Double-blinded, randomised, placebo-controlled trial of convalescent plasma for COVID-19: analyses by neutralising antibodies homologous to donors’ variants
T Khawaja, M Kajova, I Levonen, J P Pietilä, H Välimaa, J Paajanen, S H Pakkanen, A Patjas, R Montonen, S Miettinen, J Virtanen, T Smura, T Sironen, R Fagerlund, H Ugurlu, R Iheozor-Ejiofor, K Saksela, T Vahlberg, A Ranki, A Vierikko, J Ihalainen, O Vapalahti, A Kantele
Infectious Diseases, doi:10.1080/23744235.2024.2329957
Introduction: Convalescent plasma (CP) emerged as potential treatment for COVID-19 early in the pandemic. While efficacy in hospitalised patients has been lacklustre, CP may be beneficial at the first stages of disease. Despite multiple new variants emerging, no trials have involved analyses on variant-specific antibody titres of CP. Methods: We recruited hospitalised COVID-19 patients within 10 days of symptom onset and, employing a doubleblinded approach, randomised them to receive 200 ml convalescent plasma with high (HCP) or low (LCP) neutralising antibody (NAb) titre against the ancestral strain (Wuhan-like variant) or placebo in 1:1:1 ratio. Primary endpoints comprised intubation, corticosteroids for symptom aggravation, and safety assessed as serious adverse events. For a preplanned ad hoc analysis, the patients were regrouped by infused CP's NAb titers to variants infecting the recipients i.e. by titres of homologous HCP (hHCP) or LCP (hLCP). Results: Of the 57 patients, 18 received HCP, 19 LCP and 20 placebo, all groups smaller than planned. No significant differences were found for primary endpoints. In ad hoc analysis, hHCPrecipients needed significantly less respiratory support, and appeared to be given corticosteroids less frequently (1/14; 7.1%) than those receiving hLCP (9/23; 39.1%) or placebo (8/20; 40%), (p ¼ 0.077). Discussion: Our double-blinded, placebo-controlled CP therapy trial remained underpowered and does not allow any firm conclusions for early-stage hospitalised COVID-19 patients. Interestingly, however, regrouping by homologous -recipients' variantspecific -CP titres suggested benefits for hHCP. We encourage similar re-analysis of ongoing/previous larger CP studies.
Disclosure statement The authors report there are no competing interests to declare.
References
Abani, Abbas, Abbas, Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial, The Lancet,
doi:10.1016/S0140-6736(21)00897-7Agarwal, Mukherjee, Kumar, Convalescent plasma in the management of moderate covid-19 in adults in India: open label phase II multicentre randomised controlled trial (PLACID trial), BMJ,
doi:10.1136/bmj.m3939Bar, Shaw, Choi, A randomized controlled study of convalescent plasma for individuals hospitalized with COVID-19 pneumonia, J Clin Investig,
doi:10.1172/JCI155114Bartelt, Markmann, Nelson, Outcomes of convalescent plasma with defined high versus lower neutralizing antibody titers against SARS-CoV-2 among hospitalized patients: CoronaVirus inactivating plasma (CoVIP) study, mBio,
doi:10.1128/mbio.01751-22Bastard, Rosen, Zhang, Autoantibodies against type I IFNs in patients with life-threatening COVID-19, Science,
doi:10.1126/science.abd4585Bhimraj, Shumaker, Baden, Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19, Infectious Diseases Society of America
