Change in Donor Characteristics and Antibodies to SARS-CoV-2 in Donated Blood in the US, June-August 2020 | Infectious Diseases | JAMA | JAMA Network
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Figure.  Frequency of Reactivity in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Antibody Testing by Week, June 15 to August 23, 2020, in the 4 US Census Regions
Frequency of Reactivity in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Antibody Testing by Week, June 15 to August 23, 2020, in the 4 US Census Regions

Each region is represented by a different line; the dashed line represents the total percentage seroreactivity. Each point is the mean of the overall data for that week (for each of the 10 weeks), with error bars representing the associated 95% CIs. The text provides the total number of anti–SARS-CoV-2 reactives and the key also provides the total number reactive/total number of donations by US Census region, including the number of donations tested.

Table.  Analysis of Donor Population Characteristics Associated With American Red Cross Blood Donations and SARS-CoV-2 Antibody–Reactive Donors
Analysis of Donor Population Characteristics Associated With American Red Cross Blood Donations and SARS-CoV-2 Antibody–Reactive Donors
1.
US Food and Drug Administration. Investigational COVID-19 convalescent plasma: guidance for industry. Published April 2020. Updated May 2020. Accessed August 10, 2020. https://www.fda.gov/media/136798/download
2.
US Food and Drug Administration. Instructions for use: Vitros Immunodiagnostics Anti-SARS-Cov-2 IgG. Accessed August 10, 2020. https://www.fda.gov/media/137363/download
3.
Roback  JD, Guarner  J.  Convalescent plasma to treat COVID-19: possibilities and challenges.   JAMA. 2020;323:1561-1562. doi:10.1001/jama.2020.4940 PubMedGoogle Scholar
4.
CDC COVID-19 Response Team.  Geographic differences in COVID-19 cases, deaths, and incidence: United States, February 12-April 7, 2020.   MMWR Morb Mortal Wkly Rep. 2020;69(15):465-471. doi:10.15585/mmwr.mm6915e4PubMedGoogle Scholar
5.
Tenforde  MW, Billig Rose  E, Lindsell  CJ,  et al; CDC COVID-19 Response Team.  Characteristics of adult outpatients and inpatients with COVID-19: 11 academic medical centers, United States, March-May 2020.   MMWR Morb Mortal Wkly Rep. 2020;69(26):841-846. doi:10.15585/mmwr.mm6926e3PubMedGoogle Scholar
6.
Katz  LM.  Is SARS-CoV-2 transfusion transmitted?   Transfusion. 2020;60(6):1111-1114. doi:10.1111/trf.15831 PubMedGoogle Scholar
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    EXPAND ALL
    Choosing the Correct Serological Tests For COVID-19 Seroprevalence Surveys
    Yang Xu, MD, PhD | Shanghai University of Medicine and Health Sciences
    The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) brought with it rapid development of serologic assays for identification of COVID-19 infections. While Food and Drug Administration (FDA) emergency use authorization (EUA) is required for clinical application of SARS-CoV-2 serologic tests, submission for EUA is currently an optional process for manufacturers of serologic assays. The absence of FDA supervision of serologic tests is concerning given that the commercially available serologic assays are highly variable, differing in the specification, the antibody isotype detected, the targeted antigen, and the allowable specimens (1). How to choose the correct serological tests will play a role during our global response to this pandemic.

    Dodd et al. (2) reported an important seroprevalence that the positive rate of serological testing in 953,926 blood donors was 1.82% by the VITROS anti-SARS-CoV-2 Spike IgG test.

    Pollán et al. (3) reported the positive rate of serological testing was lower by anti-SARS-CoV-2 Spike IgG test than that by the Architect anti-SARS-CoV-2 nucleocapsid IgG test in PCR confirmed cases in Spain, suggesting that there is cross-reactivity in the anti-SARS-CoV-2 nucleocapsid IgG test.

    Pallett et al. (4) reported false positive rate was 2% by the EDI anti-SARS-CoV-2 nucleocapsid IgG test and the Abbott anti-SARS-CoV-2 nucleocapsid IgG test (Supplementary Table). The authors further tested 405 asymptomatic healthcare workers and 43 samples were positive among them. However, negative controls were not analyzed by anti-SARS-CoV-2 nucleocapsid IgG test in 405 asymptomatic healthcare workers, which could affect the conclusion of the seroprevalence survey.

    Grzelak et al. (5) also found that the false positive rate of COVID-19 in antibody testing with a SARS-CoV-2 nucleocapsid protein is 4.7% in France. The authors tested 491 samples collected pre-pandemic and 23 samples were positive among them.

