SARS-CoV-2 genomic surveillance in Malaysia: displacement of B.1.617.2 with AY lineages as the dominant Delta variants and the introduction of Omicron during the fourth epidemic wave.

OBJECTIVES: This study reported SARS-CoV-2 whole genome sequencing results from June 2021 to January 2022 from seven genome sequencing centers in Malaysia as part of the national surveillance program. METHODS: COVID-19 samples that tested positive by reverse transcription polymerase chain reaction and with cycle threshold values <30 were obtained throughout Malaysia. Sequencing of SARS-CoV-2 complete genomes was performed using Illumina, Oxford Nanopore, or Ion Torrent platforms. A total of 6163 SARS-CoV-2 complete genome sequences were generated over the surveillance period. All sequences were submitted to the Global Initiative on Sharing All Influenza Data database. RESULTS: From June 2021 to January 2022, Malaysia experienced the fourth wave of COVID-19 dominated by the Delta variant of concern, including the original B.1.617.2 lineage and descendant AY lineages. The B.1.617.2 lineage was identified as the early dominant circulating strain throughout the country but over time, was displaced by AY.59 and AY.79 lineages in Peninsular (west) Malaysia, and the AY.23 lineage in east Malaysia. In December 2021, pilgrims returning from Saudi Arabia facilitated the introduction and spread of the BA.1 lineage (Omicron variant of concern) in the country. CONCLUSION: The changing trends of circulating SARS-CoV-2 lineages were identified, with differences observed between west and east Malaysia. This initiative highlighted the importance of leveraging research expertise in the country to facilitate pandemic response and preparedness.

The one health perspective to improve environmental surveillance of zoonotic viruses: lessons from COVID-19 and outlook beyond

The human population has doubled in the last 50 years from about 3.7 billion to approximately 7.8 billion. With this rapid expansion, more people live in close contact with wildlife, livestock, and pets, which in turn creates increasing opportunities for zoonotic diseases to pass between animals and people. At present an estimated 75% of all emerging virus-associated infectious diseases possess a zoonotic origin, and outbreaks of Zika, Ebola and COVID-19 in the past decade showed their huge disruptive potential on the global economy. Here, we describe how One Health inspired environmental surveillance campaigns have emerged as the preferred tools to monitor human-adjacent environments for known and yet to be discovered infectious diseases, and how they can complement classical clinical diagnostics. We highlight the importance of environmental factors concerning interactions between animals, pathogens and/or humans that drive the emergence of zoonoses, and the methodologies currently proposed to monitor them—the surveillance of wastewater, for example, was identified as one of the main tools to assess the spread of SARS-CoV-2 by public health professionals and policy makers during the COVID-19 pandemic. One-Health driven approaches that facilitate surveillance, thus harbour the potential of preparing humanity for future pandemics caused by aetiological agents with environmental reservoirs. Via the example of COVID-19 and other viral diseases, we propose that wastewater surveillance is a useful complement to clinical diagnosis as it is centralized, robust, cost-effective, and relatively easy to implement.

Efficacy of Bivalirudin for Therapeutic Anticoagulation in COVID-19 Patients Requiring ECMO Support.

