| Bias | Author's judgement | Support for judgement |
| Confounding |
Serious |
"Quote:"All of the factors judged to be clinically relevant to the study outcome were considered possible confounders in the multivariable model" "The collected data included demographic data, the Charlson Comorbidity Index (CCI) unadjusted for age, date of onset of symptoms, signs and symptoms at the time of presentation, laboratory findings, and disease severity at the time of starting the study treatment" Comments: No imbalances for age, sex, CCI and obesity between groups (Table 1). The study population was divided into two groups based on when they started treatment from the onset of symptoms. |
| Selection of participants into the study |
Serious |
Quote: "The study population was divided into two groups: an early treatment (ET) group of patients who started LPV+HCQ treatment <5 days from the onset of symptoms; and a delayed treatment (DT) group of patients who started treatment ≥5 days from the onset of symptoms" "There were no significant between-groups differences in terms of their demographic characteristics or disease severity, but the patients in the DT group had a higher burden of co-morbidities (median CCI=3, IQR 1-5 vs 2, IQR 0-3; p=0.041)... They also had higher median white blood cell (p=0.017) and neutrophil counts (p=0.030), higher median C-reactive protein levels (p=0.045) and lower median PaO2 levels (p <0.001)" "The patients were included in the intention-to-treat analysis if they had received at least one dose of the scheduled treatment. Patients who died on the day of starting treatment were excluded from the analysis" Comments:"Retrospective study, no adjustement for selection bias" "A priori the start of treatment and follow-up are the same for participants depending on the study group" |
| Intervention classification |
Low |
Quote: "The study population was divided into two groups: an early treatment (ET) group of patients who started LPV+HCQ treatment <5 days from the onset of symptoms; and a delayed treatment (DT) group of patients who started treatment ≥5 days from the onset of symptoms" "The patients’ clinical status was monitored from the day of treatment initiation to day 30, and data concerning the requirement of oxygen support, laboratory values, serious adverse events, and discharge or death were recorded" Comments: "No details about how the numbers of days from the onset of symptoms was collected, or the data source" |
| Deviation from intended intervention |
NI |
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 |
Qoute: "Forty patients (22.7%) discontinued the treatment before completing the minimum 5-day course, with no significant difference between the ET and DT group (16.3% vs 25.5%; p=0.296). The reasons for discontinuing were a switch to another treatment protocol (18, 45%), adverse events (n=14, 35%), early discharge (n=5, 12.5%), death (n=2, 5%), and possible interaction with other treatments (n=1)" Comment: The living status of the patients discharged before day 30 was assessed by means of telephone calls to the patients themselves) Risk assessed to be low for outcome: mortality |
| Measurements of outcomes |
Moderate |
Quote: "The living status of the patients discharged before day 30 was assessed by means of telephone calls to the patients themselves" Commnent: Observer reported outcome. Risk assessed to be low for outcome: mortality |
| Selection of the reported results |
Moderate |
Comment: There is no a-priori registered protocol or statistical analysis plan available Risk assessed to be moderate for the outcome: mortality. |