Table 4a. Corticosteroids: Selected Clinical Data

Last Updated: February 11, 2021

The clinical trials described in this table do not represent all the trials that the Panel reviewed while developing the recommendations for corticosteroids. The studies summarized below are those that have had the greatest impact on the Panel’s recommendations.

Table 4a. Corticosteroids: Selected Clinical Data
Study Design Methods Results Limitations and Interpretation
Dexamethasone in Hospitalized Patients With COVID-19—Preliminary Report (RECOVERY Trial)1

Multi-center, randomized open-label adaptive trial in hospitalized patients with suspected or confirmed COVID-19 (n = 6,425)

Country: United Kingdom

Key Inclusion Criteria:
  • Hospitalization with clinically suspected or laboratory-confirmed SARS-CoV-2 infection

Key Exclusion Criteria:

  • Physician determination that risks of participation too great based on patient’s medical history or an indication for corticosteroid therapy outside of the study

Interventions:

  • Patients randomized 2:1 to receive:
    • Dexamethasone 6 mg PO or IV once daily plus SOC for up to 10 days or until hospital discharge, whichever came first, or
    • SOC alone

Primary Endpoints:

  • All-cause mortality at 28 days after randomization
Number of Participants:
  • Dexamethasone plus SOC (n = 4,321) and SOC (n = 2,104)

Participant Characteristics:

  • Mean age was 66 years.
  • 64% of participants were men.
  • 56% of participants had ≥1 comorbidity; 24% had diabetes.
  • 89% of participants had laboratory-confirmed SARS-CoV-2 infection.
  • At randomization, 16% of participants received invasive mechanical ventilation or ECMO, 60% required supplemental oxygen but not invasive ventilation, and 24% required no oxygen supplementation.
  • 0% to 3% of the participants in both arms received RDV, HCQ, LPV/RTV, or tocilizumab; approximately 8% of participants in SOC alone arm received dexamethasone after randomization.

Outcomes:

  • 28-day mortality was 22.9% in dexamethasone arm and 25.7% in SOC arm (age-adjusted rate ratio 0.83; 95% CI, 0.75–0.93; P < 0.001).
  • The treatment effect of dexamethasone varied by baseline severity of COVID-19. Survival benefit appeared greatest among participants who required invasive mechanical ventilation at randomization. Among these participants, 28-day mortality was 29.3% in dexamethasone arm vs. 41.4% in SOC arm (rate ratio 0.64; 95% CI, 0.51–0.81).
  • Among patients who required supplemental oxygen but not mechanical ventilation at randomization, 28-day mortality was 23.3% in dexamethasone arm vs. 26.2% in SOC arm (rate ratio 0.82; 95% CI, 0.72–0.94).
  • No survival benefit in participants who did not require oxygen therapy at enrollment. Among these participants, 28-day mortality was 17.8% in dexamethasone arm vs. 14.0% in SOC arm (rate ratio 1.19; 95% CI, 0.91–1.55).
Limitations:
  • Open label study
  • This preliminary study analysis did not include the results for key secondary endpoints (e.g., cause-specific mortality, need for renal replacement), AEs, and the efficacy of dexamethasone in key subgroups (e.g., patients with comorbidities).
  • Study participants with COVID-19 who required oxygen (but not mechanical ventilation) had variable disease severity; it is unclear whether all patients in this heterogeneous group derived benefit from dexamethasone, or whether benefit is restricted to those requiring higher levels of supplemental oxygen or oxygen delivered through a high-flow device.
  • The age distribution of participants differed by respiratory status at randomization.
  • The survival benefit of dexamethasone for mechanically ventilated patients aged >80 years is unknown because only 1% of the participants in this group were ventilated.
  • It is unclear whether younger patients were more likely to receive mechanical ventilation than patients aged >80 years, given similar disease severity at baseline, with older patients preferentially assigned to oxygen therapy.
  • The high baseline mortality of this patient population may limit generalizability of the study results to populations with a lower baseline mortality.

