Background: Few longitudinal data on COVID-19 symptoms across the full spectrum of disease severity are available. We evaluated symptom onset, severity and recovery up to nine months after illness onset. Methods: The RECoVERED Study is a prospective cohort study based in Amsterdam, the Netherlands. Participants aged>18 years were recruited following SARS-CoV-2 diagnosis via the local Public Health Service and from hospitals. Standardised symptom questionnaires were completed at recruitment, at one week and month after recruitment, and monthly thereafter. Clinical severity was defined according to WHO criteria. Kaplan-Meier methods were used to compare time from illness onset to symptom recovery, by clinical severity. We examined determinants of time to recovery using multivariable Cox proportional hazards models. Results: Between 11 May 2020 and 31 January 2021, 301 COVID-19 patients (167[55%] male) were recruited, of whom 99/301(32.9%) had mild, 140/301(46.5%) moderate, 30/301(10.0%) severe and 32/301(10.6%) critical disease. The proportion of participants reporting at least one persistent symptom at 12 weeks after illness onset was greater in those with severe/critical disease (81.7%[95%CI=68.7-89.7%]) compared to those with mild or moderate disease (33.0%[95%CI=23.0-43.3%] and 63.8%[95%CI=54.8-71.5%]). At nine months after illness onset, almost half of all participants (42.1%[95%CI=35.6-48.5]) continued to report ≥1 symptom. Recovery was slower in participants with BMI≥30kg/m2 (HR 0.51[95%CI=0.30-0.87]) compared to those with BMI<25kg/m2, after adjusting for age, sex and number of comorbidities. Conclusions: COVID-19 symptoms persisted for nine months after illness onset, even in those with mild disease. Obesity was the most important determinant of time to recovery from symptoms.

BACKGROUND In hospitalized COVID-19 patients dosing and timing of corticosteroids varies 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 the most sick 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 critical illness in COVID-19 patients. 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 COVID-19 patients. METHODS This is a retrospective observational multicenter study that includes adult patients who were hospitalized due to COVID-19 in the Netherlands. We will utilize the differences in therapeutic strategies between hospitals (per protocol high-dose corticosteroids or not) over time to determine whether high-dose corticosteroids has 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 modelling appropriate for each data structure to answer the research questions at hand. RESULTS As of April 2023, data have been collected of 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 COVID-19 patients, from hospital admission to the ward or ICU 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. CLINICALTRIAL ClinicalTrials.gov identifier (NCT number): NCT05403359. Registered 3 June 2022.

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/NCT05403359 International Registered Report Identifier (IRRID) DERR1-10.2196/48183