OBJECTIVES: The Coronavirus Disease 2019 (COVID-19) pandemic has been associated with cases of refractory acute respiratory distress syndrome (ARDS) sometimes requiring support with extracorporeal membrane oxygenation (ECMO). Bivalirudin can be used for anticoagulation in patients on ECMO support, but its efficacy and safety in patients with COVID-19 is unknown. The authors set out to compare the pharmacologic characteristics and dosing requirements of bivalirudin in patients requiring ECMO support for ARDS due to COVID-19 versus ARDS from other etiologies. DESIGN AND SETTING: This retrospective case-control study was performed at Indiana University Health Methodist Hospital in Indianapolis, Indiana. PARTICIPANTS: Patients were included if they were on venovenous ECMO support between June 2019 and June 2020, and divided into two groups: ARDS secondary to COVID-19 and those with ARDS from another etiology (Non-COVID). INTERVENTIONS: Patient demographics, such as age, sex, weight, chronic comorbid conditions, baseline antiplatelet and anticoagulant use, antiplatelet use during ECMO, and need for renal replacement therapy were collected, and compared between groups. Time to activated partial thromboplastin time (aPTT) goal, percentage of time at aPTT goal, bivalirudin rates, total bivalirudin requirements, total duration on bivalirudin, total duration on ECMO, mortality, and complications associated with ECMO were collected and compared between groups. MEASUREMENTS AND MAIN RESULTS: A total of 42 patients met inclusion criteria (n = 19 COVID-19, n = 23 non-COVID). However, percentages of aPTTs at goal were maintained more consistently in patients with COVID-19 versus non-COVID (86% v 74%: p < 0.01). Higher median (IQR) daily rates (3.1 µg/kg/min [2.3-5.2] v 2.4 µg/kg/min [1.7-3.3]: p = 0.05) and higher median (IQR) maximum rates of bivalirudin (5 µg/kg/min [3.7-7.5] v 3.8 µg/kg/min [2.5-5]: p = 0.03) were required in the COVID-19 group versus the non-COVID group. Time to goal aPTT was similar between groups. There were no differences in complications associated with anticoagulation, as demonstrated by similar rates of bleeding and thrombosis between both groups. CONCLUSIONS: Patients on ECMO with ARDS from COVID-19 require more bivalirudin overall and higher rates of bivalirudin to maintain goal aPTTs compared with patients without COVID-19. However, COVID-19 patients more consistently maintain goal aPTT. Future randomized trials are needed to support efficacy and safety of bivalirudin for anticoagulation of COVID-19 patients on ECMO.

Clinical and laboratory characteristics of patients with novel coronavirus disease-2019 infection and deep venous thrombosis.

OBJECTIVE: Early reports suggest that patients with novel coronavirus disease-2019 (COVID-19) infection carry a significant risk of altered coagulation with an increased risk for venous thromboembolic events. This report investigates the relationship of significant COVID-19 infection and deep venous thrombosis (DVT) as reflected in the patient clinical and laboratory characteristics. METHODS: We reviewed the demographics, clinical presentation, laboratory and radiologic evaluations, results of venous duplex imaging and mortality of COVID-19-positive patients (18-89 years) admitted to the Indiana University Academic Health Center. Using oxygen saturation, radiologic findings, and need for advanced respiratory therapies, patients were classified into mild, moderate, or severe categories of COVID-19 infection. A descriptive analysis was performed using univariate and bivariate Fisher's exact and Wilcoxon rank-sum tests to examine the distribution of patient characteristics and compare the DVT outcomes. A multivariable logistic regression model was used to estimate the adjusted odds ratio of experiencing DVT and a receiver operating curve analysis to identify the optimal cutoff for d-dimer to predict DVT in this COVID-19 cohort. Time to the diagnosis of DVT from admission was analyzed using log-rank test and Kaplan-Meier plots. RESULTS: Our study included 71 unique COVID-19-positive patients (mean age, 61 years) categorized as having 3% mild, 14% moderate, and 83% severe infection and evaluated with 107 venous duplex studies. DVT was identified in 47.8% of patients (37% of examinations) at an average of 5.9 days after admission. Patients with DVT were predominantly male (67%; P = .032) with proximal venous involvement (29% upper and 39% in the lower extremities with 55% of the latter demonstrating bilateral involvement). Patients with DVT had a significantly higher mean d-dimer of 5447 ± 7032 ng/mL (P = .0101), and alkaline phosphatase of 110 IU/L (P = .0095) than those without DVT. On multivariable analysis, elevated d-dimer (P = .038) and alkaline phosphatase (P = .021) were associated with risk for DVT, whereas age, sex, elevated C-reactive protein, and ferritin levels were not. A receiver operating curve analysis suggests an optimal d-dimer value of 2450 ng/mL cutoff with 70% sensitivity, 59.5% specificity, and 61% positive predictive value, and 68.8% negative predictive value. CONCLUSIONS: This study suggests that males with severe COVID-19 infection requiring hospitalization are at highest risk for developing DVT. Elevated d-dimers and alkaline phosphatase along with our multivariable model can alert the clinician to the increased risk of DVT requiring early evaluation and aggressive treatment.

Factors associated with fatal coronavirus disease 2019 infections among cancer patients in the US FDA Adverse Event Reporting System database.

