19/CR2/TAPA-1 complex of B lymphocytes: Linking natural to acquired immunity. Annu. Rev. Immunol. 13, 127–149 (1995). 10.1146/annurev.iy.13.040195.001015
- Charles E. D., Brunetti C., Marukian S., Ritola K. D., Talal A. H., Marks K., Jacobson I. M., Rice C. M., Dustin L. B., Clonal B cells in patients with hepatitis C virus-associated mixed cryoglobulinemia contain an expanded anergic CD21low B-cell subset. Blood 117, 5425–5437 (2011). 10.1182/blood-2010-10-312942
- Illingworth J., Butler N. S., Roetynck S., Mwacharo J., Pierce S. K., Bejon P., Crompton P. D., Marsh K., Ndungu F. M., Chronic exposure to Plasmodium falciparum is associated with phenotypic evidence of B and T cell exhaustion. J. Immunol. 190, 1038–1047 (2013). 10.4049/jimmunol.1202438
- Thorarinsdottir K., Camponeschi A., Gjertsson I., Mårtensson I. L., CD21 -/low B cells: A Snapshot of a Unique B Cell Subset in Health and Disease. Scand. J. Immunol. 82, 254–261 (2015). 10.1111/sji.12339
- Visentini M., Cagliuso M., Conti V., Carbonari M., Casato M., Fiorilli M., The V(H)1-69-expressing marginal zone B cells expanded in HCV-associated mixed cryoglobulinemia display proliferative anergy irrespective of CD21(low) phenotype. Blood 118, 3440–3441, author reply 3442 (2011). 10.1182/blood-2011-05-353821
- Weiss G. E., Crompton P. D., Li S., Walsh L. A., Moir S., Traore B., Kayentao K., Ongoiba A., Doumbo O. K., Pierce S. K., Atypical memory B cells are greatly expanded in individuals living in a malaria-endemic area. J. Immunol. 183, 2176–2182 (2009). 10.4049/jimmunol.0901297
- Gies V., Schickel J. N., Jung S., Joublin A., Glauzy S., Knapp A. M., Soley A., Poindron V., Guffroy A., Choi J. Y., Gottenberg J. E., Anolik J. H., Martin T., Soulas-Sprauel P., Meffre E., Korganow A. S., Impaired TLR9 responses in B cells from patients with systemic lupus erythematosus. JCI Insight 3, e96795 (2018). 10.1172/jci.insight.96795
- Kahan S. M., Wherry E. J., Zajac A. J., T cell exhaustion during persistent viral infections. Virology 479-480, 180–193 (2015). 10.1016/j.virol.2014.12.033
- Fenwick C., Joo V., Jacquier P., Noto A., Banga R., Perreau M., Pantaleo G., T-cell exhaustion in HIV infection. Immunol. Rev. 292, 149–163 (2019). 10.1111/imr.12823
- Dias C. N. S., Gois B. M., Lima V. S., Guerra-Gomes I. C., Araújo J. M. G., Gomes J. A. S., Araújo D. A. M., Medeiros I. A., Azevedo F. L. A. A., Veras R. C., Janebro D. I., Amaral I. P. G. D., Keesen T. S. L., Human CD8 T-cell activation in acute and chronic chikungunya infection. Immunology 155, 499–504 (2018). 10.1111/imm.12992
- Ndhlovu Z. M., Kamya P., Mewalal N., Kløverpris H. N., Nkosi T., Pretorius K., Laher F., Ogunshola F., Chopera D., Shekhar K., Ghebremichael M., Ismail N., Moodley A., Malik A., Leslie A., Goulder P. J., Buus S., Chakraborty A., Dong K., Ndung’u T., Walker B. D., Magnitude and Kinetics of CD8+ T Cell Activation during Hyperacute HIV Infection Impact Viral Set Point. Immunity 43, 591–604 (2015). 10.1016/j.immuni.2015.08.012
- Demers K. R., Makedonas G., Buggert M., Eller M. A., Ratcliffe S. J., Goonetilleke N., Li C. K., Eller L. A., Rono K., Maganga L., Nitayaphan S., Kibuuka H., Routy J. P., Slifka M. K., Haynes B. F., McMichael A. J., Bernard N. F., Robb M. L., Betts M. R., Temporal Dynamics of CD8+ T Cell Effector Responses during Primary HIV Infection. PLOS Pathog. 12, e1005805 (2016). 10.1371/journal.ppat.1005805
- Agrati C., Castilletti C., Casetti R., Sacchi A., Falasca L., Turchi F., Tumino N., Bordoni V., Cimini E., Viola D., Lalle E., Bordi L., Lanini S., Martini F., Nicastri E., Petrosillo N., Puro V., Piacentini M., Di Caro A., Kobinger G. P., Zumla A., Ippolito G., Capobianchi M. R., Longitudinal characterization of dysfunctional T cell-activation during human acute Ebola infection. Cell Death Dis. 7, e2164 (2016). 10.1038/cddis.2016.55
- Sandalova E., Laccabue D., Boni C., Tan A. T., Fink K., Ooi E. E., Chua R., Shafaeddin Schreve B., Ferrari C., Bertoletti A., Contribution of herpesvirus specific CD8 T cells to anti-viral T cell response in humans. PLOS Pathog. 6, e1001051 (2010). 10.1371/journal.ppat.1001051
- Wang X., Xu W., Hu G., Xia S., Sun Z., Liu Z., Xie Y., Zhang R., Jiang S., Lu L., RETRACTED ARTICLE: SARS-CoV-2 infects T lymphocytes through its spike protein-mediated membrane fusion. Cell. Mol. Immunol. (2020).
