Convalescence plasma treatment of COVID-19: results from a prematurely terminated randomized controlled open-label study in Southern Sweden
Karin Holm, Maria N Lundgren, Jens Kjeldsen-Kragh, Oskar Ljungquist, Blenda Böttiger, Christian Wikén, Jonas Öberg, Nils Fernström, Ebba Rosendal, Anna K Överby, Julia Wigren Byström, Mattias Forsell, Mona Landin-Olsson, Magnus Rasmussen
BMC Research Notes, doi:10.1186/s13104-021-05847-7
Objective: Convalescent plasma has been tried as therapy for various viral infections. Early observational studies of convalescent plasma treatment for hospitalized COVID-19 patients were promising, but randomized controlled studies were lacking at the time. The objective of this study was to investigate if convalescent plasma is beneficial to hospitalized patients with COVID-19. Results: Hospitalized patients with confirmed COVID-19 and an oxygen saturation below 94% were randomized 1:1 to receive convalescent plasma in addition to standard of care or standard of care only. The primary outcome was number of days of oxygen treatment to keep saturation above 93% within 28 days from inclusion. The study was prematurely terminated when thirty-one of 100 intended patients had been included. The median time of oxygen treatment among survivors was 11 days (IQR 6-15) for the convalescent plasma group and 7 days (IQR 5-9) for the standard of care group (p = 0.4, median difference -4). Two patients in the convalescent plasma group and three patients in the standard of care group died (p = 0.64, OR 0.49, 95% CI 0.08-2.79). Thus no significant differences were observed between the groups.
Abbreviations
Supplementary Information The online version contains supplementary material available at https:// doi. org/ 10. 1186/ s13104-021-05847-7. Additional file 1. SARS-CoV2 antibody detection and microneutralization assay. Authors' contributions KH: study design, inclusion of patients and donors, data collection and analysis, manuscript writing. MNL: study design, transfusion medicine expertise, donor screening and responsible for plasma collection and plasma analysis, data analysis and manuscript writing. JKK: study design, transfusion medicine expertise, data analysis and critical revision of the manuscript. OL, CW, JÖ: inclusion of patients, data collection and analysis, critical revision of the manuscript. NF: study design, inclusion of patients and donors, data collection. BB: study design, responsible for virology sampling and data analysis, critical revision of the manuscript. ER, AKÖ, JWB, MF: responsible for measuring
Declarations Ethics approval and consent to participate The Swedish Ethical Review Authority approved the study (Reference Number #2020-01744, 2020-03595). Written informed consent was required from donors and patients on inclusion.
Consent to publish Not applicable.
Competing interests The authors declare no competing interests.
Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
References
Agarwal, Mukherjee, Kumar, Chatterjee, Bhatnagar et al., Convalescent plasma in the management of moderate covid-19 in adults in India: open label phase II multicentre randomised controlled trial (PLACID Trial), BMJ (Clin Res ed),
doi:10.1136/bmj.m3939Arabi, Hajeer, Luke, Raviprakash, Balkhy et al., Feasibility of using convalescent plasma immunotherapy for MERS-CoV infection, Saudi Arabia, Emerg Infect Dis,
doi:10.3201/eid2209.151164Betrains, Godinas, Woei, Rosseels, Van Herck et al., Convalescent plasma treatment of persistent severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in patients with lymphoma with impaired humoral immunity and lack of neutralising antibodies, Br J Haematol,