Burnouf, Yazer, International forum on the collection and use of COVID-19 convalescent plasma: protocols, challenges and lessons learned: summary, Vox Sang,
doi:10.1111/vox.13113Cantoni, Wilkie, Bentley, Correlation between pseudotyped virus and authentic virus neutralisation assays, a systematic review and meta-analysis of the literature, Front Immunol,
doi:10.3389/fimmu.2023.1184362Casadevall, Joyner, Pirofski, Convalescent plasma therapy in COVID-19: unravelling the data using the principles of antibody therapy, Expert Rev Respir Med
Corman, Landt, Kaiser, Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR. Euro Surveillance: bulletin Europeen, Sur Les Maladies Transmissibles ¼ Eur Commun Dis Bull
Focosi, Franchini, Pirofski, COVID-19 convalescent plasma and clinical trials: understanding conflicting outcomes, Clin Microbiol Rev,
doi:10.1128/cmr.00200-21Franchini, Cruciani, Casadevall, Safety of COVID-19 convalescent plasma: a definitive systematic review and meta-analysis of randomized controlled trials, Transfusion,
doi:10.1111/trf.17701Franchini, Focosi, Percivalle, Variant of concern-Matched COVID-19 convalescent plasma usage in seronegative hospitalized patients, Viruses,
doi:10.3390/v14071443Fred, Kuivanen, Ugurlu, Antidepressant and antipsychotic drugs reduce viral infection by SARS-CoV-2 and fluoxetine shows antiviral activity against the novel variants in vitro, Front Pharmacol,
doi:10.3389/fphar.2021.755600Haveri, Smura, Kuivanen, Serological and molecular findings during SARS-CoV-2 infection: the first case study in Finland, january to february 2020. Euro Surveillance: bulletin Europeen Sur Les, Maladies Transmissibles ¼ Eur Commun Dis Bull
Horby, Lim, Emberson, Dexamethasone in hospitalized patients with covid-19, N Engl J Med
Jalkanen, Kolehmainen, H€ Akkinen, Hk, COVID-19 mRNA vaccine induced antibody responses against three SARS-CoV-2 variants, Nat Commun,
doi:10.1038/s41467-021-24285-4Jokinen, Edelman, Krohn, Neutralizing natural anti-IL-17F autoantibodies protect autoimmune polyendocrine syndrome type 1 (APS-1) patients from asthma, Clin Immunol,
doi:10.1016/j.clim.2020.108512Joyner, Senefeld, Klassen, Effect of convalescent plasma on mortality among hospitalized patients with COVID-19: initial three-Month experience, medRxiv,
doi:10.1101/2020.08.12.20169359Kant, Nguyen, Blomqvist, Incidence trends for SARS-CoV-2 alpha and beta variants, Finland, spring 2021, Emerg Infect Dis,
doi:10.3201/eid2712.211631Kantele, Kareinen, SARS-CoV-2 infections among healthcare workers at helsinki university hospital, Finland, spring 2020: serosurvey, symptoms and risk factors, Travel Med Infect Dis,
doi:10.1016/j.tmaid.2020.101949Knip, Parviainen, Turtinen, SARS-CoV-2 and type 1 diabetes in children in Finland: an observational study, Lancet Diabetes Endocrinol,
doi:10.1016/S2213-8587(23)00041-4Kurki, Kantonen, Kaivola, APOE epsilon4 associates with increased risk of severe COVID-19, cerebral microhaemorrhages and post-COVID mental fatigue: a finnish biobank, autopsy and clinical study, Acta Neuropathol Commun,
doi:10.1186/s40478-021-01302-7Levine, Fukuta, Huaman, Coronavirus disease 2019 convalescent plasma outpatient therapy to prevent outpatient hospitalization: a meta-analysis of individual participant data from 5 randomized trials, Clin Infect Dis,
doi:10.1093/cid/ciad088Li, Zhang, Hu, Effect of convalescent plasma therapy on time to clinical improvement in patients with severe and life-threatening COVID-19, JAMA,
