Background:In hospitalized patients with COVID-19, the dosing and timing of corticosteroids vary widely. Low-dose dexamethasone therapy reduces mortality in patients requiring respiratory support, but it remains unclear how to treat patients when this therapy fails. In critically ill patients, high-dose corticosteroids are often administered as salvage late in the disease course, whereas earlier administration may be more beneficial in preventing disease progression. Previous research has revealed that increased levels of various biomarkers are associated with mortality, and whole blood transcriptome sequencing has the ability to identify host factors predisposing to critical illness in patients with COVID-19.Objective:Our goal is to determine the most optimal dosing and timing of corticosteroid therapy and to provide a basis for personalized corticosteroid treatment regimens to reduce morbidity and mortality in hospitalized patients with COVID-19.Methods:This is a retrospective, observational, multicenter study that includes adult patients who were hospitalized due to COVID-19 in the Netherlands. We will use the differences in therapeutic strategies between hospitals (per protocol high-dose corticosteroids or not) over time to determine whether high-dose corticosteroids have an effect on the following outcome measures: mechanical ventilation or high-flow nasal cannula therapy, in-hospital mortality, and 28-day survival. We will also explore biomarker profiles in serum and bronchoalveolar lavage fluid and use whole blood transcriptome analysis to determine factors that influence the relationship between high-dose corticosteroids and outcome. Existing databases that contain routinely collected electronic data during ward and intensive care admissions, as well as existing biobanks, will be used. We will apply longitudinal modeling appropriate for each data structure to answer the research questions at hand.Results:As of April 2023, data have been collected for a total of 1500 patients, with data collection anticipated to be completed by December 2023. We expect the first results to be available in early 2024.Conclusions:This study protocol presents a strategy to investigate the effect of high-dose corticosteroids throughout the entire clinical course of hospitalized patients with COVID-19, from hospital admission to the ward or intensive care unit until hospital discharge. Moreover, our exploration of biomarker and gene expression profiles for targeted corticosteroid therapy represents a first step towards personalized COVID-19 corticosteroid treatment.Trial Registration:ClinicalTrials.gov NCT05403359; https://clinicaltrials.gov/ct2/show/NCT05403359International Registered Report Identifier (IRRID):DERR1-10.2196/48183
MULTIFILE
ObjectiveThis study investigates the feasibility of delivering inspiratory muscle training as part of the physical therapy treatment for patients with post-COVID dyspnoea.DesignMixed-methods pilot study.Subjects/patientsPatients with complaints of dyspnoea after COVID-19 infection and their physical therapists.MethodsThe Amsterdam University of Applied Sciences and the Amsterdam University Medical Centers conducted this study. Participants performed daily inspiratory muscle training at home for 6 weeks, consisting of 30 repetitions against a pre-set resistance. The primary outcome was feasibility assessed as acceptability, safety, adherence and patient- and professional experience obtained through diaries and semi-structured interviews. The secondary outcome was maximal inspiratory pressure.ResultsSixteen patients participated. Nine patients and 2 physical therapists partook in semi-structured interviews. Two patients dropped out before initiating the training. Adherence was 73.7%, and no adverse events occurred. Protocol deviations occurred in 29.7% of the sessions. Maximal inspiratory pressure changed from 84.7% of predicted at baseline to 111.3% at follow-up. Qualitative analysis identified barriers to training: ‘Getting acquainted with the training material’ and ‘Finding the right schedule’. Facilitators were: ‘Support from physical therapists’ and ‘Experiencing improvements’.ConclusionDelivering inspiratory muscle training to patients with post-COVID dyspnoea seems feasible. Patients valued the simplicity of the intervention and reported perceived improvements. However, the intervention should be carefully supervised, and training parameters adjusted to individual needs and capacity.
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Non-intubated patients with acute respiratory failure due to COVID-19 could benefit from awake proning. Awake proning is an attractive intervention in settings with limited resources, as it comes with no additional costs. However, awake proning remains poorly used probably because of unfamiliarity and uncertainties regarding potential benefits and practical application. To summarize evidence for benefit and to develop a set of pragmatic recommendations for awake proning in patients with COVID-19 pneumonia, focusing on settings where resources are limited, international healthcare professionals from high and low- and middle-income countries (LMICs) with known expertise in awake proning were invited to contribute expert advice. A growing number of observational studies describe the effects of awake proning in patients with COVID-19 pneumonia in whom hypoxemia is refractory to simple measures of supplementary oxygen. Awake proning improves oxygenation in most patients, usually within minutes, and reduces dyspnea and work of breathing. The effects are maintained for up to 1 hour after turning back to supine, and mostly disappear after 6–12 hours. In available studies, awake proning was not associated with a reduction in the rate of intubation for invasive ventilation. Awake proning comes with little complications if properly implemented and monitored. Pragmatic recommendations including indications and contraindications were formulated and adjusted for resource-limited settings. Awake proning, an adjunctive treatment for hypoxemia refractory to supplemental oxygen, seems safe in non-intubated patients with COVID-19 acute respiratory failure. We provide pragmatic recommendations including indications and contraindications for the use of awake proning in LMICs.
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