Interpretation:

  • In hospitalized patients with severe COVID-19 who required oxygen support, using dexamethasone 6 mg daily for up to 10 days reduced mortality at 28 days, with the greatest benefit seen in those who were mechanically ventilated at baseline.
  • There was no observed survival benefit of dexamethasone in patients who did not require oxygen support at baseline.
Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta-Analysis (REACT Working Group)2

Meta-analysis of 7 RCTs of corticosteroids in critically ill patients with COVID-19 (n = 1,703)

Countries: Multinational

Key Inclusion Criteria:
  • RCTs evaluating corticosteroids in critically ill patients with COVID-19 (identified via comprehensive search of ClinicalTrials.gov, Chinese Clinical Trial Registry, and EU Clinical Trials Register)

Interventions:

  • Corticosteroids (i.e., dexamethasone, hydrocortisone, methylprednisolone)
  • Usual care or placebo

Primary Endpoint:

  • All-cause mortality up to 30 days after randomization
Number of Participants:
  • Corticosteroids (n = 678) and usual care or placebo (n = 1,025)

Participant Characteristics:

  • Median age was 60 years.
  • 29% of patients were women.
  • 1,559 patients (91.5%) were on mechanical ventilation.
  • 47% of patients were on vasoactive agents at randomization across the 6 trials that reported this information.

Outcomes

  • Mortality was assessed at 28 days in 5 trials, 21 days in 1 trial, and 30 days in 1 trial.
  • Reported all-cause mortality at 28 days: Death occurred in 222 of 678 patients (32.7%) in corticosteroids group vs. 425 of 1,025 patients (41.5%) in usual care or placebo group; summary OR 0.66 (95% CI, 0.53–0.82; P < 0.001).
  • The fixed-effect summary ORs for the association with all-cause mortality were:
    • Dexamethasone: OR 0.64 (95% CI, 0.50–0.82; P < 0.001) in 3 trials with 1,282 patients
    • Hydrocortisone: OR 0.69 (95% CI, 0.43–1.12; P = 0.13) in 3 trials with 374 patients.
    • Methylprednisolone: OR 0.91 (95% CI, 0.29–2.87; P = 0.87) in 1 trial with 47 patients
    • For patients on mechanical ventilation (n = 1,559): OR 0.69 (95% CI, 0.55–0.86), with mortality of 30% for corticosteroids vs. 38% for usual care or placebo
    • For patients not on mechanical ventilation (n = 144): OR 0.41 (95% CI, 0.19–0.88) with mortality of 23% for corticosteroids vs. 42% for usual care or placebo
  • Across the 6 trials that reported SAEs, 18.1% of patients randomized to corticosteroids and 23.4% randomized to usual care or placebo experienced SAEs.
Limitations:
  • The design of the trials included in the meta-analysis differed in several ways, including the following:
    • Definition of critical illness
    • Specific corticosteroid used
    • Dose of corticosteroid
    • Duration of corticosteroid treatment
    • Type of control group (i.e., usual care or placebo)
    • Reporting of SAEs
  • The RECOVERY trial accounted for 59% of the participants, and 3 trials enrolled <50 patients each.
  • Some studies confirmed SARS-CoV-2 infection for participant inclusion while others enrolled participants with either probable or confirmed infection.
  • Although the risk of bias was low in 6 of the 7 trials, it was assessed as “some concerns” for 1 trial (which contributed only 47 patients).

Interpretation:

  • Systemic corticosteroids decrease 28-day mortality in critically ill patients with COVID-19 without safety concerns.
  • Most of the participants were from the RECOVERY trial, thus the evidence of benefit in the meta-analysis is strongest for dexamethasone, the corticosteroid used in the RECOVERY trial.
Methylprednisolone as Adjunctive Therapy for Patients Hospitalized With COVID-19 (Metcovid): A Randomised, Double-Blind, Phase IIb, Placebo-Controlled Trial3

Randomized, double-blind, placebo-controlled, single-center study of short-course methylprednisolone in hospitalized patients with confirmed or suspected COVID-19 pneumonia (n = 416)

Country: Brazil

Key Inclusion Criteria:
  • Aged ≥18 years
  • Suspected or confirmed COVID-19
  • SpO2 ≤94% on room air or while using supplementary oxygen or under invasive mechanical ventilation

Key Exclusion Criteria:

  • Hypersensitivity to methylprednisolone
  • Chronic use of corticosteroids or immunosuppressive agents
  • HIV, decompensated cirrhosis, chronic renal failure

Interventions:

  • Methylprednisolone IV 0.5 mg/kg twice daily for 5 days
  • Placebo (saline) IV

Primary Endpoint:

  • Mortality by Day 28

Secondary Endpoint:

