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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Among hospitalized COVID-19 patients, early broadly functional antibodies against the SARS-CoV-2 spike protein were associated with survival.
“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]
Non-neutralizing antibodies may protect through Fc-mediated functions such as phagocytosis, cellular cytotoxicity, and natural killer cell activation.
“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]
A bias toward nucleocapsid antibodies over Spike antibodies in fatal cases is consistent with a role for Spike antibodies in reducing viral loads.
“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-citationImmunity to SARS-CoV-2: Lessons Learned
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- 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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