Coronavirus Disease 2019 Causing Infection of Transplanted Lung Allograft: A Pitfall of Prolonged Shedding of Severe Acute Respiratory Syndrome Coronavirus-2 Pretransplant.

Coronavirus disease 2019 (COVID-19) pandemic has led to considerable morbidity and mortality across the world. Lung transplant is a viable option for a few with COVID-19-related lung disease. Whom and when to transplant has been the major question impacting the transplant community given the novelty of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We describe a pitfall of presumed prolonged shedding of SARS-CoV-2 in a patient with COVID-19 associated acute respiratory distress syndrome leading to COVID-19 pneumonia after lung transplant. This raises concerns that replication-competent SARS-CoV-2 virus can persist for months post-infection and can lead to re-infection of grafts in the future.

Race affects adverse outcomes of deep vein thrombosis, pulmonary embolism, and acute kidney injury in coronavirus disease 2019 hospitalized patients.

OBJECTIVE: The purpose of the present study was to explore the racial disparities in the incidence of deep vein thrombosis (DVT), pulmonary embolism (PE), and acute kidney injury (AKI) in hospitalized patients with coronavirus disease 2019 (COVID-19). METHODS: A retrospective analysis was performed of prospectively collected data of consecutive COVID-19 patients hospitalized from March 11, 2020 to May 27, 2021. The primary outcome measures were the incidence of DVT/PE and mortality. The secondary outcome measures included differences in the length of hospitalization, need for intensive care unit care, readmission, and AKI. Multivariable regression models were used to assess for independent predictors of the primary and secondary outcome measures. RESULTS: The present study included 876 hospitalized patients with COVID-19. The mean age was 64.4 ± 16.2 years, and 355 were women (40.5%). Of the 876 patients, 694 (79.2%) had identified as White, 111 (12.7%) as Black/African American, 48 (5.5%) as Asian, and 23 (2.6%) as other. The overall incidence of DVT/PE was 8.7%. The DVT/PE incidence rates differed across the race groups and was highest for Black/African American patients (n = 18; 16.2%), followed by Asian patients (n = 5; 10.4%), White patients (n = 52; 7.5%), and other (n = 1; 4.4%; P = .03). All but one of the hospitalization outcomes examined demonstrated no differences according to race, including the hospitalization stay (P = .33), need for intensive care unit care (P = .20), readmission rates (P = .52), and hospital all-cause mortality (P = .29). The AKI incidence differed among races, affecting a higher proportion of Black/African American patients (P=.003). On multivariable regression analysis, Black/African American race (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.0-4.0; P = .04) and higher D-dimer levels (OR, 1.1; 95% CI, 1.1-1.2; P < .0001) were predictors of DVT/PE. In addition, Black/African American race (OR, 2.3; 95% CI, 1.4-3.7; P = .001), lower hemoglobin levels (OR, 0.84; 95% CI, 0.8-0.9; P ≤ .0001), male sex (OR, 1.7; 95% CI, 1.2-2.4; P = .005), hypertension (OR, 2.1; 95% CI, 1.4-3.1; P = .0005), and older age (OR, 1.02; 95% CI, 1.006-1.03; P = .003) were predictors of AKI. CONCLUSIONS: In our single-center case series, we found a higher incidence of DVT/PE and AKI among Black/African American patients with COVID-19. Black/African American race and D-dimer levels were independent predictors of DVT/PE, and Black/African American race, hemoglobin, and D-dimer levels were independent predictors of AKI.

Neurofilament light chain and vaccination status associate with clinical outcomes in severe COVID-19.

Blood neurofilament light chain (NFL) is proposed to serve as an estimate of disease severity in hospitalized patients with coronavirus disease 2019 (COVID-19). We show that NFL concentrations in plasma collected from 880 patients with COVID-19 within 5 days of hospital admission were elevated compared to controls. Higher plasma NFL associated with worse clinical outcomes including the need for mechanical ventilation, intensive care, prolonged hospitalization, and greater functional disability at discharge. No difference in the studied clinical outcomes between black/African American and white patients was found. Finally, vaccination associated with less disability at time of hospital discharge. In aggregate, our findings support the utility of measuring NFL shortly after hospital admission to estimate disease severity and show that race does not influence clinical outcomes caused by COVID-19 assuming equivalent access to care, and that vaccination may lessen the degree of COVID-19-caused disability.

