Spike Antibody Levels of Nursing Home Residents With or Without Prior COVID-19 3 Weeks After a Single BNT162b2 Vaccine Dose | Geriatrics | JAMA | JAMA Network
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Figure.  Levels of IgG Antibody Against the SARS-CoV-2 Spike (S) Protein After a Single Dose of Vaccine in Nursing Home Residents
Levels of IgG Antibody Against the SARS-CoV-2 Spike (S) Protein After a Single Dose of Vaccine in Nursing Home Residents

Between March and June 2020, nursing home residents facing a COVID-19 outbreak had repeated reverse transcriptase–polymerase chain reaction (RT-PCR) testing. They underwent testing for IgG antibodies against the SARS-CoV-2 nucleocapsid (N) protein 6 weeks after the end of the outbreak. There were 60 residents who had no prior SARS-CoV-2 infection (repeated negative RT-PCR result for COVID-19 and were seronegative for N-protein IgG after the outbreak) and 42 had SARS-CoV-2 infection (COVID-19). Of the 42 residents who had SARS-CoV-2 infection, 36 had a positive RT-PCR result and were seropositive for N-protein IgG, 5 had repeated negative RT-PCR results but were seropositive for N-protein IgG after the outbreak, and 1 had a positive RT-PCR result during the outbreak but was seronegative for N-protein IgG after the outbreak. Levels of S-protein IgG that were measured 3 weeks after a single BNT162b2 vaccine dose was administered in January 2021 (1 dot per resident) were significantly lower in residents without prior COVID-19 vs those with prior COVID-19 (P < .001). Among residents with prior COVID-19, levels of S-protein IgG were not statistically significantly different between residents with a positive RT-PCR result for COVID-19 and were either seropositive or seronegative for N-protein IgG compared with those with a negative RT-PCR result for COVID-19 and were seropositive for N-protein IgG (P = .25). The horizontal blue and orange lines represent median values for S-protein IgG.

Table.  Demographic Characteristics and Seroconversion Level of 96 Residents by COVID-19 Status During Past 7 to 10 Months
Demographic Characteristics and Seroconversion Level of 96 Residents by COVID-19 Status During Past 7 to 10 Months
1.
Wise  J.  Covid-19: people who have had infection might only need one dose of mRNA vaccine.   BMJ. 2021;372(n308):n308. doi:10.1136/bmj.n308PubMedGoogle ScholarCrossref
2.
Saadat  S, Tehrani  ZR, Logue  J,  et al.  Binding and neutralization antibody titers after a single vaccine dose in health care workers previously infected with SARS-CoV-2.   JAMA. Published online March 1, 2021.doi:10.1001/jama.2021.3341PubMedGoogle Scholar
3.
Blain  H, Gamon  L, Tuaillon  E,  et al.  Atypical symptoms, SARS-CoV-2 test results and immunisation rates in 456 residents from eight nursing homes facing a COVID-19 outbreak.   Age Ageing. Published online February 23, 2021. doi:10.1093/ageing/afab050 Google Scholar
4.
Blain  H, Rolland  Y, Schols  JMGA,  et al.  August 2020 interim EuGMS guidance to prepare European long-term care facilities for COVID-19.   Eur Geriatr Med. 2020;11(6):899-913. doi:10.1007/s41999-020-00405-zPubMedGoogle ScholarCrossref
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    2 Comments for this article
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    Validation
    Luis Gustavo Campos da Silva |
    Does the presence of the neutralizing antibodies indicate imune protection “for sure”?
    Although some small studies suggest this might be possible, there is some evidence that shows us it cannot be directly correlated as cause-effect: presence of antibodies might not provide protection; absence of antibodies does not mean that one is unprotected.

    Not to mention the humoral defense, only a few diseases respond directly to antibodies, such as tetanus and venomous snakebites and scorpion accidents. This could also be behind the reason for so many failed attempts on convalescent plasma treatments in the past - including the
    recent COVID-19.

    The FDA has informed lab test producers they must make clear “The clinical applicability of detection or correlation with neutralizing activity for antibodies to antigens (covid) is currently unknown and results cannot be interpreted as an indicate of degree of immunity or protection from infection” (1).

    Reference

    1. https://www.fda.gov/media/146746/download
    CONFLICT OF INTEREST: None Reported
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    Not all patients with PCR-documented SARS-Cov-2 infection developed antibodies against the virus
    Manuel Sanchez Molla, Professor; MD PhD | Miguel Hernandez University, Cathedra of Family Medicine, Department of Medicina Clínical Elche (Alicante); Elche General University Hospital
    We have carefully read your letter, which we found very interesting.

    Not all patients who are reverse transcriptase–polymerase chain reaction (RT-PCR)-positive for SARS-Cov-2 on nasopharyngeal swab testing make a measurable immune response.

    We have found in epidemiological surveillance of nursing homes via periodic screening with nasopharyngeal RT-PCR a group of 12 patients with asymptomatic SARS-Cov-2 infection with a high cycle threshold (Ct), which correlates with a low viral load. We followed this group.