Aim: To explore factors affecting coronavirus disease 2019 (COVID-19) mortality among cancer patients based on a pharmacovigilance database. Methods: US FDA Adverse Event Reporting System (FAERS) quarterly data extract files were reviewed for quarters two, three and four of 2020 (i.e., April to December). Patients with an indication related to malignancy and a reported COVID-related reaction were selected. Multivariate logistic regression analysis for factors associated with a fatal outcome was conducted. Results: A total of 2708 patients were included. The following factors were associated with fatal COVID-19 infection: older age (odds ratio [OR]: 1.03; 95% CI: 1.01-1.04), male sex (OR: 1.43; 95% CI: 1.07-1.91), non-US report source (OR: 2.46; 95% CI: 1.93-3.13), hematological malignancy (OR: 1.62; 95% CI: 1.28-2.07), potentially immunosuppressive treatment (OR: 1.83; 95% CI: 1.30-2.58) and diagnosis in quarter two versus quarter four (OR: 1.62; 95% CI: 1.27-2.07). Conclusion: Within FAERS reports, cancer patients who are older, males and receiving immunosuppressive treatment and those with hematological malignancies were at a higher risk of death because of COVID-19 infection.

Lay abstract In this study, individuals with a diagnosis of cancer who were older and males and those receiving immunosuppressive treatment seemed to be at a higher risk of a fatal outcome of coronavirus disease 2019 infection.

Mobile consulting as an option for delivering healthcare services in low-resource settings in low- and middle-income countries: A mixed-methods study.

OBJECTIVE: Remote or mobile consulting is being promoted to strengthen health systems, deliver universal health coverage and facilitate safe clinical communication during coronavirus disease 2019 and beyond. We explored whether mobile consulting is a viable option for communities with minimal resources in low- and middle-income countries. METHODS: We reviewed evidence published since 2018 about mobile consulting in low- and middle-income countries and undertook a scoping study (pre-coronavirus disease) in two rural settings (Pakistan and Tanzania) and five urban slums (Kenya, Nigeria and Bangladesh), using policy/document review, secondary analysis of survey data (from the urban sites) and thematic analysis of interviews/workshops with community members, healthcare workers, digital/telecommunications experts, mobile consulting providers, and local and national decision-makers. Project advisory groups guided the study in each country. RESULTS: We reviewed four empirical studies and seven reviews, analysed data from 5322 urban slum households and engaged with 424 stakeholders in rural and urban sites. Regulatory frameworks are available in each country. Mobile consulting services are operating through provider platforms (n = 5-17) and, at the community level, some direct experience of mobile consulting with healthcare workers using their own phones was reported - for emergencies, advice and care follow-up. Stakeholder willingness was high, provided challenges are addressed in technology, infrastructure, data security, confidentiality, acceptability and health system integration. Mobile consulting can reduce affordability barriers and facilitate care-seeking practices. CONCLUSIONS: There are indications of readiness for mobile consulting in communities with minimal resources. However, wider system strengthening is needed to bolster referrals, specialist services, laboratories and supply chains to fully realise the continuity of care and responsiveness that mobile consulting services offer, particularly during/beyond coronavirus disease 2019.

Patient-related barriers to some virtual healthcare services among cancer patients in the USA: a population-based study.

Objective: To assess the patient-related barriers to access of some virtual healthcare tools among cancer patients in the USA in a population-based cohort. Materials & methods: National Health Interview Survey datasets (2011-2018) were reviewed and adult participants (≥18 years old) with a history of cancer diagnosis and complete information about virtual healthcare utilization (defined by [a] filling a prescription on the internet in the past 12 months and/or [b] communicating with a healthcare provider through email in the past 12 months) were included. Information about video-conferenced phone calls and telephone calls are not available in the National Health Interview Survey datasets; and thus, they were not examined in this study. Multivariable logistic regression analysis was used to evaluate factors associated with the utilization of virtual care tools. Results: A total of 25,121 participants were included in the current analysis; including 4499 participants (17.9%) who utilized virtual care in the past 12 months and 20,622 participants (82.1%) who did not utilize virtual care in the past 12 months. The following factors were associated with less utilization of virtual healthcare tools in multivariable logistic regression: older age (continuous odds ratio [OR] with increasing age: 0.987; 95% CI: 0.984-0.990), African-American race (OR for African American vs white race: 0.608; 95% CI: 0.517-0.715), unmarried status (OR for unmarried compared with married status: 0.689; 95% CI: 0.642-0.739), lower level of education (OR for education ≤high school vs >high school: 0.284; 95% CI: 0.259-0.311), weaker English proficiency (OR for no proficiency vs very good proficiency: 0.224; 95% CI: 0.091-0.552) and lower yearly earnings (OR for earnings <$45,000 vs earnings >$45,000: 0.582; 95% CI: 0.523-0.647). Conclusion: Older patients, those with African-American race, lower education, lower earnings and weak English proficiency are less likely to access the above studied virtual healthcare tools. Further efforts are needed to tackle disparities in telemedicine access.

