COVID-19 Symptom Severity Predicts Neutralizing Antibody Activity in a Community-based Serological Study

Overview

Journal Sci Rep

Specialty Science

Date 2022 Jul 19

PMID 35851303

Authors

Amelia Sancilio

Joshua M Schrock

Alexis R Demonbreun

Richard T DAquila

Brian Mustanski

Lauren A Vaught

Nina L Reiser

Matt P Velez

Ryan R Hsieh

Daniel T Ryan

Rana Saber

Elizabeth M McNally

Thomas W McDade

Affiliations

Soon will be listed here.

Abstract

Serological testing for SARS-CoV-2 IgG antibodies is used to assess their presence in blood samples from exposed individuals and provides a measure of the magnitude of immune response to infection. The measurement of neutralizing antibodies (NAbs) in particular provides information about the severity of prior infection and level of protective immunity against re-infection. Much of the work investigating the association between prior infection severity and NAb levels has been conducted among clinical populations, and less is known about this relationship in the general population. Accordingly, we utilize data from a large (n = 790) community-based cohort of unvaccinated, seropositive participants. We analyzed the association between NAb response, measured via surrogate virus neutralization assay, with patterns of symptoms and household exposure. Our results indicate no detectable NAb activity in 63.8% of the seropositive participants (n = 504). Those with detectable NAb levels demonstrated a positive relationship between NAb activity and both self-reported previous symptom severity and household exposure. These findings are significant in light of recent concerns about degree of protective immunity conferred by prior infection or vaccination, and we highlight the value of community-based research for investigating variation in immune response.

Citing Articles

Explaining Racial and Ethnic Inequities in SARS-CoV-2-Related Outcomes: Results from a Serosurvey in Chicago.

Eyo C, Schrock J, Hayford C, Ryan D, Saber R, Benbow N J Racial Ethn Health Disparities. 2025; .

PMID: 40063297 DOI: 10.1007/s40615-025-02362-4.

Integrating Interpretability in Machine Learning and Deep Neural Networks: A Novel Approach to Feature Importance and Outlier Detection in COVID-19 Symptomatology and Vaccine Efficacy.

Jacob Khoury S, Zoabi Y, Scheinowitz M, Shomron N Viruses. 2025; 16(12.

PMID: 39772174 PMC: 11680429. DOI: 10.3390/v16121864.

Quantitating SARS-CoV-2 neutralizing antibodies from human dried blood spots.

Berman K, Van Slyke G, Novak H, Rock J, Bievenue R, Damjanovic A Microbiol Spectr. 2024; :e0084624.

PMID: 39470282 PMC: 11619372. DOI: 10.1128/spectrum.00846-24.

Lower Humoral and Cellular Immunity Following Asymptomatic SARS-CoV-2 Infection Compared to Symptomatic Infection in Education (The ACE Cohort).

Hopkins G, Gomez N, Tucis D, Bartlett L, Steers G, Burns E J Clin Immunol. 2024; 44(6):147.

PMID: 38856804 PMC: 11164737. DOI: 10.1007/s10875-024-01739-0.

Clinical and serological predictors of post COVID-19 condition-findings from a Canadian prospective cohort study.

Collins E, Galipeau Y, Arnold C, Bhereur A, Booth R, Buchan A Front Public Health. 2024; 12:1276391.

PMID: 38784593 PMC: 11111987. DOI: 10.3389/fpubh.2024.1276391.

References

Saadat S, Tehrani Z, Logue J, Newman M, Frieman M, Harris A . Binding and Neutralization Antibody Titers After a Single Vaccine Dose in Health Care Workers Previously Infected With SARS-CoV-2. JAMA. 2021; 325(14):1467-1469. PMC: 7922233. DOI: 10.1001/jama.2021.3341. View

Demonbreun A, Sancilio A, Velez M, Ryan D, Saber R, Vaught L . Comparison of IgG and neutralizing antibody responses after one or two doses of COVID-19 mRNA vaccine in previously infected and uninfected individuals. EClinicalMedicine. 2021; 38:101018. PMC: 8276631. DOI: 10.1016/j.eclinm.2021.101018. View

Anichini G, Terrosi C, Gandolfo C, Gori Savellini G, Fabrizi S, Miceli G . SARS-CoV-2 Antibody Response in Persons with Past Natural Infection. N Engl J Med. 2021; 385(1):90-92. PMC: 8063888. DOI: 10.1056/NEJMc2103825. View

Liu L, To K, Chan K, Wong Y, Zhou R, Kwan K . High neutralizing antibody titer in intensive care unit patients with COVID-19. Emerg Microbes Infect. 2020; 9(1):1664-1670. PMC: 7473321. DOI: 10.1080/22221751.2020.1791738. View

