key: cord-0747250-6lf8qchq
authors: Brault, Clément; Zerbib, Yoann; Kontar, Loay; Fouquet, Ugo; Carpentier, Mathieu; Metzelard, Matthieu; Soupison, Thierry; De Cagny, Bertrand; Maizel, Julien; Slama, Michel
title: COVID-19– versus non–COVID-19–related Acute Respiratory Distress Syndrome: Differences and Similarities
date: 2020-11-01
journal: Am J Respir Crit Care Med
DOI: 10.1164/rccm.202005-2025le
sha: 3b5c432ca61cccb135d134ff13660ae53bb55131
doc_id: 747250
cord_uid: 6lf8qchq

nan

The current pandemic of coronavirus disease (COVID-19) is responsible for a massive influx of patients with acute respiratory We defined "oxygenation response to prone position" as patients in whom the Pa O 2 /FI O 2 ratio increased by at least 20% or at least 20 mm Hg during the first prone position session (2) . In all patients, we performed a stepwise LRM with an increase in the PEEP every 2 minutes (from 25 to 40 cm H 2 O) and a stable driving pressure of 15 cm H 2 O. We defined "oxygenation response to LRM" as patients in whom the Pa O 2 /FI O 2 ratio increased by at least 20% 2-4 hours after the first LRM. The study was approved by the local independent ethics committee.

We included a total of 63 patients with moderate to severe primary ARDS, including 24 (38%) patients with a confirmed SARS-CoV-2 infection and 39 (62%) patients with other causes of ARDS (most aspiration or community-acquired pneumonia, and influenzarelated ARDS in six cases). The overall median (interquartile range [IQR]) age was 61 (51-69). Patients in the COVID-19 group were older (P = 0.02) and more likely to suffer from obesity (P = 0.04) and diabetes (P = 0.03). The prevalence of immunodeficiency was significantly higher in the non-COVID-19 group (P = 0.004). The median (IQR) time between symptom onset and orotracheal intubation was longer in the COVID-19 group (10 vs. 5 d; P = 0.0001) ( Table 1) . With regard to the computed tomography (CT) scan, a diffuse pattern with ground-glass opacity predominated in the COVID-19 group (P = 0.03 and P = 0.01, respectively). Alveolar consolidation was relatively common in both the COVID-19 and non-COVID-19 groups (61% vs. 60%; P . 0.99), whereas pleural effusion was more common in the non-COVID-19 group (P = 0.0003) ( Table 1) .

There were no significant intergroup differences with regard to the ventilator settings, such as the predicted VT, the respiratory rate, and the PEEP. The driving pressure and the respiratory system compliance were 13 (10-15) cm H 2 O and 33 (26-41) ml/cm H 2 O in the COVID-19 group and 15 (12-18) cm H 2 O and 29 (22-37) ml/cm H 2 O in the non-COVID-19 group (P = 0.12 and P = 0.13, respectively) ( Table 1) . Arterial blood variables (including pH, Pa O 2 , and Pa CO 2 ) were also similar in the two groups, as was the ventilatory ratio-a surrogate for dead space ventilation (P = 0.46). Lastly, about half of the patients in each group had severe ARDS (Table 1) .

Concerning the treatment of ARDS, an oxygenation response to LRMs was observed in 15 (63%) of the patients in the COVID-19 group and in 28 (72%) in the non-COVID-19 group (P = 0.44). Overall, 43 (68%) patients underwent a prone position session. The oxygenation response to prone positioning did not differ significantly when comparing the two groups (82 vs. 91%; P = 0.10).

With regard to other supportive therapies, the frequency and duration of neuromuscular blockade and inhaled nitric oxide administration were similar in the two groups. On discharge from the ICU, the survival rate was 42% in the COVID-19 group and 46% in the non-COVID-19 group (P = 0.80). The median length of stay in the ICU and duration of mechanical ventilation were similar in the two groups (Table 1 and Figure 1 ).

Our results showed that the main characteristics of pressure measurements and respiratory mechanics (such as the plateau pressure, driving pressure, and respiratory system compliance) did not differ significantly when comparing COVID-19 and non-COVID-19 ARDS. Overall, the median (IQR) respiratory system compliance was 30 (23-40) ml/cm H 2 O; the two groups did not differ significantly in this respect. This value is close to those reported in the literature for COVID-19 and non-COVID-19 ARDS (3) (4) (5) (6) . Our results go against the assumptions initially made by many clinicians (ourselves included) whereby lung mechanics in COVID-19 ARDS are relatively unaffected but gas exchanges are more severely impaired than in non-COVID-19 ARDS (1). In fact, our results suggest that the dissociation between lung mechanics and gas exchange is no greater in COVID-19 ARDS than in non-COVID-19 ARDS. In contrast, we observed significant differences in the pattern of chest CT scan involvement: diffuse ground-glass opacity was more frequent in COVID-19 ARDS, whereas pleural effusion was less frequent.

Our second key finding was that the potential for lung recruitment appears to be maintained in COVID-19 ARDS, because the effects of LRMs or prone positioning are similar to those observed in non-COVID-19 ARDS. Our results are in line with recent publications (6) (7) (8) . Pan and colleagues evaluated the potential for lung recruitment (as the recruitment-to-inflation ratio) in COVID-19 ARDS. The researchers found that lung recruitability was generally poor on the first day of observation but increased by alternating the prone and supine positions (8) . This can be easily explained by the appearance of basilar consolidation over the course of COVID-19 ARDS. This consolidation accounts for 13-53% of the CT patterns, depending on when the scan is performed; the later the CT scan, the more frequent the consolidation (9, 10) . In the present study, the predominant pattern in COVID-19 ARDS was diffuse ground-glass opacity, together with alveolar consolidation in about 60% of cases. This consolidation might be explained by the long median (IQR) time interval between the onset of symptoms and orotracheal intubation (10 [7-15] d) in our study population. Other studies have reported similar findings, but we cannot rule out the possible occurrence of "patient self-inflicted lung injury" due to excessive breathing efforts and delayed intubation (4, 7) .

Our study had some important limitations. First, the study population was small and we did not prespecify the target sample size. Second, we only assess basic respiratory mechanical variables; the comparison of advanced parameters (such as transpulmonary pressures or ventilation-perfusion mismatches) might have revealed additional intergroup differences.

The main features of respiratory mechanics, the response to treatment (such as the oxygenation response to LRMs or prone position), and prognosis are similar in COVID-19 and non-COVID-19 ARDS. The oxygenation response to LRM and a high PEEP appear to be very heterogeneous in COVID-19 ARDS; this would argue in favor of a personalized ventilation strategy. n Complement Inhibition with the C5 Blocker LFG316 in Severe COVID-19

To the Editor:

In critically ill patients with coronavirus disease (COVID-19) , a hyperinflammatory host response contributes to organ dysfunction and death. The role of complement in these events is unclear. Complement activation yields powerful proinflammatory effectors, notably C5a and membrane attack complex, and triggers coagulation (1); it has been implicated in bacterial sepsis and septic shock, sepsis-like syndromes associated with coronavirus infections, and COVID-19-associated microvascular injury and thrombosis (2) (3) (4) . Recently, the C5a/C5aR1 axis was implicated in 

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Author disclosures are available with the text of this letter at www.atsjournals.org.