Influenza and pneumonia-attributed deaths among cancer patients in the United States; a population-based study.

Objective: To assess the patterns and trends of influenza and pneumonia-attributed deaths among cancer patients in the United States.Methods: Surveillance, Epidemiology and End Results (SEER) database was accessed and cancer patients diagnosed 1975-2016 who have been included in the SEER-9 registries were included. The primary endpoint of the study is standardized mortality rate (SMR; calculated as observed/ Expected (O/E) ratio for death from influenza and pneumonia among cancer patients).Results: The current study evaluates a total of 3,579,199 cancer patients (diagnosed 1975-2016) within the SEER-9 registries; and influenza and pneumonia-attributed deaths represent 1.5% of the recorded deaths for this cohort. SMR for influenza/ pneumonia-attributed death within the first year following cancer diagnosis was 1.88 (1.83-1.94);while SMR for influenza/pneumonia-attributed death following the first year was 1.11 (1.10-1.12). Within the first year following cancer diagnosis, SMR from influenza/pneumonia was higher among individuals with black race (SMR for white race: 1.75 (95% CI: 1.69-1.81) while SMR for black race: 2.90 (95% CI: 2.65-3.16), lung cancer (SMR for lung cancer: 4.39 (95% CI: 4.11-4.69)), head and neck cancer (SMR for oral cavity/ pharynx cancer: 4.02 (95% CI: 3.50-4.59)), lymphomas (SMR for lymphoma: 3.28 (95% CI: 2.92-3.68)), leukemias (SMR for leukemia: 3.32 (95% CI: 2.89-3.80)) and myeloma (SMR for myeloma: 3.91 (95% CI: 3.28-4.63)).Conclusions: Cancer patients are more likely to have influenza/ pneumonia-attributed death compared to the general US population. This risk is higher among patients with lung cancer, head and neck cancer, and hematological malignancies.

Development of Taqman-Based Real-Time RT-PCR Assay Based on N Gene for The Quantitative Detection of Feline Morbillivirus (preprint)

Background: Feline morbillivirus (FeMV) is a member of genus Morbillivirus which has been associated with the chronic kidney disease in cats even though a definite relationship is still unclear. Morbilliviruses are associated with severe diseases such as Peste des petits ruminants, canine distemper and measles. FeMV has been detected in many countries including Malaysia. This study aims to develop a Taqman real-time RT-PCR (qRT-PCR) assay targeting the N gene of FeMV in clinical samples to detect early phase of FeMV infection. Results: : A specific assay was developed since no amplification was observed in viral strains from the same Paramyxoviridae family, such as canine distemper virus (CDV), Newcastle disease virus (NDV) and measles virus (MeV), and other feline viruses, such as feline coronavirus (FCoV) and feline leukemia virus (FeLV). The lower detection limit of the assay was 1.74 x 10 4 copies/L with Cq value of 34.32 0.5 based on the cRNA copy number. The coefficient of variations (CV) values calculated for both intra- and inter-assay were low, ranging from 0.34% - 0.53% and 1.38% - 2.03%, respectively. Besides that, the clinical sample evaluation using this assay showed a higher detection rate, with 26 (37%) clinical samples being FeMV-positive compared to 11 (15.5%) using conventional RT-PCR, proving a more sensitive assay compared to the conventional RT-PCR. Conclusions: : The Taqman-based real-time RT PCR assay targeting the N gene described here is more sensitive, specific, rapid and reproducible compared to the conventional RT-PCR assay targeting the N gene and it could be used to detect early infection in cats.

Delirium Incidence, Duration, and Severity in Critically Ill Patients With Coronavirus Disease 2019.

