Key summary of German national treatment guidance for hospitalized COVID-19 patients : Key pharmacologic recommendations from a national German living guideline using an Evidence to Decision Framework (last updated 17.05.2021)

Jakob J Malin¹, Christoph D Spinner², Uwe Janssens³, Tobias Welte⁴, Steffen Weber-Carstens⁵, Gereon Schälte⁶, Petra Gastmeier⁷, Florian Langer⁸, Martin Wepler⁹, Michael Westhoff¹⁰, Michael Pfeifer^{11

12}, Klaus F Rabe¹³, Florian Hoffmann¹⁴, Bernd W Böttiger¹⁵, Julia Weinmann-Menke¹⁶, Alexander Kersten¹⁷, Peter Berlit¹⁸, Marcin Krawczyk¹⁹, Wiebke Nehls²⁰, Falk Fichtner²¹, Sven Laudi²¹, Miriam Stegemann²², Nicole Skoetz²³, Monika Nothacker²⁴, Gernot Marx²⁵, Christian Karagiannidis²⁶, Stefan Kluge²⁷

Affiliations

¹ Division of Infectious Diseases, Department I of Internal Medicine, University of Cologne, Cologne, Germany. jakob.malin@uk-koeln.de.
² Department of Internal Medicine II, School of Medicine, Technical University of Munich, University Hospital Rechts Der Isar, Munich, Germany.
³ Medical Clinic and Medical Intensive Care Medicine, St Antonius Hospital, Eschweiler, Germany.
⁴ Department of Respiratory Medicine and German Centre of Lung Research (DZL), Hannover Medical School, Hannover, Germany.
⁵ Department of Anesthesiology and Operative Intensive Care Medicine (CCM/CVK), Charité-Universitätsmedizin Berlin, Berlin, Germany.
⁶ Department of Anaesthesiology, Medical Faculty Aachen, Rhenish Westphalian Technical University (RWTH), Aachen, Germany.
⁷ Institute of Hygiene and Environmental Medicine, Charité-University Medicine, Berlin, Germany.
⁸ Department of Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
⁹ Department of Anesthesiology and Intensive Care Medicine, University Hospital Ulm, Ulm, Germany.
¹⁰ Department of Pneumology, Intensive Care and Sleep Medicine, Hemer Lung Clinic Centre of Pneumology and Thoracic Surgery, 58675, Hemer, Germany.
¹¹ Department of Internal Medicine II, University Hospital Regensburg, Regensburg, Germany.
¹² Department of Pneumology, Donaustauf Hospital, Donaustauf, Germany.
¹³ LungenClinic Grosshansdorf, Airway Research Centre North, German Centre for Lung Research, Grosshansdorf, Germany.
¹⁴ Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, Ludwig-Maximilians-University Munich, Munich, Germany.
¹⁵ Department of Anesthesiology and Intensive Care Medicine, Medical Faculty and University Hospital Cologne, University of Cologne, Cologne, Germany.
¹⁶ Division of Nephrology, Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
¹⁷ Department of Cardiology, Angiology and Intensive Care, Medical Faculty RWTH Aachen, Aachen, Germany.
¹⁸ Germany German Society of Neurology, Berlin, Germany.
¹⁹ Department of Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany.
²⁰ Department of Palliative Care and Geriatric Medicine, Helios Clinic Emil Von Behring, Berlin, Germany.
²¹ Department of Anesthesiology and Intensive Care, University Hospital of Leipzig, Leipzig, Germany.
²² Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany.
²³ Evidence-Based Oncology, Department I of Internal Medicine and Center for Integrated Oncology Aachen Bonn Cologne Dusseldorf, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany.
²⁴ Institute for Medical Knowledge Management, Association of the Scientific Medical Societies (AWMF), Universität Marburg, Marburg, Germany.
²⁵ Department of Intensive Care Medicine and Intermediate Care, Medical Faculty, University Hospital RWTH Aachen, Aachen, Germany.
²⁶ Department of Pneumology and Critical Care Medicine, Cologne-Merheim Hospital, ARDS and ECMO Centre, Kliniken Der Stadt Köln, Witten/Herdecke University Hospital, Cologne, Germany.
²⁷ Department of Intensive Care, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

PMID: 34228347
PMCID: PMC8259552
DOI: 10.1007/s15010-021-01645-2

Key summary of German national treatment guidance for hospitalized COVID-19 patients : Key pharmacologic recommendations from a national German living guideline using an Evidence to Decision Framework (last updated 17.05.2021)

Jakob J Malin et al. Infection. 2022 Feb.

