Qualifying coronavirus disease 2019 convalescent plasma donors in Israel
Corresponding Author
Marina Izak
National Blood Services, Magen David Adom, Ramat Gan, Israel
Correspondence
Marina Izak, Faculty of Health Sciences, Magen David Adom, Ramat Gan, Israel.
Email: [email protected]
Search for more papers by this authorVeronica Gendelman
National Blood Services, Magen David Adom, Ramat Gan, Israel
Search for more papers by this authorSharron Bransburg-Zabary
National Blood Services, Magen David Adom, Ramat Gan, Israel
Search for more papers by this authorEvgeniy Stoyanov
National Blood Services, Magen David Adom, Ramat Gan, Israel
Search for more papers by this authorRoni Gat
Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel
Clinical Research Center, Soroka University Medical Center, Beer Sheva, Israel
Search for more papers by this authorDaniel Cohen
School of Public Health, Tel Aviv University, Tel Aviv, Israel
Search for more papers by this authorJacob Chen
Trauma and Combat Medicine Branch, Israel Defense Forces Medical Corps, Ramat Gan, Israel
Hospital Management, Meir Medical Center, KfarSaba, Israel
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Search for more papers by this authorYasmin Maor
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Infectious Disease Unit, Wolfson Medical Center, Holon, Israel
Search for more papers by this authorAvi Benov
Trauma and Combat Medicine Branch, Israel Defense Forces Medical Corps, Ramat Gan, Israel
The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
Search for more papers by this authorOren Zimhony
Infectious Disease Unit, Kaplan Medical Center, Rehovot, Israel
Search for more papers by this authorEilat Shinar
National Blood Services, Magen David Adom, Ramat Gan, Israel
Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel
Search for more papers by this authorCorresponding Author
Marina Izak
National Blood Services, Magen David Adom, Ramat Gan, Israel
Correspondence
Marina Izak, Faculty of Health Sciences, Magen David Adom, Ramat Gan, Israel.
Email: [email protected]
Search for more papers by this authorVeronica Gendelman
National Blood Services, Magen David Adom, Ramat Gan, Israel
Search for more papers by this authorSharron Bransburg-Zabary
National Blood Services, Magen David Adom, Ramat Gan, Israel
Search for more papers by this authorEvgeniy Stoyanov
National Blood Services, Magen David Adom, Ramat Gan, Israel
Search for more papers by this authorRoni Gat
Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel
Clinical Research Center, Soroka University Medical Center, Beer Sheva, Israel
Search for more papers by this authorDaniel Cohen
School of Public Health, Tel Aviv University, Tel Aviv, Israel
Search for more papers by this authorJacob Chen
Trauma and Combat Medicine Branch, Israel Defense Forces Medical Corps, Ramat Gan, Israel
Hospital Management, Meir Medical Center, KfarSaba, Israel
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Search for more papers by this authorYasmin Maor
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Infectious Disease Unit, Wolfson Medical Center, Holon, Israel
Search for more papers by this authorAvi Benov
Trauma and Combat Medicine Branch, Israel Defense Forces Medical Corps, Ramat Gan, Israel
The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
Search for more papers by this authorOren Zimhony
Infectious Disease Unit, Kaplan Medical Center, Rehovot, Israel
Search for more papers by this authorEilat Shinar
National Blood Services, Magen David Adom, Ramat Gan, Israel
Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel
Search for more papers by this authorAbstract
Background and Objectives
Passive immunization using investigational COVID-19 convalescent plasma (CCP) is a promising therapeutic strategy and could improve outcome if transfused early and contain high levels of anti-SARS-CoV-2 antibodies. We report the management of a national CCP collection and distribution program in Israel.
Materials and Methods
From 1 April 2020 to 15 January 2021, 4020 volunteer donors donated 5221 CCP units and 837 (20.8%) donors donated more than once. Anti-nucleocapsid IgG antibodies were determined using chemiluminescent immunoassay method (Abbott). A statistical model based on repeated IgG tests in sequential donations was created to predict the time of antibody decline below sample/cut-off (S/CO) level of 4.0.