- Sarzi-Puttini P., Giorgi V., Sirotti S., Marotto D., Ardizzone S., Rizzardini G., Antinori S., Galli M., COVID-19, cytokines and immunosuppression: What can we learn from severe acute respiratory syndrome? Clin. Exp. Rheumatol. 38, 337–342 (2020).
- Tan Y. X., Tan T. H., Lee M. J., Tham P. Y., Gunalan V., Druce J., Birch C., Catton M., Fu N. Y., Yu V. C., Tan Y. J., Induction of apoptosis by the severe acute respiratory syndrome coronavirus 7a protein is dependent on its interaction with the Bcl-XL protein. J. Virol. 81, 6346–6355 (2007). 10.1128/JVI.00090-07
- Yue Y., Nabar N. R., Shi C. S., Kamenyeva O., Xiao X., Hwang I. Y., Wang M., Kehrl J. H., SARS-Coronavirus Open Reading Frame-3a drives multimodal necrotic cell death. Cell Death Dis. 9, 904 (2018). 10.1038/s41419-018-0917-y
- Yao X. H., Li T. Y., He Z. C., Ping Y. F., Liu H. W., Yu S. C., Mou H. M., Wang L. H., Zhang H. R., Fu W. J., Luo T., Liu F., Chen C., Xiao H. L., Guo H. T., Lin S., Xiang D. F., Shi Y., Li Q. R., Huang X., Cui Y., Li X. Z., Tang W., Pan P. F., Huang X. Q., Ding Y. Q., Bian X. W., Zhonghua Bing Li Xue Za Zhi 49, E009 (2020) [A pathological report of three COVID-19 cases by minimally invasive autopsies].
- Barton L. M., Duval E. J., Stroberg E., Ghosh S., Mukhopadhyay S., COVID-19 Autopsies, Oklahoma, USA. Am. J. Clin. Pathol. 153, 725–733 (2020). 10.1093/ajcp/aqaa062
- Walker L. J., Kang Y. H., Smith M. O., Tharmalingham H., Ramamurthy N., Fleming V. M., Sahgal N., Leslie A., Oo Y., Geremia A., Scriba T. J., Hanekom W. A., Lauer G. M., Lantz O., Adams D. H., Powrie F., Barnes E., Klenerman P., Human MAIT and CD8αα cells develop from a pool of type-17 precommitted CD8+ T cells. Blood 119, 422–433 (2012). 10.1182/blood-2011-05-353789
- Billerbeck E., Kang Y.-H., Walker L., Lockstone H., Grafmueller S., Fleming V., Flint J., Willberg C. B., Bengsch B., Seigel B., Ramamurthy N., Zitzmann N., Barnes E. J., Thevanayagam J., Bhagwanani A., Leslie A., Oo Y. H., Kollnberger S., Bowness P., Drognitz O., Adams D. H., Blum H. E., Thimme R., Klenerman P., Analysis of CD161 expression on human CD8+ T cells defines a distinct functional subset with tissue-homing properties. Proc. Natl. Acad. Sci. U.S.A. 107, 3006–3011 (2010). 10.1073/pnas.0914839107
- van Wilgenburg B., Scherwitzl I., Hutchinson E. C., Leng T., Kurioka A., Kulicke C., de Lara C., Cole S., Vasanawathana S., Limpitikul W., Malasit P., Young D., Denney L., Moore M. D., Fabris P., Giordani M. T., Oo Y. H., Laidlaw S. M., Dustin L. B., Ho L. P., Thompson F. M., Ramamurthy N., Mongkolsapaya J., Willberg C. B., Screaton G. R., Klenerman P.; STOP-HCV consortium , MAIT cells are activated during human viral infections. Nat. Commun. 7, 11653 (2016). 10.1038/ncomms11653
