Severity of respiratory failure at admission and in-hospital mortality in patients with COVID-19: a prospective observational multicentre study

BMJ Open. 2020 Oct 10;10(10):e043651. doi: 10.1136/bmjopen-2020-043651.


Objectives: COVID-19 causes lung parenchymal and endothelial damage that lead to hypoxic acute respiratory failure (hARF). The influence of hARF severity on patients' outcomes is still poorly understood.

Design: Observational, prospective, multicentre study.

Setting: Three academic hospitals in Milan (Italy) involving three respiratory high dependency units and three general wards.

Participants: Consecutive adult hospitalised patients with a virologically confirmed diagnosis of COVID-19. Patients aged <18 years or unable to provide informed consent were excluded.

Interventions: Anthropometrical, clinical characteristics and blood biomarkers were assessed within the first 24 hours from admission. hARF was graded as follows: severe (partial pressure of oxygen to fraction of inspired oxygen ratio (PaO2/FiO2) <100 mm Hg); moderate (PaO2/FiO2 101-200 mm Hg); mild (PaO2/FiO2 201-300 mm Hg) and normal (PaO2/FiO2 >300 mm Hg).

Primary and secondary outcome measures: The primary outcome was the assessment of clinical characteristics and in-hospital mortality based on the severity of respiratory failure. Secondary outcomes were intubation rate and application of continuous positive airway pressure during hospital stay.

Results: 412 patients were enrolled (280 males, 68%). Median (IQR) age was 66 (55-76) years with a PaO2/FiO2 at admission of 262 (140-343) mm Hg. 50.2% had a cardiovascular disease. Prevalence of mild, moderate and severe hARF was 24.4%, 21.9% and 15.5%, respectively. In-hospital mortality proportionally increased with increasing impairment of gas exchange (p<0.001). The only independent risk factors for mortality were age ≥65 years (HR 3.41; 95% CI 2.00 to 5.78, p<0.0001), PaO2/FiO2 ratio ≤200 mm Hg (HR 3.57; 95% CI 2.20 to 5.77, p<0.0001) and respiratory failure at admission (HR 3.58; 95% CI 1.05 to 12.18, p=0.04).

Conclusions: A moderate-to-severe impairment in PaO2/FiO2 was independently associated with a threefold increase in risk of in-hospital mortality. Severity of respiratory failure is useful to identify patients at higher risk of mortality.

Trial registration number: NCT04307459.

Keywords: COVID-19; respiratory infections; respiratory medicine (see thoracic medicine); respiratory physiology; virology.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Aged
  • Betacoronavirus
  • Blood Gas Analysis
  • Coronavirus Infections / metabolism
  • Coronavirus Infections / mortality
  • Coronavirus Infections / pathology*
  • Coronavirus Infections / virology
  • Female
  • Hospital Mortality*
  • Hospitalization*
  • Hospitals
  • Humans
  • Hypoxia
  • Intensive Care Units
  • Italy / epidemiology
  • Lung / metabolism
  • Lung / pathology
  • Lung / virology
  • Male
  • Middle Aged
  • Oxygen / blood*
  • Pandemics
  • Partial Pressure
  • Pneumonia, Viral / metabolism
  • Pneumonia, Viral / mortality
  • Pneumonia, Viral / pathology*
  • Pneumonia, Viral / virology
  • Prospective Studies
  • Respiratory Distress Syndrome, Adult / etiology*
  • Respiratory Distress Syndrome, Adult / mortality
  • Respiratory Distress Syndrome, Adult / therapy
  • Respiratory Distress Syndrome, Adult / virology
  • Respiratory Insufficiency / etiology
  • Respiratory Insufficiency / mortality
  • Respiratory Insufficiency / therapy
  • Respiratory Insufficiency / virology
  • Risk Factors
  • Severe Acute Respiratory Syndrome / etiology*
  • Severe Acute Respiratory Syndrome / mortality
  • Severe Acute Respiratory Syndrome / therapy
  • Severe Acute Respiratory Syndrome / virology
  • Severity of Illness Index*


  • Oxygen

Supplementary concepts

  • COVID-19
  • severe acute respiratory syndrome coronavirus 2

Associated data