. 2022 Feb;50(1):93-106.

doi: 10.1007/s15010-021-01645-2. Epub 2021 Jul 6.

Authors

Affiliations

¹ Division of Infectious Diseases, Department I of Internal Medicine, University of Cologne, Cologne, Germany. jakob.malin@uk-koeln.de.
² Department of Internal Medicine II, School of Medicine, Technical University of Munich, University Hospital Rechts Der Isar, Munich, Germany.
³ Medical Clinic and Medical Intensive Care Medicine, St Antonius Hospital, Eschweiler, Germany.
⁴ Department of Respiratory Medicine and German Centre of Lung Research (DZL), Hannover Medical School, Hannover, Germany.
⁵ Department of Anesthesiology and Operative Intensive Care Medicine (CCM/CVK), Charité-Universitätsmedizin Berlin, Berlin, Germany.
⁶ Department of Anaesthesiology, Medical Faculty Aachen, Rhenish Westphalian Technical University (RWTH), Aachen, Germany.
⁷ Institute of Hygiene and Environmental Medicine, Charité-University Medicine, Berlin, Germany.
⁸ Department of Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
⁹ Department of Anesthesiology and Intensive Care Medicine, University Hospital Ulm, Ulm, Germany.
¹⁰ Department of Pneumology, Intensive Care and Sleep Medicine, Hemer Lung Clinic Centre of Pneumology and Thoracic Surgery, 58675, Hemer, Germany.
¹¹ Department of Internal Medicine II, University Hospital Regensburg, Regensburg, Germany.
¹² Department of Pneumology, Donaustauf Hospital, Donaustauf, Germany.
¹³ LungenClinic Grosshansdorf, Airway Research Centre North, German Centre for Lung Research, Grosshansdorf, Germany.
¹⁴ Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, Ludwig-Maximilians-University Munich, Munich, Germany.
¹⁵ Department of Anesthesiology and Intensive Care Medicine, Medical Faculty and University Hospital Cologne, University of Cologne, Cologne, Germany.
¹⁶ Division of Nephrology, Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
¹⁷ Department of Cardiology, Angiology and Intensive Care, Medical Faculty RWTH Aachen, Aachen, Germany.
¹⁸ Germany German Society of Neurology, Berlin, Germany.
¹⁹ Department of Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany.
²⁰ Department of Palliative Care and Geriatric Medicine, Helios Clinic Emil Von Behring, Berlin, Germany.
²¹ Department of Anesthesiology and Intensive Care, University Hospital of Leipzig, Leipzig, Germany.
²² Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany.
²³ Evidence-Based Oncology, Department I of Internal Medicine and Center for Integrated Oncology Aachen Bonn Cologne Dusseldorf, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany.
²⁴ Institute for Medical Knowledge Management, Association of the Scientific Medical Societies (AWMF), Universität Marburg, Marburg, Germany.
²⁵ Department of Intensive Care Medicine and Intermediate Care, Medical Faculty, University Hospital RWTH Aachen, Aachen, Germany.
²⁶ Department of Pneumology and Critical Care Medicine, Cologne-Merheim Hospital, ARDS and ECMO Centre, Kliniken Der Stadt Köln, Witten/Herdecke University Hospital, Cologne, Germany.
²⁷ Department of Intensive Care, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

PMID: 34228347
PMCID: PMC8259552
DOI: 10.1007/s15010-021-01645-2

Erratum in

Correction to: Key summary of German national treatment guidance for hospitalized COVID‑19 patients : Key pharmacologic recommendations from a national German living guideline using an Evidence to Decision Framework (last updated 17.05.2021).
Malin JJ, Spinner CD, Janssens U, Welte T, Weber-Carstens S, Schälte G, Gastmeier P, Langer F, Wepler M, Westhoff M, Pfeifer M, Rabe KF, Hoffmann F, Böttiger BW, Weinmann-Menke J, Kersten A, Berlit P, Krawczyk M, Nehls W, Fichtner F, Laudi S, Stegemann M, Skoetz N, Nothacker M, Marx G, Karagiannidis C, Kluge S. Malin JJ, et al. Infection. 2022 Feb;50(1):107-108. doi: 10.1007/s15010-021-01665-y. Infection. 2022. PMID: 34414563 Free PMC article. No abstract available.

