Treatment effect modifiers in hospitalised patients with COVID-19 receiving remdesivir and dexamethasone

Cæcilie Leding; Jacob Bodilsen; Christian Brieghel; Zitta Barrella Harboe; Marie Helleberg; Claire Holm; Simone Bastrup Israelsen; Janne Jensen; Tomas Østergaard Jensen; Isik Somuncu Johansen; Stine Johnsen; Ole Kirk; Birgitte Lindegaard; Christian Niels Meyer; Rajesh Mohey; Lars Pedersen; Stig Lønberg Nielsen; Lars Haukali Omland; Daria Podlekareva; Pernille Ravn; Jonathan Starling; Merete Storgaard; Christian Søborg; Ole Schmeltz Søgaard; Torben Tranborg; Lothar Wiese; Signe Heide Westring Worm; Hanne Rolighed Christensen; Thomas Benfield

doi:10.1080/23744235.2023.2187081

Treatment effect modifiers in hospitalised patients with COVID-19 receiving remdesivir and dexamethasone

Cæcilie Leding^*, Jacob Bodilsen, Christian Brieghel, Zitta Barrella Harboe, Marie Helleberg, Claire Holm, Simone Bastrup Israelsen, Janne Jensen, Tomas Østergaard Jensen, Isik Somuncu Johansen, Stine Johnsen, Ole Kirk, Birgitte Lindegaard, Christian Niels Meyer, Rajesh Mohey, Lars Pedersen, Stig Lønberg Nielsen, Lars Haukali Omland, Daria Podlekareva, Pernille RavnJonathan Starling, Merete Storgaard, Christian Søborg, Ole Schmeltz Søgaard, Torben Tranborg, Lothar Wiese, Signe Heide Westring Worm, Hanne Rolighed Christensen, Thomas Benfield

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Abstract

Objective: Cardiovascular complications and congenital malformations are known traits in Turner syndrome (TS), which increases mortality. Women with TS have varying phenotype and cardiovascular risks. A biomarker assessing the risk for cardiovascular complications could potentially reduce mortality in high-risk TS and reduce screening in TS participants with low cardiovascular risk.

Design, patients, participants and measurements: As part of a study initiated in 2002, 87 TS participants and 64 controls were invited to magnetic resonance imaging of the aorta, anthropometry, and biochemical markers. TS participants were re-examined thrice lastly in 2016. The focus of this paper is the additional measurements of transforming growth factor beta (TGFβ), matrix metalloproteinase (MMP's), tissue inhibitor of matrix metalloproteinase (TIMP), peripheral blood DNA and their associations with TS and the cardiovascular risk and congenital heart disease.

Results: TS participants had lower TGFβ1 and TGFβ2 values compared to controls. snp11547635 heterozygosity was not associated with any biomarkers but was associated with increased risk of aortic regurgitation. TIMP4 and TGFβ1 were correlated with the aortic diameter at several measuring positions. During follow-up, the antihypertensive treatment decreased the descending aortic diameter and increased TGFβ1 and TGFβ2 levels in TS.

Conclusion: TGFβ and TIMP's are altered in TS and may play a role in the development of coarctation and dilated aorta. snp11547635 heterozygosity was not found to impact biochemical markers. Further studies should investigate these biomarkers to further unravel the pathogenesis of the increased cardiovascular risk in TS participants.

Originalsprog	Engelsk
Tidsskrift	Infectious Diseases
Vol/bind	55
Udgave nummer	5
Sider (fra-til)	351-360
Antal sider	10
ISSN	2374-4235
DOI	https://doi.org/10.1080/23744235.2023.2187081
Status	Udgivet - maj 2023

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10.1080/23744235.2023.2187081Licens: CC BY-NC-ND 4.0

Leding et al (2023) Treatment effect modifiers in hospitalised patients with COVID-19 receiving remdesivir and dexamethasoneForlagets udgivne version, 2,05 MBLicens: CC BY-NC-ND 4.0