doi:10.1111/bjh.17266Casadevall, Pirofski, The convalescent sera option for containing COVID-19, J Clin Invest,
doi:10.1172/JCI138003Cheng, Wong, Soo, Wong, Lee et al., Use of convalescent plasma therapy in SARS patients in Hong Kong, Eur J Clin Microbiol Infect Dis,
doi:10.1007/s10096-004-1271-9Duan, Liu, Li, Zhang, Yu et al., Effectiveness of convalescent plasma therapy in severe COVID-19 patients, Proc Natl Acad Sci,
doi:10.1073/pnas.2004168117Hegerova, Gooley, Sweerus, Maree, Bailey et al., Use of convalescent plasma in hospitalized patients with COVID-19: case series, Blood,
doi:10.1182/blood.2020006964Horby, Estcourt, Peto, Emberson, Staplin et al., Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial,
doi:10.1101/2021.03.09.21252736Hueso, Pouderoux, Péré, Beaumont, Raillon et al., Convalescent plasma therapy for B-cell-depleted patients with protracted COVID-19, Blood,
doi:10.1182/blood.2020008423Hung, To, Lee, Lee, Chan et al., Convalescent plasma treatment reduced mortality in patients with severe pandemic influenza A (H1N1) 2009 virus infection, Clin Infect Dis,
doi:10.1093/cid/ciq106Joyner, Wright, Fairweather, Senefeld, Bruno et al., Early safety indicators of COVID-19 convalescent plasma in 5000 patients, J Clin Investig,
doi:10.1172/JCI140200Libster, Marc, Wappner, Coviello, Bianchi et al., Early high-titer plasma therapy to prevent severe Covid-19 in older adults, N Engl J Med,
doi:10.1056/NEJMoa2033700Mair-Jenkins, Saavedra-Campos, Baillie, Cleary, Khaw et al., The effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: a systematic review and exploratory meta-analysis, J Infect Dis,
doi:10.1093/infdis/jiu396Rodionov, Biener, Spieth, Achleitner, Hölig et al., Potential benefit of convalescent plasma transfusions in immunocompromised patients with COVID-19, Lancet Microbe,
doi:10.1016/S2666-5247(21)00030-6Rojas, Rodríguez, Monsalve, Acosta-Ampudia, Camacho et al., Convalescent plasma in Covid-19: possible mechanisms of action, Autoimmun Rev,
doi:10.1016/j.autrev.2020.102554Sahr, Ansumana, Massaquoi, Idriss, Sesay et al., Evaluation of convalescent whole blood for treating Ebola Virus Disease in Freetown, Sierra Leone, J Infect,
doi:10.1016/j.jinf.2016.11.009Senefeld, Klassen, Ford, Wiggins, Bostrom et al., Therapeutic use of convalescent plasma in COVID-19 patients with immunodeficiency, medRxiv,
doi:10.1101/2020.11.08.20224790Simonovich, Pratx, Scibona, Beruto, Vallone et al., A randomized trial of convalescent plasma in Covid-19 severe pneumonia, N Engl J Med,
doi:10.1056/NEJMoa2031304Zhou, Zhong, Guan, Treatment with convalescent plasma for influenza A (H5N1) Infection, N Engl J Med,
doi:10.1056/NEJMc070359{ 'indexed': {'date-parts': [[2023, 1, 14]], 'date-time': '2023-01-14T10:53:58Z', 'timestamp': 1673693638449},
'reference-count': 20,
'publisher': 'Springer Science and Business Media LLC',
'issue': '1',
'license': [ { 'start': { 'date-parts': [[2021, 12, 1]],
'date-time': '2021-12-01T00:00:00Z',
'timestamp': 1638316800000},
'content-version': 'tdm',
'delay-in-days': 0,
'URL': 'https://creativecommons.org/licenses/by/4.0'},
{ 'start': { 'date-parts': [[2021, 12, 4]],
'date-time': '2021-12-04T00:00:00Z',
'timestamp': 1638576000000},
'content-version': 'vor',
'delay-in-days': 3,
'URL': 'https://creativecommons.org/licenses/by/4.0'}],
'funder': [{'DOI': '10.13039/501100009780', 'name': 'region skåne', 'doi-asserted-by': 'publisher'}],
'content-domain': {'domain': ['link.springer.com'], 'crossmark-restriction': False},
'published-print': {'date-parts': [[2021, 12]]},
'abstract': '<jats:title>Abstract</jats:title><jats:sec>\n'
' <jats:title>Objective</jats:title>\n'
' <jats:p>Convalescent plasma has been tried as therapy for various viral '