- Davenport E. E., Burnham K. L., Radhakrishnan J., Humburg P., Hutton P., Mills T. C., Rautanen A., Gordon A. C., Garrard C., Hill A. V., Hinds C. J., Knight J. C., Genomic landscape of the individual host response and outcomes in sepsis: A prospective cohort study. Lancet Respir. Med. 4, 259–271 (2016). 10.1016/S2213-2600(16)00046-1
- Faivre V., Lukaszewicz A. C., Payen D., Downregulation of Blood Monocyte HLA-DR in ICU Patients Is Also Present in Bone Marrow Cells. PLOS ONE 11, e0164489 (2016). 10.1371/journal.pone.0164489
- Monneret G., Lepape A., Voirin N., Bohé J., Venet F., Debard A.-L., Thizy H., Bienvenu J., Gueyffier F., Vanhems P., Persisting low monocyte human leukocyte antigen-DR expression predicts mortality in septic shock. Intensive Care Med. 32, 1175–1183 (2006). 10.1007/s00134-006-0204-8
- A. R. G. Flannery, S., Dhudasia, M.B, SARS-CoV-2 Seroprevalence Among Parturient Women. Research Square, DOI: (2020).10.21203/-27402/v21201
- Stadlbauer D., Amanat F., Chromikova V., Jiang K., Strohmeier S., Arunkumar G. A., Tan J., Bhavsar D., Capuano C., Kirkpatrick E., Meade P., Brito R. N., Teo C., McMahon M., Simon V., Krammer F., SARS-CoV-2 Seroconversion in Humans: A Detailed Protocol for a Serological Assay, Antigen Production, and Test Setup. Curr. Protoc. Microbiol. 57, e100 (2020). 10.1002/cpmc.100
- Meng W., Zhang B., Schwartz G. W., Rosenfeld A. M., Ren D., Thome J. J. C., Carpenter D. J., Matsuoka N., Lerner H., Friedman A. L., Granot T., Farber D. L., Shlomchik M. J., Hershberg U., Luning Prak E. T., An atlas of B-cell clonal distribution in the human body. Nat. Biotechnol. 35, 879–884 (2017). 10.1038/nbt.3942
- Vander Heiden J. A., Yaari G., Uduman M., Stern J. N., O’Connor K. C., Hafler D. A., Vigneault F., Kleinstein S. H., pRESTO: A toolkit for processing high-throughput sequencing raw reads of lymphocyte receptor repertoires. Bioinformatics 30, 1930–1932 (2014). 10.1093/bioinformatics/btu138
- Rosenfeld A. M., Meng W., Chen D. Y., Zhang B., Granot T., Farber D. L., Hershberg U., Luning Prak E. T., Computational Evaluation of B-Cell Clone Sizes in Bulk Populations. Front. Immunol. 9, 1472 (2018). 10.3389/fimmu.2018.01472
- Ye J., Ma N., Madden T. L., Ostell J. M., IgBLAST: An immunoglobulin variable domain sequence analysis tool. Nucleic Acids Res. 41 (W1), W34-40 (2013). 10.1093/nar/gkt382
- Rosenfeld A. M., Meng W., Luning Prak E. T., Hershberg U., ImmuneDB, a Novel Tool for the Analysis, Storage, and Dissemination of Immune Repertoire Sequencing Data. Front. Immunol. 9, 2107 (2018). 10.3389/fimmu.2018.02107
- Bolotin D. A., Poslavsky S., Mitrophanov I., Shugay M., Mamedov I. Z., Putintseva E. V., Chudakov D. M., MiXCR: Software for comprehensive adaptive immunity profiling. Nat. Methods 12, 380–381 (2015). 10.1038/nmeth.3364
- Levenshtein V. I., Binary codes capable of correcting deletions, insertions and reversals. Sov. Phys. Dokl. 10, 707–710 (1966).
Source: PubMed