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Leding, C., Bodilsen, J., Brieghel, C., Harboe, Z. B., Helleberg, M., Holm, C., Israelsen, S. B., Jensen, J., Jensen, T. Ø., Johansen, I. S., Johnsen, S., Kirk, O., Lindegaard, B., Meyer, C. N., Mohey, R., Pedersen, L., Nielsen, S. L., Omland, L. H., Podlekareva, D., ... Benfield, T. (2023). Treatment effect modifiers in hospitalised patients with COVID-19 receiving remdesivir and dexamethasone. Infectious Diseases, 55(5), 351-360. https://doi.org/10.1080/23744235.2023.2187081

@article{792052b951f547a69e275c4d38b7c865,

title = "Treatment effect modifiers in hospitalised patients with COVID-19 receiving remdesivir and dexamethasone",

abstract = "Background: The combined effectiveness of remdesivir and dexamethasone in subgroups of hospitalised patients with COVID-19 is poorly investigated. Methods: In this nationwide retrospective cohort study, we included 3826 patients with COVID-19 hospitalised between February 2020 and April 2021. The primary outcomes were use of invasive mechanical ventilation and 30-day mortality, comparing a cohort treated with remdesivir and dexamethasone with a previous cohort treated without remdesivir and dexamethasone. We used inverse probability of treatment weighting logistic regression to assess associations with progression to invasive mechanical ventilation and 30-day mortality between the two cohorts. The analyses were conducted overall and by subgroups based on patient characteristics. Results: Odds ratio for progression to invasive mechanical ventilation and 30-day mortality in individuals treated with remdesivir and dexamethasone compared to treatment with standard of care alone was 0.46 (95% confidence interval, 0.37–0.57) and 0.47 (95% confidence interval, 0.39–0.56), respectively. The reduced risk of mortality was observed in elderly patients, overweight patients and in patients requiring supplemental oxygen at admission, regardless of sex, comorbidities and symptom duration. Conclusions: Patients treated with remdesivir and dexamethasone had significantly improved outcomes compared to patients treated with standard of care alone. These effects were observed in most patient subgroups.",

keywords = "30-day mortality, COVID-19, Clinical outcome, SARS-CoV-2, dexamethasone, remdesivir",

author = "C{\ae}cilie Leding and Jacob Bodilsen and Christian Brieghel and Harboe, {Zitta Barrella} and Marie Helleberg and Claire Holm and Israelsen, {Simone Bastrup} and Janne Jensen and Jensen, {Tomas {\O}stergaard} and Johansen, {Isik Somuncu} and Stine Johnsen and Ole Kirk and Birgitte Lindegaard and Meyer, {Christian Niels} and Rajesh Mohey and Lars Pedersen and Nielsen, {Stig L{\o}nberg} and Omland, {Lars Haukali} and Daria Podlekareva and Pernille Ravn and Jonathan Starling and Merete Storgaard and Christian S{\o}borg and S{\o}gaard, {Ole Schmeltz} and Torben Tranborg and Lothar Wiese and Worm, {Signe Heide Westring} and Christensen, {Hanne Rolighed} and Thomas Benfield",

year = "2023",

month = may,

doi = "10.1080/23744235.2023.2187081",

language = "English",

volume = "55",

pages = "351--360",

journal = "Infectious Diseases",

issn = "2374-4235",

publisher = "Taylor & Francis",

number = "5",

}

Leding, C, Bodilsen, J, Brieghel, C, Harboe, ZB, Helleberg, M, Holm, C, Israelsen, SB, Jensen, J, Jensen, TØ, Johansen, IS, Johnsen, S, Kirk, O, Lindegaard, B, Meyer, CN, Mohey, R, Pedersen, L, Nielsen, SL, Omland, LH, Podlekareva, D, Ravn, P, Starling, J, Storgaard, M, Søborg, C, Søgaard, OS, Tranborg, T, Wiese, L, Worm, SHW, Christensen, HR & Benfield, T 2023, 'Treatment effect modifiers in hospitalised patients with COVID-19 receiving remdesivir and dexamethasone', Infectious Diseases, bind 55, nr. 5, s. 351-360. https://doi.org/10.1080/23744235.2023.2187081

TY - JOUR

T1 - Treatment effect modifiers in hospitalised patients with COVID-19 receiving remdesivir and dexamethasone

