COVID-19 conundrum: clinical phenotyping based on pathophysiology as a promising approach to guide therapy in a novel illness

Abstract

We read with interest the recent editorial by B os et al. [1] on the perils of premature phenotyping in coronavirus disease 2019 (COVID-19). The authors concluded that a normal compliance variant of acute respiratory distress syndrome (ARDS) does not exist, based on two small cohort studies reporting low respiratory system compliance in COVID-19 patients [2, 3]. However, this assumption may be erroneous, as, first, the admission and intubation thresholds are highly variable across units, resulting in marked heterogeneity. Secondly, several studies demonstrate that a high proportion of mechanically ventilated COVID-19 patients exhibit near-normal lung compliance [4–6].

Predicting clinical outcome with phenotypic clusters in COVID-19 pneumonia: an analysis of 12,066 hospitalized patients from the Spanish registry SEMI-COVID-19

“…Accordingly, it would be necessary to study each of the present clinical clusters genetically and to verify that each cluster has a differentiated genetic background. In the literature, some studies attempted to phenotype patients with COVID-19 as a function of the immune response, and others is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted September 15, 2020. ; https://doi.org/10.1101/2020.09.14.20193995 doi: medRxiv preprint suggested phenotyping as a function of pathophysiology [16,17]. It would be interesting to combine all methods of phenotyping.…”

The Use of High-Flow Nasal Oxygen in the ICU as a First-Line Therapy for Acute Hypoxemic Respiratory Failure Secondary to Coronavirus Disease 2019

“…These varying findings are likely due to the heterogeneity that exists in the underlying etiologies and clinical courses of AHRF, coupled with the heterogeneity in the studies comparing various combinations of noninvasive respiratory support modalities (e.g., HFNO vs NIV via face mask, or HFNO vs standard oxygen therapy) ( 23 ). These nuances may be especially important to consider with a novel respiratory disease such as COVID-19, which may have its own unique phenotype(s) ( 24 , 25 ). Thus, beyond the findings from our study, further investigation is warranted to guide clinicians in understanding the role of HFNO and/or NIV in potentially delaying or avoiding endotracheal intubation without sacrificing favorable patient outcomes.…”

Response to COVID-19 phenotyping correspondence

“…Cherian et al take issue with our interpretation of the respiratory physiology of COVID-19, arguing that it is based merely on "small cohort studies," instead arguing that "a high proportion of mechanically ventilated COVID-19 patients exhibit near-normal lung compliance." [1] Yet the low respiratory compliance of COVID- 19 patients has now been extensively demonstrated by studies totaling more than 800 COVID-19 patients [2][3][4][5][6][7][8], including a direct comparison with non-COVID ARDS patients that revealed no difference in respiratory compliance. [8] In contrast, the three case series cited by the correspondents in support of their claim comprise cohorts of, respectively, 16, 10 and 26 patients [9][10][11].…”

“…The objective of our editorial was to challenge the subclassification of patients with COVID-19 that frequently occurred in the early weeks of the pandemic based on "discussions" and "close observations" before they became entrenched dogmas. [1] An unintended consequence of such a challenge may be that it evokes negative emotions with the reader, especially in these troubling and polarising times. We were, therefore, saddened to learn that our Editorial caused irritation among Gattinoni et al [25].…”