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

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Abstract

Background

Several randomised clinical trials have studied convalescent plasma (CP) for COVID-19 using different protocols, with different SARS-CoV-2 neutralising-antibody-titres, at different time-points and severities of illness.

Methods

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 (NT50) ≥1/320 was the product of choice for the study.

Results

Between May 2nd, 2020 and January 26th, 2021, 320 patients were randomised to convalescent plasma and 163 patients to the control group according to a 2:1 allocation scheme. A median volume of 884 mL convalescent plasma (IQR 806–906 mL) was administered, and 80.68% of the units came from donors with neutralising-antibody-titres (NT50) ≥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) versus control: 84.05% (n=137) – Odds ratio 0.99 (0.59–1.66) – p-value=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 19/320 patients in the intervention group (5.94%).

Conclusions

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 the clinical status, or a reduced mortality.

Abstract

Early transfusion of 4 units of high neutralising-antibody-titre convalescent plasma in hospitalised COVID-19 patients does not reduce mortality or the need for mechanical ventilation.

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Most cited references 23

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Dexamethasone in Hospitalized Patients with Covid-19 — Preliminary Report

Mark Peters (2021)

Abstract Background Coronavirus disease 2019 (Covid-19) is associated with diffuse lung damage. Glucocorticoids may modulate inflammation-mediated lung injury and thereby reduce progression to respiratory failure and death. Methods In this controlled, open-label trial comparing a range of possible treatments in patients who were hospitalized with Covid-19, we randomly assigned patients to receive oral or intravenous dexamethasone (at a dose of 6 mg once daily) for up to 10 days or to receive usual care alone. The primary outcome was 28-day mortality. Here, we report the preliminary results of this comparison. Results A total of 2104 patients were assigned to receive dexamethasone and 4321 to receive usual care. Overall, 482 patients (22.9%) in the dexamethasone group and 1110 patients (25.7%) in the usual care group died within 28 days after randomization (age-adjusted rate ratio, 0.83; 95% confidence interval [CI], 0.75 to 0.93; P<0.001). The proportional and absolute between-group differences in mortality varied considerably according to the level of respiratory support that the patients were receiving at the time of randomization. In the dexamethasone group, the incidence of death was lower than that in the usual care group among patients receiving invasive mechanical ventilation (29.3% vs. 41.4%; rate ratio, 0.64; 95% CI, 0.51 to 0.81) and among those receiving oxygen without invasive mechanical ventilation (23.3% vs. 26.2%; rate ratio, 0.82; 95% CI, 0.72 to 0.94) but not among those who were receiving no respiratory support at randomization (17.8% vs. 14.0%; rate ratio, 1.19; 95% CI, 0.91 to 1.55). Conclusions In patients hospitalized with Covid-19, the use of dexamethasone resulted in lower 28-day mortality among those who were receiving either invasive mechanical ventilation or oxygen alone at randomization but not among those receiving no respiratory support. (Funded by the Medical Research Council and National Institute for Health Research and others; RECOVERY ClinicalTrials.gov number, NCT04381936; ISRCTN number, 50189673.)

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Remdesivir for the Treatment of Covid-19 — Final Report

John H. Beigel, Kay Tomashek, Lori Dodd … (2022)

Abstract Background Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), none have yet been shown to be efficacious. Methods We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults hospitalized with Covid-19 with evidence of lower respiratory tract involvement. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only. Results A total of 1063 patients underwent randomization. The data and safety monitoring board recommended early unblinding of the results on the basis of findings from an analysis that showed shortened time to recovery in the remdesivir group. Preliminary results from the 1059 patients (538 assigned to remdesivir and 521 to placebo) with data available after randomization indicated that those who received remdesivir had a median recovery time of 11 days (95% confidence interval [CI], 9 to 12), as compared with 15 days (95% CI, 13 to 19) in those who received placebo (rate ratio for recovery, 1.32; 95% CI, 1.12 to 1.55; P<0.001). The Kaplan-Meier estimates of mortality by 14 days were 7.1% with remdesivir and 11.9% with placebo (hazard ratio for death, 0.70; 95% CI, 0.47 to 1.04). Serious adverse events were reported for 114 of the 541 patients in the remdesivir group who underwent randomization (21.1%) and 141 of the 522 patients in the placebo group who underwent randomization (27.0%). Conclusions Remdesivir was superior to placebo in shortening the time to recovery in adults hospitalized with Covid-19 and evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACTT-1 ClinicalTrials.gov number, NCT04280705.)