Neurofilament light chain and vaccination status associate with clinical outcomes in severe COVID-19

Blood neurofilament light chain (NFL) is proposed to serve as an estimate of disease severity in hospitalized patients with coronavirus disease 2019 (COVID-19). We show that NFL concentrations in plasma collected from 880 patients with COVID-19 within 5 days of hospital admission were elevated compared to controls. Higher plasma NFL associated with worse clinical outcomes including the need for mechanical ventilation, intensive care, prolonged hospitalization, and greater functional disability at discharge. No difference in the studied clinical outcomes between black/African American and white patients was found. Finally, vaccination associated with less disability at time of hospital discharge. In aggregate, our findings support the utility of measuring NFL shortly after hospital admission to estimate disease severity and show that race does not influence clinical outcomes caused by COVID-19 assuming equivalent access to care, and that vaccination may lessen the degree of COVID-19-caused disability. Graphical

Use of Self-Collected Saliva Samples for the Detection of SARS-CoV-2.

OBJECTIVE: Using a US Food and Drug Administration (FDA) emergency use authorization (EUA) reverse transcription polymerase chain reaction (RT-PCR) method, we examined the analytic performance accuracy of saliva specimens as compared to nasopharyngeal (NP) specimens in symptomatic patients. Correlation between test results and symptoms was also evaluated. METHODS: Over a 5-week period in 2020, 89 matched saliva and nasopharyngeal swabs were collected from individuals exhibiting symptoms consistent with SARS-CoV-2. Specimens were tested with an FDA EUA-approved RT-PCR method, and performance characteristics were compared. RESULTS: The concordance rate between saliva and nasopharyngeal testing was 93.26%. The mean cycle threshold value of saliva when compared to the NP specimen was 3.56 cycles higher. As compared to NP swab, saliva testing demonstrates acceptable agreement but lower sensitivity. CONCLUSION: When compared to a reference method using NP swabs, the use of saliva testing proved to be a reliable method. Self-collected saliva testing for SARS-CoV-2 allows for a viable option when trained staff or collection materials are in short supply.

Resolution of acute pulmonary embolism using anticoagulation therapy alone in coronavirus disease 2019.

OBJECTIVE: To investigate the radiographic resolution of acute pulmonary embolism (PE) using contrast-enhanced computed tomography (CECT) examinations in patients diagnosed with acute PE while hospitalized with coronavirus disease 2019 (COVID-19) and to understand the mid-term and long-term implications of anticoagulation therapy. METHODS: We identified patients with acute PE per CECT and at least one follow-up CECT from March 11, 2020, to May 27, 2021, using a prospective registry of all hospitalized patients with COVID-19 infection receiving care within a multicenter Health System. Initial and follow-up CECT examinations were reviewed independently by two radiologists to evaluate for PE resolution. The Modified Miller Score was used to assess for thrombus burden at diagnosis and on follow-up. RESULTS: Of the 6070 hospitalized patients with COVID-19 infection, 5.7% (348/6070) were diagnosed with acute PE and 13.5% (47/348) had a follow-up CECT examination. The mean ± standard deviation time to follow-up imaging was 44 ± 48 days (range, 3-161 days). Of 47 patients, 47 (72.3%) had radiographic resolution of PE, with a mean time to follow-up of 48 ± 43 days (range, 6-239 days). All patients received anticoagulation monotherapy for a mean of 149 ± 95 days and this included apixaban (63.8%), warfarin (12.8%), and rivaroxaban (8.5%), among others. The mean Modified Miller Score at PE diagnosis and follow-up was 4.8 ± 4.2 (range, 1-14) and 1.4 ± 3.3 (range, 0-16; P < .0001), respectively. Nine patients (19%) died at a mean of 13 ± 8 days after follow-up CECT (range, 1-27 days) and at a mean of 28 ± 16 days after admission (range, 11-68 days). Seen of the nine deaths (78%) deaths were associated with progression of COVID-19 pneumonia. CONCLUSIONS: Hospitalized patients with COVID-19 have a clinically apparent 5.7% rate of developing PE. In patients with follow-up imaging, 72.3% had radiographic thrombus resolution at a mean of 44 days while on anticoagulation. Prospective studies of the natural history of PEs with COVID-19 that include systematic follow-up imaging are warranted to help guide anticoagulation recommendations.