'infections. Early observational studies of convalescent plasma treatment for hospitalized '
'COVID-19 patients were promising, but randomized controlled studies were lacking at the time. '
'The objective of this study was to investigate if convalescent plasma is beneficial to '
'hospitalized patients with COVID-19.</jats:p>\n'
' </jats:sec><jats:sec>\n'
' <jats:title>Results</jats:title>\n'
' <jats:p>Hospitalized patients with confirmed COVID-19 and an oxygen '
'saturation below 94% were randomized 1:1 to receive convalescent plasma in addition to '
'standard of care or standard of care only. The primary outcome was number of days of oxygen '
'treatment to keep saturation above 93% within 28\xa0days from inclusion. The study was '
'prematurely terminated when thirty-one of 100 intended patients had been included. The median '
'time of oxygen treatment among survivors was 11\xa0days (IQR 6–15) for the convalescent '
'plasma group and 7\xa0days (IQR 5–9) for the standard of care group '
'(<jats:italic>p</jats:italic>\u2009=\u20090.4, median difference -4). Two patients in the '
'convalescent plasma group and three patients in the standard of care group died '
'(<jats:italic>p</jats:italic>\u2009=\u20090.64, OR 0.49, 95% CI 0.08–2.79). Thus no '
'significant differences were observed between the groups.</jats:p>\n'
' <jats:p><jats:italic>Trial registration</jats:italic> ClinicalTrials '
'NCT04600440, retrospectively registered Oct 23, 2020.</jats:p>\n'
' </jats:sec>',
'DOI': '10.1186/s13104-021-05847-7',
'type': 'journal-article',
'created': {'date-parts': [[2021, 12, 4]], 'date-time': '2021-12-04T09:02:48Z', 'timestamp': 1638608568000},
'update-policy': 'http://dx.doi.org/10.1007/springer_crossmark_policy',
'source': 'Crossref',
'is-referenced-by-count': 12,
'title': 'Convalescence plasma treatment of COVID-19: results from a prematurely terminated randomized '
'controlled open-label study in Southern Sweden',
'prefix': '10.1186',
'volume': '14',
'clinical-trial-number': [ { 'clinical-trial-number': 'nct04600440',
'registry': '10.18810/clinical-trials-gov'}],
'author': [ { 'ORCID': 'http://orcid.org/0000-0002-8289-5949',
'authenticated-orcid': False,
'given': 'Karin',
'family': 'Holm',
'sequence': 'first',
'affiliation': []},
{'given': 'Maria N.', 'family': 'Lundgren', 'sequence': 'additional', 'affiliation': []},
{'given': 'Jens', 'family': 'Kjeldsen-Kragh', 'sequence': 'additional', 'affiliation': []},
{'given': 'Oskar', 'family': 'Ljungquist', 'sequence': 'additional', 'affiliation': []},
{'given': 'Blenda', 'family': 'Böttiger', 'sequence': 'additional', 'affiliation': []},
{'given': 'Christian', 'family': 'Wikén', 'sequence': 'additional', 'affiliation': []},
{'given': 'Jonas', 'family': 'Öberg', 'sequence': 'additional', 'affiliation': []},
{'given': 'Nils', 'family': 'Fernström', 'sequence': 'additional', 'affiliation': []},
{'given': 'Ebba', 'family': 'Rosendal', 'sequence': 'additional', 'affiliation': []},
{'given': 'Anna K.', 'family': 'Överby', 'sequence': 'additional', 'affiliation': []},
{'given': 'Julia', 'family': 'Wigren Byström', 'sequence': 'additional', 'affiliation': []},
{'given': 'Mattias', 'family': 'Forsell', 'sequence': 'additional', 'affiliation': []},
{'given': 'Mona', 'family': 'Landin-Olsson', 'sequence': 'additional', 'affiliation': []},
{'given': 'Magnus', 'family': 'Rasmussen', 'sequence': 'additional', 'affiliation': []}],
'member': '297',
'published-online': {'date-parts': [[2021, 12, 4]]},
'reference': [ { 'issue': '7',
'key': '5847_CR1',
'doi-asserted-by': 'publisher',
'DOI': '10.1016/j.autrev.2020.102554',
'volume': '19',
'author': 'M Rojas',
'year': '2020',
'unstructured': 'Rojas M, Rodríguez Y, Monsalve DM, Acosta-Ampudia Y, Camacho B, Gallo '
