Glucocorticoid therapy does not delay viral clearance in COVID-19 patients

Ji, Jingjing; Zhang, Jinxia; Shao, Zonghong; Xie, Qiuyou; Zhong, Li; Liu, Zhifeng

doi:10.1186/s13054-020-03287-6

Cited by 14 publications

(19 citation statements)

References 3 publications

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“…Recently, Chang et al reported that delayed virus clearance increased the risk of death ( 12 , 13 ). However, glucocorticoid (an immunosuppressive anti-inflammatory agent) administration (1 to 2 mg/kg for 3 to 5 days) to COVID-19 patients did not affect the duration of virus clearance ( 14 ); hence, the effect of inhibiting neutralizing antibodies on viral load appears to be dependent on the nature of the immunosuppressant used. ACE2 is part of the renin-angiotensin system (RAS), which acts as the receptor for SARS-CoV-2 ( 15 – 17 ).…”

Section: Introductionmentioning

confidence: 99%

Critical Determinants of Cytokine Storm and Type I Interferon Response in COVID-19 Pathogenesis

2021

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SUMMARY Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), a rapidly evolving pandemic worldwide with at least 68 million COVID-19-positive cases and a mortality rate of about 2.2%, as of 10 December 2020. About 20% of COVID-19 patients exhibit moderate to severe symptoms. Severe COVID-19 manifests as acute respiratory distress syndrome (ARDS) with elevated plasma proinflammatory cytokines, including interleukin 1β (IL-1β), IL-6, tumor necrosis factor α (TNF-α), C-X-C motif chemokine ligand 10 (CXCL10/IP10), macrophage inflammatory protein 1 alpha (MIP-1α), and chemokine (C-C motif) ligand 2 (CCL2), with low levels of interferon type I (IFN-I) in the early stage and elevated levels of IFN-I during the advanced stage of COVID-19. Most of the severe and critically ill COVID-19 patients have had preexisting comorbidities, including hypertension, diabetes, cardiovascular diseases, and respiratory diseases. These conditions are known to perturb the levels of cytokines, chemokines, and angiotensin-converting enzyme 2 (ACE2), an essential receptor involved in SARS-CoV-2 entry into the host cells. ACE2 downregulation during SARS-CoV-2 infection activates the angiotensin II/angiotensin receptor (AT1R)-mediated hypercytokinemia and hyperinflammatory syndrome. However, several SARS-CoV-2 proteins, including open reading frame 3b (ORF3b), ORF6, ORF7, ORF8, and the nucleocapsid (N) protein, can inhibit IFN type I and II (IFN-I and -II) production. Thus, hyperinflammation, in combination with the lack of IFN responses against SARS-CoV-2 early on during infection, makes the patients succumb rapidly to COVID-19. Therefore, therapeutic approaches involving anti-cytokine/anti-cytokine-signaling and IFN therapy would favor the disease prognosis in COVID-19. This review describes critical host and viral factors underpinning the inflammatory “cytokine storm” induction and IFN antagonism during COVID-19 pathogenesis. Therapeutic approaches to reduce hyperinflammation and their limitations are also discussed.

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Section: Introductionmentioning

confidence: 99%

Critical Determinants of Cytokine Storm and Type I Interferon Response in COVID-19 Pathogenesis

2021

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“…were also observed in several patients after the methylprednisolone treatment (103)(104)(105). In addition, there are heated debates as to whether corticosteroid therapy will delay viral clearance in COVID-19 (106,107). Therefore, the pros and cons should be carefully weighed before using glucocorticoids in the treatment of COVID-19 patients.…”

Section: Corticosteroidsmentioning

confidence: 99%

Controlling Cytokine Storm Is Vital in COVID-19

et al. 2020

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Corona virus disease 2019 (COVID-19) has caused a global outbreak and severely posed threat to people’s health and social stability. Mounting evidence suggests that immunopathological changes, including diminished lymphocytes and elevated cytokines, are important drivers of disease progression and death in coronavirus infections. Cytokine storm not only limits further spread of virus in the body but also induces secondary tissue damage through the secretion of large amounts of active mediators and inflammatory factors. It has been determined that cytokine storm is a major cause of deaths in COVID-19; therefore, in order to reverse the deterioration of severe and critically ill patients from this disease, the cytokine storm has become a key therapeutic target. Although specific mechanisms of the occurrences of cytokine storms in COVID-19 have not been fully illuminated, hyper-activated innate immune responses, and dysregulation of ACE2 (angiotensin converting enzyme 2) expression and its downstream pathways might provide possibilities. Tailored immunoregulatory therapies have been applied to counteract cytokine storms, such as inhibition of cytokines, corticosteroids, blood purification therapy, and mesenchymal stem cell therapy. This review will summarize advances in the research of cytokine storms induced by COVID-19, as well as potential intervention strategies to control cytokine storms.

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“…Recently, Liu and coworkers proposed that administration of glucocorticoids in severe COVID-19 is associated with increased 28-day mortality and delayed SARS-CoV-2 coronavirus RNA clearance [34]. However, Ji et al reported that glucocorticoid therapy does not delay viral clearance in COVID-19 patients [35]. To analyze the effect of glucocorticoids on patients with severe pneumonia, Liu and colleagues found that there was no significant difference between patients using low dose (</= 2 mg/kg day) and high dose (> 2 mg/kg day) methylprednisolone in inhibiting IL-6 production.…”

Section: Glucocorticoids and Covid-19 Therapymentioning

confidence: 99%

Glucocorticoids are double-edged sword in the treatment of COVID-19 and cancers

Yang¹,

Yu²

2021

Int. J. Biol. Sci.

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Glucocorticoids are important steroid hormones. As an outstanding scientific discovery, the scientist who discovered glucocorticoids was awarded the Nobel Prize in Physiology and Medicine in 1950. Cortisone (hydrocortisone) is a natural glucocorticoid, which is secreted with circadian rhythm by the cortical cells of adrenal glands. Physiologically, about 10-20 mg of hydrocortisone are secreted each day for maintaining homeostasis. Since the biological half-life of natural glucocorticoid is short, scientists developed various synthetic glucocorticoids including prednisone, prednisolone, methylprednisolone, triamcinolone, dexamethasone, betamethasone, and so on. These synthetic glucocorticoids are generated by modifying some structures based on the cortisone backbone, leading to extension of their biological half-life with stronger activities. In the face of severe infection, allergy, shock, trauma, pain, and other stresses, the demand for glucocorticoids increases dramatically. It is critical to supplement extra glucocorticoids to protect the biological functions of vital organs. However, the amount and duration of glucocorticoid administration need to be carefully adjusted, because a series of side effects may occur after long-term or high-dose usage of glucocorticoids. This review article will discuss the application of glucocorticoids in the treatment of patients with severe or critical COVID-19 and solid tumors of advanced stage. The controversy of using glucocorticoid in medical community will also be discussed. This review article will help doctors and basic researchers better understand the practical application of glucocorticoids.

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Glucocorticoid therapy does not delay viral clearance in COVID-19 patients

Cited by 14 publications

References 3 publications

Critical Determinants of Cytokine Storm and Type I Interferon Response in COVID-19 Pathogenesis

Critical Determinants of Cytokine Storm and Type I Interferon Response in COVID-19 Pathogenesis

Controlling Cytokine Storm Is Vital in COVID-19

Glucocorticoids are double-edged sword in the treatment of COVID-19 and cancers

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