Humoral Responses After SARS-CoV-2 mRNA Vaccination and Breakthrough Infection in Cancer Patients.

OBJECTIVE: To evaluate the magnitude of humoral response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccines in patients with cancer receiving active therapies. PATIENTS AND METHODS: Patients 18 years or older in whom SARS-CoV-2 spike antibody (anti-S Ab) levels were measured after 2 doses of SARS-CoV-2 mRNA vaccines were included. Patients with prior coronavirus disease 2019 (COVID-19) infection or receiving other immunosuppressive therapy were excluded. RESULTS: Among 201 patients who met the criteria, 61 were immunocompetent, 91 had a hematologic malignancy, and 49 had a solid malignancy while receiving treatments associated with cytopenia, including chemotherapy or cyclin-dependent kinase 4 and 6 inhibitors. A significantly greater proportion of immunocompetent patients (96.7% [59 of 61]) had anti-S Ab titers of 500 U/mL or greater compared to patients with hematologic (7.7% [7 of 91) and solid (55.1% [27 of 49]) malignancy (P<.001). Despite 2 doses of SARS-CoV-2 mRNA vaccines, 52.7% of patients with hematologic malignancy (48 of 91) and 8.2% of those with solid malignancy (4 of 49) receiving cytopenic therapy had no seroconversion (spike antibody titers <0.8 U/mL). Two patients subsequently had development of breakthrough COVID-19 infection after full vaccination. CONCLUSION: A substantial proportion of patients with hematologic and solid malignancies receiving chemotherapies and CDK4/6i had poor humoral responses after SARS-CoV-2 mRNA vaccination. Our study adds to a growing body of literature suggesting that immunosuppressed patients have a suboptimal humoral response to COVID-19 vaccination. Our study also underscores the importance of assessing antibody response after COVID-19 vaccines in these vulnerable patients.

Biomarkers of thromboinflammation correlate to COVID-19 infection and admission status in emergency department patients

Background COVID-19-associated coagulopathy is incompletely understood. Objectives To characterize thrombin generation, Von Willebrand Factor (VWF), neutrophil extracellular traps (NETs), and their role in COVID-19 risk stratification in the emergency department (ED). Patients/methods Plasma samples from 67 ED COVID-19 patients were compared to 38 healthy volunteers (HVs). Thrombin generation (calibrated automated thrombogram, CAT) was expressed as lag time (LT, min), peak height (PH, min), and time to peak (ttPeak, min). Citrullinated nucleosomes and histones were quantified with ELISA, VWF antigen and activity (IU/dL) through latex immunoassay, Factor VIII (IU/dL) through one-stage optical clot detection, and VWF multimers with western blot densitometry. Wilcoxon testing and multivariable logistic regression were performed. Results presented as median [Q1, Q3];p < 0.05 significant. Results COVID-19 patients had longer LT (4.00 [3.26, 4.67];2.95 [2.67, 3.10], p < 0.001) and ttPeak (7.33 [6.33, 8.04];6.45 [6.00, 7.50], p = 0.004), greater VWF antigen (212 [158, 275];110 [91, 128], p < 0.001) and Factor VIII levels (148 [106, 190];106 [86, 129], p < 0.001), with decreased high molecular weight multimers (Normalized multimer ratio 0.807 [0.759, 0.869];0.891 [0.858, 0.966], p < 0.001), than HVs. COVID-19 patients requiring admission from the ED had longer LT and ttPeak with greater VWF antigen and Factor VIII levels than those not admitted. Two and three variable models of CAT parameters and VWF correlated with COVID-19 and admission status (C-statistics 0.677 to 0.922). Conclusions Thrombin generation kinetics and VWF levels, independent of NETs, may have a role in predicting admission need for COVID-19 patients.

Serum neurofilament light protein correlates with unfavorable clinical outcomes in hospitalized patients with COVID-19.

