Intravenous IgM-enriched immunoglobulins in critical COVID-19: a multicentre propensity-weighted cohort study

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Background

A profound inflammation-mediated lung injury with long-term acute respiratory distress and high mortality is one of the major complications of critical COVID-19. Immunoglobulin M (IgM)-enriched immunoglobulins seem especially capable of mitigating the inflicted inflammatory harm. However, the efficacy of intravenous IgM-enriched preparations in critically ill patients with COVID-19 is largely unclear.

Methods

In this retrospective multicentric cohort study, 316 patients with laboratory-confirmed critical COVID-19 were treated in ten German and Austrian ICUs between May 2020 and April 2021. The primary outcome was 30-day mortality. Analysis was performed by Cox regression models. Covariate adjustment was performed by propensity score weighting using machine learning-based SuperLearner to overcome the selection bias due to missing randomization. In addition, a subgroup analysis focusing on different treatment regimens and patient characteristics was performed.

Results

Of the 316 ICU patients, 146 received IgM-enriched immunoglobulins and 170 cases did not, which served as controls. There was no survival difference between the two groups in terms of mortality at 30 days in the overall cohort (HR _adj: 0.83; 95% CI: 0.55 to 1.25; p = 0.374). An improved 30-day survival in patients without mechanical ventilation at the time of the immunoglobulin treatment did not reach statistical significance (HR _adj: 0.23; 95% CI: 0.05 to 1.08; p = 0.063). Also, no statistically significant difference was observed in the subgroup when a daily dose of ≥ 15 g and a duration of ≥ 3 days of IgM-enriched immunoglobulins were applied (HR _adj: 0.65; 95% CI: 0.41 to 1.03; p = 0.068).

Conclusions

Although we cannot prove a statistically reliable effect of intravenous IgM-enriched immunoglobulins, the confidence intervals may suggest a clinically relevant effect in certain subgroups. Here, an early administration (i.e. in critically ill but not yet mechanically ventilated COVID-19 patients) and a dose of ≥ 15 g for at least 3 days may confer beneficial effects without concerning safety issues. However, these findings need to be validated in upcoming randomized clinical trials.

Trial registration DRKS00025794, German Clinical Trials Register, https://www.drks.de. Registered 6 July 2021.

Supplementary Information

The online version contains supplementary material available at 10.1186/s13054-022-04059-0.

Related collections

Most cited references 35

Record: found
Abstract: found
Article: not found

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Fei Zhou, Ting Yu, Ronghui Du … (2020)

Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64–128·55; p=0·0033) on admission. Median duration of viral shedding was 20·0 days (IQR 17·0–24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors. The longest observed duration of viral shedding in survivors was 37 days. Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

0 comments Cited 13471 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support.

Paul A. Harris, Robert Taylor, Robert Thielke … (2009)

Research electronic data capture (REDCap) is a novel workflow methodology and software solution designed for rapid development and deployment of electronic data capture tools to support clinical and translational research. We present: (1) a brief description of the REDCap metadata-driven software toolset; (2) detail concerning the capture and use of study-related metadata from scientific research teams; (3) measures of impact for REDCap; (4) details concerning a consortium network of domestic and international institutions collaborating on the project; and (5) strengths and limitations of the REDCap system. REDCap is currently supporting 286 translational research projects in a growing collaborative network including 27 active partner institutions.

0 comments Cited 9856 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Dexamethasone in Hospitalized Patients with Covid-19 — Preliminary Report

Mark Peters (2020)

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.)

0 comments Cited 4859 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Tim Rahmel: Tim.Rahmel@ruhr-uni-bochum.de

Journal

Journal ID (nlm-ta): Crit Care

Title: Critical Care

Publisher: BioMed Central (London )

ISSN (Print): 1364-8535

ISSN (Electronic): 1466-609X

Publication date (Electronic): 7 July 2022

Publication date PMC-release: 7 July 2022

Publication date Collection: 2022

Volume: 26

Electronic Location Identifier: 204

Affiliations

[1 ]GRID grid.465549.f, ISNI 0000 0004 0475 9903, Klinik Für Anästhesiologie, Intensivmedizin Und Schmerztherapie, , Universitätsklinikum Knappschaftskrankenhaus Bochum, ; 44892 Bochum, Germany