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Estimates of the severity of coronavirus disease 2019: a model-based analysis

Robert Verity, Lucy C Okell, Ilaria Dorigatti … (2020)

Summary Background In the face of rapidly changing data, a range of case fatality ratio estimates for coronavirus disease 2019 (COVID-19) have been produced that differ substantially in magnitude. We aimed to provide robust estimates, accounting for censoring and ascertainment biases. Methods We collected individual-case data for patients who died from COVID-19 in Hubei, mainland China (reported by national and provincial health commissions to Feb 8, 2020), and for cases outside of mainland China (from government or ministry of health websites and media reports for 37 countries, as well as Hong Kong and Macau, until Feb 25, 2020). These individual-case data were used to estimate the time between onset of symptoms and outcome (death or discharge from hospital). We next obtained age-stratified estimates of the case fatality ratio by relating the aggregate distribution of cases to the observed cumulative deaths in China, assuming a constant attack rate by age and adjusting for demography and age-based and location-based under-ascertainment. We also estimated the case fatality ratio from individual line-list data on 1334 cases identified outside of mainland China. Using data on the prevalence of PCR-confirmed cases in international residents repatriated from China, we obtained age-stratified estimates of the infection fatality ratio. Furthermore, data on age-stratified severity in a subset of 3665 cases from China were used to estimate the proportion of infected individuals who are likely to require hospitalisation. Findings Using data on 24 deaths that occurred in mainland China and 165 recoveries outside of China, we estimated the mean duration from onset of symptoms to death to be 17·8 days (95% credible interval [CrI] 16·9–19·2) and to hospital discharge to be 24·7 days (22·9–28·1). In all laboratory confirmed and clinically diagnosed cases from mainland China (n=70 117), we estimated a crude case fatality ratio (adjusted for censoring) of 3·67% (95% CrI 3·56–3·80). However, after further adjusting for demography and under-ascertainment, we obtained a best estimate of the case fatality ratio in China of 1·38% (1·23–1·53), with substantially higher ratios in older age groups (0·32% [0·27–0·38] in those aged <60 years vs 6·4% [5·7–7·2] in those aged ≥60 years), up to 13·4% (11·2–15·9) in those aged 80 years or older. Estimates of case fatality ratio from international cases stratified by age were consistent with those from China (parametric estimate 1·4% [0·4–3·5] in those aged <60 years [n=360] and 4·5% [1·8–11·1] in those aged ≥60 years [n=151]). Our estimated overall infection fatality ratio for China was 0·66% (0·39–1·33), with an increasing profile with age. Similarly, estimates of the proportion of infected individuals likely to be hospitalised increased with age up to a maximum of 18·4% (11·0–7·6) in those aged 80 years or older. Interpretation These early estimates give an indication of the fatality ratio across the spectrum of COVID-19 disease and show a strong age gradient in risk of death. Funding UK Medical Research Council.

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Author and article information

Journal

Journal ID (nlm-ta): Eur Respir J

Journal ID (iso-abbrev): Eur Respir J

Journal ID (publisher-id): ERJ

Journal ID (hwp): erj

Title: The European Respiratory Journal

Publisher: European Respiratory Society

ISSN (Print): 0903-1936

ISSN (Electronic): 1399-3003

Publication date (Electronic): 26 August 2021

Publication date PMC-release: 26 August 2021

Electronic Location Identifier: 2101724

Affiliations

[1 ]Department of Hematology, University Hospitals Leuven and Department of Microbiology and Immunology, Laboratory of Molecular Immunology (Rega Institute), KU Leuven, Leuven, Belgium

[2 ]Center for Cancer Biology, Vlaams Instituut voor Biotechnologie (VIB), Leuven and Center for Human Genetics, KU Leuven, Leuven, Belgium

[3 ]Belgian Red Cross, Blood Services, Mechelen, Belgium. Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium

[4 ]Belgian Red Cross, Service du Sang, Namur, Belgium

[5 ]Immune Response Service; Infectious Diseases in Humans Scientific Directorate, Sciensano, Brussels, Belgium

[6 ]Department of Infectious Diseases, CHU Saint-Pierre, Universite Libre de Bruxelles (ULB), School of Public Health, Universite Libre de Bruxelles (ULB), Institute for Medical Immunology, Universite Libre de Bruxelles (ULB), Belgium

