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Since the start of the pandemic just over a year ago, more than 100 000 scientific articles on COVID-19 have been published, according to PubMed. A multitude of hypotheses were formulated regarding therapeutic approaches. For our guideline we primarily restricted ourselves on randomized controlled trials that were undertaken in patients with COVID-19.

In the meantime the guideline has been updated again. Thanks to the collaboration with the COVID-19 -Evidenzökosystem-Projekt (CEOsys, the COVID-19 evidence ecosystem project) important questions of therapeutic relevance were backed up by systematic evidence syntheses, which raises the quality to classification S3 (1).

Several randomized trials confirmed that treatment with systemic corticosteroids in severely and critically ill COVID-19 patients reduces mortality to a significant extent (1). In the largest published study, an absolute mortality reduction of 12% was achieved in invasively ventilated patients and 3% in patients requiring oxygen (2).

No difference was seen in patients who did not require oxygen therapy. The most unequivocal evidence exists for the substance dexamethasone, with a daily dose of 6 mg and a therapeutic duration of 10 days. Higher steroid dosages are currently not backed up by sufficient evidence, and the current guideline therefore includes no recommendation to this effect (3). The optimal timing, dose, and duration of treatment remain, however, the subject of further studies.

Especially in severe cases of COVID-19, it has been observed that many patients had a low serum concentration of vitamin D3. However, the reverse conclusion, that the low vitamin concentration is the cause for the severe disease course, does not apply. The published randomized trials in hospital inpatients with COVID-19 showed no benefit for the administration of vitamin D3 compared with standard treatment as regards patient relevant endpoints (4).

On this background the guideline group articulated in the updated guideline a recommendation against vitamin D3 (1). Furthermore, German Nutrition Society does not make a blanket recommendation for vitamin D supplementation to reduce the risk of SARS-CoV-2 infection or the severity of the disease course of COVID-19 (www.dge.de/presse/pm/vitamin-d-und-covid-19/).

We agree with the explanations of Prof Gottlieb and colleagues regarding oxygen therapy. In general, hypoxemia should be prevented as much as hyperoxemia.

DOI: 10.3238/arztebl.m2021.0181

On behalf of the authors
Prof. Dr. med. Stefan Kluge
Klinik für Intensivmedizin
Universitätsklinikum Hamburg-Eppendorf
skluge@uke.de

Conflict of interest statement
Prof. Kluge received research support from Ambu, Daiichi Sankyo, ETView Ltd, Fisher & Paykel, Pfizer, and Xenios. He received lecture fees from Astra, C.R. Bard, Baxter, Biotest, Cytosorbents, Fresenius, Gilead, Mitsubishi Tanabe Pharma, MSD, Pfizer, Philips, and ZOLL. He received speaker’s honoraria from Bayer, Fresenius, Gilead, MSD, and Pfizer.

1.
Kluge S, Janssens U, Welte T, et al.: S3-Leitlinie – Empfehlungen zur stationären Therapie von Patienten mit COVID-19. www.awmf.org/leitlinien/detail/ll/113-001.html (last accessed on 23 February 2021).
2.
Horby P, Lim WS, Emberson JR, et al.: Dexamethasone in hospitalized patients with Covid-19. N Engl J Med 2021; 384: 693–704 CrossRef MEDLINE PubMed Central
3.
van Paassen J, Vos JS, Hoekstra EM, Neumann KMI, Boot PC, Arbous SM: Corticosteroid use in COVID-19 patients: a systematic review and meta-analysis on clinical outcomes. Critical Care (London, England). 2020; 24: 696 CrossRef MEDLINE PubMed Central
4.
Murai IH, Fernandes AL, Sales LP, et al.: Effect of a single high dose of Vitamin D3 on hospital length of stay in patients with moderate to severe COVID-19: a randomized clinical trial. JAMA 2021; e2026848 CrossRef MEDLINE
5.
Kluge S, Janssens U, Spinner CD, Pfeifer M, Marx G, Karagiannidis C: Clinical practice guideline: recommendations on in-hospital treatment of patients with COVID-19. Dtsch Arztebl Int 2021; 118: 1–7 VOLLTEXT
1.Kluge S, Janssens U, Welte T, et al.: S3-Leitlinie – Empfehlungen zur stationären Therapie von Patienten mit COVID-19. www.awmf.org/leitlinien/detail/ll/113-001.html (last accessed on 23 February 2021).
2.Horby P, Lim WS, Emberson JR, et al.: Dexamethasone in hospitalized patients with Covid-19. N Engl J Med 2021; 384: 693–704 CrossRef MEDLINE PubMed Central
3.van Paassen J, Vos JS, Hoekstra EM, Neumann KMI, Boot PC, Arbous SM: Corticosteroid use in COVID-19 patients: a systematic review and meta-analysis on clinical outcomes. Critical Care (London, England). 2020; 24: 696 CrossRef MEDLINE PubMed Central
4.Murai IH, Fernandes AL, Sales LP, et al.: Effect of a single high dose of Vitamin D3 on hospital length of stay in patients with moderate to severe COVID-19: a randomized clinical trial. JAMA 2021; e2026848 CrossRef MEDLINE
5.Kluge S, Janssens U, Spinner CD, Pfeifer M, Marx G, Karagiannidis C: Clinical practice guideline: recommendations on in-hospital treatment of patients with COVID-19. Dtsch Arztebl Int 2021; 118: 1–7 VOLLTEXT

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