doi:10.1001/jama.2020.10044Libster, P� Erez Marc, Wappner, 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, 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/jiu396Misset, Piagnerelli, Hoste, Convalescent plasma for covid-19-induced ARDS in mechanically ventilated patients, N Engl J Med,
doi:10.1056/NEJMoa2209502Nguyen, Plyusnin, Sironen, a bioinformatic pipeline for reference-based consensus assembly and lineage assignment for SARS-CoV-2 sequences, BMC Bioinformatics,
doi:10.1186/s12859-021-04294-2R€ Ossler, Riepler, Bante, SARS-CoV-2 omicron variant neutralization in serum from vaccinated and convalescent persons, N Engl J Med,
doi:10.1056/NEJMc2119236Senefeld, Gorman, Johnson, Mortality rates among hospitalized patients with COVID-19 treated with convalescent plasma: a systematic review and meta-analysis, Mayo Clin Proc Innov Qual Outcomes,
doi:10.1016/j.mayocpiqo.2023.09.001Simonovich, Pratx, Scibona, A randomized trial of convalescent plasma in covid-19 severe pneumonia, N Engl J Med,
doi:10.1056/NEJMoa2031304Sullivan, Franchini, Joyner, Analysis of anti-SARS-CoV-2 omicron-neutralizing antibody titers in different vaccinated and unvaccinated convalescent plasma sources, Nat Commun,
doi:10.1038/s41467-022-33864-ySullivan, Gebo, Shoham, Early outpatient treatment for covid-19 with convalescent plasma, N Engl J Med,
doi:10.1056/NEJMoa2119657Tong, Baumgart, Evangelidis, Core outcome measures for trials in people with coronavirus disease 2019: respiratory failure, multiorgan failure, shortness of breath, and recovery, Crit Care Med,
doi:10.1097/CCM.0000000000004817Vauhkonen, Nguyen, Kant, Introduction and rapid spread of SARS-CoV-2 omicron variant and dynamics of BA.1 and BA.1.1 sublineages, Finland, december 2021, Emerg Infect Dis,
doi:10.3201/eid2806.220515Virtanen, Uusitalo, Korhonen, Kinetics of neutralizing antibodies of COVID-19 patients tested using clinical D614G, B.1.1.7, and B 1.351 isolates in microneutralization assays, Viruses,
doi:10.3390/v13060996{ 'indexed': {'date-parts': [[2024, 3, 22]], 'date-time': '2024-03-22T01:30:27Z', 'timestamp': 1711071027504},
'reference-count': 46,
'publisher': 'Informa UK Limited',
'license': [ { 'start': { 'date-parts': [[2024, 3, 21]],
'date-time': '2024-03-21T00:00:00Z',
'timestamp': 1710979200000},
'content-version': 'vor',
'delay-in-days': 0,
'URL': 'http://creativecommons.org/licenses/by/4.0/'}],
'funder': [ {'name': 'Finnish Government Subsidy for Health Science Research', 'award': ['TYH 2021315']},
{'name': 'Finnish Medical Foundationand the Academy of Finland', 'award': ['335527']}],
'content-domain': {'domain': ['www.tandfonline.com'], 'crossmark-restriction': True},
'DOI': '10.1080/23744235.2024.2329957',
'type': 'journal-article',
'created': {'date-parts': [[2024, 3, 21]], 'date-time': '2024-03-21T18:41:53Z', 'timestamp': 1711046513000},
'page': '1-11',
'update-policy': 'http://dx.doi.org/10.1080/tandf_crossmark_01',
'source': 'Crossref',
'is-referenced-by-count': 0,
'title': 'Double-blinded, randomised, placebo-controlled trial of convalescent plasma for COVID-19: '
'analyses by neutralising antibodies homologous to donors’ variants',
'prefix': '10.1080',
'author': [ { 'given': 'T.',
'family': 'Khawaja',
'sequence': 'first',
'affiliation': [ { 'name': 'Meilahti Vaccine Research Center, MeVac, Department of '
