More details about outcomes and disease severity
List of outcomes:
On the 1st of February 2021, the protocol of the review on pharmacological and nonpharmacological treatments was amended to consider only the following outcomes:
Clinical improvement (D28 / D60 or more) defined as a hospital discharge or improvement on the scale used by trialists to evaluate clinical progression and recovery. We will describe the scale and the threshold used to define improvement where appropriate.
WHO Clinical Progression Score level 7 or above (i.e., Mechanical ventilation +/- additional organ support (ECMO, vasopressors or dialysis) OR death (D28 / D60 or more)
All-cause mortality (D28 / D60 or more)
Viral negative conversion (D7)
Incidence of any adverse events
Incidence of serious adverse events (SAEs)
Time to clinical improvement
Time to WHO Clinical Progression Score level 7 or above
Time to death
Time to viral negative conversion
Disease severity was classified as described below according to the clinical status or clinical management of patients. This classification relies on existing classification and clinical expertise (WHO 2020a, WHO 2020b). We considered the description of eligibility criteria as well as the baseline characteristics of participants and classified the severity as follow:
- Mild disease ambulatory — "outpatients" whose clinical symptoms are mild with no sign of pneumonia on imaging.
- Mild disease — clinical symptoms requiring hospitalization but no need for supplemental oxygen
- Moderate disease — fever and respiratory symptoms with radiological findings of pneumonia and requiring standard oxygen therapy O2 (3–5 L/min).
- Severe disease — meeting any of the following criteria:
- respiratory distress (≧ 30 breaths/min)
- oxygen saturation ≤ 93% at rest in ambient air or oxygen saturation ≤97% with O2 > 5 L/min
- PaO2/FiO2 ≦ 300 mmHg (l mmHg=0.133 kPa). PaO2/FiO2 in high-altitude areas (> 1000 m above sea level) is corrected by the following formula: PaO2/FiO2 x [atmospheric pressure (mmHg)/760]
- patients hospitalized on Non-invasive ventilation (NIV)/High flow Nasal oxygen (HFNO).
- Critical disease — cases meeting any of the following criteria
- respiratory failure requiring invasive mechanical ventilation
- other organ failure requiring Intensive Care Unit care
Worth mentioning that since the classification of severity class was heterogenous among studies, we reclassified the participant disease severity based on the above severity criteria. Consequently, the severity reported by investigators might differ from the severity reported in this review.