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Persistence and Protective Potential of SARS-CoV-2 Antibody Levels After COVID-19 Vaccination in a West Virginia Nursing Home Cohort

Educational Objective
To identify the key insights or developments described in this article
1 Credit CME
Key Points

Question  What are the persistence and protective potential of SARS-CoV-2 antibody levels after vaccination in West Virginia nursing home residents and staff?

Findings  In this cross-sectional study of 2139 participants from West Virginia nursing home facilities, antibody levels decreased with time after vaccination but were restored with booster doses. During the Delta surge, individuals experiencing breakthrough infection had significantly lower antibody levels, but no significant association was found between antibody level and infection observed during the Omicron surge.

Meaning  Although these findings support the recommendation of booster doses to augment waning antibody responses, data are not conclusive in providing an antibody correlate of protection against infection.


Importance  West Virginia prioritized SARS-CoV-2 vaccine delivery to nursing home facilities because of increased risk of severe illness in elderly populations. However, the persistence and protective role of antibody levels remain unclear.

Objective  To examine the persistence of humoral immunity after COVID-19 vaccination and the association of SARS-CoV-2 antibody levels and subsequent infection among nursing home residents and staff.

Design, Setting, and Participants  In this cross-sectional study, blood samples were procured between September 13 and November 30, 2021, from vaccinated residents and staff at participating nursing home facilities in the state of West Virginia for measurement of SARS-CoV-2 antibody (anti–receptor binding domain [RBD] IgG). SARS-CoV-2 infection and vaccination history were documented during specimen collection and through query of the state SARS-CoV-2 surveillance system through January 16, 2022.

Exposure  SARS-CoV-2 vaccination (with BNT162b2, messenger RNA-1273, or Ad26.COV2.S).

Main Outcomes and Measures  Anti-RBD IgG levels were assessed using multivariate analysis to examine associations between time since vaccination or infection, age, sex, booster doses, and vaccine type. Antibody levels from participants who became infected after specimen collection were compared with those without infection to correlate antibody levels with subsequent infection.

Results  Among 2139 SARS-CoV-2 vaccinated residents and staff from participating West Virginia nursing facilities (median [range] age, 67 [18-103] years; 1660 [78%] female; 2045 [96%] White), anti-RBD IgG antibody levels decreased with time after vaccination or infection (mean [SE] estimated coefficient, −0.025 [0.0015]; P < .001). Multivariate regression modeling of participants with (n = 608) and without (n = 1223) a known history of SARS-CoV-2 infection demonstrated significantly higher mean (SE) antibody indexes with a third (booster) vaccination (with infection: 11.250 [1.2260]; P < .001; without infection: 8.056 [0.5333]; P < .001). Antibody levels (calculated by dividing the sample signal by the mean calibrator signal) were significantly lower among participants who later experienced breakthrough infection during the Delta surge (median, 2.3; 95% CI, 1.8-2.9) compared with those without breakthrough infection (median, 5.8; 95% CI, 5.5-6.1) (P = .002); however, no difference in absorbance indexes was observed in participants with breakthrough infections occurring after specimen collection (median, 5.9; 95% CI, 3.7-11.1) compared with those without breakthrough infection during the Omicron surge (median, 5.8; 95% CI, 5.6-6.2) (P = .70).

Conclusions and Relevance  In this cross-sectional study, anti-RBD IgG levels decreased after vaccination or infection. Higher antibody responses were found in individuals who received a third (booster) vaccination. Although lower antibody levels were associated with breakthrough infection during the Delta surge, no significant association was found between antibody level and infection observed during the Omicron surge. The findings of this cross-sectional study suggest that among nursing home residents, COVID-19 vaccine boosters are important and updated vaccines effective against emerging SARS-CoV-2 variants are needed.

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Article Information

Accepted for Publication: July 27, 2022.

Published: September 13, 2022. doi:10.1001/jamanetworkopen.2022.31334

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2022 Smoot K et al. JAMA Network Open.

Corresponding Author: Sally Hodder, MD, Clinical & Translational Sciences Institute, West Virginia University School of Medicine, One Medical Center Drive, Morgantown, WV 26506 (slhodder@hsc.wvu.edu).

Author Contributions: Drs Perrotta and Hodder had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Tacker, Kimble, Wen, Marsh, Perrotta, Hodder.

Acquisition, analysis, or interpretation of data: Smoot, Yang, Tacker, Welch, Khodaverdi, Kimble, Wen, Amjad, Perrotta, Hodder.

Drafting of the manuscript: Smoot, Yang, Tacker, Khodaverdi, Kimble, Wen, Perrotta.

Critical revision of the manuscript for important intellectual content: Smoot, Yang, Tacker, Welch, Kimble, Wen, Amjad, Marsh, Perrotta, Hodder.

Statistical analysis: Yang, Khodaverdi, Wen.

Obtained funding: Marsh, Perrotta, Hodder.

Administrative, technical, or material support: Yang, Tacker, Welch, Kimble, Marsh, Perrotta, Hodder.

Supervision: Kimble, Perrotta, Hodder.

Conflict of Interest Disclosures: Dr Welch reported receiving grants from the State of West Virginia during the conduct of the study. Mr Kimble reported receiving grant funding from the state of West Virginia and the National Institutes of Health during the conduct of the study. Dr Marsh reported receiving grants from West Virginia University State funding during the conduct of the study and state and federal grants from West Virginia University outside the submitted work. Dr Hodder reported receiving grants from the National Institutes of Health and the West Virginia Department of Health and Human Services during the conduct of the study. No other disclosures were reported.

Funding/Support: This study was supported by grant BPH2200000001 from the West Virginia Department of Health and Human Services, Bureau of Public Health and partially supported by grants U54GM104942-05S2 and U54GM104942 from the National Institute of General Medical Sciences (Dr Hodder).

Role of the Funder/Sponsor: The funding sources 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 the decision to submit the manuscript for publication.

Additional Contributions: We gratefully acknowledge the staff, residents, and residents’ families of participating West Virginia nursing homes.

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AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

  • 1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
  • 1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
  • 1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
  • 1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
  • 1.00 CME points in the American Board of Surgery’s (ABS) Continuing Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.

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