OBJECTIVES: To determine delirium occurrence rate, duration, and severity in patients admitted to the ICU with coronavirus disease 2019. DESIGN: Retrospective data extraction study from March 1, 2020, to June 7, 2020. Delirium outcomes were assessed for up to the first 14 days in ICU. SETTING: Two large, academic centers serving the state of Indiana. PATIENTS: Consecutive patients admitted to the ICU with positive severe acute respiratory syndrome coronavirus 2 nasopharyngeal swab polymerase chain reaction test from March 1, 2020, to June 7, 2020, were included. Individuals younger than 18 years of age, without any delirium assessments, or without discharge disposition were excluded. MEASUREMENTS AND MAIN RESULTS: Primary outcomes were delirium rates and duration, and the secondary outcome was delirium severity. Two-hundred sixty-eight consecutive patients were included in the analysis with a mean age of 58.4 years (sd, 15.6 yr), 40.3% were female, 44.4% African American, 20.7% Hispanic, and a median Acute Physiology and Chronic Health Evaluation II score of 18 (interquartile range, 13-25). Delirium without coma occurred in 29.1% of patients, delirium prior to coma in 27.9%, and delirium after coma in 23.1%. The first Confusion Assessment Method for the ICU assessment was positive for delirium in 61.9%. Hypoactive delirium was the most common subtype (87.4%). By day 14, the median number of delirium/coma-free were 5 days (interquartile range, 4-11 d), and median Confusion Assessment Method for the ICU-7 score was 6.5 (interquartile range, 5-7) indicating severe delirium. Benzodiazepines were ordered for 78.4% of patients in the cohort. Mechanical ventilation was associated with greater odds of developing delirium (odds ratio, 5.0; 95% CI, 1.1-22.2; p = 0.033) even after adjusting for sedative medications. There were no between-group differences in mortality. CONCLUSIONS: Delirium without coma occurred in 29.1% of patients admitted to the ICU. Delirium persisted for a median of 5 days and was severe. Mechanical ventilation was significantly associated with odds of delirium even after adjustment for sedatives. Clinical attention to manage delirium duration and severity, and deeper understanding of the virus' neurologic effects is needed for patients with coronavirus disease 2019.

Maintaining Blood Glucose Levels in Range (70-150 mg/dL) is Difficult in COVID-19 Compared to Non-COVID-19 ICU Patients-A Retrospective Analysis.

Beta cell dysfunction is suggested in patients with COVID-19 infections. Poor glycemic control in ICU is associated with poor patient outcomes. This is a single center, retrospective analysis of 562 patients in an intensive care unit from 1 March to 30 April 2020. We review the time in range (70-150 mg/dL) spent by critically ill COVID-19 patients and non-COVID-19 patients, along with the daily insulin use. Ninety-three in the COVID-19 cohort and 469 in the non-COVID-19 cohort were compared for percentage of blood glucose TIR (70-150 mg/dL) and average daily insulin use. The COVID-19 cohort spent significantly less TIR (70-150 mg/dL) compared to the non-COVID-19 cohort (44.4% vs. 68.5%). Daily average insulin use in the COVID-19 cohort was higher (8.37 units versus 6.17 units). ICU COVID-19 patients spent less time in range (70-150 mg/dL) and required higher daily insulin dose. A higher requirement for ventilator and days on ventilator was associated with a lower TIR. Mortality was lower for COVID-19 patients who achieved a higher TIR.

Mortality Rates in a Diverse Cohort of Mechanically Ventilated Patients With Novel Coronavirus in the Urban Midwest.