'JE, et al. Convalescent plasma in Covid-19: possible mechanisms of '
'action. Autoimmun Rev. 2020;19(7): 102554. '
'https://doi.org/10.1016/j.autrev.2020.102554.',
'journal-title': 'Autoimmun Rev'},
{ 'issue': '4',
'key': '5847_CR2',
'doi-asserted-by': 'publisher',
'first-page': '447',
'DOI': '10.1093/cid/ciq106',
'volume': '52',
'author': 'IF Hung',
'year': '2011',
'unstructured': 'Hung IF, To KK, Lee CK, Lee KL, Chan K, Yan WW, et al. Convalescent '
'plasma treatment reduced mortality in patients with severe pandemic '
'influenza A (H1N1) 2009 virus infection. Clin Infect Dis. '
'2011;52(4):447–56. https://doi.org/10.1093/cid/ciq106.',
'journal-title': 'Clin Infect Dis'},
{ 'issue': '1',
'key': '5847_CR3',
'doi-asserted-by': 'publisher',
'first-page': '80',
'DOI': '10.1093/infdis/jiu396',
'volume': '211',
'author': 'J Mair-Jenkins',
'year': '2014',
'unstructured': 'Mair-Jenkins J, Saavedra-Campos M, Baillie JK, Cleary P, Khaw F-M, Lim '
'WS, et al. The effectiveness of convalescent plasma and hyperimmune '
'immunoglobulin for the treatment of severe acute respiratory infections '
'of viral etiology: a systematic review and exploratory meta-analysis. J '
'Infect Dis. 2014;211(1):80–90. https://doi.org/10.1093/infdis/jiu396.',
'journal-title': 'J Infect Dis'},
{ 'issue': '14',
'key': '5847_CR4',
'doi-asserted-by': 'publisher',
'first-page': '1450',
'DOI': '10.1056/NEJMc070359',
'volume': '357',
'author': 'B Zhou',
'year': '2007',
'unstructured': 'Zhou B, Zhong N, Guan Y. Treatment with convalescent plasma for '
'influenza A (H5N1) Infection. N Engl J Med. 2007;357(14):1450–1. '
'https://doi.org/10.1056/NEJMc070359.',
'journal-title': 'N Engl J Med'},
{ 'issue': '1',
'key': '5847_CR5',
'doi-asserted-by': 'publisher',
'first-page': '44',
'DOI': '10.1007/s10096-004-1271-9',
'volume': '24',
'author': 'Y Cheng',
'year': '2005',
'unstructured': 'Cheng Y, Wong R, Soo YOY, Wong WS, Lee CK, Ng MHL, et al. Use of '
'convalescent plasma therapy in SARS patients in Hong Kong. Eur J Clin '
'Microbiol Infect Dis. 2005;24(1):44–6. '
'https://doi.org/10.1007/s10096-004-1271-9.',
'journal-title': 'Eur J Clin Microbiol Infect Dis'},
{ 'issue': '9',
'key': '5847_CR6',
'doi-asserted-by': 'publisher',
'first-page': '1554',
'DOI': '10.3201/eid2209.151164',
'volume': '22',
'author': 'YM Arabi',
'year': '2016',
'unstructured': 'Arabi YM, Hajeer AH, Luke T, Raviprakash K, Balkhy H, Johani S, et al. '
'Feasibility of using convalescent plasma immunotherapy for MERS-CoV '
'infection, Saudi Arabia. Emerg Infect Dis. 2016;22(9):1554–61. '
'https://doi.org/10.3201/eid2209.151164.',
'journal-title': 'Emerg Infect Dis'},
{ 'issue': '3',
'key': '5847_CR7',
'doi-asserted-by': 'publisher',
'first-page': '302',
'DOI': '10.1016/j.jinf.2016.11.009',
'volume': '74',
'author': 'F Sahr',
'year': '2017',
'unstructured': 'Sahr F, Ansumana R, Massaquoi TA, Idriss BR, Sesay FR, Lamin JM, et al. '
'Evaluation of convalescent whole blood for treating Ebola Virus Disease '
'in Freetown, Sierra Leone. J Infect. 2017;74(3):302–9. '
'https://doi.org/10.1016/j.jinf.2016.11.009.',
'journal-title': 'J Infect'},
{ 'issue': '9',
'key': '5847_CR8',
'doi-asserted-by': 'publisher',
'first-page': '4791',
'DOI': '10.1172/JCI140200',
'volume': '130',
'author': 'MJ Joyner',
'year': '2020',
'unstructured': 'Joyner MJ, Wright RS, Fairweather D, Senefeld JW, Bruno KA, Klassen SA, '
'et al. Early safety indicators of COVID-19 convalescent plasma in 5000 '
'patients. J Clin Investig. 2020;130(9):4791–7. '
'https://doi.org/10.1172/JCI140200.',
'journal-title': 'J Clin Investig'},
{ 'issue': '6',
'key': '5847_CR9',
'doi-asserted-by': 'publisher',
'first-page': '759',
'DOI': '10.1182/blood.2020006964',
