Understanding the presence of adaptive immune responses that are associated with protection from disease (potential protective immunity) caused by SARS-CoV-2 at the population level is critical for public policy. Potential protective immunity can be acquired either through vaccination or past infection.1-3 We used history of vaccination or presence of antibodies specific to the receptor binding domain (RBD antibodies) of the spike protein of the SARS-CoV-2 virus as potential markers for potential protective immunity as both are strongly associated with presence of neutralizing antibodies.4,5 We conducted surveys and serologic tests in a representative community sample to estimate the fraction of the Los Angeles County (LAC) adult population that had potential protective immunity in April 2021. We tested for differences in potential protective immunity by demographics and whether presence of RBD antibodies waned with time since infection.
This cross-sectional study was approved by the LAC Department of Public Health (DPH) institutional review board and electronic informed consent was obtained. This study follows the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.
We tested for RBD antibodies using an FDA emergency use authorized assay (Luminex xMAP SARS-CoV-2). We established 8 testing sites in LAC and residents who lived within a 15-mile radius (99% of LAC population) were eligible for participation. Testing was offered from April 9 to April 25, 2021. We used a proprietary database representing about a quarter of the LAC population maintained by a market research firm (LRW Group, a Material Company), to select participants. A random sample of these residents were invited, with quotas for enrollment for subgroups based on demographics of LAC residents. All participants were invited to participate in antibody testing and participants self-selected to consent for testing. Participants who had participated in a similar study conducted in April 2020 were oversampled.6 Weights were used to adjust results for LAC 2019 census estimates of demographics and LAC DPH data on confirmed COVID-19 cases and COVID-19 vaccination rates by race and ethnicity, age, and gender. Data on race and ethnicity were self reported by residents; race and ethnicity data were collected to document disparities in rate of potential protective immunity by race and ethnicity.
We used these weighted data to estimate the fraction of LAC adults that had received at least 1 dose of vaccine or had RBD antibodies, as a whole, and by vaccination status, demographics, and area poverty level. Statistical analysis was performed using Stata version 15 (StataCorp) from April to November 2021.
Of 5500 adults who completed a screener to determine eligibility for the study, 2314 (42%) provided consent and 1335 (57.7%) were tested. Of the 1335 tested adults, 790 (59.2%) were female, 672 (50.3%) were aged 30 to 49 years, 186 (13.9%) were Asian individuals, 125 (9.4%) were Black individuals, 463 (34.7%) were Hispanic individuals, 498 (37.3%) were non-Hispanic White individuals, and 413 (30.9%) had annual household income less than $50 000. Table 1 shows that the weighted sample characteristics matched the LAC population on demographics as well as percentage with confirmed COVID-19 diagnosis and percentage vaccinated. Of the weighted sample, 72.2% (95% CI, 69.8%-74.4%) were either vaccinated or had RBD antibodies, with Black individuals (52.5% [95% CI, 44.2%-60.7%]) and individuals from lower-income households (64.2% [95% CI, 58.5%-69.6%]) having lower rates of protection (Table 2). Of unvaccinated adults, 28.8% (95% CI, 23.3%-34.9%) had RBD antibodies, with significantly higher prevalence of RBD antibodies in poorer neighborhoods (eg, zip code poverty level ≥30%: 71.0% [95% CI, 51.8%-84.7%]). Prevalence of RBD antibodies was near universal for the fully vaccinated (99.7% [95% CI, 99.0%-99.9%]) and for the unvaccinated (97.0% [95% CI, 90.3%-99.1%]) with a self-reported prior positive COVID-19 test.
This study found that in April 2021 approximately 72% of LAC adults had potential protective immunity against SARS-CoV-2. Despite this high level of population immunity and continuing vaccination efforts, LAC experienced a surge in COVID-19 cases in July 2021 suggesting that reaching herd immunity might be more difficult than anticipated,
Rates of potential protective immunity were much lower for Black individuals and those from lower-income households, which justifies increased vaccination efforts for these communities. The findings also suggest a much higher cumulative incidence of infection in high poverty areas, which likely contributed to the steep socioeconomic disparities in COVID-19 mortality rates observed in LAC.
Almost all of the unvaccinated individuals with prior infection had RBD antibodies, even though many participants had infections several months prior to antibody testing. This suggests that RBD antibodies were not waning.
The study has limitations. We used self-reported vaccinations and presence of antibodies as a marker for immunity instead of, for example, measuring cell-mediated immunity. Even though we weighted our estimates to match percentage of confirmed cases and percentage vaccinated—the 2 most important factors associated with protective immunity—we cannot rule out selection bias.
Accepted for Publication: November 23, 2021.
Published: January 20, 2022. doi:10.1001/jamanetworkopen.2021.44258
Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2022 Sood N et al. JAMA Network Open.
Corresponding Author: Neeraj Sood, PhD, Sol Price School of Public Policy, University of Southern California, University Park Campus, 635 Downey Way, Verna and Peter Dauterive Hall, Los Angeles, CA 90089 (nsood@healthpolicy.usc.edu).
Author Contributions: Dr Sood had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Sood, Klipp, Kotha, Kovacs, Hu.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Sood, Lam, Kotha, Kovacs, Hu.
Critical revision of the manuscript for important intellectual content: Sood, Pernet, Lam, Klipp, Kovacs, Hu.
Statistical analysis: Sood, Pernet, Lam, Kotha, Hu.
Obtained funding: Sood, Kotha, Hu.
Administrative, technical, or material support: Sood, Pernet, Klipp, Kotha, Hu.
Supervision: Sood, Klipp, Hu.
Conflict of Interest Disclosures: Dr Pernet reported being CEO of EnViro International Laboratories, a nonprofit organization working on emerging diseases and outbreak preparedness. No other disclosures were reported.
Funding/Support: We acknowledge funding from the Conrad N. Hilton Foundation, Office of the President University of Southern California, Los Angeles County Department of Public Health, the U.S. Centers for Disease Control and Prevention, the Keck School of Medicine at USC, and the Keck Family Foundation.
Role of the Funder/Sponsor: Funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Additional Contributions: We are grateful to Paul Simon and William Nicholas from Los Angeles County Department of Public Health for help with research design; Jennifer Holland, Julie McClammy, Elinor Gaida, and Jacqueline Rosales from LRW, a Material Company, for help with data collection; Anna Rodriguez-Vasquez from University of Southern California, for supervising testing sites; Kevin Ramos from University of Southern California, for help with data analysis. George Celis, Siddharth Saharan, Patricia Anthony from University of Southern California for help with antibody testing. They were not compensated for these contributions.
Additional Information: LA County adult population estimates from IPUMS USA are available at https://usa.ipums.org/usa/. LA County confirmed cases of COVID-19 as of April 25, 2021, from Los Angeles County Department of Public Health are available at http://dashboard.publichealth.lacounty.gov/covid19_surveillance_dashboard/. LA County number of adults vaccinated as of April 25, 2021, from Los Angeles County Department of Public Health are available at http://publichealth.lacounty.gov/media/coronavirus/vaccine/vaccine-dashboard.htm.
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