OBJECTIVES: Differences in mortality rates previously reported in critically ill patients with coronavirus disease 2019 have increased the need for additional data on mortality and risk factors for death. We conducted this study to describe length of stay, mortality, and risk factors associated with in-hospital mortality in mechanically ventilated patients with coronavirus disease 2019. DESIGN: Observational study. SETTING: Two urban, academic referral hospitals in Indianapolis, Indiana. PATIENTS OR SUBJECTS: Participants were critically ill patients 18 years old and older, admitted with coronavirus disease 2019 between March 1, 2020, and April 27, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Outcomes included in-hospital mortality, duration of mechanical ventilation, and length of stay. A total of 242 patients were included with mean age of 59.6 years (sd, 15.5 yr), 41.7% female and 45% African American. Mortality in the overall cohort was 19.8% and 20.5% in the mechanically ventilated subset. Patients who died were older compared with those that survived (deceased: mean age, 72.8 yr [sd, 10.6 yr] vs patients discharged alive: 54.3 yr [sd, 14.8 yr]; p < 0.001 vs still hospitalized: 59.5 yr [sd, 14.4 yr]; p < 0.001) and had more comorbidities compared with those that survived (deceased: 2 [0.5-3] vs survived: 1 [interquartile range, 0-1]; p = 0.001 vs still hospitalized: 1 [interquartile range, 0-2]; p = 0.015). Older age and end-stage renal disease were associated with increased hazard of in-hospital mortality: age 65-74 years (hazard ratio, 3.1 yr; 95% CI, 1.2-7.9 yr), age 75+ (hazard ratio, 4.1 yr; 95% CI, 1.6-10.5 yr), and end-stage renal disease (hazard ratio, 5.9 yr; 95% CI, 1.3-26.9 yr). The overall median duration of mechanical ventilation was 9.3 days (interquartile range, 5.7-13.7 d), and median ICU length of stay in those that died was 8.7 days (interquartile range, 4.0-14.9 d), compared with 9.2 days (interquartile range, 4.0-14.0 d) in those discharged alive, and 12.7 days (interquartile range, 7.2-20.3 d) in those still remaining hospitalized.Conclusions:: We found mortality rates in mechanically ventilated patients with coronavirus disease 2019 to be lower than some previously reported with longer lengths of stay.

Impact of the societal response to COVID-19 on access to healthcare for non-COVID-19 health issues in slum communities of Bangladesh, Kenya, Nigeria and Pakistan: results of pre-COVID and COVID-19 lockdown stakeholder engagements.

INTRODUCTION: With COVID-19, there is urgency for policymakers to understand and respond to the health needs of slum communities. Lockdowns for pandemic control have health, social and economic consequences. We consider access to healthcare before and during COVID-19 with those working and living in slum communities. METHODS: In seven slums in Bangladesh, Kenya, Nigeria and Pakistan, we explored stakeholder perspectives and experiences of healthcare access for non-COVID-19 conditions in two periods: pre-COVID-19 and during COVID-19 lockdowns. RESULTS: Between March 2018 and May 2020, we engaged with 860 community leaders, residents, health workers and local authority representatives. Perceived common illnesses in all sites included respiratory, gastric, waterborne and mosquitoborne illnesses and hypertension. Pre-COVID, stakeholders described various preventive, diagnostic and treatment services, including well-used antenatal and immunisation programmes and some screening for hypertension, tuberculosis, HIV and vectorborne disease. In all sites, pharmacists and patent medicine vendors were key providers of treatment and advice for minor illnesses. Mental health services and those addressing gender-based violence were perceived to be limited or unavailable. With COVID-19, a reduction in access to healthcare services was reported in all sites, including preventive services. Cost of healthcare increased while household income reduced. Residents had difficulty reaching healthcare facilities. Fear of being diagnosed with COVID-19 discouraged healthcare seeking. Alleviators included provision of healthcare by phone, pharmacists/drug vendors extending credit and residents receiving philanthropic or government support; these were inconsistent and inadequate. CONCLUSION: Slum residents' ability to seek healthcare for non-COVID-19 conditions has been reduced during lockdowns. To encourage healthcare seeking, clear communication is needed about what is available and whether infection control is in place. Policymakers need to ensure that costs do not escalate and unfairly disadvantage slum communities. Remote consulting to reduce face-to-face contact and provision of mental health and gender-based violence services should be considered.

The Effect of the COVID-19 Pandemic on Orthopedic Practices in New York.

The SARS-CoV-2 (COVID-19) crisis has strained hospitals and health systems across the world. In the United States, New York City has faced a surge of cases as the epicenter of the North American outbreak. Northwell Health, as the largest regional health system in New York City, has implemented various practices and policies to adapt to the evolving situation and prepare for future global events. [Orthopedics. 2020;43(4):245-249.].

Incidence of Venous Thromboembolism in Critically Ill Coronavirus Disease 2019 Patients Receiving Prophylactic Anticoagulation.

