The 2019 novel coronavirus (2019-nCoV) outbreak is a major challenge for clinicians. The clinical course of patients remains to be fully characterised, little data are available that describe the disease pathogenesis, and no pharmacological therapies of proven efficacy yet exist.

1 Stockman LJ

Bellamy R

Garner P SARS: systematic review of treatment effects. 2 Arabi YM

Mandourah Y

Al-Hameed F

et al. Corticosteroid therapy for critically ill patients with middle east respiratory syndrome. 3 Huang C

Wang Y

Li X

et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. 4 WHO

Clinical management of severe acute respiratory infection when novel coronavirus (nCoV) infection is suspected. Table Summary of clinical evidence to date Outcomes of corticosteroid therapy * * Hydrocortisone, methylprednisolone, dexamethasone, and prednisolone. Comment MERS-CoV Delayed clearance of viral RNA from respiratory tract 2 Arabi YM

Mandourah Y

Al-Hameed F

et al. Corticosteroid therapy for critically ill patients with middle east respiratory syndrome. Adjusted hazard ratio 0·4 (95% CI 0·2–0·7) SARS-CoV Delayed clearance of viral RNA from blood 5 Lee N

Allen Chan KC

Hui DS

et al. Effects of early corticosteroid treatment on plasma SARS-associated Coronavirus RNA concentrations in adult patients. Significant difference but effect size not quantified SARS-CoV Complication: psychosis 6 Lee DTS

Wing YK

Leung HCM

et al. Factors associated with psychosis among patients with severe acute respiratory syndrome: a case-control study. Associated with higher cumulative dose, 10 975 mg vs 6780 mg hydrocortisone equivalent SARS-CoV Complication: diabetes 7 Xiao JZ

Ma L

Gao J

et al. Glucocorticoid-induced diabetes in severe acute respiratory syndrome: the impact of high dosage and duration of methylprednisolone therapy. 33 (35%) of 95 patients treated with corticosteroid developed corticosteroid-induced diabetes SARS-CoV Complication: avascular necrosis in survivors 8 Li YM

Wang SX

Gao HS

et al. Factors of avascular necrosis of femoral head and osteoporosis in SARS patients' convalescence. Among 40 patients who survived after corticosteroid treatment, 12 (30%) had avascular necrosis and 30 (75%) had osteoporosis Influenza Increased mortality 9 Ni Y-N

Chen G

Sun J

Liang B-M

Liang Z-A The effect of corticosteroids on mortality of patients with influenza pneumonia: a systematic review and meta-analysis. Risk ratio for mortality 1·75 (95% CI 1·3–2·4) in a meta-analysis of 6548 patients from ten studies RSV No clinical benefit in children 10 McGee S

Hirschmann J Use of corticosteroids in treating infectious diseases. , 11 Corneli HM

Zorc JJ

Mahajan P

et al. A multicenter, randomized, controlled trial of dexamethasone for bronchiolitis. No effect in largest randomised controlled trial of 600 children, of whom 305 (51%) had been treated with corticosteroids CoV=coronavirus. MERS=Middle East respiratory syndrome. RSV=respiratory syncytial virus. SARS=severe acute respiratory syndrome. Corticosteroids were widely used during the outbreaks of severe acute respiratory syndrome (SARS)-CoVand Middle East respiratory syndrome (MERS)-CoV,and are being used in patients with 2019-nCoV in addition to other therapeutics.However, current interim guidance from WHO on clinical management of severe acute respiratory infection when novel coronavirus (2019-nCoV) infection is suspected (released Jan 28, 2020) advises against the use of corticosteroids unless indicated for another reason.Understanding the evidence for harm or benefit from corticosteroids in 2019-nCoV is of immediate clinical importance. Here we discuss the clinical outcomes of corticosteroid use in coronavirus and similar outbreaks ( table ).