'Infectious Diseases, University of Helsinki and Helsinki '
'University Hospital, Helsinki, Finland'},
{ 'name': 'Department of Infectious Diseases, University of Helsinki and '
'Helsinki University Hospital, Helsinki, Finland'},
{ 'name': 'Human Microbiome Research Program, Faculty of Medicine, '
'University of Helsinki, Helsinki, Finland'},
{ 'name': 'FIMAR, Multidisciplinary Center of Excellence in Antimicrobial '
'Resistance Research, University of Helsinki, Helsinki, '
'Finland'}]},
{ 'given': 'M.',
'family': 'Kajova',
'sequence': 'additional',
'affiliation': [ { 'name': 'Meilahti Vaccine Research Center, MeVac, Department of '
'Infectious Diseases, University of Helsinki and Helsinki '
'University Hospital, Helsinki, Finland'},
{ 'name': 'Department of Infectious Diseases, University of Helsinki and '
'Helsinki University Hospital, Helsinki, Finland'},
{ 'name': 'Human Microbiome Research Program, Faculty of Medicine, '
'University of Helsinki, Helsinki, Finland'},
{ 'name': 'FIMAR, Multidisciplinary Center of Excellence in Antimicrobial '
'Resistance Research, University of Helsinki, Helsinki, '
'Finland'}]},
{ 'given': 'I.',
'family': 'Levonen',
'sequence': 'additional',
'affiliation': [ { 'name': 'Meilahti Vaccine Research Center, MeVac, Department of '
'Infectious Diseases, University of Helsinki and Helsinki '
'University Hospital, Helsinki, Finland'},
{ 'name': 'Human Microbiome Research Program, Faculty of Medicine, '
'University of Helsinki, Helsinki, Finland'}]},
{ 'given': 'J. P.',
'family': 'Pietilä',
'sequence': 'additional',
'affiliation': [ { 'name': 'Meilahti Vaccine Research Center, MeVac, Department of '
'Infectious Diseases, University of Helsinki and Helsinki '
'University Hospital, Helsinki, Finland'},
{ 'name': 'Human Microbiome Research Program, Faculty of Medicine, '
'University of Helsinki, Helsinki, Finland'},
{ 'name': 'FIMAR, Multidisciplinary Center of Excellence in Antimicrobial '
'Resistance Research, University of Helsinki, Helsinki, '
'Finland'}]},
{ 'given': 'H.',
'family': 'Välimaa',
'sequence': 'additional',
'affiliation': [ { 'name': 'Meilahti Vaccine Research Center, MeVac, Department of '
'Infectious Diseases, University of Helsinki and Helsinki '
'University Hospital, Helsinki, Finland'},
{ 'name': 'Department of Virology, University of Helsinki, Helsinki, '
'Finland'}]},
{ 'given': 'J.',
'family': 'Paajanen',
'sequence': 'additional',
'affiliation': [ { 'name': 'Meilahti Vaccine Research Center, MeVac, Department of '
'Infectious Diseases, University of Helsinki and Helsinki '
'University Hospital, Helsinki, Finland'},
{ 'name': 'Department of Pulmonary Medicine, Heart and Lung Center, '
'University of Helsinki and Helsinki University Hospital, '
'Helsinki, Finland'}]},
{ 'given': 'S. H.',
'family': 'Pakkanen',
'sequence': 'additional',
'affiliation': [ { 'name': 'Meilahti Vaccine Research Center, MeVac, Department of '
'Infectious Diseases, University of Helsinki and Helsinki '
'University Hospital, Helsinki, Finland'},
{ 'name': 'Human Microbiome Research Program, Faculty of Medicine, '
'University of Helsinki, Helsinki, Finland'},
{ 'name': 'FIMAR, Multidisciplinary Center of Excellence in Antimicrobial '
'Resistance Research, University of Helsinki, Helsinki, '
'Finland'}]},
{ 'given': 'A.',
'family': 'Patjas',
'sequence': 'additional',