AU - Leding, Cæcilie

AU - Bodilsen, Jacob

AU - Brieghel, Christian

AU - Harboe, Zitta Barrella

AU - Helleberg, Marie

AU - Holm, Claire

AU - Israelsen, Simone Bastrup

AU - Jensen, Janne

AU - Jensen, Tomas Østergaard

AU - Johansen, Isik Somuncu

AU - Johnsen, Stine

AU - Kirk, Ole

AU - Lindegaard, Birgitte

AU - Meyer, Christian Niels

AU - Mohey, Rajesh

AU - Pedersen, Lars

AU - Nielsen, Stig Lønberg

AU - Omland, Lars Haukali

AU - Podlekareva, Daria

AU - Ravn, Pernille

AU - Starling, Jonathan

AU - Storgaard, Merete

AU - Søborg, Christian

AU - Søgaard, Ole Schmeltz

AU - Tranborg, Torben

AU - Wiese, Lothar

AU - Worm, Signe Heide Westring

AU - Christensen, Hanne Rolighed

AU - Benfield, Thomas

PY - 2023/5

Y1 - 2023/5

N2 - Background: The combined effectiveness of remdesivir and dexamethasone in subgroups of hospitalised patients with COVID-19 is poorly investigated. Methods: In this nationwide retrospective cohort study, we included 3826 patients with COVID-19 hospitalised between February 2020 and April 2021. The primary outcomes were use of invasive mechanical ventilation and 30-day mortality, comparing a cohort treated with remdesivir and dexamethasone with a previous cohort treated without remdesivir and dexamethasone. We used inverse probability of treatment weighting logistic regression to assess associations with progression to invasive mechanical ventilation and 30-day mortality between the two cohorts. The analyses were conducted overall and by subgroups based on patient characteristics. Results: Odds ratio for progression to invasive mechanical ventilation and 30-day mortality in individuals treated with remdesivir and dexamethasone compared to treatment with standard of care alone was 0.46 (95% confidence interval, 0.37–0.57) and 0.47 (95% confidence interval, 0.39–0.56), respectively. The reduced risk of mortality was observed in elderly patients, overweight patients and in patients requiring supplemental oxygen at admission, regardless of sex, comorbidities and symptom duration. Conclusions: Patients treated with remdesivir and dexamethasone had significantly improved outcomes compared to patients treated with standard of care alone. These effects were observed in most patient subgroups.

AB - Background: The combined effectiveness of remdesivir and dexamethasone in subgroups of hospitalised patients with COVID-19 is poorly investigated. Methods: In this nationwide retrospective cohort study, we included 3826 patients with COVID-19 hospitalised between February 2020 and April 2021. The primary outcomes were use of invasive mechanical ventilation and 30-day mortality, comparing a cohort treated with remdesivir and dexamethasone with a previous cohort treated without remdesivir and dexamethasone. We used inverse probability of treatment weighting logistic regression to assess associations with progression to invasive mechanical ventilation and 30-day mortality between the two cohorts. The analyses were conducted overall and by subgroups based on patient characteristics. Results: Odds ratio for progression to invasive mechanical ventilation and 30-day mortality in individuals treated with remdesivir and dexamethasone compared to treatment with standard of care alone was 0.46 (95% confidence interval, 0.37–0.57) and 0.47 (95% confidence interval, 0.39–0.56), respectively. The reduced risk of mortality was observed in elderly patients, overweight patients and in patients requiring supplemental oxygen at admission, regardless of sex, comorbidities and symptom duration. Conclusions: Patients treated with remdesivir and dexamethasone had significantly improved outcomes compared to patients treated with standard of care alone. These effects were observed in most patient subgroups.

KW - 30-day mortality

KW - COVID-19

KW - Clinical outcome

KW - SARS-CoV-2

KW - dexamethasone

KW - remdesivir

UR - http://www.scopus.com/inward/record.url?scp=85150616242&partnerID=8YFLogxK

U2 - 10.1080/23744235.2023.2187081

DO - 10.1080/23744235.2023.2187081

M3 - Journal article

C2 - 36905638

SN - 2374-4235

VL - 55

SP - 351

EP - 360

JO - Infectious Diseases

JF - Infectious Diseases

IS - 5

ER -

Treatment effect modifiers in hospitalised patients with COVID-19 receiving remdesivir and dexamethasone

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