Results
Ninety-six percent of CCP donors suffered a mild disease or were asymptomatic. Older donors had higher antibody levels. Higher antibody levels (S/CO ≥4) were detected in 35.2% of the donors. Low positive (S/CO ≥1.4–3.99) were found in 37%, and 27.8% had undetectable antibodies (S/CO ≤1.4). The model predicted decrease antibody thresholds of 0.55%/day since the first CCP donation, providing guidance for the effective timing of future collections from donors with high antibody levels.
Conclusions
An efficient CCP collection and distribution program was achieved, based on performing initial and repeated plasma collections, preferably from donors with higher antibody levels, and only antibody-rich units were supplied for therapeutic use. The inventory met the quantity and quality standards of the authorities, enabled to respond to the growing demand of the medical system and provide a product that may contribute to improve prognosis in patients with COVID-19.
CONFLICT OF INTEREST
No conflict of interest to disclose.
Supporting Information
Filename | Description |
---|---|
vox13162-sup-0001-Tables.docxWord 2007 document , 30.2 KB | Table S1.Donors' characteristics at time of first COVID-19 convalescent plasma collection. Anti-N, anti-nucleocapsid; SD, standard deviation; S/CO, sample/cutoff. Table S2. Antibody levels in age groups. Anti-N, anti-nucleocapsid; S/CO, sample/cutoff; SD, standard deviation Table S3.Anti-N antibody level decrease (%) relatively to first donation (100%) through 9½ months, based on a linear mixed model. Anti-N, anti-nucleocapsid; Ab, antibody; S/CO, sample/cutoff; CI, confidence interval. aOnly samples with anti-N IgG antibody level > 1.4 S/CO were analysed. Table S4. Time (days) until decline of anti-N IgG SARS CoV-2antibody from initial level to the level of 4.0 S/CO through subsequent donations, based on a linear mixed model. Anti-N, anti-nucleocapsid; Ab, antibody; S/CO, sample/cutoff; CI, confidence interval aOnly samples with antibody level ≥ 4.0 S/CO were analysed. bDecrease from given Ab level to the level of 4.0 S/CO, days. Table S5. Blood groups among CCP donors compared to routine blood donors in Israel. CCP, COVID-19 convalescent plasma; Anti-N, anti-nucleocapsid; Ab, antibody; S/CO, sample/cutoff. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
REFERENCES
- 1 Infectious Disease Society of America Guidelines on the Treatment and Management of Patients with COVID19. 2020. https://www.idsociety.org/COVID19guidelines. Accessed 20 November 2020.
- 2Ross CW, Hund EJ. Treatment of pneumonic disturbance complicating influenza. JAMA. 1919; 72: 640–5.
10.1001/jama.1919.02610090024007 Google Scholar
- 3Stoll HF. Value of convalescent blood and serum in treatment of influenza pneumonia. JAMA. 1919; 73: 478–82.
10.1001/jama.1919.02610330016006 Google Scholar
- 4Luke TC, Kilbane EM, Jackson JL, Hoffman SL. Meta-analysis: convalescent blood products for Spanish influenza pneumonia: a future H5N1 treatment? Ann Intern Med. 2006; 145: 599–609.
- 5Shen C, Wang Z, Zhao F, Yang Y, Li J, Yuan J, et al. Treatment of 5 critically ill patients with COVID19 with convalescent plasma. JAMA. 2020; 323: 1582–9.
- 6Zhang B, Liu S, Tan T, Huang W, Dong Y, Chen L, et al. Treatment with convalescent plasma for critically ill patients with SARS-CoV-2 infection. Chest. 2020; 158:e9-e13.
- 7Duan K, Liu B, Li C, Zhang H, Yu T, Qu J, et al. Effectiveness of convalescent plasma therapy in severe COVID19 patients. Proc Natl Acad Sci U S A. 2020; 117: 9490–6.
- 8Salazar E, Perez KK, Ashraf M, Chen J, Castillo B, Christensen PA, et al. Treatment of COVID19 patients with convalescent plasma. Am J Pathol. 2020; 190: 1680–90.
- 9Joyner MJ, Senefeld JW, Klassen SA, Mills JR, Johnson PW, Theel ES, et al. Effect of Convalescent Plasma on Mortality among Hospitalized Patients with COVID19: Initial Three-Month Experience (published online ahead of print on 12 August 2020). medRxiv 2020. https://doi.org/10.1101/2020.08.12.20169359.