'affiliation': [ { 'name': 'Meilahti Vaccine Research Center, MeVac, Department of '
'Infectious Diseases, University of Helsinki and Helsinki '
'University Hospital, Helsinki, Finland'},
{ 'name': 'Human Microbiome Research Program, Faculty of Medicine, '
'University of Helsinki, Helsinki, Finland'},
{ 'name': 'FIMAR, Multidisciplinary Center of Excellence in Antimicrobial '
'Resistance Research, University of Helsinki, Helsinki, '
'Finland'}]},
{ 'given': 'R.',
'family': 'Montonen',
'sequence': 'additional',
'affiliation': [ { 'name': 'Department of Virology, University of Helsinki, Helsinki, '
'Finland'}]},
{ 'given': 'S.',
'family': 'Miettinen',
'sequence': 'additional',
'affiliation': [ { 'name': 'Department of Virology, University of Helsinki, Helsinki, '
'Finland'},
{ 'name': 'Department of Veterinary Biosciences, Faculty of Veterinary '
'Medicine, University of Helsinki, Helsinki, Finland'}]},
{ 'given': 'J.',
'family': 'Virtanen',
'sequence': 'additional',
'affiliation': [ { 'name': 'Department of Virology, University of Helsinki, Helsinki, '
'Finland'},
{ 'name': 'Department of Veterinary Biosciences, Faculty of Veterinary '
'Medicine, University of Helsinki, Helsinki, Finland'}]},
{ 'given': 'T.',
'family': 'Smura',
'sequence': 'additional',
'affiliation': [ { 'name': 'Department of Virology, University of Helsinki, Helsinki, '
'Finland'}]},
{ 'given': 'T.',
'family': 'Sironen',
'sequence': 'additional',
'affiliation': [ { 'name': 'Department of Virology, University of Helsinki, Helsinki, '
'Finland'},
{ 'name': 'Department of Veterinary Biosciences, Faculty of Veterinary '
'Medicine, University of Helsinki, Helsinki, Finland'}]},
{ 'given': 'R.',
'family': 'Fagerlund',
'sequence': 'additional',
'affiliation': [ { 'name': 'Department of Virology, University of Helsinki, Helsinki, '
'Finland'}]},
{ 'given': 'H.',
'family': 'Ugurlu',
'sequence': 'additional',
'affiliation': [ { 'name': 'Department of Virology, University of Helsinki, Helsinki, '
'Finland'}]},
{ 'given': 'R.',
'family': 'Iheozor-Ejiofor',
'sequence': 'additional',
'affiliation': [ { 'name': 'Department of Virology, University of Helsinki, Helsinki, '
'Finland'},
{ 'name': 'Department of Veterinary Biosciences, Faculty of Veterinary '
'Medicine, University of Helsinki, Helsinki, Finland'}]},
{ 'given': 'K.',
'family': 'Saksela',
'sequence': 'additional',
'affiliation': [ { 'name': 'Department of Virology, University of Helsinki, Helsinki, '
'Finland'},
{ 'name': 'HUS Diagnostic Centre, HUSLAB, Clinical Microbiology, Helsinki '
'University Hospital, Helsinki, Finland'}]},
{ 'given': 'T.',
'family': 'Vahlberg',
'sequence': 'additional',
'affiliation': [ { 'name': 'Department of Biostatistics, University of Turku and Turku '
'University Hospital, Turku, Finland'}]},
{ 'given': 'A.',
'family': 'Ranki',
'sequence': 'additional',
'affiliation': [ { 'name': 'Department of Dermatology, Allergology and Venereology, '
'University of Helsinki and Helsinki University Hospital, '
'Helsinki, Finland'}]},
{ 'given': 'A.',
'family': 'Vierikko',
'sequence': 'additional',
'affiliation': [{'name': 'Finnish Red Cross Blood Service, Helsinki, Finland'}]},
{ 'given': 'J.',
'family': 'Ihalainen',
'sequence': 'additional',
'affiliation': [{'name': 'Finnish Red Cross Blood Service, Helsinki, Finland'}]},
{ 'given': 'O.',
'family': 'Vapalahti',
'sequence': 'additional',
