Insights into COVID-19-associated critical illness: a narrative review.

Background and Objective: Since the outbreak of the 2019 novel coronavirus disease (COVID-19), acute respiratory distress syndrome (ARDS) and sepsis resulting from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have surged in intensive care units around the world. The heterogeneity of ARDS and sepsis has long been observed, and multiple subphenotypes and endotypes correlated with different outcomes and treatment response have been identified in the search for treatable traits. Despite their similarity to typical ARDS and sepsis, COVID-19-associated ARDS and sepsis harbor distinct features, raising the question as to whether they could be considered as subphenotypes or endotypes of the historical syndromes and, accordingly, benefit from specific therapeutic strategies. This review aimed to summarize and discuss the current knowledge of COVID-19-associated critical illness and the intrinsic subphenotypes or endotypes. Methods: Literature on the pathogenesis of COVID-19 and the subphenotyping of COVID-19-associated critical illness was derived from the PubMed database and reviewed. Key Content and Findings: Accumulating evidence, varying from clinical observation to basic research, has contributed to revealing the fundamental pathophysiological features of severe COVID-19 and has advanced our knowledge of the disease. COVID-19-associated ARDS and sepsis exhibit some distinctive features compared to the classic syndromes, including remarkable vascular abnormality and coagulopathy, and distinct respiratory mechanics and immune response. Some conventional subphenotypes derived from classic ARDS and sepsis have been validated in COVID-19, while novel subphenotypes and endotypes have also been identified in patients with this disease, who experience variable clinical outcomes and treatment responses. Conclusions: Subphenotyping of COVID-19-associated ARDS and sepsis can provide new insights into the development and management of these illnesses.

Severe COVID-19 has a distinct phenotype from bacterial sepsis: a retrospective cohort study in deceased patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has caused more than 2 million deaths worldwide. Viral sepsis has been proposed as a description for severe COVID-19, and numerous therapies have been on trials based upon this hypothesis. However, whether the clinical characteristics of severe COVID-19 are similar to those of bacterial sepsis has not been elucidated. METHODS: We retrospectively compared the clinical data of non-surviving COVID-19 patients who were admitted to a 30-bed intensive care unit (ICU) in Wuhan Infectious Diseases Hospital (Wuhan, China) from 22 January 2020, to 28 February 2020, with those of non-surviving patients with bacterial sepsis who were admitted to the ICU in Zhongshan Hospital, Fudan University (Shanghai, China) from 3 July 2018, to 30 June 2020. RESULTS: A total of 53 COVID-19 patients and 26 septic patients were included in the analysis. The mean ages were 65.6 [standard deviation (SD): 11.1] and 70.4 (SD: 14.3) years in the COVID-19 cohort and sepsis cohort, respectively. The proportion of participants with hypertension was higher in non-survivors with COVID-19 than in non-survivors with sepsis (41.5% vs. 15.4%, P=0.020). The Sequential Organ Failure Assessment (SOFA) score of non-survivors with COVID-19 was lower than that of non-survivors with sepsis at ICU admission {4.0 [interquartile range (IQR): 3.0-6.0] vs. 7.5 [IQR: 5.8-11.0], P<0.001}. The clinical parameters at ICU admission assessed with principal component analysis and hierarchical cluster analysis showed that COVID-19 patients were distinct from bacterial septic patients. Compared with non-survivors with sepsis, non-survivors with COVID-19 had a higher neutrophil/lymphocyte ratio, total protein, globulin, lactate dehydrogenase (LDH), and D-dimer; a lower eosinophil count, procalcitonin, interleukin-6 (IL-6), total bilirubin, direct bilirubin, myohemoglobin, albumin/globulin ratio, activated partial thromboplastin time (APTT), prothrombin time (PT), and international normalization ratio (INR) at ICU admission. In addition, the levels of total protein, globulin, LDH, D-dimer, and IL-6 were significantly different between the two groups during the ICU stay. CONCLUSIONS: Patients with critical COVID-19 have a phenotype distinct from that of patients with bacterial sepsis. Therefore, caution should be used when applying the previous experience of bacterial sepsis to patients with severe COVID-19.