Association and predictive value of biomarkers with severe outcomes in hospitalized patients with SARS-CoV-2 infection.

This study analyzed the levels at admission of biomarkers for their association with and ability to predict risk of severe outcomes, including admission to the ICU, need for invasive mechanical ventilation (IMV), need for vasopressor use (VU), and in-hospital mortality (IHM) in 700 patients hospitalized with COVID-19. Biomarker data split by outcomes was compared using Mann-Whitney U tests; frequencies of biomarker values were compared using Chi-square tests and multivariable logistic regression analysis was performed to look at the impact of biomarkers by outcome. Patients that suffered IHM were more likely to have reduced platelet numbers and high blood urea nitrogen (BUN) levels among patients admitted to the ICU. Risk factors for mortality were related to hyper-coagulability (low platelet count and increased D-dimer) and decreased respiratory (PaO2/FiO2 ratio) and kidney function (BUN). Association with risks of other severe outcomes were as follows: ICU with hyper-inflammation (IL-6) and decreased respiratory function; IMV with low platelet count, abnormal neutrophil-lymphocyte ratio with reduced respiratory function, VU with inflammatory markers (IL-6), and low platelet count with respiratory function. Our studies confirmed the association of biomarkers of hematological, inflammatory, coagulation, pulmonary and kidney functions with disease severity. Whether these biomarkers have any mechanistic or causal role in the disease progress requires further investigation.

Acute Respiratory Distress Syndrome and Time to Weaning Off the Invasive Mechanical Ventilator among Patients with COVID-19 Pneumonia.

Acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19) pneumonia is the main cause of the pandemic's death toll. The assessment of ARDS and time on invasive mechanical ventilation (IMV) could enhance the characterization of outcomes and management of this condition. This is a city-wide retrospective study of hospitalized patients with COVID-19 pneumonia from 5 March 2020 to 30 June 2020. Patients with critical illness were compared with those with non-critical illness. We examined the severity of ARDS and other factors associated with (i) weaning patients off IMV and (ii) mortality in a city-wide study in Louisville, KY. Of 522 patients with COVID-19 pneumonia, 219 (41.9%) were critically ill. Among critically ill patients, the median age was 60 years; 53% were male, 55% were White and 32% were African American. Of all critically ill patients, 52% had ARDS, and 38% of these had severe ARDS. Of the 25% of patients who were weaned off IMV, those with severe ARDS were weaned within eleven days versus five days for those without severe ARDS, p = 0.023. The overall mortality for critically ill patients was 22% versus 1% for those not critically ill. Furthermore, the 14-day mortality was 31% for patients with severe ARDS and 12% for patients without severe ARDS, p = 0.019. Patients with severe ARDS versus non-severe ARDS needed twice as long to wean off IMV (eleven versus five days) and had double the 14-day mortality of patients without severe ARDS.

Is Microthrombosis the Main Pathology in Coronavirus Disease 2019 Severity?-A Systematic Review of the Postmortem Pathologic Findings.

This systematic review attempts to retrieve and report the findings of postmortem studies including the histopathologic data of deceased coronavirus disease 2019 patients and to review the manifestations of coronavirus disease 2019-associated thrombotic pathologies reported in the recent literature. DATA SOURCES: PubMed, Excerpta Medica Database, and Cochrane library between December 1, 2019, and August 26, 2020. STUDY SELECTION: Investigators screened 360 unique references, retrieved published autopsy series, and report on the postmortem histopathologic information on patients who had died of coronavirus disease 2019. DATA EXTRACTION: Investigators independently abstracted all available data including study design, participant demographics, key histopathologic findings, disease severity markers, duration of hospital stay, and cause of death. DATA SYNTHESIS: From the 65 eligible studies, 691 total completed autopsies were included in evidence synthesis. Histopathologic evaluation of the lungs revealed presence of diffuse alveolar damage in 323 of 443 patients and pulmonary microthrombi in 242 of 326 patients. Deep venous thrombosis and pulmonary embolism were found in 41% and ~15%, respectively, of the cadavers examined for thromboembolic events. d-dimer levels were generally higher in patients with severe clinical course of coronavirus disease 2019. Plasma levels of ferritin, lactate dehydrogenase, interleukin-6, and C-reactive protein were higher in nonsurvivors when compared with survivors. Overall, microthrombi and extensive angiogenesis of lung vasculature were the most common pathologic findings in the lungs and microthrombi in most of the assessed organ-tissue. CONCLUSIONS: Diffuse alveolar damage was the most predominant feature in the lungs of coronavirus disease 2019 patients who underwent postmortem assessment. Widespread pulmonary microthrombosis and extensive pulmonary angiogenesis, in addition to frequent pulmonary and extrapulmonary microthrombotic and thromboembolic findings in patients with coronavirus disease 2019, appear to be consistent with the disease-specific hypercoagulability. Further discovery efforts in assessing the link between coronavirus disease 2019, hypercoagulable state, and immunothrombosis are warranted. In the interim, increased attention to anticoagulant treatment approaches in coronavirus disease 2019 patients is needed.

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.