  • Early mortality at Days 7 and 14
  • Need for mechanical ventilation by Day 7
  • Need for insulin by Day 28
  • Positive blood culture at Day 7, sepsis by Day 28
  • Mortality by Day 28 in specified subgroups
Number of Participants:
  • mITT analysis (n = 393): Methylprednisolone (n = 194) and placebo (n = 199)

Participant Characteristics:

  • Mean age was 55 years.
  • 65% of patients were men.
  • 29% of patients had diabetes.
  • At enrollment, 34% of participants in each group required invasive mechanical ventilation; 51% in methylprednisolone group and 45% in placebo group required supplemental oxygen.
  • Median time from illness onset to randomization was 13 days (IQR 9–16).
  • None of the participants received anti-IL-6, anti-IL-1, RDV, or convalescent plasma.
  • Hydrocortisone use for shock among patients was 8.7% in methylprednisolone group and 7.0% in placebo group.

Primary Outcomes:

  • No difference in 28-day mortality: 37.1% in methylprednisolone arm vs. 38.2% in placebo arm (HR 0.92; 95% CI, 0.67–1.28; P = 0.63).

Secondary Outcomes:

  • No difference between groups in early mortality at Day 7 (HR 0.68; 95% CI, 0.43–1.06) or Day 14 (HR 0.82; 95% CI, 0.57–1.18)
  • No difference in need for mechanical ventilation by Day 7: 19.4% of methylprednisolone recipients vs. 16.8% of placebo recipients (P = 0.65)
  • No significant difference between the methylprednisolone and placebo groups in need for insulin (59.5% vs. 49.4% of patients), positive blood cultures at Day 7 (8.3% vs. 8.0% of patients), or sepsis by Day 28 (38.1% vs. 38.7% of patients)
  • In post hoc analysis, 28-day mortality in participants aged >60 years was lower in methylprednisolone group than in placebo group (46.6% vs. 61.9%; HR 0.63; 95% CI, 0.41–0.98).
Limitations:
  • The median days from illness onset to randomization was longer than in other corticosteroid studies.
  • The high baseline mortality of this patient population may limit generalizability of the study results to populations with a lower baseline mortality.

Interpretation:

  • Use of weight-based methylprednisolone for 5 days did not reduce overall 28-day mortality.
  • In a post hoc subgroup analysis, mortality among those aged >60 years was lower in the methylprednisolone group than in the placebo group.
Effect of Dexamethasone on Days Alive and Ventilator-Free in Patients With Moderate or Severe Acute Respiratory Distress Syndrome and COVID-19: The CoDEX Randomized Clinical Trial4

Multicenter, randomized, clinical trial in patients with COVID-19 and moderate to severe ARDS (n = 299)

Country: Brazil

Key Inclusion Criteria:
  • Aged ≥18 years
  • Confirmed or suspected COVID-19
  • On mechanical ventilation within 48 hours of meeting criteria for moderate to severe ARDS with PaO2/FiO2 ≤200 mm Hg

Key Exclusion Criteria:

  • Recent corticosteroid use
  • Use of immunosuppressive drugs in the past 21 days
  • Expected death in next 24 hours

Interventions:

  • Dexamethasone 20 mg IV daily for 5 days, then 10 mg IV daily for 5 days or until ICU discharge plus SOC
  • SOC alone

Primary Endpoint:

  • Mean number of days alive and free from mechanical ventilation by Day 28

Secondary Endpoints:

  • All-cause mortality at Day 28
  • ICU-free days by Day 28
  • Duration of mechanical ventilation by Day 28
  • Score on 6-point WHO ordinal scale at Day 15
  • SOFA score at 7 days
  • Components of the primary outcome or in the outcome of discharged alive within 28 days
Number of Participants:
  • ITT analysis (n = 299): Dexamethasone plus SOC (n = 151) and SOC alone (n = 148)

Participant Characteristics:

  • Dexamethasone group included more women than the SOC group (40% vs. 35%), more patients with obesity (31% vs. 24%), and fewer patients with diabetes (38% vs. 47%).
  • Other baseline characteristics were similar for the dexamethasone and SOC groups:
    • Mean age was 60 vs. 63 years; vasopressor use by 66% vs. 68% of patients; mean PaO2/FiO2 of 131 mm Hg vs. 133 mm Hg.
    • Median time from symptom onset to randomization was 9–10 days.
    • Median time from mechanical ventilation to randomization was 1 day.
    • No patients received RDV; anti-IL-6 and convalescent plasma were not widely available.
    • Median duration of dexamethasone therapy was 10 days (IQR 6–10 days).
    • 35% of patients in SOC alone group also received corticosteroids.

