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Figure.  Anti–SARS-CoV-2 Signal-to-Threshold Ratios at Baseline and 60 Days in Health Care Personnel Seropositive at Baseline
Anti–SARS-CoV-2 Signal-to-Threshold Ratios at Baseline and 60 Days in Health Care Personnel Seropositive at Baseline

SARS-CoV-2 indicates severe acute respiratory syndrome coronavirus 2. The dotted line at y = 1.0 indicates the threshold for seropositivity.

Table.  Seropositivity at 60 Days, Symptom Prevalence, and Mean Signal-to-Threshold Values of Anti–SARS-CoV-2 Immunoglobulin Antibodies Among 19 Health Care Personnel Seropositive at Baseline
Seropositivity at 60 Days, Symptom Prevalence, and Mean Signal-to-Threshold Values of Anti–SARS-CoV-2 Immunoglobulin Antibodies Among 19 Health Care Personnel Seropositive at Baseline
1.
Ibarrondo  FJ, Fulcher  JA, Goodman-Meza  D,  et al.  Rapid decay of anti-SARS-CoV-2 antibodies in persons with mild Covid-19.   N Engl J Med. Published online July 21, 2020. doi:10.1056/NEJMc2025179PubMedGoogle Scholar
2.
Long  QX, Tang  XJ, Shi  QL,  et al.  Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections.   Nat Med. 2020;26(8):1200-1204. doi:10.1038/s41591-020-0965-6PubMedGoogle ScholarCrossref
3.
Stubblefield  WB, Talbot  HK, Feldstein  L,  et al; Influenza Vaccine Effectiveness in the Critically Ill (IVY) Investigators.  Seroprevalence of SARS-CoV-2 among frontline healthcare personnel during the first month of caring for COVID-19 patients—Nashville, Tennessee.   Clin Infect Dis. 2020;ciaa936. doi:10.1093/cid/ciaa936PubMedGoogle Scholar
4.
Havers  FP, Reed  C, Lim  T,  et al.  Seroprevalence of antibodies to SARS-CoV-2 in 10 sites in the United States, March 23-May 12, 2020.   JAMA Intern Med. Published online July 21, 2020. doi:10.1001/jamainternmed.2020.4130PubMedGoogle Scholar
5.
Premkumar  L, Segovia-Chumbez  B, Jadi  R,  et al.  The receptor binding domain of the viral spike protein is an immunodominant and highly specific target of antibodies in SARS-CoV-2 patients.   Sci Immunol. 2020;5(48):eabc8413. doi:10.1126/sciimmunol.abc8413PubMedGoogle Scholar
6.
Grifoni  A, Weiskopf  D, Ramirez  SI,  et al.  Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals.   Cell. 2020;181(7):1489-1501.e15. doi:10.1016/j.cell.2020.05.015PubMedGoogle ScholarCrossref
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    1 Comment for this article
    Implications for Vaccine Efficacy
    Zaur Gasimov, MD | Research institute of Cardiology, Baku, Azerbaijan
    This article contributes to concerns about possible weak efficacy, longevity of anti-COVID-19 vaccines. I suggest it will be difficult to prove the effects of vaccines because of variations of difficulties in organising long-term monitoring and because of the international character of the effort. If we really want to demonstrate the efficacy of vaccines we must create an independent center for monitoring of efficacy with representatives of consecutive countries with full access to all data.
    CONFLICT OF INTEREST: None Reported
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    Research Letter
    September 17, 2020

    Change in Antibodies to SARS-CoV-2 Over 60 Days Among Health Care Personnel in Nashville, Tennessee

    Author Affiliations
    • 1CDC COVID-19 Response Team, Centers for Disease Control and Prevention, Atlanta, Georgia
    • 2Department of Emergency Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
    • 3Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
    JAMA. 2020;324(17):1781-1782. doi:10.1001/jama.2020.18796

    Declines in immunoglobulin antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among patients with symptomatic or asymptomatic infections have been documented.1,2 We assessed the duration of antibody response to SARS-CoV-2 infection in health care personnel, who may be at particular risk if antibody levels decline.