Abstract

Purpose: This executive summary of a national living guideline aims to provide rapid evidence based recommendations on the role of drug interventions in the treatment of hospitalized patients with COVID-19.

Methods: The guideline makes use of a systematic assessment and decision process using an evidence to decision framework (GRADE) as recommended standard WHO (2021). Recommendations are consented by an interdisciplinary panel. Evidence analysis and interpretation is supported by the CEOsys project providing extensive literature searches and living (meta-) analyses. For this executive summary, selected key recommendations on drug therapy are presented including the quality of the evidence and rationale for the level of recommendation.

Results: The guideline contains 11 key recommendations for COVID-19 drug therapy, eight of which are based on systematic review and/or meta-analysis, while three recommendations represent consensus expert opinion. Based on current evidence, the panel makes strong recommendations for corticosteroids (WHO scale 5-9) and prophylactic anticoagulation (all hospitalized patients with COVID-19) as standard of care. Intensified anticoagulation may be considered for patients with additional risk factors for venous thromboembolisms (VTE) and a low bleeding risk. The IL-6 antagonist tocilizumab may be added in case of high supplemental oxygen requirement and progressive disease (WHO scale 5-6). Treatment with nMABs may be considered for selected inpatients with an early SARS-CoV-2 infection that are not hospitalized for COVID-19. Convalescent plasma, azithromycin, ivermectin or vitamin D₃ should not be used in COVID-19 routine care.

Conclusion: For COVID-19 drug therapy, there are several options that are sufficiently supported by evidence. The living guidance will be updated as new evidence emerges.

Keywords: COVID-19; Living guideline; Living meta-analysis; SARS-CoV-2.

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Conflict of interest statement