Primary Outcomes:

  • The mean number of days alive and free from mechanical ventilation by Day 28 was higher in the dexamethasone group than in the SOC group (6.6 vs. 4.0 days, estimated difference of 2.3 days; 95% CI, 0.2–4.4; P = 0.04).

Secondary Outcomes:

  • There were no differences between the dexamethasone and SOC groups for the following outcomes:
    • All-cause mortality at Day 28 (56.3% vs. 61.5%: HR 0.97; 95% CI, 0.72–1.31; P = 0.85)
    • ICU-free days by Day 28 (mean of 2.1 vs. 2.0 days; P = 0.50)
    • Duration of mechanical ventilation by Day 28 (mean of 12.5 vs.13.9 days; P = 0.11)
    • Score on 6-point WHO ordinal scale at Day 15 (median score of 5 for both groups)
  • The mean SOFA score at 7 days was lower in the dexamethasone group than in the SOC group (6.1 vs. 7.5, difference -1.16; 95% CI, -1.94 to -0.38; P = 0.004).
  • The following safety outcomes were comparable for dexamethasone and SOC groups: need for insulin (31.1% vs. 28.4%), new infections (21.9% vs. 29.1%), bacteremia (7.9% vs. 9.5%), and other SAEs (3.3% vs. 6.1%).
  • In post hoc analysis, the dexamethasone group had a lower cumulative probability of death or mechanical ventilation at Day 15 than the SOC group (67.5% vs. 80.4%; OR 0.46; 95% CI, 0.26–0.81; P = 0.01).
Limitations:
  • Open-label study
  • The study was underpowered to assess some outcomes because it stopped enrollment after data from the RECOVERY trial were released.
  • During the study, 35% of the patients in the SOC group received corticosteroids for shock, bronchospasm, or other reasons.
  • Patients who were discharged from the hospital before 28 days were not followed for rehospitalization or mortality.
  • The high baseline mortality of the patient population may limit generalizability of the study results to populations with a lower baseline mortality.

Interpretation:

  • Compared with SOC alone, dexamethasone at a higher dose than used in the RECOVERY trial plus SOC increased the number of days alive and free of mechanical ventilation over 28 days of follow-up in patients with COVID-19 and moderate to severe ARDS.
  • Dexamethasone was not associated with an increased risk of AEs in this population.
  • More than one-third of those randomized to the standard care alone group also received corticosteroids; it is impossible to determine the effect of corticosteroid use in these patients on the overall study outcomes.
Effect of Hydrocortisone on 21-Day Mortality or Respiratory Support Among Critically Ill Patients With COVID-19: A Randomized Clinical Trial5

Multicenter, randomized, double-blind, sequential trial in patients with confirmed or suspected COVID-19 and acute respiratory failure (n = 149)

Country: France

Key Inclusion Criteria:
  • Aged ≥18 years
  • Confirmed SARS-CoV-2 infection or radiographically suspected COVID-19, with at least 1 of 4 severity criteria:
    • Need for mechanical ventilation with PEEP ≥5 cm H2O
    • High-flow oxygen with PaO2/FiO2 <300 mm Hg and FiO2 ≥50%
    • Reservoir mask oxygen with PaO2/FiO2 <300 mm Hg (estimated)
    • Pneumonia severity index >130 (scoring table)

Key Exclusion Criteria:

  • Septic shock
  • Do-not-intubate orders

Interventions:

  • Continuous infusion hydrocortisone 200 mg/day until Day 7, then hydrocortisone 100 mg/day for 4 days, and then hydrocortisone 50 mg/day for 3 days, for a total treatment duration of 14 days
  • Patients who showed clinical improvement by Day 4 were switched to a shorter 8-day regimen.

