Project description:Pathologic immune hyperactivation is emerging as a key feature of critical illness in COVID-19, but the mechanisms involved remain poorly understood. We carried out proteomic profiling of plasma from cross-sectional and longitudinal cohorts of hospitalized patients with COVID-19 and analyzed clinical data from our health system database of more than 3300 patients. Using a machine learning algorithm, we identified a prominent signature of neutrophil activation, including resistin, lipocalin-2, hepatocyte growth factor, interleukin-8, and granulocyte colony-stimulating factor, which were the strongest predictors of critical illness. Evidence of neutrophil activation was present on the first day of hospitalization in patients who would only later require transfer to the intensive care unit, thus preceding the onset of critical illness and predicting increased mortality. In the health system database, early elevations in developing and mature neutrophil counts also predicted higher mortality rates. Altogether, these data suggest a central role for neutrophil activation in the pathogenesis of severe COVID-19 and identify molecular markers that distinguish patients at risk of future clinical decompensation.
Project description:We performed single cell transcriptomics in 13 acute and convalescent mild versus severe COVID-19 subjects, in healthy controls and in sujects with flu-like-illness and HBV infection to assess COVID-19-specific T cell populations und function.
Project description:The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges in critical care medicine, including extreme demand for intensive care unit (ICU) resources and rapidly evolving understanding of a novel disease. Up to one-third of hospitalized patients with COVID-19 experience critical illness. The most common form of organ failure in COVID-19 critical illness is acute hypoxemic respiratory failure, which clinically presents as acute respiratory distress syndrome (ARDS) in three-quarters of ICU patients. Noninvasive respiratory support modalities are being used with increasing frequency given their potential to reduce the need for intubation. Determining optimal patient selection for and timing of intubation remains a challenge. Management of mechanically ventilated patients with COVID-19 largely mirrors that of non-COVID-19 ARDS. Organ failure is common and portends a poor prognosis. Mortality rates have improved over the course of the pandemic, likely owing to increasing disease familiarity, data-driven pharmacologics, and improved adherence to evidence-based critical care.
Project description:ObjectivesTo evaluate the presence of chronic critical illness (CCI) in COVID-19 patients and compare clinical characteristics and prognosis of patients with and without CCI admitted to intensive care unit (ICU).MethodsIt was a retrospective, observational study at a university hospital ICU. Patients were accepted as CCI if they had prolonged ICU stay (≥14 days) and got ≥1 score for cardiovascular sequential organ failure assessment (SOFA) score and ≥2 score in other parameters on day 14 of ICU admission which was described as persistent organ dysfunction.Results131 of 397 (33%) patients met CCI criteria. CCI patients were older (p = 0.003) and frailer (p < 0.001). Their Acute Physiology and Chronic Health Evaluation (APACHE) II and SOFA scores were higher, PaO2/FiO2 ratio was lower (p < 0.001). Requirement of invasive mechanical ventilation (IMV), steroid use, and septic shock on admission were higher in the CCI group (p < 0.001). CCI patients had higher ICU and hospital mortality than other patients (54.2% vs. 19.9% and 55.7% vs. 22.6%, p < 0.001, respectively). Regression analysis revealed that IMV (OR: 8.40, [5.10-13.83], p < 0.001) and PaO2/FiO2 < 150 on admission (OR: 2.25, [1.36-3.71], p = 0.002) were independent predictors for CCI.DiscussionOne-third of the COVID-19 patients admitted to the ICU were considered as CCI with significantly higher ICU and hospital mortality.
Project description:ObjectiveRecent cohort studies have identified obesity as a risk factor for poor outcomes in coronavirus disease 2019 (COVID-19). To further explore the relationship between obesity and critical illness in COVID-19, the association of BMI with baseline demographic and intensive care unit (ICU) parameters, laboratory values, and outcomes in a critically ill patient cohort was examined.MethodsIn this retrospective study, the first 277 consecutive patients admitted to Massachusetts General Hospital ICUs with laboratory-confirmed COVID-19 were examined. BMI class, initial ICU laboratory values, physiologic characteristics including gas exchange and ventilatory mechanics, and ICU interventions as clinically available were measured. Mortality, length of ICU admission, and duration of mechanical ventilation were also measured.ResultsThere was no difference found in respiratory system compliance or oxygenation between patients with and without obesity. Patients without obesity had higher initial ferritin and D-dimer levels than patients with obesity. Standard acute respiratory distress syndrome management, including prone ventilation, was equally distributed between BMI groups. There was no difference found in outcomes between BMI groups, including 30- and 60-day mortality and duration of mechanical ventilation.ConclusionsIn this cohort of critically ill patients with COVID-19, obesity was not associated with meaningful differences in respiratory physiology, inflammatory profile, or clinical outcomes.
Project description:Background and objectiveSince 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.MethodsLiterature 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 findingsAccumulating 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.ConclusionsSubphenotyping of COVID-19-associated ARDS and sepsis can provide new insights into the development and management of these illnesses.