Corticosteroids in the Treatment of Severe Covid-19 Lung Disease: The Pulmonology Perspective From the First United States Epicenter

Macauley, Precious; A, Martin; Epelbaum, Oleg

doi:10.1016/j.ijid.2020.08.051

Cited by 6 publications

(4 citation statements)

References 30 publications

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“…10 The scales gradually tipped in the other direction thanks to the realization that SARS-CoV-2 may produce lung damage by igniting a destructive immune response in that organ rather than through direct viral cytopathic effects 11 and the corollary that viral persistence may not be the driver of progressive 17) 60 ( 16) 66 ( 13 (Continues) lung disease in SARS-CoV-2. 12 Once RCTs evaluating corticosteroid therapy were launched, the dosing regimens resembled those of favorable prior studies of early corticosteroid administration in mixed ARDS populations: for example, methylprednisolone 1 mg/kg/day in the trial by Meduri et al 13 and dexamethasone 20 mg once daily followed by 10 mg once daily in the trial by Villar et al 14 The belief in some circles that COVID-19 pneumonia differs from routine ARDS in the degree of maladaptive exaggeration of the lung immune response led to sporadic reports [15][16][17][18] of the use of corticosteroids at pulse dose of 1 gm/day for at least 2 days as defined in the present study and as might be done for immune-mediated lung diseases such as pulmonary vasculitis or primary lung allograft dysfunction. Administration of corticosteroids at this magnitude has not been studied systematically in any COVID-19 pneumonia population before the present study.…”

Section: Discussionmentioning

confidence: 99%

Comparison of pulse‐dose and high‐dose corticosteroids with no corticosteroid treatment for COVID‐19 pneumonia in the intensive care unit

Yaqoob

Greenberg

Hwang

et al. 2021

Journal of Medical Virology

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Corticosteroid dosing in the range of 0.5–2 mg/kg/day of methylprednisolone equivalents has become a standard part of the management of intensive care unit (ICU) patients with COVID‐19 pneumonia based on positive results of randomized trials and a meta‐analysis. Alongside such conventional dosing, administration of 1 gm of methylprednisolone daily (pulse dosing) has also been reported in the literature with claims of favorable outcomes. Comparisons between such disparate approaches to corticosteroids for Coronavirus disease 2019 (COVID‐19) pneumonia are lacking. In this retrospective study of patients admitted to the ICU with COVID‐19 pneumonia, we compared patients treated with 0.5–2 mg/kg/day in methylprednisolone equivalents (high‐dose corticosteroids) and patients treated with 1 gm of methylprednisolone (pulse‐dose corticosteroids) to those who did not receive any corticosteroids. The endpoints of interest were hospital mortality, ICU‐free days at Day 28, and complications potentially attributable to corticosteroids. Pulse‐dose corticosteroid therapy was associated with a significant increase in ICU‐free days at Day 28 compared to no receipt: adjusted relative risk (aRR): 1.45 (95% confidence interval [CI]: 1.05–2.02; p = 0.03) and compared with high‐dose corticosteroid administration (p = 0.003). Nonetheless, receipt of high‐dose corticosteroids—but not of pulse‐dose corticosteroids—significantly reduced the odds of hospital mortality compared to no receipt: adjusted Odds ratio (aOR) 0.31 (95% CI: 0.12–0.77; p = 0.01). High‐dose corticosteroids reduced mortality compared to pulse‐dose corticosteroids (p = 0.04). Pulse‐dose corticosteroids—but not high‐dose corticosteroids—significantly increased the odds of acute kidney injury requiring renal replacement therapy compared to no receipt: aOR 3.53 (95% CI: 1.27–9.82; p = 0.02). The odds of this complication were also significantly higher in the pulse‐dose group when compared to the high‐dose group (p = 0.05 for the comparison). In this single‐center study, pulse‐dose corticosteroid therapy for COVID‐19 pneumonia in the ICU was associated with an increase in ICU‐free days but failed to impact hospital mortality, perhaps because of its association with development of severe renal failure. In line with existing trial data, the effect of high‐dose corticosteroids on mortality was favorable.