Primary Endpoint:

  • Treatment failure (defined as death or persistent dependency on mechanical ventilation or high-flow oxygen) by Day 21

Secondary Endpoints:

  • Need for intubation, rescue strategies, or oxygenation (i.e., change in PaO2/FiO2)
  • Nosocomial infections on Day 28
  • Clinical status on Day 21
Number of Participants:
  • ITT analysis (n = 149 participants): Hydrocortisone (n = 76) and placebo (n = 73)

Participant Characteristics:

  • Mean age of participants was 62 years; 70% were men; median BMI was 28.
  • 96% of participants had confirmed SARS-CoV-2 infection.
  • Median symptom duration before randomization was 9 days in hydrocortisone group vs. 10 days in placebo group.
  • 81% of the patients overall were mechanically ventilated, and 24% in hydrocortisone group and 18% in placebo group were receiving vasopressors.
  • Among the patients receiving concomitant COVID-19 treatment, 3% received RDV, 14% LPV/RTV, 13% HCQ, and 34% HCQ plus AZM.
  • Median treatment duration was 10.5 days in hydrocortisone group vs. 12.8 days in placebo group (P = 0.25).

Primary Outcome:

  • There was no difference in the proportion of patients with treatment failure by Day 21, which occurred in 32 of 76 patients (42.1%) in hydrocortisone group and 37 of 73 patients (50.7%) in placebo group (difference -8.6%; 95% CI, -24.9% to 7.7%; P = 0.29).

Secondary Outcomes:

  • There was no difference between the groups in the need for intubation, rescue strategies, or oxygenation (i.e., change in PaO2/FiO2).
    • Among the patients who did not require mechanical ventilation at baseline, 8 of 16 patients (50%) in hydrocortisone group required subsequent intubation vs. 12 of 16 (75%) in placebo group.
  • 3 SAEs were reported (cerebral vasculitis, cardiac arrest due to PE, and intra-abdominal hemorrhage from anticoagulation for PE); all occurred in the hydrocortisone group, but none were attributed to the intervention.
    • There was no difference between the groups in proportion of patients with nosocomial infections on Day 28.
  • In post hoc analysis, clinical status on Day 21 did not significantly differ between the groups except for fewer deaths in the hydrocortisone group (14.7% of patients died vs. 27.4% in placebo group; P = 0.06):
    • By Day 21, 57.3% of patients in hydrocortisone group vs. 43.8% in placebo group were discharged from the ICU and 22.7% in hydrocortisone group vs. 23.3% in placebo group were still mechanically ventilated.
Limitations:
  • Small sample size. Planned sample size of 290, but 149 enrolled because study was terminated early after the release of results from the RECOVERY trial.
  • Limited information about comorbidities (e.g., hypertension)
  • Participants’ race and/or ethnicity were not reported.
  • Nosocomial infections were recorded but not adjudicated.

Interpretation:

  • Compared to placebo, hydrocortisone did not reduce treatment failure (defined as death or persistent respiratory support) at Day 21 in ICU patients with COVID-19 and acute respiratory failure.
  • Because this study was terminated early, it is difficult to make conclusions about the efficacy and safety of hydrocortisone therapy.
  • The starting dose of hydrocortisone used in this study were slightly higher than the 6 mg dose of dexamethasone used in the RECOVERY study. The hydrocortisone dose was adjusted according to clinical response.
Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial (CAPE COD)6

Randomized, embedded, multifactorial, adaptive platform trial of patients with severe COVID-19 (n = 403)

Countries: Multinational

Key Inclusion Criteria:
  • Aged ≥18 years
  • Presumed or confirmed SARS-CoV-2 infection
  • ICU admission for respiratory or cardiovascular organ support

Key Exclusion Criteria:

  • Presumed imminent death
  • Systemic corticosteroid use
  • >36 hours since ICU admission

Interventions:

  • Hydrocortisone 50 mg 4 times daily for 7 days
  • Septic shock-based hydrocortisone 50 mg 4 times daily for the duration of shock
  • No hydrocortisone
Primary Endpoint:
  • Days free of respiratory and cardiovascular organ support up to Day 21 (For this ordinal outcome, patients who died were assigned -1 day.)
Secondary Endpoints:
  • In-hospital mortality
  • SAEs
Number of Participants
  • mITT analysis (n = 384): Fixed-dose hydrocortisone (n=137), shock-based hydrocortisone (n = 146), and no hydrocortisone (n = 101)

Participant Characteristics:

  • Mean age was 60 years.
  • 71% of patients were men.
  • Mean BMI was 29.7–30.9.
  • 50% to 64% of patients received mechanical ventilation.