Dong E, Du H, Gardner L . An interactive web-based dashboard to track COVID-19 in real time. Lancet Infect Dis. 2020; 20(5):533-534. PMC: 7159018. DOI: 10.1016/S1473-3099(20)30120-1. View

Wajnberg A, Amanat F, Firpo A, Altman D, Bailey M, Mansour M . Robust neutralizing antibodies to SARS-CoV-2 infection persist for months. Science. 2020; 370(6521):1227-1230. PMC: 7810037. DOI: 10.1126/science.abd7728. View

Jeewandara C, Jayathilaka D, Gomes L, Wijewickrama A, Narangoda E, Idampitiya D . SARS-CoV-2 neutralizing antibodies in patients with varying severity of acute COVID-19 illness. Sci Rep. 2021; 11(1):2062. PMC: 7819970. DOI: 10.1038/s41598-021-81629-2. View

Khoury D, Cromer D, Reynaldi A, Schlub T, Wheatley A, Juno J . Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection. Nat Med. 2021; 27(7):1205-1211. DOI: 10.1038/s41591-021-01377-8. View

Demonbreun A, McDade T, Pesce L, Vaught L, Reiser N, Bogdanovic E . Patterns and persistence of SARS-CoV-2 IgG antibodies in Chicago to monitor COVID-19 exposure. JCI Insight. 2021; 6(9). PMC: 8262291. DOI: 10.1172/jci.insight.146148. View

10.

Harris P, Taylor R, Minor B, Elliott V, Fernandez M, ONeal L . The REDCap consortium: Building an international community of software platform partners. J Biomed Inform. 2019; 95:103208. PMC: 7254481. DOI: 10.1016/j.jbi.2019.103208. View

11.

Bergwerk M, Gonen T, Lustig Y, Amit S, Lipsitch M, Cohen C . Covid-19 Breakthrough Infections in Vaccinated Health Care Workers. N Engl J Med. 2021; 385(16):1474-1484. PMC: 8362591. DOI: 10.1056/NEJMoa2109072. View

12.

Robbiani D, Gaebler C, Muecksch F, Lorenzi J, Wang Z, Cho A . Convergent antibody responses to SARS-CoV-2 in convalescent individuals. Nature. 2020; 584(7821):437-442. PMC: 7442695. DOI: 10.1038/s41586-020-2456-9. View

13.

Harris P, Taylor R, Thielke R, Payne J, Gonzalez N, Conde J . Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2008; 42(2):377-81. PMC: 2700030. DOI: 10.1016/j.jbi.2008.08.010. View

14.

Alene M, Yismaw L, Assemie M, Ketema D, Mengist B, Kassie B . Magnitude of asymptomatic COVID-19 cases throughout the course of infection: A systematic review and meta-analysis. PLoS One. 2021; 16(3):e0249090. PMC: 7987199. DOI: 10.1371/journal.pone.0249090. View

15.

Zhu N, Zhang D, Wang W, Li X, Yang B, Song J . A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020; 382(8):727-733. PMC: 7092803. DOI: 10.1056/NEJMoa2001017. View

16.

Long Q, Tang X, Shi Q, Li Q, Deng H, Yuan J . Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections. Nat Med. 2020; 26(8):1200-1204. DOI: 10.1038/s41591-020-0965-6. View

17.

Sancilio A, DAquila R, McNally E, Velez M, Ison M, Demonbreun A . A surrogate virus neutralization test to quantify antibody-mediated inhibition of SARS-CoV-2 in finger stick dried blood spot samples. Sci Rep. 2021; 11(1):15321. PMC: 8319431. DOI: 10.1038/s41598-021-94653-z. View

18.

Tan C, Chia W, Qin X, Liu P, Chen M, Tiu C . A SARS-CoV-2 surrogate virus neutralization test based on antibody-mediated blockage of ACE2-spike protein-protein interaction. Nat Biotechnol. 2020; 38(9):1073-1078. DOI: 10.1038/s41587-020-0631-z. View

19.

Rockstroh A, Wolf J, Fertey J, Kalbitz S, Schroth S, Lubbert C . Correlation of humoral immune responses to different SARS-CoV-2 antigens with virus neutralizing antibodies and symptomatic severity in a German COVID-19 cohort. Emerg Microbes Infect. 2021; 10(1):774-781. PMC: 8079054. DOI: 10.1080/22221751.2021.1913973. View

20.

Bosnjak B, Stein S, Willenzon S, Cordes A, Puppe W, Bernhardt G . Low serum neutralizing anti-SARS-CoV-2 S antibody levels in mildly affected COVID-19 convalescent patients revealed by two different detection methods. Cell Mol Immunol. 2020; 18(4):936-944. PMC: 7604543. DOI: 10.1038/s41423-020-00573-9. View