Discrete SARS-CoV-2 antibody titers track with functional humoral stability
Open accessAbstract
Antibodies serve as biomarkers of infection, but if sustained can confer long-term immunity. Yet, for most clinically approved vaccines, binding antibody titers only serve as a surrogate of protection. Instead, the ability of vaccine induced antibodies to neutralize or mediate Fc-effector functions is mechanistically linked to protection. While evidence has begun to point to persisting antibody responses among SARS-CoV-2 infected individuals, cases of re-infection have begun to emerge, calling the protective nature of humoral immunity against this highly infectious pathogen into question. Using a community-based surveillance study, we aimed to define the relationship between titers and functional antibody activity to SARS-CoV-2 over time. Here we report significant heterogeneity, but limited decay, across antibody titers amongst 120 identified seroconverters, most of whom had asymptomatic infection. Notably, neutralization, Fc-function, and SARS-CoV-2 specific T cell responses were only observed in subjects that elicited RBD-specific antibody titers above a threshold. The findings point to a switch-like relationship between observed antibody titer and function, where a distinct threshold of activity—defined by the level of antibodies—is required to elicit vigorous humoral and cellular response. This response activity level may be essential for durable protection, potentially explaining why re-infections occur with SARS-CoV-2 and other common coronaviruses.
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Antibody functions besides neutralization have been shown to correlate with protection.
“antibody functions other than neutralization have been shown to correlate with protection (Bartsch et al., 2021; Gorman et al., 2021; Schäfer et al., 2021).”
From SARS-CoV-2 mRNA vaccination induces functionally diverse antibodies to NTD, RBD, and S2 (2021) · cites this paper as Bartsch et al., 2021
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Serological Markers of SARS-CoV-2 Reinfection
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Self-citationImmunology and Technology of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vaccines
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Sustained Antibody-Dependent NK Cell Functions in Mild COVID-19 Outpatients During Convalescence
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Early cross-coronavirus reactive signatures of protective humoral immunity against COVID-19Preprint
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Prospects of animal models and their application in studies on adaptive immunity to SARS-CoV-2
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Quantity of IgG response to SARS-CoV-2 spike glycoprotein predicts pulmonary recovery from COVID-19
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Differential antibody production by symptomatology in SARS-CoV-2 convalescent individuals
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Influence of Non-Hormonal Drugs on Hormonal Background and Biochemical Parameters of Blood
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Modulation of Hormonal Homeostasis and Blood Biochemical Markers by Non-Hormonal Drugs
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Features of the immune response formation to SARS-CoV-2 in patients who have recovered from COVID-19
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Humoral response to SARS-CoV-2 after vaccination and booster effect in patients undergoing dialysis
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RBD-IgG levels correlate with protection in Residents Facing SARS-CoV-2 B.1.1.7 OutbreaksPreprint
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Reinfection with a Bacterial Pathogen Augments Heterogeneity in Host Disease ResponsesPreprint
Garrett-Larsen, J., Pérez‐Umphrey, A. A., Fleming-Davies, A. E., Adelman, J. S., Childs, L. M., Geary, S. J., Langwig, K. E., & Hawley, D. M. (2025) · Research Square · doi:10.21203/rs.3.rs-6856045/v1 · Cited by 1 · see citing works
Characterization of Specific Humoral Immunity in Asymptomatic SARS-CoV-2 Infection
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Role of Functional Food Additives in Regulating the Immune Response to COVID-19
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ОСОБЛИВОСТІ ФОРМУВАННЯ ІМУННОЇ ВІДПОВІДІ ПІСЛЯ ВАКЦИНАЦІЇ ВІД COVID-19
Кисельова, Г. Л., Анастасій, І. А., Тонковид, О. Б., Isaiev, V. M., Voronova, K., Шевель, І. І., Сідорова, І. В., Карпеченко, С. В., & Панченко, А. А. (2023) · Інфекційні хвороби · doi:10.11603/1681-2727.2022.4.13697
Siles, N., Schuler, M., Maguire, C. P., Amengor, D., Nguyen, A. W., Wilen, R. E., Rogers, J. E., Bazzi, S. A., Caslin, B., DiPasquale, C., et al. (2023) · medRxiv · doi:10.1101/2023.12.05.23299462
Neutralizing Antibodies against SARS-CoV2
Athavale, P. V., Athavale, V., Suryawanshi, P., Khillare, K., & Tripathy, S. (2023) · Medical Journal of Dr. D.Y. Patil Vidyapeeth · doi:10.4103/mjdrdypu.mjdrdypu_819_22
In the time of COVID-19: challenges, successes, and lessons learned from studies in cancer patients
Mack, P. C., Crawford, J. M., Chang, A., Yin, A., Klein, S. L., Shea, P., Hirsch, F. R., Zidar, D. A., Simon, V. R., Gleason, C., et al. (2025) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djaf073
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Does prior pathogen exposure augment population-level heterogeneity in transmission-relevant traits?Preprint
Garrett-Larsen, J., Pérez‐Umphrey, A. A., Fleming-Davies, A. E., Adelman, J. S., Childs, L. M., Geary, S. J., Langwig, K. E., & Hawley, D. M. (2026) · Research Square · doi:10.21203/rs.3.rs-6856045/v2
Garrett-Larsen, J., Pérez‐Umphrey, A. A., Fleming-Davies, A. E., Adelman, J. S., Childs, L. M., Geary, S. J., Langwig, K. E., & Hawley, D. M. (2026) · Scientific Reports · doi:10.1038/s41598-026-46682-9
Analysis of SARS-CoV-2 infection and vaccination in high risk participants.