C. D. Spinner received consultancy fees, speaker’s honoraria, and/or reimbursement of travel expenses from Gilead Sciences, Eli Lilly, Janssen-Cilag, MSD and received consultancy fees from Molecular Partners and Formycon in the context of COVID-19. He also received research support indirectly from Apeiron, Eli Lilly, Gilead Sciences, and Janssen-Cilag. Outside this context, he received consultancy fees, speaker’s honoraria, and reimbursement of travel expenses from AbbVie, Gilead Sciences, Janssen-Cilag, MSD, and ViiV Healthcare/GSK, as well as research support (indirectly to his employer) from Gilead Sciences, GSK, Jansen-Cilag, MSD, and ViiV Healthcare. T. Welte received consultancy fees from AstraZeneca, Basilea, Biotest, Bayer, Boehringer, GSK, Janssens, Novartis, Pfizer and Roche. He received lecture fees and travel cost support from AstraZeneca, Basilea, Biotest, Bayer, Boehringer, Berlin Chemie GSK, Infectopharm, MSD, Novartis, Pfizer, Roche and research support By DFG, BMBF, EU, WHO. S. Weber-Carstens is working in a scientific cooperation project with the company Dräger. F. Langer has received personal fees for lectures, advisory boards or consultancy and/or research support from Aspen, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, LEO Pharma, Pfizer, and Sanofi, outside the submitted work. M. Westhoff received lecture honoraria from Actelion, Boehringer, Novartis, Löwenstein, and research support from Bayer. M. Pfeifer received lecture fees from Astra-Zeneca, Boehringer, Chiesi, Glaxo-Smith-Kline, Novartis, and Roche. He received consulting fees from Boehringer, Chiesi, Novartis, and Roche, and travel support from Boehringer. K. F. Rabe has received consultancy fees from AstraZeneca, Boehringer, Sanofi Aventis, MSD, and Novartis. He received lecture fees and travel support from Roche, Chiesi Pharmaceuticals, Pfizer, TEVA Pharmaceuticals, Orion Cooperation, Berlin Chemie, Boehringer, AstraZeneca, MSD, Novartis, and Sanofi Aventis, research support from the German Federal Ministry of Education and Research. B. W. Böttiger received fees for lectures from the following companies: Forum für medizinische Fortbildung (FomF), Baxalta Deutschland GmbH, ZOLL Medical Deutschland GmbH, C.R. Bard GmbH, GS Elektromedizinische Geräte G. Stemple GmbH, Novartis Pharma GmbH, Philips GmbH Market DACH, Bioscience Valuation BSV GmbH. J. Weinmann-Menke received research support from GSK, DIAMED, Miltenyi Biotech, lecture fees from Astellas, Astra Zeneca, Norvartis, Bial, Roche, Chiesi, GSK, Boehringer-Ingelheim, Miltenyi, Bayer, Vifor, Fresenius. She received consultancy fees from Bayer, Bial, Boehringer-Ingelheim, Chiesi, Astra Zeneca and GSK. M. Nothacker is a guideline methodologist payed by the AWMF. G. Marx received consultancy fees and research support from Biotest, B.Braun, and Adrenomed, and lecture fees from B.Braun, Biotest, and Philips. He holds a patent for modulation of the TLR4 signaling pathway (European Patent 2855519). C. Karagiannidis has received consultancy fees from Bayer and Xenios. S. Kluge has received research support from Ambu, Daiichi Sankyo, ETView Ltd, Fisher & Paykel, Pfizer, and Xenios. He has received lecture honoraria from Astra, C.R. Bard, Baxter, Biotest, Cytosorbents, Daiichi Sankyo, Fresenius, Gilead, Mitsubishi Tanabe Pharma, MSD, Pfizer, Philips, ZOLL. He received consultancy fees from Bayer, Fresenius, Gilead, MSD and Pfizer. J. J. Malin, U. Janssens, G. Schälte, P. Gastmeier, M. Wepler, F. Hoffmann, A. Kersten, P. Berlit, M. Krawczyk, W. Nehls, F. Fichtner, S. Laudi, M. Stegemann and N. Skoetz report no potential conflicts of interest.

References

1. World Health Organization (WHO) Handbook for guideline development 2nd edition. 2021. https://www.who.int/publications/guidelines/handbook_2nd_ed.pdf?ua=1. (Accessed 18 May 2021).
1. Moberg J, Oxman AD, Rosenbaum S, et al. The GRADE Evidence to Decision (EtD) framework for health system and public health decisions. Health Res Policy Syst. 2018;16:45. doi: 10.1186/s12961-018-0320-2. - DOI - PMC - PubMed
1. AWMF. S3 Leitlinie Empfehlungen zur stationären Therapie von Patienten mit COVID-19 (Registernummer 113-001). Assoc Scient Med Soc Germany (AWMF). https://www.awmf.org/leitlinien/detail/ll/113-001.html. (Accessed 10 May 2021).
1. Kluge S, Janssens U, Welte T, et al. Recommendations for critically ill patients with COVID-19. Med Klin Intensivmed Notfmed. 2020;115:175–177. doi: 10.1007/s00063-020-00674-3. - DOI - PMC - PubMed
1. Kluge S, Janssens U, Spinner CD, et al. Clinical practice guideline: recommendations on inpatient treatment of patients with COVID-19. Dtsch Arztebl Int. 2021 doi: 10.3238/arztebl.m2021.0110. - DOI - PMC - PubMed

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Key summary of German national treatment guidance for hospitalized COVID-19 patients : Key pharmacologic recommendations from a national German living guideline using an Evidence to Decision Framework (last updated 17.05.2021)

Affiliations

Key summary of German national treatment guidance for hospitalized COVID-19 patients : Key pharmacologic recommendations from a national German living guideline using an Evidence to Decision Framework (last updated 17.05.2021)

Authors

Affiliations

Erratum in

Abstract

Conflict of interest statement

References

MeSH terms

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous