Early high antibody titre convalescent plasma for hospitalised COVID-19 patients: DAWn-plasma

DOI record: { "DOI": "10.1183/13993003.01724-2021", "ISSN": [ "0903-1936", "1399-3003" ], "URL": "http://dx.doi.org/10.1183/13993003.01724-2021", "abstract": "<jats:sec><jats:title>Background</jats:title><jats:p>Several randomised clinical trials have studied convalescent plasma for coronavirus disease 2019 (COVID-19) using different protocols, with different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralising antibody titres, at different time-points and severities of illness.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>In the prospective multicentre DAWn-plasma trial, adult patients hospitalised with COVID-19 were randomised to 4 units of open-label convalescent plasma combined with standard of care (intervention group) or standard of care alone (control group). Plasma from donors with neutralising antibody titres (50% neutralisation titre (NT<jats:sub>50</jats:sub>)) ≥1/320 was the product of choice for the study.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Between 2 May 2020 and 26 January 2021, 320 patients were randomised to convalescent plasma and 163 patients to the control group according to a 2:1 allocation scheme. A median (interquartile range) volume of 884 (806–906) mL) convalescent plasma was administered and 80.68% of the units came from donors with neutralising antibody titres (NT<jats:sub>50</jats:sub>) ≥1/320. Median time from onset of symptoms to randomisation was 7 days. The proportion of patients alive and free of mechanical ventilation on day 15 was not different between both groups (convalescent plasma 83.74% (n=267) <jats:italic>versus</jats:italic> control 84.05% (n=137)) (OR 0.99, 95% CI 0.59–1.66; p=0.9772). The intervention did not change the natural course of antibody titres. The number of serious or severe adverse events was similar in both study arms and transfusion-related side-effects were reported in 19 out of 320 patients in the intervention group (5.94%).</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Transfusion of 4 units of convalescent plasma with high neutralising antibody titres early in hospitalised COVID-19 patients did not result in a significant improvement of clinical status or reduced mortality.</jats:p></jats:sec>", "alternative-id": [ "10.1183/13993003.01724-2021" ], "author": [ { "affiliation": [], "family": "Devos", "given": "Timothy", "sequence": "first" }, { "ORCID": "http://orcid.org/0000-0003-3260-280X", "affiliation": [], "authenticated-orcid": false, "family": "Van Thillo", "given": "Quentin", "sequence": "additional" }, { "affiliation": [], "family": "Compernolle", "given": "Veerle", "sequence": "additional" }, { "affiliation": [], "family": "Najdovski", "given": "Tomé", "sequence": "additional" }, { 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WHO coronavirus (COVID-19) dashboard with vaccination data. 2021. https://covid19.who.int Date last accessed: 16 July 2021." }, { "DOI": "10.1001/jama.2020.4031", "article-title": "Critical care utilization for the COVID-19 outbreak in Lombardy, Italy: early experience and forecast during an emergency response", "author": "Grasselli", "doi-asserted-by": "crossref", "first-page": "1545", "journal-title": "JAMA", "key": "2022021001300748000_59.2.2101724.2", "volume": "323", "year": "2020" }, { "DOI": "10.1016/S1473-3099(20)30243-7", "doi-asserted-by": "publisher", "key": "2022021001300748000_59.2.2101724.3" }, { "DOI": "10.1016/j.lanepe.2020.100019", "article-title": "The role of organizational characteristics on the outcome of COVID-19 patients admitted to the ICU in Belgium", "author": "Taccone", "doi-asserted-by": "crossref", "first-page": "100019", "journal-title": "Lancet Reg Health Eur", "key": "2022021001300748000_59.2.2101724.4", "volume": "2", "year": "2021" }, { "DOI": "10.1056/NEJMoa2021436", "doi-asserted-by": "publisher", "key": "2022021001300748000_59.2.2101724.5" }, { "article-title": "Interleukin-6 receptor antagonists in critically ill patients with Covid-19", "first-page": "1491", "journal-title": "N Engl J Med", "key": "2022021001300748000_59.2.2101724.6", "volume": "84", "year": "2021" }, { "DOI": "10.1056/NEJMoa2030340", "doi-asserted-by": "publisher", "key": "2022021001300748000_59.2.2101724.7" }, { "DOI": "10.1056/nejmoa2101643", "doi-asserted-by": "publisher", "key": "2022021001300748000_59.2.2101724.8" }, { "DOI": "10.1056/NEJMoa2007764", "doi-asserted-by": "publisher", "key": "2022021001300748000_59.2.2101724.9" }, { "DOI": "10.1056/NEJMoa2023184", "doi-asserted-by": "publisher", "key": "2022021001300748000_59.2.2101724.10" }, { "DOI": "10.1016/j.cmi.2021.02.029", "article-title": "A real-life setting evaluation of the effect of remdesivir on viral load in COVID-19 patients admitted to a large tertiary centre in Israel", "author": "Goldberg", "doi-asserted-by": "crossref", "first-page": "917.e1", "journal-title": "Clin Microbiol Infect", "key": "2022021001300748000_59.2.2101724.11", "volume": "27", "year": "2021" }, { "DOI": "10.1136/bmj.m3939", "doi-asserted-by": "publisher", "key": "2022021001300748000_59.2.2101724.12" }, { "DOI": "10.1056/NEJMoa2031304", "doi-asserted-by": "publisher", "key": "2022021001300748000_59.2.2101724.13" }, { "DOI": "10.1038/s41467-021-23469-2", "article-title": "Effects of potent neutralizing antibodies from convalescent plasma in patients hospitalized for severe SARS-CoV-2 infection", "author": "Gharbharan", "doi-asserted-by": "crossref", "first-page": "3189", "journal-title": "Nat Commun", "key": "2022021001300748000_59.2.2101724.14", "volume": "12", "year": "2020" }, { "DOI": "10.1056/NEJMoa2033700", "doi-asserted-by": "publisher", "key": "2022021001300748000_59.2.2101724.15" }, { "DOI": "10.1001/jama.2021.2747", "article-title": "Association of convalescent plasma treatment with clinical outcomes in patients with COVID-19: a systematic review and meta-analysis", "author": "Janiaud", "doi-asserted-by": "crossref", "first-page": "1185", "journal-title": "JAMA", "key": "2022021001300748000_59.2.2101724.16", "volume": "325", "year": "2021" }, { "DOI": "10.1056/NEJMoa2031893", "doi-asserted-by": "publisher", "key": "2022021001300748000_59.2.2101724.17" }, { "DOI": "10.1186/s13063-020-04876-0", "article-title": "A randomized, multicentre, open-label phase II proof-of-concept trial investigating the clinical efficacy and safety of the addition of convalescent plasma to the standard of care in patients hospitalized with COVID-19: the Donated Antibodies Working against nCoV (DAWn-Plasma) trial", "author": "Devos", "doi-asserted-by": "crossref", "first-page": "981", "journal-title": "Trials", "key": "2022021001300748000_59.2.2101724.18", "volume": "21", "year": "2020" }, { "DOI": "10.2307/2291635", "doi-asserted-by": "publisher", "key": "2022021001300748000_59.2.2101724.19" }, { "DOI": "10.1016/s0140-6736(21)00897-7", "doi-asserted-by": "publisher", "key": "2022021001300748000_59.2.2101724.20" }, { "DOI": "10.1172/JCI150646", "article-title": "A randomized double-blind controlled trial of convalescent plasma in adults with severe COVID-19", "author": "O'Donnell", "doi-asserted-by": "crossref", "first-page": "e150646", "journal-title": "J Clin Invest", "key": "2022021001300748000_59.2.2101724.21", "volume": "131", "year": "2021" }, { "DOI": "10.1111/bjh.17266", "article-title": "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", "author": "Betrains", "doi-asserted-by": "crossref", "first-page": "1100", "journal-title": "Br J Haematol", "key": "2022021001300748000_59.2.2101724.22", "volume": "192", "year": "2021" }, { "DOI": "10.1182/blood.2020008423", "article-title": "Convalescent plasma therapy for B-cell-depleted patients with protracted COVID-19", "author": "Hueso", "doi-asserted-by": "crossref", "first-page": "2290", "journal-title": "Blood", "key": "2022021001300748000_59.2.2101724.23", "volume": "136", "year": "2020" } ], "reference-count": 23, "references-count": 23, "relation": {}, "resource": { "primary": { "URL": "http://erj.ersjournals.com/lookup/doi/10.1183/13993003.01724-2021" } }, "score": 1, "short-title": [], "source": "Crossref", "subject": [ "Pulmonary and Respiratory Medicine" ], "subtitle": [], "title": "Early high antibody titre convalescent plasma for hospitalised COVID-19 patients: DAWn-plasma", "type": "journal-article", "update-policy": "http://dx.doi.org/10.1183/ers-crossmark-policy", "volume": "59" }