[7 ]Department of Anesthesiology and Intensive Care Medicine, and Department of Infectious diseases, CHC Mont Legia, Liege, Belgium

[8 ]Department of Pulmonary Medicine, AZ Groeninge, Kortrijk, Belgium

[9 ]Department of Infectious Diseases, Brugmann University Hospital, Brussels, Belgium

[10 ]Department of Respiratory Medicine, AZ Maria Middelares Gent, Ghent, Belgium. Department of Respiratory Medicine, AZ Sint-Vincentius Deinze, Deinze, Belgium

[11 ]Department of Infectious Diseases and Internal Medicine, UZ Brussel Hospital, Brussels, Belgium

[12 ]Department of Internal Medicine and Infectious Diseases, Centre Hospitalier Regional (CHR), Liege, Belgium

[13 ]Infectious Diseases and General Internal Medicine, CHU de Liege, ULiege, Belgium

[14 ]Department of Intensive Care Medicine, Ziekenhuis Netwerk Antwerpen Campus Stuivenberg, Antwerp, Belgium

[15 ]Virology Unit, Institute of Tropical Medicine Antwerp, Antwerp and Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium

[16 ]National Influenza Centre, Sciensano, Brussels, Belgium

[17 ]Department of General Internal Medicine, University Hospitals Leuven, Leuven and Department of Microbiology, Immunology, and Transplantation, KU Leuven, Leuven, Belgium

[18 ]University of Liege, Faculty of Veterinary Medicine, Animal Pathology, Liege, Belgium

[19 ]Department of Cardiovascular Sciences, UZ and KU Leuven, Belgium

[20 ]Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Department CHROMETA, KU Leuven, Respiratory Diseases UZ Leuven, Leuven, Belgium

[21 ]KU Leuven, Rega Institute for Medical Research, Clinical and Epidemiological Virology, Leuven, Belgium

[22 ]Department of Haematology, Ghent University Hospital, Ghent, Belgium

[23 ]Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium

[24 ]I-BioStat, KU Leuven, Leuven, Belgium and University Hasselt, Hasselt, Belgium

[25 ]Department of Intensive Care Medicine, University Hospitals Leuven, and Department of Cellular and Molecular Medicine, Laboratory of Intensive Care Medicine, KU Leuven, Leuven, Belgium

[26 ]The DAWn-plasma investigators are: Georgala Aspasia; Nina Bijnens; Kris Bogaerts; Bernard Bouckaert; Helga Ceunen; Myriam Cleeren; Jan Cools; Kristof Cuppens; Barbara Debaveye; Melanie Delvallee; Paul De Munter; Daniel Desmecht, Elke Govaerts; David Grimaldi; Wim Janssens; Johan Neyts; Jill Pannecoucke; Elisabeth Porcher; Camelia Rossi; Thomas Van Assche; Katleen Vandenberghe; Emmanuel Van der Hauwaert; Steven Vanderschueren; Eric Van Wijngaerden; Geert Verbeke; Clothilde Visee; Robin Vos; Jean Cyr Yombi.

Author notes

Corresponding author: Geert Meyfroidt ( geert.meyfroidt@ 123456uzleuven.be )

Author information

Quentin Van Thillo https://orcid.org/0000-0003-3260-280X

Iwein Gyselinck https://orcid.org/0000-0002-4068-7228

Laurens Liesenborghs https://orcid.org/0000-0001-5616-8548

Peter Verhamme https://orcid.org/0000-0001-8698-2858

Article

Publisher ID: ERJ-01724-2021

DOI: 10.1183/13993003.01724-2021

PMC ID: 8576805

PubMed ID: 34446469

SO-VID: 9bab79bc-47ed-40f5-8b48-fb729c8d46d0

License:

This version is distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0. For commercial reproduction rights and permissions contact permissions@ersnet.org

History

Date received : 17 June 2021

Date accepted : 24 July 2021

Funding

Funded by: Fonds Wetenschappelijk Onderzoek , open-funder-registry 10.13039/501100003130;

Award ID: 1843118N

Funded by: Belgian Health Care Knowledge Centre (KCE)

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

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Abstract

Background

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Abstract

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European Respiratory Society: COVID-19

Most cited references 23

Dexamethasone in Hospitalized Patients with Covid-19 — Preliminary Report

Remdesivir for the Treatment of Covid-19 — Final Report

Estimates of the severity of coronavirus disease 2019: a model-based analysis

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