Primary Outcomes:

  • No difference between the groups in organ-support free-days at Day 21 (median of 0 days in each group).
  • Compared to the no hydrocortisone group, median adjusted OR for the primary outcome:
    • OR 1.43 (95% credible interval, 0.91–2.27) with 93% Bayesian probability of superiority for the fixed-dose hydrocortisone group
    • OR 1.22 (95% credible interval, 0.76–1.94) with 80% Bayesian probability of superiority for the shock-based hydrocortisone group

Secondary Outcomes:

  • No difference between the groups in mortality; 30%, 26%, and 33% of patients died in the fixed-dose, shock-based, and no hydrocortisone groups, respectively.
  • SAEs reported in 3%, 3%, and 1% of patients in the fixed-dose, shock-based, and no hydrocortisone groups, respectively.
Limitations:
  • Early termination following release of RECOVERY study results
  • Randomized study, but open label

Interpretation:

  • Corticosteroids did not significantly increase support-free days in either the fixed-dose hydrocortisone or the shock-dependent hydrocortisone group, although the early termination of the trial led to limited power to detect difference between the study arms.
Efficacy Evaluation of Early, Low-Dose, Short-Term Corticosteroids in Adults Hospitalized with Non-Severe COVID-19 Pneumonia: A Retrospective Cohort Study7

Retrospective cohort study in patients with nonsevere COVID-19 pneumonia and propensity score-matched controls (n = 55 matched case-control pairs)

Country: China

Key Inclusion Criteria:
  • Confirmed COVID-19
  • Pneumonia on chest CT scan
  • Aged ≥16 years

Key Exclusion Criteria:

  • Severe pneumonia defined as having any of the following: respiratory distress, respiratory rates >30 breaths/min, SpO2 <93%, oxygenation index <300 mm Hg, mechanical ventilation, or shock
  • Immediate ICU admission upon hospitalization
  • Use of corticosteroids after progression to severe disease

Interventions:

  • Early, low-dose corticosteroids:
    • IV methylprednisolone 20 mg/day or 40 mg/day for 3–5 days
    • PO prednisone 20 mg/day for 3 days
  • No corticosteroids
Primary Endpoint:
  • Rates of severe disease and death
Secondary Endpoint:
  • Duration of fever
  • Virus clearance time
  • Length of hospital stay
  • Use of antibiotics
Number of Participants:
  • Corticosteroids (n = 55): IV methylprednisolone (n=50) and prednisone (n = 5)
  • No corticosteroids (n = 55 matched controls chosen from 420 patients who did not receive corticosteroids)

Participant Characteristics:

  • Median age was 58–59 years.
  • Median oxygen saturation was 95%.
  • 42% of patients in corticosteroids group and 46% in no corticosteroids group had comorbidities, including 35% to 36% with hypertension and 11% to 13% with diabetes.

Primary Outcomes:

  • 7 patients (12.7%) in the corticosteroids group developed severe disease vs. 1 (1.8%) in the no corticosteroids group (P = 0.03); time to severe disease: HR 2.2 (95% CI, 2.0–2.3; P < 0.001).
  • There was 1 death in the methylprednisolone group vs. none in the no corticosteroids group.

Secondary Outcomes:

  • Each of the following outcomes was longer in the corticosteroids group than in the no corticosteroids group (P < 0.001 for each outcome): duration of fever (5 vs. 3 days), virus clearance time (18 vs. 11 days), and length of hospital stay (23 vs. 15 days).
  • More patients in the corticosteroids group than in the no corticosteroids group were prescribed antibiotics (89% vs. 24%) and antifungal therapy (7% vs. 0%).
Limitations:
  • Retrospective, case-control study
  • Small sample size (55 case-control pairs)
  • Corticosteroid therapy was selected preferentially for patients who had more risk factors for severe progression of COVID-19; the propensity score matching may not have adjusted for some of the unmeasured confounders.
  • Selection bias in favor of the no corticosteroids group may have been introduced by excluding patients who used corticosteroids after progression to severe disease from the study.

Interpretation:

  • In this nonrandomized, case-control study, methylprednisolone therapy in patients with nonsevere COVID-19 pneumonia was associated with worse outcomes, but this finding is difficult to interpret because of potential confounding factors.
  • It is unclear whether the results for methylprednisolone therapy can be generalized to therapy with other corticosteroids.