Neutralizing Antibody Responses in COVID-19 Convalescent Sera
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Abstract
Passive transfer of antibodies from COVID-19 convalescent patients is being used as an experimental treatment for eligible patients with SARS-CoV-2 infections. The United States Food and Drug Administration’s (FDA) guidelines for convalescent plasma initially recommended target antibody titers of 160. We evaluated SARS-CoV-2 neutralizing antibodies in sera from recovered COVID-19 patients using plaque reduction neutralization tests (PRNT) at moderate (PRNT50) and high (PRNT90) stringency thresholds. We found that neutralizing activity significantly increased with time post symptom onset (PSO), reaching a peak at 31–35 days PSO. At this point, the number of sera having neutralizing titers of at least 160 was approximately 93% (PRNT50) and approximately 54% (PRNT90). Sera with high SARS-CoV-2 antibody levels (>960 enzyme-linked immunosorbent assay titers) showed maximal activity, but not all high-titer sera contained neutralizing antibody at FDA recommended levels, particularly at high stringency. These results underscore the value of serum characterization for neutralization activity.
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Neutralizing antibody levels correlate with viral load and are higher in more severe disease and in older versus younger adults.
“The magnitude of these NAb responses appear to correlate with viral load, with higher responses reported in patients with more severe disease, and in older adults compared with younger adults26–29.”
From Immunological mechanisms of vaccine-induced protection against COVID-19 in humans (2021) · cites this paper as [28]
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Cites
Virological assessment of hospitalized patients with COVID-2019
Wölfel, R., Corman, V. M., Guggemos, W., Seilmaier, M., Zange, S., Müller, M. A., Niemeyer, D., Jones, T. C., Vollmar, P., Rothe, C., et al. (2020) · Nature · doi:10.1038/s41586-020-2196-x · Cited by 6,661 · see citing works
Rydyznski Moderbacher, C., Ramirez, S. I., Dan, J. M., Grifoni, A., Hastie, K. M., Weiskopf, D., Belanger, S., Abbott, R. K., Kim, C., Choi, J., et al. (2020) · Cell · doi:10.1016/j.cell.2020.09.038 · Cited by 1,790 · cited 1× · see citing works
“Strong cellular immunity could more than compensate for low virus neutralizing capacity in vaccinated or previously infected individuals or due to prior infection from non-SARS-CoV-2 coronaviruses [43, 45, 46].”
BackgroundDevelopment of an inactivated vaccine candidate for SARS-CoV-2
Gao, Q., Bao, L., Mao, H., Wang, L., Xu, K., Yang, M., Li, Y., Zhu, L., Wang, N., Lv, Z., et al. (2020) · Science · doi:10.1126/science.abc1932 · Cited by 1,434 · see citing works
Wu, F., Wang, A., Liu, M., Wang, Q., Chen, J., Xia, S., Ling, Y., Zhang, Y., Xun, J., Lu, L., et al. (2020) · doi:10.1101/2020.03.30.20047365 · Cited by 754 · see citing works
Joyner, M. J., Senefeld, J. W., Klassen, S. A., Mills, J. R., Johnson, P. W., Theel, E. S., Wiggins, C. C., Bruno, K. A., Klompas, A. M., Lesser, E. R., et al. (2020) · medRxiv · doi:10.1101/2020.08.12.20169359 · Cited by 337 · see citing works
Luchsinger, L. L., Ransegnola, B. P., Jin, D. K., Muecksch, F., Weisblum, Y., Bao, W., George, P. J., Rodriguez, M., Tricoche, N., Schmidt, F., et al. (2020) · Journal of Clinical Microbiology · doi:10.1128/jcm.02005-20 · Cited by 187 · see citing works
Brigger, D., Horn, M. P., Pennington, L. F., Powell, A. E., Siegrist, D., Weber, B., Engler, O. B., Piezzi, V., Damonti, L., Iseli, P., et al. (2020) · Allergy · doi:10.1111/all.14608 · Cited by 32 · see citing works
Flagged first, then by citations
Research works printed but not linked: 33
- Dong E, Du H, Gardner L. An interactive web-based dash- board to track COVID-19 in real time. Lancet Infect Dis 2020; 20:533-4.
- Zhou F, Yu T, Du R, et al. Clinical course and risk fac- tors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020; 395:1054-62.