    One month later we repeated RT-PCR and measured neutralizing antibodies using the Liaison® technique (IgG / IgM) using chemiluminescence technology (CLIA). We didn’t detect
    an immune response in any patient of this group and didn´t detect SARS-Cov-2 in RT-PCR nasopharyngeal swabs.

    Eight developed symptomatic reinfection 3 months later with nasopharyngeal RT-PCR detection of SARS-Cov-2 with low Ct values.

    Another study in our hospital identified a proportion of patients with COVID-19 who did not develop antibodies against the virus. Measures of viral replication determined the magnitude of the humoral immune response.

    Thus we would like to point out it’s feasible that patients with asymptomatic disease and low viral load don’t generate an immune response comparable to patients with symptomatic disease and high viral load.

    References

    1. Singanayagam A, Patel M, Charlett A, et al. Duration of infectiousness and correlation with RT-PCR cycle threshold values in cases of COVID-19, England, January to May 2020. Euro Surveill.2020;25(32):2001483.doi:10.2807/15607917.ES.2020.25.32.2001483. https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2020.25.32.200148

    2. Mar Masiá, MD, Guillermo Telenti, MD, Marta Fernández, PhD, José A García, BSc, Vanesa Agulló, BSc, Sergio Padilla, MD, Javier García-Abellán, MD, Lucía Guillén, MD, Paula Mascarell, MD, José C Asenjo, Félix Gutiérrez, MD, SARS-CoV-2 seroconversion and viral clearance in patients hospitalized with COVID-19: viral load predicts antibody response, Open Forum Infectious Diseases, 2021;,ofab005, https://doi.org/10.1093/ofid/ofab005
    CONFLICT OF INTEREST: None Reported
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    Research Letter
    April 15, 2021

    Spike Antibody Levels of Nursing Home Residents With or Without Prior COVID-19 3 Weeks After a Single BNT162b2 Vaccine Dose

    Author Affiliations
    • 1Department of Internal Medicine and Geriatrics, MUSE University, Montpellier, France
    • 2INSERM U 1058/EFS, University Hospital, Montpellier, France
    • 3Clinical Research and Epidemiology Unit, University Hospital, Montpellier, France
    • 4Department of Dermatology and Allergy, Universitätsmedizin, Berlin, Germany
    JAMA. 2021;325(18):1898-1899. doi:10.1001/jama.2021.6042

    Recent studies have suggested that, to reach immunity, immunocompetent SARS-CoV-2 seropositive adults may only require 1 dose rather than 2 doses of a messenger RNA vaccine1,2; however, these studies did not include older adults. Older adults living in nursing homes are at higher risk for severe COVID-19, and the immune response to the vaccine may differ from that of younger, healthier adults.

    We compared IgG antibody levels after a single dose of BNT162b2 (Pfizer-BioNTech) vaccine in nursing home residents with or without prior COVID-19.

    Methods

    Between March and June 2020, we studied residents from nursing homes in Montpellier, France, facing a COVID-19 outbreak.3 As soon as a resident developed COVID-19, the testing recommendations from the European Geriatric Medicine Society were followed4 in that all residents were repeatedly tested using reverse transcriptase–polymerase chain reaction (RT-PCR) on nasopharyngeal swabs until no new cases were diagnosed. Participants provided written informed consent and the study was approved by the Montpellier University hospital institutional review board.

    Six weeks after the end of the outbreak, all residents underwent blood testing for levels of IgG antibody against the SARS-CoV-2 nucleocapsid (N) protein.3 All residents from 6 nursing homes were offered a first vaccine dose in January 2021. Three weeks later, all residents underwent blood testing to quantitatively assess IgG antibody levels against the SARS-CoV-2 spike (S) protein and N protein. Levels of IgG antibody against the SARS-CoV-2 receptor-binding domain were quantified using the SARS-CoV-2 IgG II Quant assay (Abbott Diagnostics). The results were expressed as arbitrary units (AU) per milliliter (positive threshold: 50 AU/mL; upper limit: 40 000 AU/mL). The IgG antibodies against the SARS-CoV-2 N protein were detected using the SARS-CoV-2 IgG assay (Abbott Diagnostics). The results were expressed as the signal to cutoff ratio (Abbott Alinity; Abbott Diagnostics) (positive threshold: 0.8 signal to cutoff ratio).

    In residents with or without a prior history of COVID-19, we compared IgG antibody levels against SARS-CoV-2 proteins S and N by using 2-sided Wilcoxon Mann-Whitney tests. The statistical significance threshold was set at 5%. Analyses were performed using SAS Enterprise Guide version 7.3 (SAS Institute Inc).

    Results

    Of the 102 residents, 60 had no prior SARS-CoV-2 infection (COVID-19), 36 had a positive RT-PCR result and were seropositive for SARS-CoV-2 N-protein IgG in June 2020, and 6 had a positive RT-PCR result or were seropositive for SARS-CoV-2 N-protein IgG. Of the 36 residents who had a positive RT-PCR result and were seropositive for SARS-CoV-2 N-protein IgG in June 2020, 26 remained seropositive in January-February 2021 (72.2%).