OBJECTIVES: One of the defining features of the novel coronavirus disease 2019 infection has been high rates of venous thromboses. The present study aimed to describe the prevalence of venous thromboembolism in critically ill patients receiving different regimens of prophylactic anticoagulation. DESIGN: Single-center retrospective review using data from patients with confirmed severe acute respiratory syndrome coronavirus 2 requiring intubation. SETTING: Tertiary-care center in Indianapolis, IN, United States. PATIENTS: Patients hospitalized at international units Health Methodist Hospital with severe acute respiratory syndrome coronavirus 2 requiring intubation between March 23, 2020, and April 8, 2020, who underwent ultrasound evaluation for venous thrombosis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 45 patients were included. Nineteen of 45 patients (42.2%) were found to have deep venous thrombosis. Patients found to have deep venous thrombosis had no difference in time to intubation (p = 0.97) but underwent ultrasound earlier in their hospital course (p = 0.02). Sequential Organ Failure Assessment scores were similar between the groups on day of intubation and day of ultrasound (p = 0.44 and p = 0.07, respectively). D-dimers were markedly higher in patients with deep venous thrombosis, both for maximum value and value on day of ultrasound (p < 0.01 for both). Choice of prophylactic regimen was not related to presence of deep venous thrombosis (p = 0.35). Ultrasound evaluation is recommended if D-dimer is greater than 2,000 ng/mL (sensitivity 95%, specificity 46%) and empiric anticoagulation considered if D-dimer is greater than 5,500 ng/mL (sensitivity 53%, specificity 88%). CONCLUSIONS: Deep venous thrombosis is very common in critically ill patients with coronavirus disease 2019. There was no difference in incidence of deep venous thrombosis among different pharmacologic prophylaxis regimens, although our analysis is limited by small sample size. D-dimer values are elevated in the majority of these patients, but there may be thresholds at which screening ultrasound or even empiric systemic anticoagulation is indicated.

Routine Venous Thromboembolism Prophylaxis May Be Inadequate in the Hypercoagulable State of Severe Coronavirus Disease 2019.

OBJECTIVES: The aim of this study was to determine the frequency of venous thromboembolism in critically ill coronavirus disease 2019 patients and associate a degree of inflammatory marker elevation to venous thromboembolism development. DESIGN: An observational study that identified patients with severe coronavirus disease 2019 between March 12, 2020, and March 31, 2020. Data reported are those available through May 6, 2020. SETTING: A multicenter study including three Indianapolis area academic hospitals. PATIENTS: Two-hundred forty consecutive patients with confirmed severe acute respiratory syndrome coronavirus 2 infection were admitted to one of three hospitals. One-hundred nine critically ill coronavirus disease 2019 patients admitted to the ICU were included in the analysis. INTERVENTIONS: All patients received routine subcutaneous chemical venous thromboembolism prophylaxis. MEASUREMENTS AND MAIN RESULTS: The primary outcome of this study was to determine the frequency of venous thromboembolism and the degree of inflammatory and coagulation marker elevation associated with venous thromboembolism development. Descriptive statistics outlined the frequency of venous thromboembolism at any time during severe coronavirus disease 2019. Clinical course and laboratory metrics were compared between patients that developed venous thromboembolism and patients that did not develop venous thromboembolism. Hypercoagulable thromboelastography was defined as two or more hypercoagulable parameters. MAIN RESULTS: One-hundred nine patients developed severe coronavirus disease 2019 requiring ICU care. The mean (± SD) age was 61 ± 16 years and 57% were male. Seventy-five patients (69%) were discharged home, 7 patients (6%) remain in the hospital, and 27 patients (25%) died. Venous thromboembolism was diagnosed in 31 patients (28%) 8 ± 7 days after hospital admission, including two patients diagnosed with venous thromboembolism at presentation to the hospital. Elevated admission D-dimer and peak D-dimer were associated with venous thromboembolism development (p < 0.05). D-dimer greater than 2,600 ng/mL predicted venous thromboembolism with an area under the receiver operating characteristic curve of 0.760 (95% CI, 0.661-0.858; p < 0.0001), sensitivity of 89.7%, and specificity of 59.5%. Twelve patients (11%) had thromboelastography performed and 58% of these patients had a hypercoagulable study. The calculated coagulation index was hypercoagulable in 50% of patients with thromboelastography. CONCLUSIONS: These data show that coronavirus disease 2019 results in a hypercoagulable state. Routine chemical venous thromboembolism prophylaxis may be inadequate in preventing venous thromboembolism in severe coronavirus disease 2019.