'affiliation': [ { 'name': 'Department of Virology, University of Helsinki, Helsinki, '
'Finland'},
{ 'name': 'Department of Veterinary Biosciences, Faculty of Veterinary '
'Medicine, University of Helsinki, Helsinki, Finland'},
{ 'name': 'HUS Diagnostic Centre, HUSLAB, Clinical Microbiology, Helsinki '
'University Hospital, Helsinki, Finland'}]},
{ 'given': 'A.',
'family': 'Kantele',
'sequence': 'additional',
'affiliation': [ { 'name': 'Meilahti Vaccine Research Center, MeVac, Department of '
'Infectious Diseases, University of Helsinki and Helsinki '
'University Hospital, Helsinki, Finland'},
{ 'name': 'Department of Infectious Diseases, University of Helsinki and '
'Helsinki University Hospital, Helsinki, Finland'},
{ 'name': 'Human Microbiome Research Program, Faculty of Medicine, '
'University of Helsinki, Helsinki, Finland'},
{ 'name': 'FIMAR, Multidisciplinary Center of Excellence in Antimicrobial '
'Resistance Research, University of Helsinki, Helsinki, '
'Finland'}]}],
'member': '301',
'published-online': {'date-parts': [[2024, 3, 21]]},
'reference': [ { 'key': 'e_1_3_3_2_1',
'doi-asserted-by': 'publisher',
'DOI': '10.7326/0003-4819-145-8-200610170-00139'},
{'key': 'e_1_3_3_3_1', 'doi-asserted-by': 'publisher', 'DOI': '10.1093/infdis/jiu396'},
{ 'key': 'e_1_3_3_4_1',
'unstructured': 'Directorate-General for Health and Food Safety An EU programme of '
'COVID-19 convalescent plasma collection and transfusion: guidance on '
'collection testing processing storage distribution and monitored use. '
'Brussels: european Comission; 2021.'},
{ 'key': 'e_1_3_3_5_1',
'doi-asserted-by': 'publisher',
'DOI': '10.1016/j.mayocp.2020.06.028'},
{'key': 'e_1_3_3_6_1', 'doi-asserted-by': 'publisher', 'DOI': '10.1111/trf.17701'},
{'key': 'e_1_3_3_7_1', 'doi-asserted-by': 'publisher', 'DOI': '10.1136/bmj.m3939'},
{'key': 'e_1_3_3_8_1', 'doi-asserted-by': 'publisher', 'DOI': '10.1001/jama.2020.10044'},
{'key': 'e_1_3_3_9_1', 'doi-asserted-by': 'publisher', 'DOI': '10.1056/NEJMoa2031304'},
{ 'key': 'e_1_3_3_10_1',
'doi-asserted-by': 'publisher',
'DOI': '10.1101/2020.08.12.20169359'},
{ 'key': 'e_1_3_3_11_1',
'doi-asserted-by': 'publisher',
'DOI': '10.1016/S0140-6736(21)00897-7'},
{ 'key': 'e_1_3_3_12_1',
'doi-asserted-by': 'publisher',
'DOI': '10.1371/journal.ppat.1009721'},
{'key': 'e_1_3_3_13_1', 'doi-asserted-by': 'publisher', 'DOI': '10.1038/s41467-021-24285-4'},
{ 'key': 'e_1_3_3_14_1',
'doi-asserted-by': 'publisher',
'DOI': '10.1016/j.tmaid.2020.101949'},
{'key': 'e_1_3_3_15_1', 'doi-asserted-by': 'publisher', 'DOI': '10.1186/s40478-021-01302-7'},
{'key': 'e_1_3_3_16_1', 'doi-asserted-by': 'publisher', 'DOI': '10.1111/vox.13113'},
{ 'key': 'e_1_3_3_17_1',
'volume-title': 'Guide to the preparation, use and quality assurance of blood components',
'author': 'European Directorate for the Quality of Medicines & HealthCare (EDQM)',
'year': '2020',
'unstructured': 'European Directorate for the Quality of Medicines & HealthCare (EDQM). '
'Guide to the preparation, use and quality assurance of blood components. '
'20th ed. Strasbourg: Council of Europe; 2020.',
'edition': '20'},
{ 'key': 'e_1_3_3_18_1',
'doi-asserted-by': 'publisher',
'DOI': '10.1097/CCM.0000000000004817'},
{ 'key': 'e_1_3_3_19_1',
'doi-asserted-by': 'publisher',
'DOI': '10.1016/S1473-3099(20)30483-7'},
{ 'issue': '3',
'key': 'e_1_3_3_20_1',
'first-page': '23',
'article-title': 'Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR',