'volume': '136',
'author': 'L Hegerova',
'year': '2020',
'unstructured': 'Hegerova L, Gooley TA, Sweerus KA, Maree C, Bailey N, Bailey M, et al. '
'Use of convalescent plasma in hospitalized patients with COVID-19: case '
'series. Blood. 2020;136(6):759–62. '
'https://doi.org/10.1182/blood.2020006964.',
'journal-title': 'Blood'},
{ 'issue': '4',
'key': '5847_CR10',
'doi-asserted-by': 'publisher',
'first-page': '1545',
'DOI': '10.1172/JCI138003',
'volume': '130',
'author': 'A Casadevall',
'year': '2020',
'unstructured': 'Casadevall A, Pirofski L-A. The convalescent sera option for containing '
'COVID-19. J Clin Invest. 2020;130(4):1545–8. '
'https://doi.org/10.1172/JCI138003.',
'journal-title': 'J Clin Invest'},
{ 'issue': '17',
'key': '5847_CR11',
'doi-asserted-by': 'publisher',
'first-page': '9490',
'DOI': '10.1073/pnas.2004168117',
'volume': '117',
'author': 'K Duan',
'year': '2020',
'unstructured': 'Duan K, Liu B, Li C, Zhang H, Yu T, Qu J, et al. Effectiveness of '
'convalescent plasma therapy in severe COVID-19 patients. Proc Natl Acad '
'Sci. 2020;117(17):9490–6. https://doi.org/10.1073/pnas.2004168117.',
'journal-title': 'Proc Natl Acad Sci'},
{ 'key': '5847_CR12',
'doi-asserted-by': 'publisher',
'unstructured': 'Horby PW, Estcourt L, Peto L, Emberson JR, Staplin N, Spata E, et al. '
'Convalescent plasma in patients admitted to hospital with COVID-19 '
'(RECOVERY): a randomised, controlled, open-label, platform trial. '
'medRxiv. 2021:2021.03.09.21252736. '
'https://doi.org/10.1101/2021.03.09.21252736',
'DOI': '10.1101/2021.03.09.21252736'},
{ 'key': '5847_CR13',
'doi-asserted-by': 'publisher',
'author': 'VA Simonovich',
'year': '2020',
'unstructured': 'Simonovich VA, Burgos Pratx LD, Scibona P, Beruto MV, Vallone MG, '
'Vazquez C, et al. A randomized trial of convalescent plasma in Covid-19 '
'severe pneumonia. N Engl J Med. 2020. '
'https://doi.org/10.1056/NEJMoa2031304.',
'journal-title': 'N Engl J Med',
'DOI': '10.1056/NEJMoa2031304'},
{ 'key': '5847_CR14',
'doi-asserted-by': 'publisher',
'author': 'R Libster',
'year': '2021',
'unstructured': 'Libster R, Perez Marc G, Wappner D, 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. https://doi.org/10.1056/NEJMoa2033700.',
'journal-title': 'N Engl J Med',
'DOI': '10.1056/NEJMoa2033700'},
{ 'key': '5847_CR15',
'doi-asserted-by': 'publisher',
'DOI': '10.1136/bmj.m3939',
'volume': '371',
'author': 'A Agarwal',
'year': '2020',
'unstructured': 'Agarwal 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 multicentre randomised controlled trial '
'(PLACID Trial). BMJ (Clin Res ed). 2020;371: m3939. '
'https://doi.org/10.1136/bmj.m3939.',
'journal-title': 'BMJ (Clin Res ed)'},
{ 'key': '5847_CR16',
'doi-asserted-by': 'publisher',
'unstructured': 'Senefeld JW, Klassen SA, Ford SK, Wiggins CC, Bostrom BC, Thompson MA, '
'et al. Therapeutic use of convalescent plasma in COVID-19 patients with '
'immunodeficiency. medRxiv. 2020:2020.11.08.20224790. '
'https://doi.org/10.1101/2020.11.08.20224790',
'DOI': '10.1101/2020.11.08.20224790'},
{ 'issue': '4',
'key': '5847_CR17',
'doi-asserted-by': 'publisher',
'DOI': '10.1016/S2666-5247(21)00030-6',
'volume': '2',
'author': 'RN Rodionov',
'year': '2021',
'unstructured': 'Rodionov RN, Biener A, Spieth P, Achleitner M, Hölig K, Aringer M, et '
'al. Potential benefit of convalescent plasma transfusions in '
'immunocompromised patients with COVID-19. Lancet Microbe. 2021;2(4): '
'e138. https://doi.org/10.1016/S2666-5247(21)00030-6.',
'journal-title': 'Lancet Microbe'},
{ 'key': '5847_CR18',
'doi-asserted-by': 'publisher',
'author': 'A Betrains',
'year': '2020',
'unstructured': 'Betrains A, Godinas L, Woei AJF, Rosseels W, Van Herck Y, Lorent N, et '