12 Tang NL-S

Chan PK-S

Wong C-K

et al. Early enhanced expression of interferon-inducible protein-10 (CXCL-10) and other chemokines predicts adverse outcome in severe acute respiratory syndrome. 13 Peiris JSM

Chu CM

Cheng VCC

et al. Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study. , 14 Beijing Group of National Research Project for SARS

Dynamic changes in blood cytokine levels as clinical indicators in severe acute respiratory syndrome. 15 Arabi YM

Balkhy HH

Hayden FG

et al. Middle East respiratory syndrome. 16 Nicholls JM

Poon LLM

Lee KC

et al. Lung pathology of fatal severe acute respiratory syndrome. Acute lung injury and acute respiratory distress syndrome are partly caused by host immune responses. Corticosteroids suppress lung inflammation but also inhibit immune responses and pathogen clearance. In SARS-CoV infection, as with influenza, systemic inflammation is associated with adverse outcomes.In SARS, inflammation persists after viral clearance.Pulmonary histology in both SARS and MERS infections reveals inflammation and diffuse alveolar damage,with one report suggesting haemophagocytosis.Theoretically, corticosteroid treatment could have a role to suppress lung inflammation.

2 Arabi YM

Mandourah Y

Al-Hameed F

et al. Corticosteroid therapy for critically ill patients with middle east respiratory syndrome. In a retrospective observational study reporting on 309 adults who were critically ill with MERS,almost half of patients (151 [49%]) were given corticosteroids (median hydrocortisone equivalent dose [ie, methylprednisolone 1:5, dexamethasone 1:25, prednisolone 1:4] of 300 mg/day). Patients who were given corticosteroids were more likely to require mechanical ventilation, vasopressors, and renal replacement therapy. After statistical adjustment for immortal time and indication biases, the authors concluded that administration of corticosteroids was not associated with a difference in 90-day mortality (adjusted odds ratio 0·8, 95% CI 0·5–1·1; p=0·12) but was associated with delayed clearance of viral RNA from respiratory tract secretions (adjusted hazard ratio 0·4, 95% CI 0·2–0·7; p=0·0005). However, these effect estimates have a high risk of error due to the probable presence of unmeasured confounders.

1 Stockman LJ

Bellamy R

Garner P SARS: systematic review of treatment effects. 6 Lee DTS

Wing YK

Leung HCM

et al. Factors associated with psychosis among patients with severe acute respiratory syndrome: a case-control study. 5 Lee N

Allen Chan KC

Hui DS

et al. Effects of early corticosteroid treatment on plasma SARS-associated Coronavirus RNA concentrations in adult patients. 7 Xiao JZ

Ma L

Gao J

et al. Glucocorticoid-induced diabetes in severe acute respiratory syndrome: the impact of high dosage and duration of methylprednisolone therapy. , 8 Li YM

Wang SX

Gao HS

et al. Factors of avascular necrosis of femoral head and osteoporosis in SARS patients' convalescence. In a meta-analysis of corticosteroid use in patients with SARS, only four studies provided conclusive data, all indicating harm.The first was a case-control study of SARS patients with (n=15) and without (n=30) SARS-related psychosis; all were given corticosteroid treatment, but those who developed psychosis were given a higher cumulative dose than those who did not (10 975 mg hydrocortisone equivalent vs 6780 mg; p=0·017).The second was a randomised controlled trial of 16 patients with SARS who were not critically ill; the nine patients who were given hydrocortisone (mean 4·8 days [95% CI 4·1–5·5] since fever onset) had greater viraemia in the second and third weeks after infection than those who were given 0·9% saline control.The remaining two studies reported diabetes and avascular necrosis as complications associated with corticosteroid treatment.

9 Ni Y-N

Chen G

Sun J

Liang B-M

Liang Z-A The effect of corticosteroids on mortality of patients with influenza pneumonia: a systematic review and meta-analysis. A 2019 systematic review and meta-analysisidentified ten observational studies in influenza, with a total of 6548 patients. The investigators found increased mortality in patients who were given corticosteroids (risk ratio [RR] 1·75, 95% CI 1·3–2·4; p=0·0002). Among other outcomes, length of stay in an intensive care unit was increased (mean difference 2·1, 95% CI 1·2–3·1; p<0·0001), as was the rate of secondary bacterial or fungal infection (RR 2·0, 95% CI 1·0–3·8; p=0·04).