Brain imaging studies of patients with COVID-19 show evidence of macro- and microhemorrhagic lesions, multifocal white matter hyperintensities, and lesions consistent with posterior reversible leukoencephalopathy. Imaging studies, however, are subject to selection bias, and prospective studies are challenging to scale. Here, we evaluated whether serum neurofilament light chain (NFL), a neuroaxonal injury marker, could predict the extent of neuronal damage in a cohort of 142 hospitalized patients with COVID-19. NFL was elevated in the serum of patients with COVID-19 compared to healthy controls, including those without overt neurological manifestations. Higher NFL serum concentrations were associated with worse clinical outcomes. In 100 hospitalized patients with COVID-19 treated with remdesivir, a trend toward lower NFL serum concentrations was observed. These data suggest that patients with COVID-19 may experience neuroaxonal injury and may be at risk for long-term neurological sequelae. Neuroaxonal injury should be considered as an outcome in acute pharmacotherapeutic trials for COVID-19.

Deep vein thrombosis and pulmonary embolism among hospitalized coronavirus disease 2019-positive patients predicted for higher mortality and prolonged intensive care unit and hospital stays in a multisite healthcare system.

OBJECTIVE: We assessed the incidence of deep vein thrombosis (DVT) and pulmonary embolism (PE) in hospitalized patients with coronavirus disease 2019 (COVID-19) compared with that in a matched cohort with similar cardiovascular risk factors and the effects of DVT and PE on the hospital course. METHODS: We performed a retrospective review of prospectively collected data from COVID-19 patients who had been hospitalized from March 11, 2020 to September 4, 2020. The patients were randomly matched in a 1:1 ratio by age, sex, hospital of admission, smoking history, diabetes mellitus, and coronary artery disease with a cohort of patients without COVID-19. The primary end point was the incidence of DVT/PE and the odds of developing DVT/PE using a conditional logistic regression model. The secondary end point was the hospitalization outcomes for COVID-19 patients with and without DVT/PE, including mortality, intensive care unit (ICU) admission, ICU stay, and length of hospitalization (LOH). Multivariable regression analysis was performed to identify the variables associated with mortality, ICU admission, discharge disposition, ICU duration, and LOH. RESULTS: A total of 13,310 patients had tested positive for COVID-19, 915 of whom (6.9%) had been hospitalized across our multisite health care system. The mean age of the hospitalized patients was 60.8 ± 17.0 years, and 396 (43.3%) were women. Of the 915 patients, 82 (9.0%) had had a diagnosis of DVT/PE confirmed by ultrasound examination of the extremities and/or computed tomography angiography of the chest. The odds of presenting with DVT/PE in the setting of COVID-19 infection was greater than that without COVID-19 infection (0.6% [5 of 915] vs 9.0% [82 of 915]; odds ratio [OR], 18; 95% confidence interval [CI], 8.0-51.2; P < .001). The vascular risk factors were not different between the COVID-19 patients with and without DVT/PE. Mortality (P = .02), the need for ICU stay (P < .001), duration of ICU stay (P < .001), and LOH (P < .001) were greater in the DVT/PE cohort than in the cohort without DVT/PE. On multivariable logistic regression analysis, the hemoglobin (OR, 0.71; 95% CI, 0.46-0.95; P = .04) and D-dimer (OR, 1.0; 95% CI, 0.33-1.56; P = .03) levels were associated with higher mortality. Higher activated partial thromboplastin times (OR, 1.1; 95% CI, 1.00-1.12; P = .03) and higher interleukin-6 (IL-6) levels (OR, 1.0; 95% CI, 1.01-1.07; P = .05) were associated with a greater risk of ICU admission. IL-6 (OR, 1.0; 95% CI, 1.00-1.02; P = .05) was associated with a greater risk of rehabilitation placement after discharge. On multivariable gamma regression analysis, hemoglobin (coefficient, -3.0; 95% CI, 0.03-0.08; P = .005) was associated with a prolonged ICU stay, and the activated partial thromboplastin time (coefficient, 2.0; 95% CI, 0.003-0.006; P = .05), international normalized ratio (coefficient, -3.2; 95% CI, 0.06-0.19; P = .002) and IL-6 (coefficient, 2.4; 95% CI, 0.0011-0.0027; P = .02) were associated with a prolonged LOH. CONCLUSIONS: A significantly greater incidence of DVT/PE occurred in hospitalized COVID-19-positive patients compared with a non-COVID-19 cohort matched for cardiovascular risk factors. Patients affected by DVT/PE were more likely to experience greater mortality, to require ICU admission, and experience prolonged ICU stays and LOH compared with COVID-19-positive patients without DVT/PE. Advancements in DVT/PE prevention are needed for patients hospitalized for COVID-19 infection.