10.1101/2020.08.12.20169359 Google Scholar
- 10Liu STH, Lin HM, Baine I, Wajnberg A, Gumprecht JP, Rahman F, et al. Convalescent plasma treatment of severe COVID-19: a propensity score-matched control study. Nat Med. 2020; 26: 1708–13.
- 11Salazar E, Christensen PA, Graviss EA, Nguyen DT, Castillo B, Chen J, et al. Significantly decreased mortality in a large cohort of coronavirus disease 2019 (COVID-19) patients transfused early with convalescent plasma containing high-titer anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein IgG. Am J Pathol. 2021; 191: 90–107.
- 12Libster R, Pérez Marc G, Wappner S, Coviello S, Bianchi A, Braem V, et al. Early high-titer plasma therapy to prevent severe covid-19 in older adults. N Engl J Med. 2021; 384: 610–8.
- 13Joyner MJ, Carter RE, Senefeld JW, Klassen SA, Mills JR, Johnson PW, et al. Convalescent plasma antibody levels and the risk of death from Covid-19 (published online ahead of print on 13 January 2021). N Engl J Med. 2021; 384: 1015–27.
- 14Simonovich VA, Burgos Pratx LD, Scibona P, Beruto MV, Vallone MG, Vázquez C, et al. A randomized trial of convalescent plasma in COVID-19 severe pneumonia. N Engl J Med. 2021; 384: 619–29.
- 15Agarwal A, Mukherjee A, Kumar G, Chatterjee P, Bhatnagar T, Malhotra P. Convalescent plasma in the management of moderate covid-19 in adults in India: open-label phase II multicenter randomized controlled trial (PLACID trial). BMJ. 2020; 371:m3939.
- 16 FDA: revision of the Emergency Use Authorization (EUA) for COVID-19 convalescent plasma. https://www.fda.gov/news-events/fda-brief/fda-brief-fda-updates-emergency-use-authorization-covid-19-convalescent-plasma-reflect-new-data. Accessed 4 February 2021.
- 17Eckhardt CM, Cummings MJ, Rajagopalan KN, Borden S, Bitan ZC, Wolf A, et al. Evaluating the efficacy and safety of human anti-SARS-CoV-2 convalescent plasma in severely ill adults with COVID-19: a structured summary of a study protocol for a randomized controlled trial. Trials. 2020; 21:499.
- 18Wouters E, Steenhuis M, Schrezenmeier H, Tiberghien P, Harvala H, Feys HB, et al. Evaluation of SARS-CoV-2 antibody titers and potency for convalescent plasma donation: a brief commentary (published online ahead of print on 23 December 2020). Vox Sang. 2020; 116(5): 493–6.
- 19Maor Y, Cohen D, Paran N, Israely T, Ezra V, Axelrod O, et al. Compassionate use of convalescent plasma for treatment of moderate and severe pneumonia in COVID19 patients and association with IgG antibody levels in donated plasma. EClinicalMedicine. 2020; 26:100525.
- 20 FDA: Recommendations for investigational COVID-19 convalescent plasma. https://www.fda.gov/media/136798. Accessed 15 January 2021.
- 21 MOH. https://www.health.gov.il/Subjects/disease/corona/Documents/bz-259818720.pdf. Accessed 9 July 2020.
- 22Wendel S, Kutner JM, Machado R, Fontão-Wendel R, Bub C, Fachini R, et al. Screening for SARS-CoV-2 antibodies in convalescent plasma in Brazil: preliminary lessons from a voluntary convalescent donor program. Transfusion. 2020; 60: 2938–51.
- 23Shimoni Z, Niven MJ, Pitlick S, Bulvik S. Treatment of West Nile virus encephalitis with intravenous immunoglobulin. Emerg Infect Dis. 2001; 7: 759.
- 24Flower B, Brown JC, Simmons B, Moshe M, Frise R, Penn R, et al. Clinical and laboratory evaluation of SARS-CoV-2 lateral flow assays for use in a national COVID-19 seroprevalence survey. Thorax. 2020; 75: 1082–8.