    Four seasonal “common cold” human coronaviruses, 229E, HKU1, NL63, and OC43, are continuously circulating among the global population for about 10-15% of acute respiratory tract infections (6). Mateus and colleagues revealed that memory CD4+ T cells recognizing four common cold coronaviruses can exhibit substantial cross-reactivity to the homologous epitope in SARS-CoV-2 (7).

    Therefore, the anti-SARS-CoV-2 nucleocapsid IgG test may cause the false positive rate of COVID-19. How to choose the correct serological tests needs to be addressed in public health, because it may influence findings of seroprevalence surveys.

    References
    1. EUA authorized serology test performance. https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/eua-authorized-serology-test-performance (accessed September 18, 2020).
    2. Dodd RY, Xu M, Stramer SL. JAMA. 2020 Sep 14. doi: 10.1001/jama.2020.18598.
    3. Pollán M, Pérez-Gómez B, Pastor-Barriuso R, et al. Lancet 2020; 396: 535-44.
    4. Pallett SJC, Rayment M, Patel A, et al. Lancet Respir Med. 2020; 8:885-94.
    5. Grzelak L, et al. A comparison of four serological assays for detecting anti–SARS-CoV-2 antibodies in human serum samples from different populations. Sci. Transl. Med. 2020;12:eabc3103. doi: 10.1126/scitranslmed.abc3103.
    6. Heikkinen T, Järvinen A, The common cold. Lancet. 2003;361:51–9.
    7. Mateus J, et al, Selective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans. Science. 2020. doi: 10.1126/science.abd3871.
    CONFLICT OF INTEREST: None Reported
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    Research Letter
    September 14, 2020

    Change in Donor Characteristics and Antibodies to SARS-CoV-2 in Donated Blood in the US, June-August 2020

    Author Affiliations
    • 1American Red Cross Scientific Affairs, Gaithersburg, Maryland
    JAMA. 2020;324(16):1677-1679. doi:10.1001/jama.2020.18598

    The coronavirus disease 2019 (COVID-19) pandemic has challenged the adequacy of the blood supply. To attract new donors and support the collection of convalescent plasma,1 many blood collection organizations have implemented and publicized routine testing of donations for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. We examined whether testing of donations for SARS-CoV-2 antibodies was associated with changes in donor characteristics and reactivity of donated blood.

    Methods

    The American Red Cross collects about 40% of blood in the US from 44 states, and initiated testing of all donations on June 15, 2020, using the Ortho VITROS anti–SARS-CoV-2 S1 Total Ig assay detecting total immunoglobulin. Sensitivity is 90% and specificity is 100%, as reported using a limited data set.2 Each donation sample is tested once; results are reported to donors electronically. Samples with signal levels above the manufacturer-defined cutoff are defined as reactive. Routine donor information is collected and identified only by code. The change in first-time vs repeat donors was compared in the first 2 weeks before testing was initiated (June 1-14, 2020) vs after testing (June 15–August 23, 2020). Temporal changes in seroreactivity rates overall and by US Census regions were evaluated over the study period (June 15–August 23) by linear regression. Bivariable analyses were conducted to compare the proportions of donor characteristics with χ2 tests. Multivariable logistic regression compared reactive rates among subgroups, adjusting for sex, age group, race/ethnicity, and region, including interactions.

    We conducted all analyses using SAS Software (version 9.4; SAS Institute Inc). Two-sided P values less than .05 defined statistical significance; data are presented with 95% CIs. The institutional review board of the American Red Cross considered the study exempt as human subjects research; each donor is provided a research study information sheet as part of the donation consent process.

    Results

    Of 953 926 donations tested, 17 336 (1.82% [95% CI, 1.79%-1.84%]) were reactive; 4786 (28%) were from first-time donors and 12 550 (72%) from repeat donors for anti–SARS-CoV-2 rates of 2.99% (95% CI, 2.90%-3.07%) among first-time donors and 1.58% (95% CI, 1.55%-1.61%) among repeat donors (P < .001) (Table). In the 2 weeks prior to initiation of testing, 11% of donors were first-time donors compared with 17% (P < .001) after that time. By multivariable analysis, the odds of reactivity were higher in donors aged 18 to 24 years compared with donors who were aged 55 years and older (odds ratio [OR], 2.43 [95% CI, 1.94-3.04]; P < .001), African American (OR, 2.58 [95% CI, 1.71-3.88]; P < .001), and Hispanic (OR, 2.31 [95% CI, 1.77-3.00]; P < .001) compared with White donors, and donors from the Northeast compared with the West (OR, 1.83 [95% CI, 1.57-2.12]; P < .001). Reactive rates increased over the study period, from 1.18% (95% CI, 1.11%-1.25%) to 2.58% (95% CI, 2.48%-2.69%; P < .001). Rates increased significantly in all Census regions except the Northeast (1.46% [95% CI, 1.3%-1.64%] to 2.06% [95% CI, 1.86%-2.28%]; P = .09), with the greatest increases in the South (1.09% [95% CI, 0.97%-1.23%] to 2.96% [95% CI, 2.75%-3.19%]; P < .001) and West (0.88% [95% CI, 0.75%-1.03%] to 2.42% [95% CI, 2.19%-2.67%]; P < .001) (Figure).

