A specific low-density neutrophil population correlates with hypercoagulation and disease severity in hospitalized COVID-19 patients.

SARS coronavirus 2 (SARS-CoV-2) is a novel viral pathogen that causes a clinical disease called coronavirus disease 2019 (COVID-19). Although most COVID-19 cases are asymptomatic or involve mild upper respiratory tract symptoms, a significant number of patients develop severe or critical disease. Patients with severe COVID-19 commonly present with viral pneumonia that may progress to life-threatening acute respiratory distress syndrome (ARDS). Patients with COVID-19 are also predisposed to venous and arterial thromboses that are associated with a poorer prognosis. The present study identified the emergence of a low-density inflammatory neutrophil (LDN) population expressing intermediate levels of CD16 (CD16Int) in patients with COVID-19. These cells demonstrated proinflammatory gene signatures, activated platelets, spontaneously formed neutrophil extracellular traps, and enhanced phagocytic capacity and cytokine production. Strikingly, CD16Int neutrophils were also the major immune cells within the bronchoalveolar lavage fluid, exhibiting increased CXCR3 but loss of CD44 and CD38 expression. The percentage of circulating CD16Int LDNs was associated with D-dimer, ferritin, and systemic IL-6 and TNF-α levels and changed over time with altered disease status. Our data suggest that the CD16Int LDN subset contributes to COVID-19-associated coagulopathy, systemic inflammation, and ARDS. The frequency of that LDN subset in the circulation could serve as an adjunct clinical marker to monitor disease status and progression.

Outcomes and Risk Factors for Cardiovascular Events in Hospitalized COVID-19 Patients.

OBJECTIVE: To analyze outcomes and risk factors of cardiovascular events in a metropolitan coronavirus disease 2019 (COVID-19) database, and to perform a subgroup analysis in African American populations to determine whether outcomes and risk factors are influenced by race. DESIGN: Retrospective cohort analysis from March 9, 2020 to June 20, 2020. SETTING: Population-based study in Louisville, KY, USA. PARTICIPANTS: Seven hundred adult inpatients hospitalized with COVID-19. INTERVENTIONS: N/A. MEASUREMENTS AND MAIN RESULTS: This cohort consisted of 126 patients (18%) with cardiovascular events and 574 patients without cardiovascular events. Patients with cardiovascular events had a much higher mortality rate than those without cardiovascular events (45.2% v 8.7%, p < 0.001). There was no difference between African American and white patients regarding mortality (43.9% v 46.3%, p = 1) and length of stay for survivors (11 days v 9.5 days, p = 0.301). Multiple logistics regression analysis suggested that male, race, lower SaO2/FIO2, higher serum potassium, lower serum albumin, and number of cardiovascular comorbidities were highly associated with the occurrence of cardiovascular events in COVID-19 patients. Lower serum albumin and neoplastic and/or immune-compromised diseases were highly associated with cardiovascular events for African American COVID-19 patients. SaO2/FIO2 ratio and cardiovascular comorbidity count were significantly associated with cardiovascular events in white patients. CONCLUSIONS: Cardiovascular events were prevalent and associated with worse outcomes in hospitalized patients with COVID-19. Outcomes of cardiovascular events in African American and white COVID-19 patients were similar after propensity score matching analysis. There were common and unique risk factors for cardiovascular events in African American COVID-19 patients when compared with white patients.

Short-Term Outcomes of Patients With COVID-19 Undergoing Invasive Mechanical Ventilation: A Retrospective Observational Study From Wuhan, China.

Background: COVID-19 has spread rapidly worldwide. Many patients require mechanical ventilation. The goal of this study was to investigate the clinical course and outcomes of patients with COVID-19 undergoing mechanical ventilation and identify factors associated with death. Methods: Eighty-three consecutive critically ill patients with confirmed COVID-19 undergoing invasive mechanical ventilation were included in this retrospective, single-center, observational study from January 31 to March 15, 2020. Demographic, clinical, laboratory, radiological, and mechanical ventilation data were collected and analyzed. The primary outcome was 28-day mortality after endotracheal intubation. The secondary outcomes included the incidences of SARS-CoV-2-related cardiac, liver, and kidney injury. Results: Seventy-four out of 83 (89.2%) patients achieved oxygen saturation above 93% after intubation. Forty-nine out of 83 (59%) patients died and 34 (41%) patients survived after 28 days of observation. Multivariable regression showed increasing odds of death associated with cardiac injury (odds ratio 15.60, 95% CI 4.20-74.43), liver injury (5.40, 1.46-23.56), and kidney injury (8.39, 1.63-61.41), and decreasing odds of death associated with the higher PaO2/FiO2 ratio before intubation (0.97, 0.95-0.99). PaO2/FiO2 ratio before intubation demonstrated a positive linear correlation with platelet count (r = 0.424, P = 0.001), and negative linear correlation with troponin I (r = -0.395, P = 0.008). Conclusions: Cardiac, liver, and kidney injury may be associated with death for critically ill patients with COVID-19 undergoing invasive mechanical ventilation. The severity of pre-intubation hypoxia may be associated with a poorer outcome of patients with COVID-19 undergoing invasive mechanical ventilation. Larger, multi-institutional, prospective studies should be conducted to confirm these preliminary results.