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Section: Discussionmentioning

confidence: 99%

Comparison of pulse‐dose and high‐dose corticosteroids with no corticosteroid treatment for COVID‐19 pneumonia in the intensive care unit

Yaqoob

Greenberg

Hwang

et al. 2021

Journal of Medical Virology

Self Cite

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“…Current guidelines recommend stopping corticosteroids on hospital discharge [104,105]. Some studies have described cryptogenic and secondary organising pneumonia in COVID-19, and a longer or tapering duration of steroids has been used in these cases [113,114]. However, most cases of COVID-19 organising pneumonia appear to have a good prognosis [115].…”

Section: Corticosteroidsmentioning

confidence: 99%

Clinical features and acute management of COVID-19 in adults

Khan¹,

Lamb²,

Moores³

2021

Covid-19

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COVID-19 is a multisystem disease that requires holistic management. Most patients will experience mild symptoms including cough, fever and mild dyspnoea. A small proportion of patients will have severe manifestations including respiratory failure, ARDS and multiorgan failure. Extrapulmonary features are common and include gastrointestinal, thromboembolic, neurological, cardiac, renal, endocrine and dermatological manifestations. The care of COVID-19 patients requires close attention to these features. This includes respiratory support (such as supplemental oxygen, NIV and awake proning); fluid, electrolyte and nutrition management; prevention, detection and treatment of thrombotic events; management of diabetic complications; review of medications; appropriate use of antibiotics; and evidence-based use of therapeutic agents such as corticosteroids, antivirals such as remdesivir and other emerging therapies such as immunomodulating agents. Early planning for treatment escalation and decision making around the appropriateness of cardiopulmonary resuscitation are crucial as deterioration can be rapid. Prolonged symptoms occur in a minority of patients and longitudinal follow-up is required.

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“…The classic synthetic glucocorticoid dexamethasone has previously shown in a randomized clinical trial mortality benefit in severely sick hospitalized patients with coronavirus disease 2019 (COVID-19) ( RECOVERY Collaborative Group, Horby P, Lim WS, Emberson JR, Mafham M, 2020 ). As severe COVID-19 is seemingly characterized by a feedforward inflammatory circuit involving systemic elevations in cytokine and chemokine levels, often referred to as cytokine storm, the observed benefit is presumably ascribed to broad anti-inflammatory and immunosuppressive effects of glucocorticoids ( Cain and Cidlowski, 2020 , Macauley et al, 2020 ). The latter, a class of steroid hormones, act by binding ubiquitously expressed glucocorticoid receptor, a ligand-activated transcription factor encoded by NR3C1 gene in humans, which, upon translocation to the nucleus, binds to canonical glucocorticoid response elements and leads to transcriptional activation of its targets including anti-inflammatory genes such as TSC22D3 , DUSP1 , and SGK1 ( Cain and Cidlowski, 2020 , Hudson et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Inferring molecular mechanisms of dexamethasone therapy in severe COVID-19 from existing transcriptomic data

Sharma

2021

Gene

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Dexamethasone, a synthetic glucocorticoid, has previously shown mortality benefit in severe coronavirus disease 2019 (COVID-19) in a randomized controlled trial. As the illness is considered to reflect a hyperinflammatory state, this therapeutic effectiveness is presumably ascribed to broad anti-inflammatory activities of glucocorticoids. Here, an unbiased analysis of available transcriptomic data on lung and blood immune cells from severe COVID-19 patients, and matching cellular models of dexamethasone treatment is presented that supports this presumption. Comparison of differentially expressed genes in severe COVID-19 with that in dexamethasone treated cells reveals a small set of genes that are regulated in opposite direction between the disease and the drug, and are enriched for genes and processes related to glucocorticoid pathway and receptor binding. This expression signature differentiates various cytokines as a whole from a set of anti-cytokine/anti-inflammatory agents, with the former resembling COVID-19 and the latter dexamethasone in gene regulation. The signature apparently relates to TNF- α, IL-1α, IL-1β, IFN-α, IFN-β, and IFN-γ signaling, but not IL-6 signaling, suggesting that therapeutic effect of dexamethasone in COVID-19 does not involve IL-6 pathway. However, as all these observations are purely based on bioinformatic analysis, experimental evidence will be required to validate the inferences drawn. In conclusion, the present analysis seems to provide a proof of concept for therapeutic mechanisms of dexamethasone in COVID-19.

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Corticosteroids in the Treatment of Severe Covid-19 Lung Disease: The Pulmonology Perspective From the First United States Epicenter

Cited by 6 publications

References 30 publications

Comparison of pulse‐dose and high‐dose corticosteroids with no corticosteroid treatment for COVID‐19 pneumonia in the intensive care unit

Comparison of pulse‐dose and high‐dose corticosteroids with no corticosteroid treatment for COVID‐19 pneumonia in the intensive care unit

Clinical features and acute management of COVID-19 in adults

Inferring molecular mechanisms of dexamethasone therapy in severe COVID-19 from existing transcriptomic data

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