Transcriptome network analyses in human coronavirus infections suggest a rational use of immunomodulatory drugs for COVID-19 therapy

Wong, Henry Sung Ching; Guo, Cheng-Yan; Lin, Gan Hong; Lee, Kang Yun; Okada, Yukinori; Chang, Wei Chiao

doi:10.1016/j.ygeno.2020.12.041

Cited by 11 publications

(8 citation statements)

References 47 publications

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“…31 Furthermore, recent transcriptome analysis indicates that budesonide, alongside others which include dexamethasone and ciclesonide is a novel therapeutic immunomodulatory target. 32 Several randomized trials have demonstrated the benefits of systemic corticosteroids for treatment of people hospitalized with COVID-19. 8,9 Our findings are immediately relevant for clinical practice as they suggest that early treatment in the community with inhaled corticosteroids is effective at speeding recovery, which has important benefits for patients and wider society.…”

Section: Discussionmentioning

confidence: 99%

Inhaled budesonide for COVID-19 in people at higher risk of adverse outcomes in the community: interim analyses from the PRINCIPLE trial

Bafadhel

Dorward³

et al. 2021

Preprint

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BACKGROUND Inhaled budesonide has shown efficacy for treating COVID-19 in the community but has not yet been tested in effectiveness trials. METHODS We performed a multicenter, open-label, multi-arm, adaptive platform randomized controlled trial involving people aged ≥65 years, or ≥50 years with comorbidities, and unwell ≤14 days with suspected COVID-19 in the community (PRINCIPLE). Participants were randomized to usual care, usual care plus inhaled budesonide (800μg twice daily for 14 days), or usual care plus other interventions. The co-primary endpoints are time to first self-reported recovery, and hospitalization/death related to COVID-19, both measured over 28 days from randomisation and analysed using Bayesian models. RESULTS The trial opened on April 2, 2020. Randomization to inhaled budesonide began on November 27, 2020 and was stopped on March 31, 2021 based on an interim analysis using data from March 4, 2021. Here, we report updated interim analysis data from March 25, 2021, at which point the trial had randomized 4663 participants with suspected COVID-19. Of these, 2617 (56.1%) tested SARS-CoV-2 positive and contributed data to this interim budesonide primary analysis; 751 budesonide, 1028 usual care and 643 to other interventions. Time to first self-reported recovery was shorter in the budesonide group compared to usual care (hazard ratio 1.208 [95% BCI 1.076 - 1.356], probability of superiority 0.999, estimated benefit [95% BCI] of 3.011 [1.134 - 5.41] days). Among those in the interim budesonide primary analysis who had the opportunity to contribute data for 28 days follow up, there were 59/692 (8.5%) COVID-19 related hospitalizations/deaths in the budesonide group vs 100/968 (10.3%) in the usual care group (estimated percentage benefit, 2.1% [95% BCI -0.7% - 4.8%], probability of superiority 0.928). CONCLUSIONS In this updated interim analysis, inhaled budesonide reduced time to recovery by a median of 3 days in people with COVID-19 with risk factors for adverse outcomes. Once 28 day follow up is complete for all participants randomized to budesonide, final analyses of time to recovery and hospitalization/death will be published. (Funded by the National Institute of Health Research/ United Kingdom Research Innovation [MC_PC_19079]; PRINCIPLE ISRCTN number, ISRCTN86534580.)

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Section: Discussionmentioning

confidence: 99%

Inhaled budesonide for COVID-19 in people at higher risk of adverse outcomes in the community: interim analyses from the PRINCIPLE trial

Bafadhel

Dorward³

et al. 2021

Preprint

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“…The peripheral alveoli may be the key site of inflammation as per previous outcomes. Overall, it is here reported that inhaled ciclesonide therapy gave positive results against serious COVID-19 pneumonia (Wong et al 2021 ). The net effects of corticosteroids in COVID-19 seem to be beneficial by reducing the release of pro-inflammatory cytokines (Fig.…”

Section: Mechanism Of Action In Covid-19mentioning

confidence: 73%

COVID-19 and corticosteroids: a narrative review

et al. 2022

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It has been reported that corticosteroid therapy was effective in the management of severe acute respiratory syndrome (SARS) and the Middle East Respiratory Syndrome (MERS), and recently in coronavirus disease 2019 (COVID-19). Corticosteroids are potent anti-inflammatory drugs that mitigate the risk of acute respiratory distress syndrome (ARDS) in COVID-19 and other viral pneumonia, despite a reduction of viral clearance; corticosteroids inhibit the development of cytokine storm and multi-organ damage. The risk–benefit ratio should be assessed for critical COVID-19 patients. In conclusion, corticosteroid therapy is an effective way in the management of COVID-19, it reduces the risk of complications primarily acute lung injury and the development of ARDS. Besides, corticosteroid therapy mainly dexamethasone and methylprednisolone are effective in reducing the severity of COVID-19 and associated comorbidities such as chronic obstructive pulmonary diseases (COPD), rheumatoid arthritis, and inflammatory bowel disease (IBD).

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“…Among the immune system proteins that stood out were C1QA, which is crucial in the activation of the classical pathway of the complement system ( Ghebrehiwet, Hosszu, Valentino, & Peerschke, 2012 ; Kouser et al, 2015 ; Nayak, Pednekar, Reid, & Kishore, 2012 ), and CD93, involved in the regulation of phagocytosis of apoptotic cells in vivo . Transcriptomics approaches have also been extensively applied to study SARS-CoV-2 infection ( Butler et al, 2021 ; Chakraborty, Sharma, Bhattacharya, Zayed, & Lee, 2021 ; Islam et al, 2021 ; O'Donnell et al, 2021 ; Sun et al, 2020 ; Wong et al, 2021 ). We identified regulated pathways linked to misfolded proteins in the lung of infected patients, as previously reported ( Rosa-Fernandes et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Exploring COVID-19 pathogenesis on command-line: A bioinformatics pipeline for handling and integrating omics data

Macedo-da-Silva

Rosa-Fernandes²,

Marie³

et al. 2022

Advances in Protein Chemistry and Structural Biology

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Transcriptome network analyses in human coronavirus infections suggest a rational use of immunomodulatory drugs for COVID-19 therapy

Cited by 11 publications

References 47 publications

Inhaled budesonide for COVID-19 in people at higher risk of adverse outcomes in the community: interim analyses from the PRINCIPLE trial

Inhaled budesonide for COVID-19 in people at higher risk of adverse outcomes in the community: interim analyses from the PRINCIPLE trial

COVID-19 and corticosteroids: a narrative review

Exploring COVID-19 pathogenesis on command-line: A bioinformatics pipeline for handling and integrating omics data

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