Deep RNA sequencing of intensive care unit patients with COVID-19.

COVID-19 has impacted millions of patients across the world. Molecular testing occurring now identifies the presence of the virus at the sampling site: nasopharynx, nares, or oral cavity. RNA sequencing has the potential to establish both the presence of the virus and define the host's response in COVID-19. Single center, prospective study of patients with COVID-19 admitted to the intensive care unit where deep RNA sequencing (> 100 million reads) of peripheral blood with computational biology analysis was done. All patients had positive SARS-CoV-2 PCR. Clinical data was prospectively collected. We enrolled fifteen patients at a single hospital. Patients were critically ill with a mortality of 47% and 67% were on a ventilator. All the patients had the SARS-CoV-2 RNA identified in the blood in addition to RNA from other viruses, bacteria, and archaea. The expression of many immune modulating genes, including PD-L1 and PD-L2, were significantly different in patients who died from COVID-19. Some proteins were influenced by alternative transcription and splicing events, as seen in HLA-C, HLA-E, NRP1 and NRP2. Entropy calculated from alternative RNA splicing and transcription start/end predicted mortality in these patients. Current upper respiratory tract testing for COVID-19 only determines if the virus is present. Deep RNA sequencing with appropriate computational biology may provide important prognostic information and point to therapeutic foci to be precisely targeted in future studies.

Cardiac index is associated with oxygenation in COVID-19 acute respiratory distress syndrome.

Eleven participants with COVID-19 acute respiratory distress syndrome requiring mechanical ventilation underwent pulmonary artery catheterization for clinical indications. Clinical interventions or events concurrent with hemodynamic were recorded. Increased cardiac index was associated with worse hypoxemia. Modulation of cardiac index may improve hypoxemia in patients with COVID-19 acute respiratory distress syndrome.

A Survey-based Estimate of COVID-19 Incidence and Outcomes among Patients with Pulmonary Arterial Hypertension or Chronic Thromboembolic Pulmonary Hypertension and Impact on the Process of Care.

Rationale: Patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) typically undergo frequent clinical evaluation. The incidence and outcomes of coronavirus disease (COVID-19) and its impact on routine management for patients with pulmonary vascular disease is currently unknown.Objectives: To assess the cumulative incidence and outcomes of recognized COVID-19 for patients with PAH/CTEPH followed at accredited pulmonary hypertension centers, and to evaluate the pandemic's impact on clinic operations at these centers.Methods: A survey was e-mailed to program directors of centers accredited by the Pulmonary Hypertension Association. Descriptive analyses and linear regression were used to analyze results.Results: Seventy-seven center directors were successfully e-mailed a survey, and 58 responded (75%). The cumulative incidence of COVID-19 recognized in individuals with PAH/CTEPH was 2.9 cases per 1,000 patients, similar to the general U.S. population. In patients with PAH/CTEPH for whom COVID-19 was recognized, 30% were hospitalized and 12% died. These outcomes appear worse than the general population. A large impact on clinic operations was observed including fewer clinic visits and substantially increased use of telehealth. A majority of centers curtailed diagnostic testing and a minority limited new starts of medical therapy. Most centers did not use experimental therapies in patients with PAH/CTEPH diagnosed with COVID-19.Conclusions: The cumulative incidence of COVID-19 recognized in patients with PAH/CTEPH appears similar to the broader population, although outcomes may be worse. Although the total number of patients with PAH/CTEPH recognized to have COVID-19 was small, the impact of COVID-19 on broader clinic operations, testing, and treatment was substantial.

COVID-19 critical illness pathophysiology driven by diffuse pulmonary thrombi and pulmonary endothelial dysfunction responsive to thrombolysis.

Patients with severe COVID-19 disease have been characterized as having the acute respiratory distress syndrome (ARDS). Critically ill COVID-19 patients have relatively well-preserved lung mechanics despite severe gas exchange abnormalities, a feature not consistent with classical ARDS but more consistent with pulmonary vascular disease. Many patients with severe COVID-19 also demonstrate markedly abnormal coagulation, with elevated d-dimers and higher rates of venous thromboembolism. We present four cases of patients with severe COVID-19 pneumonia with severe respiratory failure and shock, with evidence of markedly elevated dead-space ventilation who received tPA. All showed post treatment immediate improvements in gas exchange and/or hemodynamics. We suspect that severe COVID-19 pneumonia causes respiratory failure via pulmonary microthrombi and endothelial dysfunction. Treatment for COVID-19 pneumonia may warrant anticoagulation for milder cases and thrombolysis for more severe disease.