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Distinct Early Serological Signatures Track with SARS-CoV-2 Survival
Open accessAbstract
As SARS-CoV-2 infections and death counts continue to rise, it remains unclear why some individuals recover from infection, whereas others rapidly progress and die. Although the immunological mechanisms that underlie different clinical trajectories remain poorly defined, pathogen-specific antibodies often point to immunological mechanisms of protection. Here, we profiled SARS-CoV-2-specific humoral responses in a cohort of 22 hospitalized individuals. Despite inter-individual heterogeneity, distinct antibody signatures resolved individuals with different outcomes. Although no differences in SARS-CoV-2-specific IgG levels were observed, spike-specific humoral responses were enriched among convalescent individuals, whereas functional antibody responses to the nucleocapsid were elevated in deceased individuals. Furthermore, this enriched immunodominant spike-specific antibody profile in convalescents was confirmed in a larger validation cohort. These results demonstrate that early antigen-specific and qualitative features of SARS-CoV-2-specific antibodies point to differences in disease trajectory, highlighting the potential importance of functional antigen-specific humoral immunity to guide patient care and vaccine development.
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“In patients hospitalized with COVID-19, the early presence of broadly functional antibodies directed at the SARS-CoV-2 spike (S) protein (see also Box 1) correlated with survival25”
From Immunological mechanisms of vaccine-induced protection against COVID-19 in humans (2021) · cites this paper as [25]
In the citing paper
“Non-NAbs can also have an important role in protection, however, via Fc-mediated effector functions including antibody-dependent phagocytosis, antibody-dependent cellular cytotoxicity and antibody-dependent natural killer cell activation10,25,31.”
From Immunological mechanisms of vaccine-induced protection against COVID-19 in humans (2021) · cites this paper as [25]
In the citing paper
“A bias toward nucleocapsid antibodies over Spike antibodies in fatal cases was observed in a pair of studies (Atyeo et al., 2020; Zohar et al., 2020), which is consistent with a role for Spike antibodies in reducing viral loads.”
From Adaptive immunity to SARS-CoV-2 and COVID-19 (2021) · cites this paper as Atyeo et al., 2020
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Self-citationSerodominant SARS-CoV-2 Nucleocapsid Peptides Map to Unstructured Protein Regions
Vandervaart, J. P., Inniss, N. L., Ling-Hu, T., Minasov, G., Wiersum, G., Rosas‐Lemus, M., Shuvalova, L., Achenbach, C. J., Hultquist, J. F., Satchell, K. J. F., et al. (2023) · Microbiology Spectrum · doi:10.1128/spectrum.00324-23 · Cited by 15
Cross-reactive antibody responses against SARS-CoV-2 and seasonal common cold coronavirusesPreprint
Klompus, S., Leviatan, S., Vogl, T. J., Kalka, I. N., Godneva, A., Shinar, E., Weinberger, A., & Segal, E. (2020) · medRxiv · doi:10.1101/2020.09.01.20182220 · Cited by 15
Multisystem Inflammatory Syndrome in Children and SARS-CoV-2 Serology
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Immunity against seasonal human coronavirus OC43 mitigates fatal deterioration of COVID-19
Yamaguchi, T., Shinagawa, T., Kobata, H., & Nakagawa, H. (2021) · International Journal of Infectious Diseases · doi:10.1016/j.ijid.2021.07.015 · Cited by 14
Recent Developments in the Understanding of Immunity, Pathogenesis and Management of COVID-19
Yegiazaryan, A., Abnousian, A., Alexander, L. J., Badaoui, A., Flaig, B., Sheren, N., Aghazarian, A., Alsaigh, D., Amin, A., Mundra, A., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23169297 · Cited by 14
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Self-citationPathogenesis Guided Therapeutic Management of COVID-19: An Immunological Perspective