    Discussion

    This study found that, after the introduction of antibody testing, the proportion of first-time donors increased, and donations from younger and racial and ethnic minority donors were more likely to be reactive. In addition, reactivity rates increased with time. This increase may be due to donors with higher rates of prior exposure donating to obtain antibody test results, particularly first-time donors, but may also reflect increased exposure in the general population or increased recognition of the need for convalescent plasma.3

    The distribution of anti–SARS-CoV-2 reactive test results was similar to results reported for patients with clinically diagnosed COVID-19, with higher rates among African American and Hispanic donors and those from the Northeast.4,5 However, blood donors are not representative of the overall population. Additionally, first-time donors differ from repeat donors largely because repeat donors have already been screened for transfusion-transmissible infections and other health conditions. Blood donors reactive for anti–SARS-CoV-2 are not deferred from future donation because SARS-CoV-2, to date, is not transmissible by transfusion.6

    The main limitations include that testing results represent cross-sectional findings over a relatively short period, and American Red Cross collection areas in the US underrepresent areas such as New York City, south Florida, and some Western states. Also, reactive results were not confirmed, and thus the data may overrepresent blood donor seropositivity.

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

    Corresponding Author: Roger Y. Dodd, PhD, American Red Cross Scientific Affairs, 9315 Gaither Rd, Gaithersburg, MD 20877 (roger.dodd@redcross.org).

    Accepted for Publication: September 2, 2020.

    Published Online: September 14, 2020. doi:10.1001/jama.2020.18598

    Author Contributions: Drs Dodd and Stramer 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: Dodd, Stramer.

    Acquisition, analysis, or interpretation of data: All authors.

    Drafting of the manuscript: Dodd, Stramer.

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

    Statistical analysis: Xu, Stramer.

    Administrative, technical, or material support: Dodd.

    Supervision: Dodd.

    Conflict of Interest Disclosures: All authors are employees of the American Red Cross.

    Funding/Support: This study was supported by internal funds of the American Red Cross.

    Role of the Funder/Sponsor: The funder 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 thank Gregory A. Foster, BS, a paid employee of the American Red Cross Scientific Affairs Department, for collection and formatting of the data, as well as preliminary data analyses.

    References
    1.
    US Food and Drug Administration. Investigational COVID-19 convalescent plasma: guidance for industry. Published April 2020. Updated May 2020. Accessed August 10, 2020. https://www.fda.gov/media/136798/download
    2.
    US Food and Drug Administration. Instructions for use: Vitros Immunodiagnostics Anti-SARS-Cov-2 IgG. Accessed August 10, 2020. https://www.fda.gov/media/137363/download
    3.
    Roback  JD, Guarner  J.  Convalescent plasma to treat COVID-19: possibilities and challenges.   JAMA. 2020;323:1561-1562. doi:10.1001/jama.2020.4940 PubMedGoogle Scholar
    4.
    CDC COVID-19 Response Team.  Geographic differences in COVID-19 cases, deaths, and incidence: United States, February 12-April 7, 2020.   MMWR Morb Mortal Wkly Rep. 2020;69(15):465-471. doi:10.15585/mmwr.mm6915e4PubMedGoogle Scholar
    5.
    Tenforde  MW, Billig Rose  E, Lindsell  CJ,  et al; CDC COVID-19 Response Team.  Characteristics of adult outpatients and inpatients with COVID-19: 11 academic medical centers, United States, March-May 2020.   MMWR Morb Mortal Wkly Rep. 2020;69(26):841-846. doi:10.15585/mmwr.mm6926e3PubMedGoogle Scholar
    6.
    Katz  LM.  Is SARS-CoV-2 transfusion transmitted?   Transfusion. 2020;60(6):1111-1114. doi:10.1111/trf.15831 PubMedGoogle Scholar
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