    All 36 residents with prior COVID-19 were seropositive for S-protein IgG after 1 vaccine dose vs 29 of 60 residents (49.2%) without prior COVID-19. Among residents with prior COVID-19, the median level of S-protein IgG was 40 000 AU/mL or greater (interquartile range [IQR], 22 801-≥40 000 AU/mL) vs 48.0 AU/mL (IQR, 14.0-278.0 AU/mL) in those without prior COVID-19 (P < .001; Table).

    One resident with a positive RT-PCR result in April 2020 tested seronegative for N-protein IgG in June 2020 and January 2021; the resident had a robust S-protein IgG level (≥40 000 AU/mL). Five residents were found to be seropositive for N-protein IgG in June 2020 while having repeated negative RT-PCR results in April 2020. All 5 of these residents had high levels of S-protein IgG antibody (median, ≥40 000 AU/mL; IQR, ≥40 000-≥40 000 AU/mL). Among the 6 residents with a positive RT-PCR result or who were seropositive for N-protein IgG, the levels of S-protein IgG antibody were significantly higher than among the 60 without prior COVID-19 (P < .001) and were not statistically significantly different from the 36 who had a positive RT-PCR result and were seropositive for N-protein IgG (P = .26; Figure).

    Discussion

    This preliminary study suggests that a single dose of BNT162b2 vaccine may be sufficient to obtain a high level of S-protein IgG antibody in nursing home residents previously diagnosed with COVID-19 based on RT-PCR results. This is in line with results based on IgG to spike trimer and neutralization antibody titers reported among health care workers with prior COVID-19 (diagnosed using SARS-CoV-2 IgG).2

    Measuring S-protein IgG antibody levels just before the second vaccine dose could be useful in determining whether a second dose is required in individuals whose infection history is unknown. This could limit possible adverse effects related to reactogenicity in previously infected patients and spare precious vaccine doses. Limitations of the study include the small sample size, with possible lack of representativeness, and the lack of neutralization assays.

    Section Editor: Jody W. Zylke, MD, Deputy Editor.
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    Article Information

    Corresponding Author: Hubert Blain, MD, PhD, Pôle de Gérontologie, CHU de Montpellier, 39 Avenue Charles Flahault, 34295 Montpellier Cedex 5, France (h-blain@chu-montpellier.fr).

    Accepted for Publication: April 2, 2021.

    Published Online: April 15, 2021. doi:10.1001/jama.2021.6042

    Author Contributions: Dr Blain 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: Blain, Tuaillon, Miot.

    Acquisition, analysis, or interpretation of data: Blain, Tuaillon, Gamon, Pisoni, Picot, Bousquet.

    Drafting of the manuscript: Blain, Tuaillon.

    Critical revision of the manuscript for important intellectual content: All authors.

    Statistical analysis: Gamon, Pisoni, Picot.

    Administrative, technical, or material support: Blain, Tuaillon, Pisoni.

    Supervision: Blain, Tuaillon, Bousquet.

    Conflict of Interest Disclosures: None reported.

    Additional Contributions: We thank Anna Bedbrook and Fabienne Portejoie (Department of Dermatology and Allergy, Universitätsmedizin, Berlin), Eva Pons (Master Métiers de l’Enseignement, de l’Education et de la Formation, Éducation Nationale Française, Lyon), and Samuel Alizon, PhD (Montpellier University), for editorial assistance. We also thank Joy Martin (Department of Geriatrics, Montpellier University Hospital and Secours Infirmiers) and Véronique Vera and Florence Biblocque (Montpellier University Hospital admission office) for material support. None of these contributors received any compensation for their help in carrying out the study. In addition, we thank the residents and staff members of the nursing homes involved in the study.

    References
    1.
    Wise  J.  Covid-19: people who have had infection might only need one dose of mRNA vaccine.   BMJ. 2021;372(n308):n308. doi:10.1136/bmj.n308PubMedGoogle ScholarCrossref
    2.
    Saadat  S, Tehrani  ZR, Logue  J,  et al.  Binding and neutralization antibody titers after a single vaccine dose in health care workers previously infected with SARS-CoV-2.   JAMA. Published online March 1, 2021.doi:10.1001/jama.2021.3341PubMedGoogle Scholar
    3.
    Blain  H, Gamon  L, Tuaillon  E,  et al.  Atypical symptoms, SARS-CoV-2 test results and immunisation rates in 456 residents from eight nursing homes facing a COVID-19 outbreak.   Age Ageing. Published online February 23, 2021. doi:10.1093/ageing/afab050 Google Scholar
    4.
    Blain  H, Rolland  Y, Schols  JMGA,  et al.  August 2020 interim EuGMS guidance to prepare European long-term care facilities for COVID-19.   Eur Geriatr Med. 2020;11(6):899-913. doi:10.1007/s41999-020-00405-zPubMedGoogle ScholarCrossref
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