Circulating Biomarkers of Endothelial Dysfunction Associated With Ventilatory Ratio and Mortality in ARDS Resulting From SARS-CoV-2 Infection Treated With Antiinflammatory Therapies.

Background: The association of plasma biomarkers and clinical outcomes in ARDS resulting from SARS-CoV-2 infection predate the evidence-based use of immunomodulators.

Research Question: Which plasma biomarkers are associated with clinical outcomes in patients with ARDS resulting from SARS-CoV-2 infection treated routinely with immunomodulators?

Study Design And Methods: We collected plasma from patients with ARDS resulting from SARS-CoV-2 infection within 24 h of admission to the ICU between December 2020 and March 2021 (N = 69). We associated 16 total biomarkers of inflammation (eg, IL-6), coagulation (eg, D-dimer), epithelial injury (eg, surfactant protein D), and endothelial injury (eg, angiopoietin-2) with the primary outcome of in-hospital mortality and secondary outcome of ventilatory ratio (at baseline and day 3).

Plasma NEDD9 is increased following SARS-CoV-2 infection and associates with indices of pulmonary vascular dysfunction.

Compared to healthy volunteers, participants with post-acute sequelae of SARS-CoV-2 infection (PASC) demonstrated increased plasma levels of the prothrombotic protein NEDD9, which associated inversely with indices of pulmonary vascular function. This suggests persistent pulmonary vascular dysfunction may play a role in the pathobiology of PASC.

Deep learned representations of the resting 12-lead electrocardiogram to predict at peak exercise.

Aims: To leverage deep learning on the resting 12-lead electrocardiogram (ECG) to estimate peak oxygen consumption (V˙O2peak) without cardiopulmonary exercise testing (CPET).

Methods And Results: V ˙ O 2 peak estimation models were developed in 1891 individuals undergoing CPET at Massachusetts General Hospital (age 45 ± 19 years, 38% female) and validated in a separate test set (MGH Test, n = 448) and external sample (BWH Test, n = 1076). Three penalized linear models were compared: (i) age, sex, and body mass index ('Basic'), (ii) Basic plus standard ECG measurements ('Basic + ECG Parameters'), and (iii) basic plus 320 deep learning-derived ECG variables instead of ECG measurements ('Deep ECG-V˙O2').

Preferred Language Mediates Association Between Race, Ethnicity, and Delayed Presentation in Critically Ill Patients With COVID-19.

Unlabelled: Which social factors explain racial and ethnic disparities in COVID-19 access to care and outcomes remain unclear.

Objectives: We hypothesized that preferred language mediates the association between race, ethnicity and delays to care.

Design Setting And Participants: Multicenter, retrospective cohort study of adults with COVID-19 consecutively admitted to the ICU in three Massachusetts hospitals in 2020.

Development of a Definition of Postacute Sequelae of SARS-CoV-2 Infection.

Importance: SARS-CoV-2 infection is associated with persistent, relapsing, or new symptoms or other health effects occurring after acute infection, termed postacute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID. Characterizing PASC requires analysis of prospectively and uniformly collected data from diverse uninfected and infected individuals.

Objective: To develop a definition of PASC using self-reported symptoms and describe PASC frequencies across cohorts, vaccination status, and number of infections.

Prolonged Prone Position Ventilation Is Associated With Reduced Mortality in Intubated COVID-19 Patients.

Background: Prone position ventilation (PPV) is resource-intensive, yet the optimal strategy for PPV in intubated patients with COVID-19 is unclear.

Research Question: Does a prolonged (24 or more h) PPV strategy improve mortality in intubated COVID-19 patients compared with intermittent (∼16 h with daily supination) PPV?

Study Design And Methods: Multicenter, retrospective cohort study of consecutively admitted intubated COVID-19 patients treated with PPV between March 11 and May 31, 2020. The primary outcome was 30-day all-cause mortality.

Vasculopathy and Increased Vascular Congestion in Fatal COVID-19 and Acute Respiratory Distress Syndrome.

The leading cause of death in coronavirus disease 2019 (COVID-19) is severe pneumonia, with many patients developing acute respiratory distress syndrome (ARDS) and diffuse alveolar damage (DAD). Whether DAD in fatal COVID-19 is distinct from other causes of DAD remains unknown. To compare lung parenchymal and vascular alterations between patients with fatal COVID-19 pneumonia and other DAD-causing etiologies using a multidimensional approach.

Pulmonary endothelial NEDD9 and the prothrombotic pathophenotype of acute respiratory distress syndrome due to SARS-CoV-2 infection.

