Prognostic performance of blood neurofilament light chain protein in hospitalized COVID-19 patients without major central nervous system manifestations: an individual participant data meta-analysis.

BACKGROUND AND AIMS: To investigate the prognostic value of blood neurofilament light chain protein (NfL) levels in the acute phase of coronavirus disease 2019 (COVID-19). METHODS: We conducted an individual participant data (IPD) meta-analysis after screening on MEDLINE and Scopus to May 23rd 2022. We included studies with hospitalized adult COVID-19 patients without major COVID-19-associated central nervous system (CNS) manifestations and with a measurement of blood NfL in the acute phase as well as data regarding at least one clinical outcome including intensive care unit (ICU) admission, need of mechanical ventilation (MV) and death. We derived the age-adjusted measures NfL Z scores and conducted mixed-effects modelling to test associations between NfL Z scores and other variables, encompassing clinical outcomes. Summary receiver operating characteristic curves (SROCs) were used to calculate the area under the curve (AUC) for blood NfL. RESULTS: We identified 382 records, of which 7 studies were included with a total of 669 hospitalized COVID-19 cases (mean age 66.2 ± 15.0 years, 68.1% males). Median NfL Z score at admission was elevated compared to the age-corrected reference population (2.37, IQR: 1.13-3.06, referring to 99th percentile in healthy controls). NfL Z scores were significantly associated with disease duration and severity. Higher NfL Z scores were associated with a higher likelihood of ICU admission, need of MV, and death. SROCs revealed AUCs of 0.74, 0.80 and 0.71 for mortality, need of MV and ICU admission, respectively. CONCLUSIONS: Blood NfL levels were elevated in the acute phase of COVID-19 patients without major CNS manifestations and associated with clinical severity and poor outcome. The marker might ameliorate the performance of prognostic multivariable algorithms in COVID-19.

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

A systematic review and meta-analysis of racial disparities in deep vein thrombosis and pulmonary embolism events in patients hospitalized with coronavirus disease 2019.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) is associated with an increased risk of venous thromboembolism (VTE). Recent studies have characterized racial disparities in the incidence of VTE. The aim of our study was to present a systematic review and meta-analysis to assess the association between race and VTE in patients hospitalized with COVID-19. METHODS: We performed a systematic literature review to evaluate the number of deep vein thrombosis (DVT) and pulmonary embolism (PE) events reported by racial groups in patients hospitalized with COVID-19. For the qualitative analysis, independent reviewers extracted the data from eligible studies, and we used the Newcastle-Ottawa scale to assess the quality of design and content for accurate interpretation. For the quantitative analysis, we pooled the odds ratios with Der Simonian and Laird random effects models. RESULTS: The qualitative analysis included 11 studies, with 6 included in the meta-analysis. All studies were observational, retrospective cohort studies, except for one retrospective case-control study. Six studies were eligible for the meta-analysis owing to the high interstudy heterogeneity; thus, the variable reports of racial groups reduced the cohort to Black/African American and White patients (n = 9723) in the analysis. The estimated proportion for DVT and PE events for Black/African American and White patients was 0.07 (95% confidence interval, 0.00-0.10) and 0.04 (95% confidence interval, 0.00-0.07), respectively. The P value of .13 suggested nonsignificant differences in the VTE rates between Black/African American and White patients. CONCLUSIONS: In our study, the proportion of DVT and PE events between Black/African American and White patients with COVID-19 were comparable. Future COVID-19 studies should include systematic racial group reporting to identify any disparities in the setting of VTE events.

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.

Outcomes and Surgical Considerations for Neurosurgical Patients Hospitalized with COVID-19-A Multicenter Case Series.

OBJECTIVE: Neurosurgical patients are at a higher risk of having a severe course of coronavirus disease 2019 (COVID-19). The objective of this study was to determine morbidity, hospital course, and mortality of neurosurgical patients during the coronavirus disease 2019 (COVID-19) pandemic in a multicenter health care system. METHODS: A retrospective observational study was conducted to identify all hospitalized neurosurgical patients positive for COVID-19 from March 11, 2020 to November 2, 2020 at Mayo Clinic and the Mayo Clinic Health System. RESULTS: Eleven hospitalized neurosurgical patients (0.68%) were positive for COVID-19. Four patients (36.6%) were men and 7 (63.3%) were women. The mean age was 65.7 years (range, 35-81 years). All patients had comorbidities. The mean length of stay was 13.4 days (range, 4-30 days). Seven patients had a central nervous system malignancy (4 metastases, 1 meningioma, 1 glioblastoma, and 1 schwannoma). Three patients presented with cerebrovascular complications, comprising 2 spontaneous intraparenchymal hemorrhages and 1 ischemic large-vessel stroke. One patient presented with an unstable traumatic spinal burst fracture. Four patients underwent neurosurgical/neuroendovascular interventions. Discharge disposition was to home in 5 patients, rehabilitation facility in 3, and hospice in 3. Five patients had died at follow-up, 3 within 30 days from COVID-19 complications and 2 from progression of their metastatic cancer. CONCLUSIONS: COVID-19 is rare among the inpatient neurosurgical population. In all cases, patients had multiple comorbidities. All symptomatic patients from the respiratory standpoint had complications during their hospitalization. Deaths of 3 patients who died within 30 days of hospitalization were all related to COVID-19 complications. Neurosurgical procedures were performed only if deemed emergent.

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.

Telemedicine in vascular surgery during the coronavirus disease-2019 pandemic: A multisite healthcare system experience.

