| Bias | Author's judgement | Support for judgement |
| Confounding |
Serious |
Quote: "A overlap weight propensity score for treatment allocation was estimated from a multivariable model containing patient age, sex, PaO2/FiO2, lactate, C Reactive Protein, Platelets, ICU admission and treatment with corticosteroids, enoxaparin, azithromycin or hydroxychloroquine. Dose of hydrocortisone and methylprednisolone were converted to equivalent doses of dexamethasone. The overlap weight propensity score was then applied to a logistic regression modelling the primary outcome (in-hospital mortality)" Comment: gender/age/diabetes balanced between groups. Obesity/COPD, immunosupression not assessed as confounders. Authors controlled for some post-intervention such as admission to ICU, the use of some medications such as hydroxychloroquine, enoxaparin, and azithromycin, these are time-varying confounding variables might influence the decision of starting corticosteroids. |
| Selection of participants into the study |
Serious |
Quote: "The patients were classified into two cohorts, based on exposure to corticosteroids during hospitalization"
Quote: "Clinical, demographic and laboratory data from all adult patients who were admitted to the hospital and had a positive test for SARS-CoV2 from biological material were recorded at admission."
There was no information about when patient started corticosteroids. Patients who had outcome early after the inclusion in the cohort would be more likely to be classified in non-exposed group.
Quote: "Twenty seven patients were excluded from the analysis (one patient was younger than 18 years, and 26 patients were still hospitalized at the time of the analysis)"
Comment:Patients were entered into the treatment group if they were exposed to corticosteroids during the hospital admission. There is no further information on the timeline of the study but there is a risk of immortal time bias because baseline was hospital admittance and it is unclear whether start of treatment is the same. Patients in the corticosteroids cohort were more hypoxic and the inflammation markers (CRP and LDH) were different between study groups. |
| Intervention classification |
Low |
Quote: "Clinical, demographic and laboratory data from all adult patients who were admitted to the hospital and had a positive test for SARS-CoV2 from biological material were recorded at admission" "The patients were classified into two cohorts, based on exposure to corticosteroids during hospitalization""Median equivalent doses of dexamethasone dose (cumulative dose/days of therapy) was 10 mg (1st-3rd quartile 4.5-20). Patients who were never admitted to ICU received equivalent doses of dexamethasone of 8 mg (4-16.1)" Comment: Data was extracted from the electronic medical charts of consecutive patients who had been admitted during the pandemic crisis of Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2), between February 20th and May 10th 2020. |
| Deviation from intended intervention |
NI |
Comment: The information reported is inadequate to assess whether there are deviations from the intended intervention beyond what would be expected in usual practice. It is unclear how many participants per arm received these co-interventions during follow-up. Inadequate information to assess risk for the outcome mortality. |
| Missing data |
Low |
Comment: 1454 included, 1403 analyzed (27 patients were excluded from the analysis: one patient was younger than 18 years, and 26 patients were still hospitalized at the time of the analysis). Missing values were assessed and replaced by mean substitution. Risk assessed to be low for outcome: mortality |
| Measurements of outcomes |
Low |
Comment: Time to death is an observer reported outcome whose assessment cannot be influenced by knowledge of the intervention assignment. Risk assessed to be low for outcome: mortality |
| Selection of the reported results |
Moderate |
Comment: The outcomes and analyses are clearly defined in the Methods section. There is no a-priori registered protocol or statistical analysis plan available. Risk assessed to be moderate for the outcome: mortality |