Abstract
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.
| Original language | English |
|---|---|
| Article number | e48183 |
| Journal | JMIR Research Protocols |
| Volume | 12 |
| DOIs | |
| Publication status | Published - 2023 |
Bibliographical note
Funding Information:We gratefully acknowledge all site investigators of the participating centers. PROVENT-COVID Collaborators (in alphabetic order): S Ahuja; JP van Akkeren; AG Algera; CK Algoe; RB van Amstel; P van de Berg; DC Bergmans; DI van den Bersselaar; FA Bertens; AJ Bindels; JS Breel; CL Bruna; MM de Boer; S den Boer; LS Boers; M Bogerd; LD Bos; M Botta; OL Baur; H de Bruin; LA Buiteman-Kruizinga; O Cremer; RM Determann; W Dieperink; Jv Dijk; DA Dongelmans; MJ de Graaff; MS Galekaldridge; LA Hagens; JJ Haringman; ST van der Heide; PL van der Heiden; LL Hoeijmakers; L Hol; MW Hollmann; J Horn; R van der Horst; EL Ie; D Ivanov; NP Juffermans; E Kho; ES de Klerk; AW Koopman; M Koopmans; S Kucukcelebi; MA Kuiper; DW de Lange; I Martin-Loeches; G Mazzinari; DM van Meenen; N van Mourik; SG Nijbroek; EA Oostdijk; F Paulus; CJ Pennartz; J Pillay; IM Purmer; TC Rettig; O Roca; JP Roozeman; MJ Schultz; A Serpa Neto; C Sivakorn; GS Shrestha; ME Sleeswijk; PE Spronk; AC Strang; W Stilma; P Swart; A Tri; AM Tsonas; CMA Valk; AP Vlaar; LI Veldhuis; WH van der Ven; P van Velzen; P van Vliet; P van der Voort; L van Welie; B van Wijk; T Winters; WY Wong; AR van Zanten. PROACT-COVID Collaborators (in alphabetic order): E Aydeniz; P van de Berg; DC Bergmans; M Bevers; S den Boer; LS Boers; LD Bos; M Botta; LA Buiteman-Kruizinga; W Coene; M Delmte; Vincenzo Di Leo; DA Dongelmans; TP Dormans; LM Elting; AA Esmeijer; M Gama de Abreu; AR Girbes; MJ de Graaff; DM Go; RL Goossen; HJ Hansen; JJ Haringman; L Hol; MW Hollmann; PL van der Heiden; J Horn; LE van Ingen; NP Juffermans; MA Kuiper; LJ Kuipers; E Koornstra; A Lokhorst; SG Nijbroek; I Martin-Loeches; G Mazzinari; S Myatra; F Paulus; M Offermans; T Pisters; A Prins; P van Oosten; J Pillay; IM Purmer; AS Rezaee; TCD Rettig; O Roca; NM Rosenberg; N Schavemaker; AA Sciascera; MJ Schultz; A Serpa Neto; G Shrestha; ME Sleeswijk; W Stilma; AC Strang; PE Spronk; PR Tuinman; AM Tsonas; CMA Valk; M Verboom; AP Vlaar; FL van der Ven; WH van der Ven; P van Velzen; EJ Verhoef; TD Vermeulen; P van Vliet; JJ Voorham; PH van der Voort; M van der Woude; Weiner; N Yaali; JM Zandvliet; AR van Zanten; TZ van Zijl; and SA Zonneveld. The SELECT study received an unrestricted research grant from ZonMw (grant number 0430102110010). The funders of this study did not play any role in the design of the study, nor in the writing of this manuscript or the decision to publish.
Funding Information:
The study was funded in December 2021. 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.
Publisher Copyright:
© 2023 The Author(s).