- Anderson RM, May RM. Vaccination and herd immunity to infectious diseases. Nature 1985; 318:323-9.
- Liu W, Fontanet A, Zhang PH, et al. Two-year prospec- tive study of the humoral immune response of patients with severe acute respiratory syndrome. J Infect Dis 2006; 193:792-5.
- Huang AT, Garcia-Carreras B, Hitchings MDT, et al. A systematic review of antibody mediated immunity to cor- onaviruses: antibody kinetics, correlates of protection, and association of antibody responses with severity of disease. Nat. Comm 2020; 11:4704-20.
- Tang YW, Schmitz JE, Persing DH, Stratton CW. Laboratory diagnosis of COVID-19: current issues and challenges. J Clin Microbiol 2020; 58:e00512-20.
- Krammer F, Simon V. Serology assays to manage COVID- 19. Science 2020; 68:1060-1.
- Bloch EM, Shoham S, Casadevall A, et al. Deployment of convalescent plasma for the prevention and treatment of COVID-19. J Clin Invest 2020; 130:2757-65.
- Casadevall A, Joyner MJ, Pirofski LA. A randomized trial of convalescent plasma for COVID-19-potentially hopeful signals. JAMA 2020; 324:455-7.
- Russell PK, Nisalak A, Sukhavachana P, Vivona S. A plaque reduction test for dengue virus neutralizing antibodies. J Immunol 1967; 99:285-90.
- Lindsey HS, Calisher CH, Mathews JH. Serum dilution neutralization test for California group virus identification and serology. J Clin Microbiol 1976; 4:503-10.
- Meyer EG, Simmons G, Grebe E, et al. Selecting COVID- 19 convalescent plasma for neutralizing antibody po- tency using a high-capacity SARS-CoV-2 antibody assay. medRxiv, doi: 10.1101/2020.08.31.20184895, 31 August 2020, preprint: not peer reviewed. · DOI
- Amanat F, Stadlbauer D, Strohmeier S, et al. A serological assay to detect SARS-CoV-2 seroconversion in humans. Nat Med 2020; 26:1033-6.
- Stadlbauer D, Amanat F, Chromikova V, et al. SARS-CoV-2 seroconversion in humans: a detailed protocol for a serolog- ical assay, antigen production, and test setup. Curr Protoc Microbiol 2020; 57:e100.
- Oliphant T, Nybakken GE, Austin SK, et al. Induction of epitope-specific neutralizing antibodies against West Nile virus. J Virol 2007; 81:11828-39.
- Koraka P, Suharti C, Setiati TE, et al. Kinetics of dengue virus-specific serum immunoglobulin classes and sub- classes correlate with clinical outcome of infection. J Clin Microbiol 2001; 39:4332-8.
- Yang HS, Racine-Brzostek SE, Lee WT, et al. SARS-CoV-2 antibody characterization in emergency department, hospi- talized and convalescent patients by two semi-quantitative immunoassays. Clin Chim Acta 2020; 509:117-25.
- Shambaugh C, Azshirvani S, Yu L, et al. Development of a high-throughput respiratory syncytial virus fluores- cent focus-based microneutralization assay. Clin Vaccine Immunol 2017; 24:e00225-17.
- Burton DR, Saphire EO, Parren P. A model for neutraliza- tion of viruses based on antibody coating of the virion sur- face. In: Burton DR, ed. Antibodies in viral infection. Vol. 260. Berlin: Springer-Verlag, 2001:109-43.
- Chen L, Xiong J, Bao L, Shi Y. Convalescent plasma as a potential therapy for COVID-19. Lancet Infect Dis 2020; 20:398-400.
- Joyner MJ, Bruno KA, Klassen SA, et al. Safety update: COVID-19 convalescent plasma in 20 000 hospitalized pa- tients. Mayo Clin Proc 2020; 95:1888-97.
- Shen C, Wang Z, Zhao F, et al. Treatment of 5 critically Ill patients with COVID-19 with convalescent plasma. JAMA 2020; 323:1582-9.
- Duan K, Liu B, Li C, et al. Effectiveness of convalescent plasma therapy in severe COVID-19 patients. Proc Natl Acad Sci U S A 2020; 117:9490-6.