OBJECTIVE: To assess the introduction of telemedicine as an alternative to the traditional face-to-face encounters with vascular surgery patients in the era of the coronavirus disease 2019 (COVID-19) pandemic. METHODS: A retrospective review of prospectively collected data on face-to-face and telemedicine interactions was conducted at a multisite health care system from January to August 2020 in vascular surgery patients during the COVID-19 pandemic. The end point is direct patient satisfaction comparison between face-to-face and telemedicine encounters/interactions prior and during the pandemic. RESULTS: There were 6262 patient encounters from January 1, 2020, to August 6, 2020. Of the total encounters, 790 (12.6%) were via telemedicine, which were initiated on March 11, 2020, after the World Health Organization's declaration of the COVID-19 pandemic. These telemedicine encounters were readily adopted and embraced by both the providers and patients and remain popular as an option to patients for all types of visits. Of these patients, 78.7% rated their overall health care experience during face-to-face encounters as very good and 80.6% of patients rated their health care experience during telemedicine encounters as very good (P = .78). CONCLUSIONS: Although the COVID-19 pandemic has produced unprecedented consequences to the practice of medicine and specifically of vascular surgery, our multisite health care system has been able to swiftly adapt and adopt telemedicine technologies for the care of our complex patients. Most important, the high quality of patient-reported satisfaction and health care experience has remained unchanged.

Yield of Head Imaging in Ambulatory and Hospitalized Patients With SARS-CoV-2: A Multi-Center Study of 8675 Patients.

BACKGROUND AND PURPOSE: To describe the neurological and cerebrovascular findings in patients who tested positive for SARS-CoV-2 and underwent head imaging in ambulatory and inpatient settings. METHODS: Consecutive patients aged ≥18 years with SARS-CoV-2 infection diagnosed or treated at Mayo Clinic sites from 3/11/2020 to 7/23/2020 with head CT or brain MRI within 30 days of SARS-CoV-2 diagnosis were included. Demographics, medical history, indication for SARS-CoV-2 testing, neurologic symptoms, indication for brain imaging, neuroimaging findings, etiology of cerebrovascular events, and hospital course were abstracted from medical records. RESULTS: Of 8,675 patients with SARS-CoV-2, 180 (2.07%) had head imaging. Mean age of the entire cohort was 42 ± 18 years, whereas mean age of those with head imaging was 62 ± 19 years. Common indications for imaging were headache (34.4%), encephalopathy (33.4%), focal neurologic symptom (16.7%), and trauma (13.9%). While 86.1% of patients who underwent head imaging had normal exams, cerebrovascular events occurred in 18 patients (0.21% of the total cohort). Of patients with cerebrovascular events, 8 (44.5%) had acute infarct; 6 (33.3%), acute intracranial hemorrhage; 5 (2.8%), subacute infarct; and 1 (0.6%) posterior reversible encephalopathy syndrome. In the thirteen patients with ischemic stroke, 6 (46.2%) had cryptogenic stroke; 3 (23.1%), other defined causes; 2 (15.4%), small vessel stroke; 1 (7.7%), large vessel stroke; and 1 (7.7%) cardioembolic stroke. CONCLUSION: In ambulatory and hospitalized patients with SARS-CoV-2 infection, the rate of head imaging is low, with common indications of encephalopathy and headache. Cerebrovascular events occurred rarely, and cryptogenic stroke was the most common stroke mechanism.

Mitigating the effects of COVID-19 pandemic on controlling vascular risk factors among participants in a carotid stenosis trial.

INTRODUCTION: The COVID-19 pandemic has presented challenges to managing vascular risk factors with in-person follow-up of patients with asymptomatic carotid stenosis enrolled in the CREST2 trial. CREST2 is comparing intensive medical management alone versus intensive medical management plus revascularization with endarterectomy or stenting. We performed a study to evaluate the feasibility of a home-based program for testing blood pressure (BP) and low-density lipoprotein (LDL) in CREST2. METHODS: This study involved 45 patients at 10 sites in the CREST2 trial. The initial patients were identified by the Medical Management Core (MMC) as high-risk patients defined by stage 2 hypertension, LDL > 90 mg/dl, or both. If a patient at the site declined participation, another was substituted. All patients who agreed to participate were sent a BP monitoring device and a commercially available at-home lipid test kit that uses a self-performed finger-stick blood sample that was resulted to the patient. Training on the use of the equipment and obtaining the risk factor results was done by the study coordinator by telephone. RESULTS: Ten of the 130 currently active CREST2 sites participated, 8 in the LDL portion and 5 in the BP portion (3 sites did both). Twenty-six BP devices and 23 lipid tests were sent to patients. Of the 26 patients who obtained BP readings with the devices, 9 were out of the study target and adjustments in BP medications were made in 3. Of the 23 patients sent LDL tests, 13 were able to perform the test showing 7 were out of target, leading to adjustments in lipid medications in 4. CONCLUSION: This study established the feasibility of at-home monitoring of BP and LDL in a clinical trial and identified implementation challenges prior to widespread use in the trial. (ClinicalTrials.gov number NCT02089217).

The CREST-2 experience with the evolving challenges of COVID-19: A clinical trial in a pandemic.

The coronavirus disease 2019 pandemic has disrupted the lives of whole communities and nations. The multinational multicenter National Institute of Neurological Disorders and Stroke Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial stroke prevention trial rapidly experienced the effects of the pandemic and had to temporarily suspend new enrollments and shift patient follow-up activities from in-person clinic visits to telephone contacts. There is an ethical obligation to the patients to protect their health while taking every feasible step to ensure that the goals of the trial are successfully met. Here, we describe the effects of the pandemic on the trial and steps that are being taken to mitigate the effects of the pandemic so that trial objectives can be met.