'volume': '25',
'author': 'Corman VM',
'year': '2020',
'unstructured': 'Corman VM, Landt O, Kaiser M, et\xa0al. Detection of 2019 novel '
'coronavirus (2019-nCoV) by real-time RT-PCR. Euro Surveillance: bulletin '
'Europeen Sur Les Maladies Transmissibles\u2009=\u2009Eur Commun Dis '
'Bull. 2020;25(3):23–30.',
'journal-title': 'Euro Surveillance: bulletin Europeen Sur Les Maladies '
'Transmissibles\u2009=\u2009Eur Commun Dis Bull'},
{'key': 'e_1_3_3_21_1', 'doi-asserted-by': 'publisher', 'DOI': '10.3201/eid2806.220515'},
{'key': 'e_1_3_3_22_1', 'doi-asserted-by': 'publisher', 'DOI': '10.1186/s12859-021-04294-2'},
{ 'issue': '11',
'key': 'e_1_3_3_23_1',
'first-page': '16',
'article-title': 'Serological and molecular findings during SARS-CoV-2 infection: the '
'first case study in Finland, january to february 2020',
'volume': '25',
'author': 'Haveri A',
'year': '2020',
'unstructured': 'Haveri A, Smura T, Kuivanen S, et\xa0al. Serological and molecular '
'findings during SARS-CoV-2 infection: the first case study in Finland, '
'january to february 2020. Euro Surveillance: bulletin Europeen Sur Les '
'Maladies Transmissibles\u2009=\u2009Eur Commun Dis Bull. '
'2020;25(11):16–21.',
'journal-title': 'Euro Surveillance: bulletin Europeen Sur Les Maladies '
'Transmissibles\u2009=\u2009Eur Commun Dis Bull'},
{'key': 'e_1_3_3_24_1', 'doi-asserted-by': 'publisher', 'DOI': '10.3390/v13060996'},
{'key': 'e_1_3_3_25_1', 'doi-asserted-by': 'publisher', 'DOI': '10.3201/eid2712.211631'},
{'key': 'e_1_3_3_26_1', 'doi-asserted-by': 'publisher', 'DOI': '10.3389/fphar.2021.755600'},
{ 'key': 'e_1_3_3_27_1',
'doi-asserted-by': 'publisher',
'DOI': '10.1016/S2213-8587(23)00041-4'},
{'key': 'e_1_3_3_28_1', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.clim.2020.108512'},
{'key': 'e_1_3_3_29_1', 'doi-asserted-by': 'publisher', 'DOI': '10.1128/cmr.00200-21'},
{ 'key': 'e_1_3_3_30_1',
'doi-asserted-by': 'publisher',
'DOI': '10.1146/annurev-med-042921-020956'},
{'key': 'e_1_3_3_31_1', 'doi-asserted-by': 'publisher', 'DOI': '10.1056/NEJMc2119236'},
{ 'key': 'e_1_3_3_32_1',
'doi-asserted-by': 'publisher',
'DOI': '10.1002/14651858.CD013600.pub5'},
{ 'key': 'e_1_3_3_33_1',
'unstructured': 'Bhimraj AMR Shumaker AH Baden L et\xa0al. Infectious Diseases Society of '
'America Guidelines on the Treatment and Management of Patients with '
'COVID-19.: Infectious Diseases Society of America; 2023 [cited 2024 25th '
'Jan]. Available from: '
'https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/.'},
{ 'key': 'e_1_3_3_34_1',
'unstructured': 'National Institutes of Health. COVID-19 Treatment Guidelines Panel. '
'Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. [cited 2024 '
'25th Jan]. Available from: '
'https://www.covid19treatmentguidelines.nih.gov/.'},
{'key': 'e_1_3_3_35_1', 'doi-asserted-by': 'publisher', 'DOI': '10.1093/cid/ciad088'},
{'key': 'e_1_3_3_36_1', 'doi-asserted-by': 'publisher', 'DOI': '10.1056/NEJMoa2033700'},
{'key': 'e_1_3_3_37_1', 'doi-asserted-by': 'publisher', 'DOI': '10.1056/NEJMoa2119657'},
{'key': 'e_1_3_3_38_1', 'doi-asserted-by': 'publisher', 'DOI': '10.1172/JCI155114'},
{'key': 'e_1_3_3_39_1', 'doi-asserted-by': 'publisher', 'DOI': '10.1056/NEJMoa2209502'},
{ 'issue': '8',
'key': 'e_1_3_3_40_1',
'doi-asserted-by': 'crossref',
'first-page': '693',
'DOI': '10.1056/NEJMoa2021436',