[2 ]GRID grid.22937.3d, ISNI 0000 0000 9259 8492, Klinische Abteilung Für Allgemeine Anästhesie Und Intensivmedizin, , Medizinische Universität Wien, ; Währinger Gürtel 18-20, 1090 Vienna, Austria

[3 ]GRID grid.459629.5, ISNI 0000 0004 0389 4214, Klinik Für Innere Medizin IV, Klinikum Chemnitz gGmbH, ; Flemmingstraße 2, 09116 Chemnitz, Germany

[4 ]GRID grid.14778.3d, ISNI 0000 0000 8922 7789, Klinik Für Anästhesiologie Und Intensivmedizin, , Universitätsklinikum Düsseldorf, ; Moorenstr. 5, 40225 Düsseldorf, Germany

[5 ]GRID grid.7839.5, ISNI 0000 0004 1936 9721, Klinik Für Anästhesiologie, Intensivmedizin Und Schmerztherapie Universitätsklinikum Frankfurt, , Goethe Universität, ; Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany

[6 ]GRID grid.13648.38, ISNI 0000 0001 2180 3484, Klinik Für Intensivmedizin, , Universitätsklinikum Hamburg-Eppendorf, ; Martinistraße 52, 20246 Hamburg, Germany

[7 ]GRID grid.5253.1, ISNI 0000 0001 0328 4908, Klinik Für Anästhesiologie, , Universitätsklinikum Heidelberg, ; Im Neuenheimer Feld 420, 69120 Heidelberg, Germany

[8 ]GRID grid.411544.1, ISNI 0000 0001 0196 8249, Klinik Für Anästhesiologie Und Intensivmedizin, , Universitätsklinikum Tübingen, ; Hoppe-Seyler-Str. 3, 72076 Tübingen, Germany

[9 ]GRID grid.5570.7, ISNI 0000 0004 0490 981X, Abteilung Für Medizinische Informatik, Biometrie Und Epidemiologie, , Ruhr-Universität Bochum, ; Universitätsstraße 105, 44789 Bochum, Germany

[10 ]GRID grid.4488.0, ISNI 0000 0001 2111 7257, Klinik Und Poliklinik Für Anästhesiologie Und Intensivtherapie, Universitätsklinikum Carl Gustav Carus Dresden, , Technische Universität Dresden, ; Fetscherstraße 74, 01307 Dresden, Germany

[11 ]GRID grid.420022.6, ISNI 0000 0001 0723 5126, Abteilung Für Anästhesiologie Und Intensivmedizin, AUVA Traumazentrum Wien, ; Kundratstraße 37, 1120 Vienna, Austria

[12 ]GRID grid.411760.5, ISNI 0000 0001 1378 7891, Klinik Und Poliklinik Für Anästhesiologie, Intensivmedizin, Notfallmedizin Und Schmerztherapie, , Universitätsklinikum Würzburg, ; Oberdürrbacher Str. 6, 97080 Würzburg, Germany

Article

Publisher ID: 4059

DOI: 10.1186/s13054-022-04059-0

PMC ID: 9260992

PubMed ID: 35799196

SO-VID: 62d9cd3c-371e-4b64-8345-7fe72c0bb847

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 22 April 2022

Date accepted : 13 June 2022

Funding

Funded by: Universitätsklinikum der Ruhr-Universität Bochum (1007)

Open Access :

Open Access funding enabled and organized by Projekt DEAL.

Custom metadata

ScienceOpen disciplines: Emergency medicine & Trauma

Keywords: immunoglobulins,immunoglobulin m,covid-19,coronavirus disease,sars-cov-2

Data availability:

ScienceOpen disciplines: Emergency medicine & Trauma

Keywords: immunoglobulins, immunoglobulin m, covid-19, coronavirus disease, sars-cov-2

Intravenous IgM-enriched immunoglobulins in critical COVID-19: a multicentre propensity-weighted cohort study

Read this article at

Abstract

Background

Methods

Results

Conclusions

Supplementary Information

Related collections

Novel Coronavirus Disease COVID-19

Most cited references 35

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support.

Dexamethasone in Hospitalized Patients with Covid-19 — Preliminary Report

Author and article information

Contributors

Journal

Affiliations

Article

History

Funding

Categories

Custom metadata

Comments

Comment on this article

Similar content 184

Cited by 3

Most referenced authors 1,048