Decay of Fc-dependent antibody functions after mild to moderate COVID-19
Open accessPreprint — published as 10.1016/j.xcrm.2021.100296
Abstract
The capacity of antibodies to engage with innate and adaptive immune cells via the Fc region is important in preventing and controlling many infectious diseases, and is likely critical in SARS-CoV-2 infection. The evolution of such antibodies during convalescence from COVID-19 is largely unknown. We developed novel assays to measure Fc-dependent antibody functions against SARS-CoV-2 spike (S)-expressing cells in serial samples from a cohort of 53 subjects primarily with mild-moderate COVID-19, out to a maximum of 149 days post-infection. We found that S-specific antibodies capable of engaging dimeric FcγRIIa and FcγRIIIa decayed linearly over time. S-specific antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent phagocytosis (ADP) activity within plasma declined linearly as well, in line with the decay of S-specific IgG. Although there was significant decay in S-specific plasma ADCC and ADP activity, they remained readily detectable by all assays in 94% of our cohort at the last timepoint studied, in contrast with neutralisation activity which was only detectable in 70% of our cohort by the last timepoint. Our results suggest that Fc effector functions such as ADCC and ADP could contribute to the durability of SARS-CoV-2 immunity, particularly late in convalescence when neutralising antibodies have waned. Understanding the protective potential of antibody Fc effector functions is critical for defining the durability of immunity generated by infection or vaccination.
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Residual non-neutralizing antibodies after infection may provide some protection during reinfection even when serum neutralizing activity is below the protective threshold.
“Thus, residual SARS-CoV-2-specific non-neutralizing antibodies following infection may confer some protective benefit during reinfection, even when serum neutralizing activity has declined below the threshold of protection25–27.”
From Prospects for durable immune control of SARS-CoV-2 and prevention of reinfection (2021) · cites this paper as [26]
Non-neutralizing antibodies that bind viral proteins could contribute to immune control by clearing free virus or targeting infected cells.
“Antibodies that bind to viral proteins but do not neutralize SARS-CoV-2 could still contribute to the immune control of infection through the increased clearance of free virus or by targeting infected cells for immune clearance (through antibody-dependent cellular cytotoxicity and other mechanisms)25 (preprint data, not yet peer reviewed)26.”
From Prospects for durable immune control of SARS-CoV-2 and prevention of reinfection (2021) · cites this paper as [26]
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References 60 · Cited by 80
- Authors
- Lee, W. S., Selva, K. J., Davis, S. K., Wines, B. D., Reynaldi, A., Esterbauer, R., Kelly, H. G., Haycroft, E. R., Tan, H.-X., Juno, J. A., Wheatley, A. K., Hogarth, P. M., Cromer, D., Davenport, M. P., Chung, A. W., & Kent, S. J.
- Affiliations
- The University of Melbourne (AU)
- Burnet Institute (AU)
- UNSW Sydney (AU)
- Australian Research Council (AU)
- Corresponding author
- Chung, Amy W.
- Kent, Stephen J.
- ORCID
- Venue
- Cell Reports Medicine
- Publisher
- openRxiv
- Published
- 2020-12-14
- Volume
- 2
- Issue
- 6
- Pages
- 100296-100296
- ISSN
- 2666-3791 (ISSN-L)
- PMC
- PMC8106889
- OpenAlex
- W3163651782
- Cited by
- 80
- References
- 60
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 11 · 2023: 14 · 2022: 24 · 2021: 16
- FWCI
- 5.14
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc
- Locations
- Cell Reports Medicine (publishedVersion, cc-by-nc)
- medRxiv (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- UNSWorks (University of New South Wales, Sydney, Australia) (submittedVersion, cc-by-nc-nd)
- Funders
- Australian Government
- Fast Grants
- European Commission (HORIZON2020, 681137)
- University of Melbourne
- State Government of Victoria
- National Institutes of Health (NR-52366, HHSN272201400008C)
- Australian Research Council
- National Health and Medical Research Council (1149990, GNT2002073, 1115828, 1162760, 1145303)
- Horizon 2020 (681137)
- National Institute of Allergy and Infectious Diseases (HHSN272201400008C))
- ARC Centre for Excellence in Convergent Bio-Nano Science and Technology
- Medical Research Future Fund
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Keywords
- COVID-19 pandemic, SARS-CoV-2, Fc effector functions, antibody waning, antibody-dependent cellular cytotoxicity, antibody-dependent phagocytosis, neutralizing antibodies, Fc gamma receptor, spike protein antibodies, convalescence, antibody persistence, reinfection protection
- MeSH terms
- COVID-19, SARS-CoV-2, Antibodies, Viral, Antibody-Dependent Cell Cytotoxicity, Humans, Immunoglobulin Fc Fragments, Kinetics, Neutralization Tests, Phagocytosis, Severity of Illness Index, Dimerization, Cell Line, Tumor, Spike Glycoprotein, Coronavirus
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