- Luchsinger LL, Ransegnola B, Jin D, et al. Serological anal- ysis of New York City COVID19 convalescent plasma donors. medRxiv, doi: 10.1101/2020.06.08.20124792, 9 June 2020, preprint: not peer reviewed. · DOI
- Okba NMA, Muller MA, Li W, et al. SARS-CoV-2 specific antibody responses in COVID-19 patients. medRxiv, doi:1 0.1101/2020.03.18.20038059, 20 March 2020, preprint: not peer reviewed. · DOI
- Amanat F, Stadlbauer D, Strohmeier S, et al. A serological assay to detect SARS-CoV-2 seroconversion in humans. Nat Med 2020; 26:1033-6.
- Temperton NJ, Chan PK, Simmons G, et al. Longitudinally profiling neutralizing antibody response to SARS corona- virus with pseudotypes. Emerg Infect Dis 2005; 11:411-6. COVID-19 Convalescent Sera • jid 2021:223 (1 january) • 55
- Krammer F, Weir JP, Engelhardt O, Katz JM, Cox RJ. Meeting report and review: Immunological assays and cor- relates of protection for next-generation influenza vaccines. Influenza Other Respir Viruses 2020; 14:237-43.
- Chen RT, Markowitz LE, Albrecht P, et al. Measles antibody: reevaluation of protective titers. J Infect Dis 1990; 162:1036-42.
- Plotkin SA. Correlates of protection induced by vaccina- tion. Clin Vaccine Immunol 2010; 17:1055-65.
- Grifoni A, Weiskopf D, Ramirez SI, et al. Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals. Cell 2020; 181:1489-1501.e15.
- Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ; HLH Across Speciality Collaboration, UK. COVID-19: consider cytokine storm syndromes and im- munosuppression. Lancet 2020; 395:1033-4.
- Doshi P. Covid-19: do many people have pre-existing im- munity? BMJ 2020; 370:m3563.
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Seow, J., Graham, C., Merrick, B., Acors, S., Pickering, S., Steel, K. J. A., Hemmings, O., O’Byrne, A., Kouphou, N., Galao, R. P., et al. (2020) · Nature Microbiology · doi:10.1038/s41564-020-00813-8 · Cited by 1,419 · see citing works
Immunological mechanisms of vaccine-induced protection against COVID-19 in humans
Sadarangani, M., Marchant, A., & Kollmann, T. R. (2021) · Nature Reviews Immunology · doi:10.1038/s41577-021-00578-z · Cited by 560 · see citing works
- Authors
- Lee, W. T., Girardin, R. C., Dupuis, A. P., Kulas, K. E., Payne, A. F., Wong, S. J., Arinsburg, S., Nguyen, F. T., Mendu, D. R., Firpo-Betancourt, A., Jhang, J., Wajnberg, A., Krammer, F., Cordon-Cardo, C., Amler, S., Montecalvo, M., Hutton, B., Taylor, J., & McDonough, K. A.
- Affiliations
- New York State Department of Health (US)
- Wadsworth Center, New York State Department of Health, Albany, New York, USA
- Icahn School of Medicine at Mount Sinai (US)
- Department of Pathology, Molecular, and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
- Westchester County Department of Health (US)
- Corresponding author
- Lee, William T
- ORCID
- Venue
- The Journal of Infectious Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 2020-10-26
- Volume
- 223
- Issue
- 1
- Pages
- 47-55
- ISSN
- 0022-1899 (ISSN-L)
- 1537-6613
- PMC
- PMC7665673
- OpenAlex
- W3094465755
- Cited by
- 93
- References
- 7
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 9 · 2023: 11 · 2022: 18 · 2021: 39 · 2020: 7
- FWCI
- 2.46
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- The Journal of Infectious Diseases (publishedVersion)
- medRxiv (acceptedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- New York State Department of Health
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 detection and testing
- Keywords
- SARS-CoV-2, COVID-19 pandemic, neutralizing antibodies, convalescent plasma, passive antibody transfer, plaque reduction neutralization test, antibody titer thresholds
- MeSH terms
- COVID-19, COVID-19 Serotherapy, Antibodies, Viral, Enzyme-Linked Immunosorbent Assay, Humans, Immunization, Passive, Neutralization Tests, Antibodies, Neutralizing
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