The pathobiology of in situ pulmonary thrombosis in acute respiratory distress syndrome (ARDS) due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is incompletely characterized. In human pulmonary artery endothelial cells (HPAECs), hypoxia increases neural precursor cell expressed, developmentally downregulated 9 (NEDD9) and induces expression of a prothrombotic NEDD9 peptide (N9) on the extracellular plasma membrane surface. We hypothesized that the SARS-CoV-2-ARDS pathophenotype involves increased pulmonary endothelial N9.

Code status orders in patients admitted to the intensive care unit with COVID-19: A retrospective cohort study.

Purpose: Code status orders impact clinical outcomes as well as patients' and surrogates' experiences. This is the first multicenter cohort examining code status orders of ICU patients with COVID-19 reported to date.

Materials And Methods: This is a retrospective cohort study including adult patients who tested positive for SARS-CoV-2 and were admitted to the ICU at three hospitals in Massachusetts from March 11, 2020 - May 31, 2020.

Care-engaged individuals with polysubstance use in Northeastern US are undertreated for methamphetamine use disorder: a retrospective cohort study.

Background: Stimulant use has increased across the US, with concomitant opioid and methamphetamine use doubling between 2011 and 2017. Shifting patterns of polysubstance use have led to rising psychostimulant-involved deaths. While it is known that individuals who use methamphetamine require greater access to treatment, there is still little known about methamphetamine use and treatment among individuals who are already engaged in outpatient substance use treatment.

Exercise performance in patients with post-acute sequelae of SARS-CoV-2 infection compared to patients with unexplained dyspnea.

Background: Dyspnea and exercise intolerance are commonly reported post-acute sequelae of SARS-CoV-2 infection (PASC), but routine diagnostic testing is often normal. Cardiopulmonary exercise testing (CPET) offers comprehensive assessment of dyspnea to characterize pulmonary PASC.

Methods: We performed a retrospective cohort study of CPET performed on patients reporting dyspnea and/or exercise intolerance following confirmed Covid-19 between August 1, 2020 and March 1, 2021, and compared them to age- and sex-matched patients with unexplained dyspnea referred for CPET at the same center in the pre-Covid-19 era.

Chronic Thromboembolic Pulmonary Hypertension: the Bench.

Purpose Of Review: Chronic thromboembolic pulmonary hypertension (CTEPH) is an uncommon complication of acute pulmonary embolism (PE), in which the red, platelet-rich thrombus does not resolve but forms into an organized yellow, fibrotic scar-like obstruction in the pulmonary vasculature. Here we review the pathobiology of CTEPH.

Recent Findings: Our current knowledge has predominantly been informed by studies of human samples and animal models that are inherently limited in their ability to recapitulate all aspects of the disease.

Yield of Severe Acute Respiratory Syndrome Coronavirus 2 Lower Respiratory Tract Testing After a Negative Nasopharyngeal Test Among Hospitalized Persons Under Investigation for Coronavirus Disease 2019.

Among hospitalized persons under investigation for coronavirus disease 2019 (COVID-19), more repeated severe acute respiratory syndrome coronavirus 2 nucleic acid amplification tests (NAATs) after a negative NAAT were positive from lower than from upper respiratory tract specimens (1.9% vs 1.0%, = .

A molecular single-cell lung atlas of lethal COVID-19.

Respiratory failure is the leading cause of death in patients with severe SARS-CoV-2 infection, but the host response at the lung tissue level is poorly understood. Here we performed single-nucleus RNA sequencing of about 116,000 nuclei from the lungs of nineteen individuals who died of COVID-19 and underwent rapid autopsy and seven control individuals. Integrated analyses identified substantial alterations in cellular composition, transcriptional cell states, and cell-to-cell interactions, thereby providing insight into the biology of lethal COVID-19.

NEDD9 Is a Novel and Modifiable Mediator of Platelet-Endothelial Adhesion in the Pulmonary Circulation.

Data on the molecular mechanisms that regulate platelet-pulmonary endothelial adhesion under conditions of hypoxia are lacking, but may have important therapeutic implications. To identify a hypoxia-sensitive, modifiable mediator of platelet-pulmonary artery endothelial cell adhesion and thrombotic remodeling. Network medicine was used to profile protein-protein interactions in hypoxia-treated human pulmonary artery endothelial cells.

Pulmonary vascular resistance and clinical outcomes in patients with pulmonary hypertension: a retrospective cohort study.

Background: In pulmonary hypertension subgroups, elevated pulmonary vascular resistance (PVR) of 3·0 Wood units or more is associated with poor prognosis. However, the spectrum of PVR risk in pulmonary hypertension is not known. To address this area of uncertainty, we aimed to analyse the relationship between PVR and adverse clinical outcomes in pulmonary hypertension.