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Nat Commun. 2021 Nov 25;12(1):6853. doi: 10.1038/s41467-021-27201-y.

Functional convalescent plasma antibodies and pre-infusion titers shape the early severe COVID-19 immune response.

Nature communications

Jonathan D Herman, Chuangqi Wang, Carolin Loos, Hyunah Yoon, Johanna Rivera, M Eugenia Dieterle, Denise Haslwanter, Rohit K Jangra, Robert H Bortz, Katharine J Bar, Boris Julg, Kartik Chandran, Douglas Lauffenburger, Liise-Anne Pirofski, Galit Alter

Affiliations

  1. Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
  2. Division of Infectious Disease, Brigham and Women's Hospital, Boston, MA, USA.
  3. Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
  4. Division of Infectious Diseases, Department of Medicine, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY, USA.
  5. Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA.
  6. Department of Microbiology and Immunology, Louisiana State University Health Science Center-Shreveport, Shreveport, LA, USA.
  7. Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  8. Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA. [email protected].
  9. Division of Infectious Diseases, Department of Medicine, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY, USA. [email protected].
  10. Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA. [email protected].
  11. Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA. [email protected].

PMID: 34824251 PMCID: PMC8617042 DOI: 10.1038/s41467-021-27201-y

Abstract

Transfer of convalescent plasma (CP) had been proposed early during the SARS-CoV-2 pandemic as an accessible therapy, yet trial results worldwide have been mixed, potentially due to the heterogeneous nature of CP. Here we perform deep profiling of SARS-CoV-2-specific antibody titer, Fc-receptor binding, and Fc-mediated functional assays in CP units, as well as in plasma from hospitalized COVID-19 patients before and after CP administration. The profiling results show that, although all recipients exhibit expanded SARS-CoV-2-specific humoral immune responses, CP units contain more functional antibodies than recipient plasma. Meanwhile, CP functional profiles influence the evolution of recipient humoral immunity in conjuncture with the recipient's pre-existing SARS-CoV2-specific antibody titers: CP-derived SARS-CoV-2 nucleocapsid-specific antibody functions are associated with muted humoral immune evolution in patients with high titer anti-spike IgG. Our data thus provide insights into the unexpected impact of CP-derived functional anti-spike and anti-nucleocapsid antibodies on the evolution of SARS-CoV-2-specific response following severe infection.

© 2021. The Author(s).