Reed, E. (2025) · ImmPort · doi:10.21430/m39ybc30zv
- Authors
- Bartsch, Y. C., Fischinger, S., Siddiqui, S. M., Chen, Z., Yu, J., Gebre, M., Atyeo, C., Gorman, M. J., Zhu, A. L., Kang, J., Burke, J. S., Slein, M., Gluck, M. J., Beger, S., Hu, Y., Rhee, J., Petersen, E., Mormann, B., Aubin, M. D. S., Hasdianda, M. A., Jambaulikar, G., Boyer, E. W., Sabeti, P. C., Barouch, D. H., Julg, B. D., Musk, E. R., Menon, A. S., Lauffenburger, D. A., Nilles, E. J., & Alter, G.
- Affiliations
- Ragon Institute of MGH, MIT and Harvard (US)
- Broad Institute (US)
- Beth Israel Deaconess Medical Center (US)
- SpaceX (United States) (US)
- Harvard University (US)
- Brigham and Women's Hospital (US)
- Massachusetts Institute of Technology (US)
- Corresponding author
- Menon, Anil S.
- Lauffenburger, Douglas A.
- Nilles, Eric J.
- Alter, Galit
- ORCID
- Bartsch, Yannic C.
- Fischinger, Stephanie
- Siddiqui, Sameed M.
- Chen, Zhilin
- Yu, Jingyou
- Gebre, Makda
- Atyeo, Caroline
- Zhu, Alex Lee
- Kang, Jaewon
- Burke, John S.
- Slein, Matthew
- Beger, Samuel
- Hu, Yiyuan
- Rhee, Justin
- Aubin, Michael de St
- Hasdianda, Mohammad A.
- Jambaulikar, Guruprasad
- Boyer, Edward W.
- Sabeti, Pardis C.
- Barouch, Dan H.
- Menon, Anil S.
- Lauffenburger, Douglas A.
- Nilles, Eric J.
- Alter, Galit
- Venue
- Nature Communications
- Published
- 2021-02-15
- Volume
- 12
- Issue
- 1
- Pages
- 1018-1018
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC7884400
- OpenAlex
- W3131892506
- Cited by
- 82
- References
- 41
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 2 · 2023: 11 · 2022: 32 · 2021: 29
- FWCI
- 5.86
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- ImmPort
- Funders
- U.S. Department of Health & Human Services | U.S. Food and Drug Administration (HHSF223201810172C)
- National Aeronautics and Space Administration (NNX16AO69A)
- U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (U19 AI135995, U19AI42790)
- U.S. Department of Health & Human Services | National Institutes of Health (R01AI146785, U19AI135995, U19AI42790, 1U01CA260476, CIVIC75N93019C00052)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 detection and testing
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Keywords
- SARS-CoV-2, antibody titers, humoral immunity, neutralizing antibodies, Fc effector functions, seroconversion, asymptomatic infection, T cell response, reinfection, long-term immunity, antibody waning, COVID-19 pandemic
- MeSH terms
- COVID-19, SARS-CoV-2, Adolescent, Adult, Aged, Antibodies, Viral, Female, Humans, Immunoglobulin G, Male, Middle Aged, T-Lymphocytes, Viral Vaccines, Young Adult, Immunity, Humoral, Antibodies, Neutralizing, Spike Glycoprotein, Coronavirus
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