During the current coronavirus 2019 disease (COVID-19) pandemic, research is being developed and disseminated at an accelerated pace.¹ The constant influx of data can be of varying quality and reliability often making clinical decision-making challenging.¹ To assess rapidly changing evidence, scientific medical societies have collaborated to develop a living treatment guideline for hospitalised patients with COVID-19.¹ This endeavour is supported by Association of the Scientific Medical Societies in Germany (AWMF) and the COVID-19 Evidence Ecosystem Project (CEOsys).¹ Using the Grading of recommendations assessment, development and evaluation (GRADE) Evidence to Decision Framework, the German living guideline proposes 11 key recommendations for the most pertinent drug interventions.¹

Key recommendations: Immunomodulatory therapy

COVID-19 elicits a host inflammatory response and triggers a cytokine storm resulting in the need for immunomodulatory agents to quell the onset of inflammation and ultimately hinder disease progression.² Patients with severe or critical COVID-19 should be treated with dexamethasone as several randomised controlled trials (RCTs) demonstrated a decrease in mortality.¹ RCTs also highlighted a clinical benefit in administering tocilizumab to patients using high dose supplemental oxygen progressing to severe COVID-19.¹ Tocilizumab should not be used in patients with no or low supplemental oxygen requirements and in those on invasive ventilation.¹

Key recommendations: Antiviral therapy

Since the beginning of the pandemic several types of antiviral therapies have been studied for COVID-19.¹ No fundamental recommendations based on recent RCTs can be made neither for nor against therapy with remdesivir in non-ventilated patients with COVID-19 pneumonia and oxygen demand.¹ Based on current evidence in hospitalised patients with COVID-19, convalescent plasma should not be used and recommendations cannot be made for specific subgroups.¹ Other potential antiviral therapies include neutralising monoclonal antibodies and evidence emphasises the need for early intervention.³ In early SARS-CoV-2-infected hospitalised patients without respiratory COVID-19 symptoms with at least one risk factor for a severe course of disease, SARS-CoV-2 specific nMAB may be utlisied.¹ With that being said, bamlanivimab should not be administered to treat patients hospitalised due to moderate to severe COVID-19.¹

Key recommendations: Anticoagulation therapy

Patients with COVID-19 have demonstrated a change in blood coagulation levels, associating COVID-19 with a prothrombotic state.^1,4 This prothrombotic state warrants the need for hospitalised patients with COVID-19 to receive prophylactic anticoagulation with standard dose low molecular weight heparin in the absence of contraindications–with the alternative being fondaparinux.¹ If hospitalised patients have additional risk factors for venous thromboembolism, intensified anticoagulation may be used if there is a low bleeding risk.¹

Evaluating incoming research

Based on current data, the German treatment guidance provided recommendations on immunomodulatory, antiviral and anticoagulation therapies.¹ The guidance also commented on several miscellaneous drugs (i.e. azithromycin, ivermectin and vitamin D3 should not be administered in hospitalised patients with COVID-19).¹ In order to stay abreast of current research and streamline clinical recommendations, the living guidance will be updated as new evidence develops.¹

References

1. Malin JJ et al. Infection. 2021;1–14
2. Rizk JG et al. Drugs. 2020;80:1267–92
3. Taylor PC et al. Nat Rev Immunol. 2021;21:382–93
4. Han H et al. Clin Chem Lab Med. 2020;58:1116–20