    Methods

    We evaluated anti–SARS-CoV-2 antibodies at baseline and approximately 60 days later in a convenience sample of health care personnel at Vanderbilt University Medical Center who regularly had direct contact with adult patients with coronavirus disease 2019.3 Staff were informed about the study through emails and meetings and volunteered to participate. Participants completed a survey for symptoms of viral illness since February 1, 2020, and underwent phlebotomy for serology testing between April 3 and April 13, 2020 (baseline visit), and between June 2 and June 27 (60-day visit). The project was determined to be nonresearch public health surveillance by Vanderbilt University Medical Center and the Centers for Disease Control and Prevention. Each participant agreed to join the study.

    Serum samples were tested for anti–SARS-CoV-2 antibodies using a validated enzyme-linked immunosorbent assay against the prefusion-stabilized extracellular domain of the SARS-CoV-2 spike protein.3 A specimen was considered reactive if the signal-to-threshold ratio at a serum dilution of 1:100 with background correction was greater than 1.0, with higher ratios indicating higher antibody titers. At this cutoff, assay specificity and sensitivity were 99% and 96%, respectively.4 We describe the change in seropositivity in the overall study cohort, stratified by presence or absence of symptoms (fever, cough, dyspnea, myalgias, sore throat, vomiting, diarrhea, dysgeusia, or anosmia). We evaluated the change in mean and median signal-to-threshold ratios at baseline and 60 days in those who were seropositive at baseline and those who were seropositive vs seronegative at 60 days. Data were analyzed with Stata version 16.

    Results

    Approximately 600 health care personnel were eligible; serum samples were collected at baseline from the first 249 volunteers (64.5% female; 91.6% White; median age, 33 years; range, 21-70 years), and 230 (92%) returned for a second blood draw. Participants included 42.2% nurses, 34.5% physicians and advanced practice clinicians, 6.8% radiology technicians, and 16.5% other health care personnel. Nineteen (7.6%) had anti–SARS-CoV-2 antibodies detected at baseline. Of these, 8 participants (42%) had antibodies that persisted above the seropositivity threshold at 60 days, whereas 11 (58%) became seronegative. Thus, overall seropositivity changed from 7.6% at baseline (19/249) to 3.2% (8/249) at 60 days. Six of 8 participants (75%) who remained seropositive reported symptoms prior to the baseline visit and 2 (25%) were asymptomatic. Five of 11 participants (45%) in whom antibodies decreased below the seropositivity threshold reported symptoms prior to the baseline visit, whereas 6 (55%) were asymptomatic.

    All 19 participants who were seropositive at baseline had antibody decreases at 60 days (Figure). Participants who remained seropositive at 60 days had higher signal-to-threshold ratios at baseline (mean, 4.8; range, 1.9-6.2) compared with participants whose ratios decreased below threshold at 60 days (mean, 1.4; range, 1.1-2.3) (Table). Antibodies declined from a mean signal-to-threshold ratio of 4.8 at baseline to 2.3 at 60 days in participants who remained seropositive and from 1.4 at baseline to 0.6 at 60 days in those whose antibody levels decreased below the threshold.

    Discussion

    Anti–SARS-CoV-2 antibodies to the spike protein, which have correlated with neutralizing antibodies,5 decreased over 60 days in health care personnel, with 58% of seropositive individuals becoming seronegative. The consistency in decline in the signal-to-threshold ratio regardless of the baseline ratio and a higher proportion of asymptomatic participants becoming seronegative support the interpretation as a true decline over a 2-month period rather than an artifact of assay performance. If replicated, these results suggest that cross-sectional seroprevalence studies to evaluate population immunity may underestimate rates of prior infections because antibodies may only be transiently detectable following infection.

    The window after recovering from SARS-CoV-2 infection when people could donate serum that has sufficiently high antibody levels may be limited. Implications for health care personnel with antibodies assigned to care for infected patients depend on whether decline in these antibodies increases risk of reinfection and disease, which remains unknown, especially given the lack of data on memory B-cell and T-cell responses.6 Limitations of this study include its single-center setting, small sample size, convenience sampling, and lack of information on timing of infection to evaluate antibody kinetics.

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

    Corresponding Author: Manish M. Patel, MD, Influenza Division, Centers for Disease Control and Prevention, 1600 Clifton Rd, MS H24-7, Atlanta, GA 30329 (mpatel@cdc.gov).

    Accepted for Publication: September 4, 2020.

    Published Online: September 17, 2020. doi:10.1001/jama.2020.18796

    Author Contributions: Drs Patel and Self 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: Patel, Thornburg, Stubblefield, Talbot, Feldstein, Self.

    Acquisition, analysis, or interpretation of data: Patel, Thornburg, Stubblefield, Talbot, Coughlin, Self.

    Drafting of the manuscript: Patel, Self.

    Critical revision of the manuscript for important intellectual content: Thornburg, Stubblefield, Talbot, Coughlin, Feldstein, Self.

    Statistical analysis: Patel, Coughlin.

    Obtained funding: Patel, Self.

    Administrative, technical, or material support: Stubblefield, Talbot, Coughlin, Feldstein, Self.

    Supervision: Patel, Thornburg, Self.

    Conflict of Interest Disclosures: Dr Coughlin reported US Patent 7,728,110B2, an isolated human monoclonal antibody that specifically binds to SARS-CoV S protein. No other disclosures were reported.

    Funding/Support: This work was funded by Centers for Disease Control and Prevention contract 75D30120C07637 (Dr Self).

    Role of the Funder/Sponsor: The Centers for Disease Control and Prevention was involved in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, and approval of the manuscript; and decision to submit the manuscript for publication.

    Disclaimer: The findings and conclusions of this report are those of the authors and do not necessarily reflect the official position of the Centers for Disease Control and Prevention.

    References
    1.
    Ibarrondo  FJ, Fulcher  JA, Goodman-Meza  D,  et al.  Rapid decay of anti-SARS-CoV-2 antibodies in persons with mild Covid-19.   N Engl J Med. Published online July 21, 2020. doi:10.1056/NEJMc2025179PubMedGoogle Scholar
    2.
    Long  QX, Tang  XJ, Shi  QL,  et al.  Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections.   Nat Med. 2020;26(8):1200-1204. doi:10.1038/s41591-020-0965-6PubMedGoogle ScholarCrossref
    3.
    Stubblefield  WB, Talbot  HK, Feldstein  L,  et al; Influenza Vaccine Effectiveness in the Critically Ill (IVY) Investigators.  Seroprevalence of SARS-CoV-2 among frontline healthcare personnel during the first month of caring for COVID-19 patients—Nashville, Tennessee.   Clin Infect Dis. 2020;ciaa936. doi:10.1093/cid/ciaa936PubMedGoogle Scholar
    4.
    Havers  FP, Reed  C, Lim  T,  et al.  Seroprevalence of antibodies to SARS-CoV-2 in 10 sites in the United States, March 23-May 12, 2020.   JAMA Intern Med. Published online July 21, 2020. doi:10.1001/jamainternmed.2020.4130PubMedGoogle Scholar
    5.
    Premkumar  L, Segovia-Chumbez  B, Jadi  R,  et al.  The receptor binding domain of the viral spike protein is an immunodominant and highly specific target of antibodies in SARS-CoV-2 patients.   Sci Immunol. 2020;5(48):eabc8413. doi:10.1126/sciimmunol.abc8413PubMedGoogle Scholar
    6.
    Grifoni  A, Weiskopf  D, Ramirez  SI,  et al.  Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals.   Cell. 2020;181(7):1489-1501.e15. doi:10.1016/j.cell.2020.05.015PubMedGoogle ScholarCrossref
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