'article-title': 'Dexamethasone in hospitalized patients with covid-19',
'volume': '384',
'author': 'Horby P',
'year': '2021',
'unstructured': 'Horby P, Lim WS, Emberson JR, Recovery Collaborative Group., et\xa0al. '
'Dexamethasone in hospitalized patients with covid-19. N Engl J Med. '
'2021;384(8):693–704.',
'journal-title': 'N Engl J Med'},
{ 'key': 'e_1_3_3_41_1',
'doi-asserted-by': 'publisher',
'DOI': '10.1016/j.mayocpiqo.2023.09.001'},
{'key': 'e_1_3_3_42_1', 'doi-asserted-by': 'publisher', 'DOI': '10.1128/mbio.01751-22'},
{ 'issue': '5',
'key': 'e_1_3_3_43_1',
'doi-asserted-by': 'crossref',
'first-page': '381',
'DOI': '10.1080/17476348.2023.2208349',
'article-title': 'Convalescent plasma therapy in COVID-19: unravelling the data using the '
'principles of antibody therapy',
'volume': '17',
'author': 'Casadevall A',
'year': '2023',
'unstructured': 'Casadevall A, Joyner MJ, Pirofski LA, et\xa0al. Convalescent plasma '
'therapy in COVID-19: unravelling the data using the principles of '
'antibody therapy. Expert Rev Respir Med. 2023;17(5):381–395.',
'journal-title': 'Expert Rev Respir Med'},
{'key': 'e_1_3_3_44_1', 'doi-asserted-by': 'publisher', 'DOI': '10.1038/s41467-022-33864-y'},
{'key': 'e_1_3_3_45_1', 'doi-asserted-by': 'publisher', 'DOI': '10.3389/fimmu.2023.1184362'},
{'key': 'e_1_3_3_46_1', 'doi-asserted-by': 'publisher', 'DOI': '10.3390/v14071443'},
{'key': 'e_1_3_3_47_1', 'doi-asserted-by': 'publisher', 'DOI': '10.1126/science.abd4585'}],
'container-title': 'Infectious Diseases',
'original-title': [],
'language': 'en',
'link': [ { 'URL': 'https://www.tandfonline.com/doi/pdf/10.1080/23744235.2024.2329957',
'content-type': 'unspecified',
'content-version': 'vor',
'intended-application': 'similarity-checking'}],
'deposited': { 'date-parts': [[2024, 3, 21]],
'date-time': '2024-03-21T18:42:09Z',
'timestamp': 1711046529000},
'score': 1,
'resource': {'primary': {'URL': 'https://www.tandfonline.com/doi/full/10.1080/23744235.2024.2329957'}},
'subtitle': [],
'short-title': [],
'issued': {'date-parts': [[2024, 3, 21]]},
'references-count': 46,
'alternative-id': ['10.1080/23744235.2024.2329957'],
'URL': 'http://dx.doi.org/10.1080/23744235.2024.2329957',
'relation': {},
'ISSN': ['2374-4235', '2374-4243'],
'subject': [ 'Infectious Diseases', 'Microbiology (medical)', 'General Immunology and Microbiology',
'General Medicine'],
'container-title-short': 'Infectious Diseases',
'published': {'date-parts': [[2024, 3, 21]]},
'assertion': [ { 'value': 'The publishing and review policy for this title is described in its Aims & '
'Scope.',
'order': 1,
'name': 'peerreview_statement',
'label': 'Peer Review Statement'},
{ 'value': 'http://www.tandfonline.com/action/journalInformation?show=aimsScope&journalCode=infd20',
'URL': 'http://www.tandfonline.com/action/journalInformation?show=aimsScope&journalCode=infd20',
'order': 2,
'name': 'aims_and_scope_url',
'label': 'Aim & Scope'},
{ 'value': '2023-12-18',
'order': 0,
'name': 'received',
'label': 'Received',
'group': {'name': 'publication_history', 'label': 'Publication History'}},
{ 'value': '2024-03-08',
'order': 1,
'name': 'accepted',
'label': 'Accepted',
'group': {'name': 'publication_history', 'label': 'Publication History'}},
{ 'value': '2024-03-21',
'order': 2,
'name': 'published',
'label': 'Published',
'group': {'name': 'publication_history', 'label': 'Publication History'}}]}