Cardiovascular Changes in Patients With COVID-19 From Wuhan, China.

Background: Coronavirus disease 2019 (COVID-19) is rapidly spreading and resulting in a significant loss of life around the world. However, specific information characterizing cardiovascular changes in COVID-19 is limited. Methods: In this single-centered, observational study, we enrolled 38 adult patients with COVID-19 from February 10 to March 13, 2020. Clinical records, laboratory findings, echocardiography, and electrocardiogram reports were collected and analyzed. Results: Of the 38 patients enrolled, the median age was 68 years [interquartile range (IQR), 55-74] with a slight female majority (21, 55.3%). Nineteen (50.0%) patients had hypertension. Seven (33.3%) had ST-T segment and T wave changes, and four (19%) had sinus tachycardia. Twenty (52.6%) had an increase in ascending aorta (AAO) diameter, 22 (57.9%) had an increase in left atrium (LA) size, and 28 (73.7%) presented with ventricular diastolic dysfunction. Correlation analysis showed that the AAO diameter was significantly associated with C-reactive protein (r = 0.4313) and creatine kinase-MB (r = 0.0414). LA enlargement was significantly associated with C-reactive protein (r = 0.4377), brain natriuretic peptide (r = 0.7612), creatine kinase-MB (r = 0.4940), and aspartate aminotransferase (r = 0.2947). Lymphocyte count was negatively associated with the AAO diameter (r = -0.5329) and LA enlargement (r = -0.3894). Conclusions: Hypertension was a common comorbidity among hospitalized patients with COVID-19, and cardiac injury was the most common complication. Changes in cardiac structure and function manifested mainly in the left heart and AAO in these patients. Abnormal AAO and LA size were found to be associated with severe inflammation and cardiac injury. Alternatively, ascending aortic dilation and LA enlargement might be present before infection but characterized the patient at risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Anticoagulation Management in Severe Coronavirus Disease 2019 Patients on Extracorporeal Membrane Oxygenation.

OBJECTIVE: To explore special coagulation characteristics and anticoagulation management in extracorporeal membrane oxygenation (ECMO)-assisted patients with coronavirus disease 2019 (COVID-19). DESIGN: Single-center, retrospective observation of a series of patients. PARTICIPANTS: Laboratory-confirmed severe COVID-19 patients who received venovenous ECMO support from January 20-May 20, 2020. INTERVENTIONS: This study analyzed the anticoagulation management and monitoring strategies, bleeding complications, and thrombotic events during ECMO support. MEASUREMENTS AND MAIN RESULTS: Eight of 667 confirmed COVID-19 patients received venovenous ECMO and had an elevated D-dimer level before and during ECMO support. An ECMO circuit pack (oxygenator and tubing) was replaced a total of 13 times in all 8 patients, and coagulation-related complications included oxygenator thrombosis (7/8), tracheal hemorrhage (5/8), oronasal hemorrhage (3/8), thoracic hemorrhage (3/8), bleeding at puncture sites (4/8), and cannulation site hemorrhage (2/8). CONCLUSIONS: Hypercoagulability and secondary hyperfibrinolysis during ECMO support in COVID-19 patients are common and possibly increase the propensity for thrombotic events and failure of the oxygenator. Currently, there is not enough evidence to support a more aggressive anticoagulation strategy.

Extracorporeal Membrane Oxygenation for Coronavirus Disease 2019 in Shanghai, China.

Severe cases of coronavirus disease 2019 (COVID-19) cannot be adequately managed with mechanical ventilation alone. The role and outcome of extracorporeal membrane oxygenation (ECMO) in the management of COVID-19 is currently unclear. Eight COVID-19 patients have received ECMO support in Shanghai with seven with venovenous (VV) ECMO support and one veno arterial (VA) ECMO during cardiopulmonary resuscitation. As of March 25, 2020, four patients died (50% mortality), three patients (37.5%) were successfully weaned off ECMO after 22, 40, and 47 days support, respectively, but remain on mechanical ventilation. One patient is still on VV ECMO with mechanical ventilation. The partial pressure of oxygen/fractional of inspired oxygen ratio before ECMO initiation was between 54 and 76, and all were well below 100. The duration of mechanical ventilation before ECMO ranged from 4 to 21 days. Except the one emergent VA ECMO during cardiopulmonary resuscitation, other patients were on ECMO support for between 18 and 47 days. In conclusion, ensuring effective, timely, and safe ECMO support in COVID-19 is key to improving clinical outcomes. Extracorporeal membrane oxygenation support might be an integral part of the critical care provided for COVID-19 patients in centers with advanced ECMO expertise.