- 25Andrey DO, Cohen P, Meyer B, Torriani G, Yerly S, Mazza L, et al. Head-to-head accuracy comparison of three commercial COVID19 IgM/IgG serology rapid tests. J Clin Med. 2020; 9: 2369.
- 26Luchsinger LL, Ransegnola BP, Jin DK, Muecksch F, Weisblum Y, Bao W, et al. Serological assays estimate highly variable SARS-CoV-2 neutralizing antibody activity in recovered COVID-19 patients. J Clin Microbiol. 2020; 58:e02005-20.
- 27Wajnberg A, Amanat F, Firpo A, Altman DR, Bailey MJ, Mansour M, et al. Robust neutralizing antibodies to SARS-CoV-2 infection persist for months. Science. 2020; 370: 1227–30.
- 28Theel ES, Harring J, Hilgart H, Granger D. Performance characteristics of four high-throughput immunoassays for detection of IgG antibodies against SARS-CoV-2. J Clin Microbiol. 2020; 58:e01243-20.
- 29Manalac J, Yee J, Calayag K, Nguyen L, Patel PM, Zhou D, et al. Evaluation of Abbott anti-SARS-CoV-2 CMIA IgG and Euroimmun ELISA IgG/IgA assays in a clinical lab. Clin Chim Acta. 2020; 510: 687–90.
- 30Meschi S, Colavita F, Bordi L, Matusali G, Lapa D, Amendola A, et al. Performance evaluation of Abbott ARCHITECT SARS-CoV-2 IgG immunoassay in comparison with indirect immunofluorescence and virus microneutralization test. J Clin Virol. 2020; 129:104539.
- 31 BELTEST-IT COV-2 Rapid Test (PharmAct) https://pharmact.de/en/beltest-it-cov-2. Accessed 10 June 2020.
- 32Ellinghaus D, Degenhardt F, Bujanda L, Buti M, Albillos A, Invernizzi P, et al. Genomewide association study of severe COVID19 with respiratory failure. N Engl J Med. 2020; 383: 1522–34.
- 33Wu BB, Gu DZ, Yu JN, Yang J, Shen WQ. Association between ABO blood groups and COVID19 infection, severity and demise: a systematic review and meta-analysis. Infect Genet Evol. 2020; 84:104485.
- 34Wang HE, Ostrosky-Zeicher L, Katz J, Wanger A, Bai Y, Sridhar S, et al. Screening donors for COVID-19 convalescent plasma (published online ahead of print on 24 December 2020). Transfusion. 2020; 61: 1047–52.
- 35Long QX, Tang XJ, Shi QL, Li Q, Deng HJ, Yuan J, et al. Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections. Nat Med. 2020; 26: 1200–4.
- 36Röltgen K, Wirz OF, Stevens BA, Powell AE, Hogan CA, Najeeb J, et al. SARS-CoV-2 antibody responses correlate with resolution of RNAemia but are short-lived in patients with mild illness (published online ahead of print on 8 August 2020). medRxiv. 2020. https://doi.org/10.1101/2020.08.15.20175794.
10.1101/2020.08.15.20175794 Google Scholar
- 37Lynch KL, Whitman JD, Lacanienta NP, Beckerdite EW, Kastner SA, Shy BR, et al. Magnitude and kinetics of anti-SARS-CoV-2 antibody responses and their relationship to disease severity (published online ahead of print on 14 July 2020). Clin Infect Dis. 2020; 72: 301–8.
- 38Brochot E, Demey B, Touzé A, Belouzard S, Dubuisson J, Schmit JL, et al. Anti-spike, anti-nucleocapsid and neutralizing antibodies in SARS-CoV-2 inpatients and asymptomatic individuals. Front Microbiol. 2020; 11:584251.
- 39Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med. 2020; 383: 2603–15.
- 40Mo H, Zeng G, Ren X, Li H, Ke C, Tan Y, et al. Longitudinal profile of antibodies against SARS-coronavirus in SARS patients and their clinical significance. Respirology. 2006; 11: 49–53.
- 41Kellam P, Barclay W. The dynamics of humoral immune responses following SARS-CoV-2 infection and the potential for re-infection. J Gen Virol. 2020; 101: 791–7.