10 McGee S

Hirschmann J Use of corticosteroids in treating infectious diseases. 17 Lee FE-H

Walsh EE

Falsey AR The effect of steroid use in hospitalized adults with respiratory syncytial virus-related illness. Corticosteroids have been investigated for respiratory syncytial virus (RSV) in clinical trials in children, with no conclusive evidence of benefit and are therefore not recommended.An observational study of 50 adults with RSV infection, in which 33 (66%) were given corticosteroids, suggested impaired antibody responses at 28 days in those given corticosteroids.

18 Chen N

Zhou M

Dong X

et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. 19 Ashbaugh DG

Bigelow DB

Petty TL

Levine BE Acute respiratory distress in adults. 20 Lewis SR

Pritchard MW

Thomas CM

Smith AF Pharmacological agents for adults with acute respiratory distress syndrome. Life-threatening acute respiratory distress syndrome occurs in 2019-nCoV infection.However, generalising evidence from acute respiratory distress syndrome studies to viral lung injury is problematic because these trials typically include a majority of patients with acute respiratory distress syndrome of non-pulmonary or sterile cause. A review of treatments for acute respiratory distress syndrome of any cause, based on six studies with a total of 574 patients,concluded that insufficient evidence exists to recommend corticosteroid treatment.

3 Huang C

Wang Y

Li X

et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. , 18 Chen N

Zhou M

Dong X

et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. 21 Venkatesh B

Finfer S

Cohen J

et al. Adjunctive glucocorticoid therapy in patients with septic shock. , 22 Annane D

Renault A

Brun-Buisson C

et al. Hydrocortisone plus fludrocortisone for adults with septic shock. 21 Venkatesh B

Finfer S

Cohen J

et al. Adjunctive glucocorticoid therapy in patients with septic shock. , 22 Annane D

Renault A

Brun-Buisson C

et al. Hydrocortisone plus fludrocortisone for adults with septic shock. 23 Fougères E

Teboul J-L

Richard C

Osman D

Chemla D

Monnet X Hemodynamic impact of a positive end-expiratory pressure setting in acute respiratory distress syndrome: importance of the volume status. Septic shock has been reported in seven (5%) of 140 patients with 2019-nCoV included in published reports as of Jan 29, 2020.Corticosteroids are widely used in septic shock despite uncertainty over their efficacy. Most patients in septic shock trials have bacterial infection, leading to vasoplegic shock and myocardial insufficiency.In this group, there is potential that net benefit might be derived from steroid treatment in severe shock.However, shock in severe hypoxaemic respiratory failure is often a consequence of increased intrathoracic pressure (during invasive ventilation) impeding cardiac filling, and not vasoplegia.In this context, steroid treatment is unlikely to provide a benefit.

No clinical data exist to indicate that net benefit is derived from corticosteroids in the treatment of respiratory infection due to RSV, influenza, SARS-CoV, or MERS-CoV. The available observational data suggest increased mortality and secondary infection rates in influenza, impaired clearance of SARS-CoV and MERS-CoV, and complications of corticosteroid therapy in survivors. If it is present, the effect of steroids on mortality in those with septic shock is small, and is unlikely to be generalisable to shock in the context of severe respiratory failure due to 2019-nCoV.

Overall, no unique reason exists to expect that patients with 2019-nCoV infection will benefit from corticosteroids, and they might be more likely to be harmed with such treatment. We conclude that corticosteroid treatment should not be used for the treatment of 2019-nCoV-induced lung injury or shock outside of a clinical trial.

JKB is a member of the WHO panel on clinical management for 2019-nCoV. CDR and JEM declare no competing interests.

Article Info Publication History Identification DOI: https://doi.org/10.1016/S0140-6736(20)30317-2 Copyright © 2020 Elsevier Ltd. All rights reserved. ScienceDirect Access this article on ScienceDirect