'al. Convalescent plasma treatment of persistent severe acute respiratory '
'syndrome coronavirus-2 (SARS-CoV-2) infection in patients with lymphoma '
'with impaired humoral immunity and lack of neutralising antibodies. Br J '
'Haematol. 2020. https://doi.org/10.1111/bjh.17266.',
'journal-title': 'Br J Haematol',
'DOI': '10.1111/bjh.17266'},
{ 'issue': '20',
'key': '5847_CR19',
'doi-asserted-by': 'publisher',
'first-page': '2290',
'DOI': '10.1182/blood.2020008423',
'volume': '136',
'author': 'T Hueso',
'year': '2020',
'unstructured': 'Hueso T, Pouderoux C, Péré H, Beaumont AL, Raillon LA, Ader F, et al. '
'Convalescent plasma therapy for B-cell-depleted patients with protracted '
'COVID-19. Blood. 2020;136(20):2290–5. '
'https://doi.org/10.1182/blood.2020008423.',
'journal-title': 'Blood'},
{ 'key': '5847_CR20',
'doi-asserted-by': 'publisher',
'unstructured': 'WHO Working Group on the Clinical Characterisation and Management of '
'COVID-19 infection. A minimal common outcome measure set for COVID-19 '
'clinical research. Lancet Infect Dis. 2020;20(8):e192–7. '
'https://doi.org/10.1016/s1473-3099(20)30483-7.',
'DOI': '10.1016/s1473-3099(20)30483-7'}],
'container-title': 'BMC Research Notes',
'original-title': [],
'language': 'en',
'link': [ { 'URL': 'https://link.springer.com/content/pdf/10.1186/s13104-021-05847-7.pdf',
'content-type': 'application/pdf',
'content-version': 'vor',
'intended-application': 'text-mining'},
{ 'URL': 'https://link.springer.com/article/10.1186/s13104-021-05847-7/fulltext.html',
'content-type': 'text/html',
'content-version': 'vor',
'intended-application': 'text-mining'},
{ 'URL': 'https://link.springer.com/content/pdf/10.1186/s13104-021-05847-7.pdf',
'content-type': 'application/pdf',
'content-version': 'vor',
'intended-application': 'similarity-checking'}],
'deposited': { 'date-parts': [[2021, 12, 4]],
'date-time': '2021-12-04T21:41:30Z',
'timestamp': 1638654090000},
'score': 1,
'resource': { 'primary': { 'URL': 'https://bmcresnotes.biomedcentral.com/articles/10.1186/s13104-021-05847-7'}},
'subtitle': [],
'short-title': [],
'issued': {'date-parts': [[2021, 12]]},
'references-count': 20,
'journal-issue': {'issue': '1', 'published-print': {'date-parts': [[2021, 12]]}},
'alternative-id': ['5847'],
'URL': 'http://dx.doi.org/10.1186/s13104-021-05847-7',
'relation': {},
'ISSN': ['1756-0500'],
'subject': ['General Biochemistry, Genetics and Molecular Biology', 'General Medicine'],
'container-title-short': 'BMC Res Notes',
'published': {'date-parts': [[2021, 12]]},
'assertion': [ { 'value': '2 July 2021',
'order': 1,
'name': 'received',
'label': 'Received',
'group': {'name': 'ArticleHistory', 'label': 'Article History'}},
{ 'value': '12 November 2021',
'order': 2,
'name': 'accepted',
'label': 'Accepted',
'group': {'name': 'ArticleHistory', 'label': 'Article History'}},
{ 'value': '4 December 2021',
'order': 3,
'name': 'first_online',
'label': 'First Online',
'group': {'name': 'ArticleHistory', 'label': 'Article History'}},
{'order': 1, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Declarations'}},
{ 'value': 'The Swedish Ethical Review Authority approved the study (Reference Number '
'#2020-01744, 2020-03595). Written informed consent was required from donors and '
'patients on inclusion.',
'order': 2,
'name': 'Ethics',
'group': {'name': 'EthicsHeading', 'label': 'Ethics approval and consent to participate'}},
{ 'value': 'Not applicable.',
'order': 3,
'name': 'Ethics',
'group': {'name': 'EthicsHeading', 'label': 'Consent to publish'}},
{ 'value': 'The authors declare no competing interests.',
'order': 4,
'name': 'Ethics',
'group': {'name': 'EthicsHeading', 'label': 'Competing interests'}}],
'article-number': '440'}
