By Betty Tran, MD, MSc

Associate Professor of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago

SYNOPSIS: Comparison of a small COVID-19 acute respiratory distress syndrome (ARDS) cohort with a historical pre-COVID-19 ARDS cohort found some differences in physiologic parameters and biomarkers, but not enough evidence to warrant deviation from known management guidelines.

SOURCE: Bain W, Yang H, Shah FA, et al. COVID-19 versus non-COVID-19 acute respiratory distress syndrome: Comparison of demographics, physiologic parameters, inflammatory biomarkers, and clinical outcomes. Ann Am Thorac Soc 2021;18:1202-1210.

In an effort to identify key characteristics that distinguish acute respiratory distress syndrome (ARDS) caused by COVID-19 disease vs. non-COVID-19 ARDS, Bain and colleagues prospectively enrolled critically ill adults with COVID-19 and ARDS from the University of Pittsburgh Presbyterian and Shadyside hospitals into their Acute Lung Injury Registry (ALIR) from April 4 through Sept. 15, 2020. Overall, 27 patients were compared to 65 historical (pre-April 2020) ALIR patients with ARDS due to viral, bacterial, or culture-negative pneumonia.

Compared to non-COVID-19 ARDS patients, those with COVID-19 had higher body mass index (BMI) and were more likely to be Black; there were no other differences in terms of age, comorbidities, or Sequential Organ Failure Assessment scores. COVID-19 patients were more likely to receive prone positioning (70.4%, P < 0.01), continuous neuromuscular blockade (NMB) (74.1%, P < 0.01), and extracorporeal membrane oxygenation support (ECMO) (28%, P < 0.01). Median arterial oxygen pressure to fraction of inspired oxygen (PaO2/FiO2) in COVID-19 patients on the day of intubation was 120 (interquartile range [IQR], 72.0-147.5); this was not significantly different compared to the non-COVID-19 group.

There were no significant differences in terms of static lung compliance on the day of intubation (median in COVID-19 was 33.7 mL/cm H2O; IQR, 25.1-45.5) or longitudinally. Minute ventilation was lower in patients with COVID-19 without significant differences in carbon dioxide clearance.

In terms of biomarkers, interleukin-6 (IL-6) levels were significantly lower in COVID-19 ARDS early (0-4 days of intubation) compared to bacterial and culture-negative ARDS (but not viral ARDS). This also was seen for interleukin-8 (IL-8), but not for interleukin-10 (IL-10). Overall, COVID-19 patients with ARDS spent more time on the ventilator after adjustment for age, sex, and nursing home residence, but no differences were noted in 60-day mortality between groups.


Overall, this was a small comparison of patients with ARDS caused by COVID-19 vs. pneumonia from other infectious etiologies limited to two academic medical centers; therefore, their results should be viewed as hypothesis-generating in light of other concurrent and subsequent studies.

In this study, patients with COVID-19 pneumonia were more likely to have a higher BMI and to be Black compared to non-COVID-19 ARDS patients. The Centers for Disease Control and Prevention (CDC) has consistently reported that racial and ethnic minority groups are disproportionately represented among COVID-19 cases and deaths compared to their percentage among the total U.S. population.1,2 Although the study did not find differences in baseline comorbidities, such as hypertension, chronic obstructive pulmonary disease, or diabetes, between the groups, we know that these chronic disease states, including obesity, contribute to the racial disparities in COVID-19 disease and outcomes. Other contributing factors are social/environmental and include housing density, types of jobs held (essential vs. ability to work from home), and reliance on public transportation.

The finding that COVID-19 ARDS patients were more likely to undergo proning, continuous NMB, and ECMO suggests that these patients were more hypoxic and critically ill, despite no differences being found in median PaO2/FiO2 ratio, applied positive end-expiratory pressure (PEEP), or static lung compliance. A possible explanation for this could be that a significant number of COVID-19 ARDS patients developed subsequent bacterial pneumonia with resultant minimal differences in physiologic parameters compared to non-COVID-19 ARDS.

The authors did report that the COVID-19 group had fewer ventilator-free days up to day 28, which would certainly put them at risk for developing a ventilator-associated pneumonia. It also is possible that as COVID-19 topped headlines in the lay and medical communities continuously during this time, healthcare providers were more likely to reach for interventions such as proning, NMB, and ECMO early and more frequently compared to prior, even though these are known options in the management of acute hypoxic respiratory failure. A final possibility is that infection with SARS-CoV-2 involves a prolonged course for other biologic reasons despite similar physiologic parameters.

Finally, the finding that COVID-19 ARDS patients had lower early levels of IL-6 compared to patients with non-COVID-19 ARDS is not consistent with current recommendations for the use of anti-IL-6 therapies, such as tocilizumab, especially early in patients exhibiting rapid respiratory decompensation, based on recent clinical trial data from the RECOVERY and REMAP-CAP trials.3,4 As such, the development of ARDS in COVID-19 may not be summarized as neatly as hoped via serum IL-6 levels alone.

As COVID-19 cases surge again because of the Delta variant, continued efforts at identifying therapeutic targets and elucidating phenotypes will be needed to improve clinical outcomes.


  1. Centers for Disease Control and Prevention. Disparities in COVID-19 Illness. Updated Dec 10, 2020,
  2. Centers for Disease Control and Prevention. Disparities in Deaths from COVID-19. Updated Dec 10, 2020,
  3. RECOVERY Collaborative Group. Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): A randomised, controlled, open-label, platform trial. Lancet 2021;397:1637-1645.
  4. The REMAP-CAP Investigators; Gordon AC, Mouncey PR, Al-Beidh F, et al. Interleukin-6 receptor antagonists in critically ill patients with COVID-19. N Engl J Med 2021;384:1491-1502.