References

  1. JAMA. 2020 Apr 7;323(13):1239-1242 - PubMed
  2. J Clin Invest. 2020 Jun 1;130(6):2757-2765 - PubMed
  3. Eur J Clin Microbiol Infect Dis. 2005 Jan;24(1):44-6 - PubMed
  4. Nat Med. 2018 Oct;24(10):1590-1598 - PubMed
  5. J Clin Microbiol. 2020 Oct 21;58(11): - PubMed
  6. Viruses. 2014 Aug 07;6(8):2991-3018 - PubMed
  7. Lancet Infect Dis. 2020 May;20(5):533-534 - PubMed
  8. J Clin Invest. 2020 Apr 1;130(4):1545-1548 - PubMed
  9. Sci Immunol. 2020 Oct 8;5(52): - PubMed
  10. Nat Commun. 2020 Aug 6;11(1):3924 - PubMed
  11. J Clin Invest. 2020 Sep 1;130(9):4791-4797 - PubMed
  12. N Engl J Med. 2020 Oct 15;383(16):1522-1534 - PubMed
  13. Cell Host Microbe. 2020 Sep 9;28(3):486-496.e6 - PubMed
  14. Clin Infect Dis. 2011 Feb 15;52(4):447-56 - PubMed
  15. JCI Insight. 2021 Feb 22;6(4): - PubMed
  16. Cell. 2021 Apr 1;184(7):1804-1820.e16 - PubMed
  17. Lancet. 2021 May 29;397(10289):2049-2059 - PubMed
  18. JAMA Neurol. 2020 Jul 2;: - PubMed
  19. Cell Host Microbe. 2021 Mar 10;29(3):463-476.e6 - PubMed
  20. J Immunol Methods. 2011 Mar 7;366(1-2):8-19 - PubMed
  21. Ann Intern Med. 2006 Oct 17;145(8):599-609 - PubMed
  22. J Immunol Methods. 2017 Apr;443:33-44 - PubMed
  23. Immunity. 2020 Sep 15;53(3):524-532.e4 - PubMed
  24. Chest. 2013 Aug;144(2):464-473 - PubMed
  25. Hum Vaccin Immunother. 2017 Jun 3;13(6):1-9 - PubMed
  26. N Engl J Med. 2021 Mar 8;384(15):1466-1468 - PubMed
  27. Sci Rep. 2021 Jan 28;11(1):2608 - PubMed
  28. Metabolomics. 2010 Mar;6(1):119-128 - PubMed
  29. J Virol. 2015 Sep;89(17):8733-48 - PubMed
  30. N Engl J Med. 2020 Dec 17;383(25):2451-2460 - PubMed
  31. Clin Microbiol Infect. 2004 Jul;10(7):676-8 - PubMed
  32. Microorganisms. 2020 Nov 28;8(12): - PubMed
  33. J Immunol Methods. 2004 Nov;294(1-2):15-22 - PubMed
  34. N Engl J Med. 2021 Jan 21;384(3):238-251 - PubMed
  35. Nat Rev Immunol. 2003 May;3(5):413-25 - PubMed
  36. J Infect Dis. 2021 Aug 16;224(4):565-574 - PubMed
  37. J Exp Med. 2021 Mar 1;218(3): - PubMed
  38. Vaccines (Basel). 2020 Nov 20;8(4): - PubMed
  39. BMC Infect Dis. 2020 Oct 21;20(1):786 - PubMed
  40. Cell Host Microbe. 2013 Feb 13;13(2):169-80 - PubMed
  41. J Immunol Methods. 2019 Aug;471:46-56 - PubMed
  42. Am J Pathol. 2021 Jan;191(1):4-17 - PubMed
  43. Cell. 2016 Oct 6;167(2):433-443.e14 - PubMed
  44. J Clin Invest. 2020 Nov 2;130(11):6141-6150 - PubMed
  45. Lancet. 2020 Feb 15;395(10223):497-506 - PubMed
  46. Nature. 2010 Oct 14;467(7317):832-8 - PubMed
  47. Clin Vaccine Immunol. 2010 Jul;17(7):1055-65 - PubMed
  48. N Engl J Med. 2021 Mar 17;384(15):1468-1470 - PubMed
  49. Science. 2020 Aug 14;369(6505):806-811 - PubMed
  50. BMJ. 2020 Oct 22;371:m3939 - PubMed
  51. JAMA. 2020 Aug 4;324(5):460-470 - PubMed
  52. Natl Sci Rev. 2020 Jun;7(6):998-1002 - PubMed
  53. Am J Public Health. 2020 Aug;110(8):1160-1161 - PubMed
  54. N Engl J Med. 2021 Feb 18;384(7):619-629 - PubMed
  55. Nat Commun. 2021 May 27;12(1):3189 - PubMed
  56. J Clin Invest. 2021 Jul 1;131(13): - PubMed
  57. Methods Mol Biol. 2015;1282:1-23 - PubMed
  58. J Immunol Methods. 2019 Oct;473:112630 - PubMed
  59. Nat Rev Immunol. 2018 Jan;18(1):46-61 - PubMed
  60. N Engl J Med. 2021 Feb 18;384(7):610-618 - PubMed
  61. Cell. 2015 Nov 5;163(4):988-98 - PubMed
  62. Hum Brain Mapp. 2016 Apr;37(4):1486-511 - PubMed
  63. Signal Transduct Target Ther. 2021 Feb 2;6(1):48 - PubMed

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