Kumar, A., Prasoon, P., Shekhawat, P. S., Pareek, V., Faiq, M. A., Kumari, C., Narayan, R. K., Kulandhasamy, M., & Kant, K. (2020) · International Reviews of Immunology · doi:10.1080/08830185.2020.1840566 · Cited by 12
Kealy, L. C., & Good‐Jacobson, K. L. (2021) · Oxford Open Immunology · doi:10.1093/oxfimm/iqab018 · Cited by 14
BNT162b2 induces robust cross-variant SARS-CoV-2 immunity in children
Bartsch, Y. C., Chen, J. W., Kang, J., Burns, M. D., Denis, K. S., Sheehan, M. L., Davis, J. P., Edlow, A. G., Balazs, A. B., Yonker, L. M., et al. (2022) · npj Vaccines · doi:10.1038/s41541-022-00575-w · Cited by 14
Self-citationSharma, A., Ong, J., Loke, M. F., Chua, E. G., Lee, J., Choi, H., Tan, Y., Lal, S. K., & Chow, V. T. K. (2021) · Microorganisms · doi:10.3390/microorganisms9061193 · Cited by 13
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Sustained Antibody-Dependent NK Cell Functions in Mild COVID-19 Outpatients During Convalescence
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Ad26.COV2.S priming provided a solid immunological base for mRNA-based COVID-19 booster vaccination
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Early cross-coronavirus reactive signatures of protective humoral immunity against COVID-19Preprint
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Self-citationA look-back at convalescent plasma to treat COVID-19
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Comparison of the humoral and cellular immunity in COVID-19 convalescents
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Coronavac inactivated vaccine triggers durable, cross-reactive Fc-mediated phagocytosis activities
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Metadata
- Authors
- Atyeo, C., Fischinger, S., Zohar, T., Slein, M. D., Burke, J., Loos, C., McCulloch, D. J., Newman, K. L., Wolf, C., Yu, J., Shuey, K., Feldman, J., Hauser, B. M., Caradonna, T., Schmidt, A. G., Suscovich, T. J., Linde, C., Cai, Y., Barouch, D., Ryan, E. T., Charles, R. C., Lauffenburger, D., Chu, H., & Alter, G.
- Affiliations
- Harvard University (US)
- Ragon Institute of MGH, MIT and Harvard (US)
- University of Washington (US)
- Beth Israel Deaconess Medical Center (US)
- Boston Children's Hospital (US)
- Massachusetts General Hospital (US)
- Massachusetts Institute of Technology (US)
- Corresponding author
- Chu, Helen
- Alter, Galit
- ORCID
- Atyeo, Caroline
- Fischinger, Stephanie
- Zohar, Tomer
- Slein, Matthew D.
- Burke, John
- Loos, Carolin
- McCulloch, Denise J.
- Newman, Kira L.
- Wolf, Caitlin
- Yu, Jingyou
- Shuey, Kiel
- Feldman, Jared
- Hauser, Blake Marie
- Caradonna, Tim
- Schmidt, Aaron G.
- Suscovich, Todd J.
- Linde, Caitlyn
- Cai, Yongfei
- Barouch, Dan
- Ryan, Edward T.
- Charles, Richelle C.
- Lauffenburger, Douglas
- Chu, Helen
- Alter, Galit
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2020-09
- Volume
- 53
- Issue
- 3
- Pages
- 524-532.e4
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC7392190
- OpenAlex
- W3045933491
- Cited by
- 349
- References
- 52
- Citations by year
- 2026: 7 · 2025: 20 · 2024: 30 · 2023: 41 · 2022: 69 · 2021: 138 · 2020: 44
- FWCI
- 9.58
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Immunity (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Universitätsbibliographie, Universität Duisburg-Essen (submittedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- Funders
- National Institute of Allergy and Infectious Diseases
- Centers for Disease Control and Prevention
- Bill and Melinda Gates Foundation
- 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, humoral immunity, spike-specific antibodies, nucleocapsid antibodies, disease outcome prediction, convalescence, hospitalized patients, immunodominant epitopes
- MeSH terms
- Betacoronavirus, COVID-19, SARS-CoV-2, Coronavirus Nucleocapsid Proteins, Adult, Aged, Aged, 80 and over, Antibodies, Viral, Female, Humans, Immunoglobulin G, Male, Middle Aged, Phosphoproteins, Pneumonia, Viral, Coronavirus Infections, Nucleocapsid Proteins, Immunity, Humoral, Pandemics, Spike Glycoprotein, Coronavirus
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