Which biomarker(s) to predict worsening of SARS-CoV2 infection? An ancillary study from the COVIDeF cohort

Introduction: COVID-19 has been responsible for millions of deaths and intensive care unit (ICU) admissions all over the world. Identifying the patients at risk of developing a severe form is crucial for an optimized orientation and allocation of resources. The main objective of our study was to identify among a selection of biomarkers, those predictive of short term worsening in COVID-19. Method(s): This is an ancillary study using clinical data and collected biobanking from the multicentric cohort study COVIDeF, which included prospectively from March 31th 2020 to March 30th 2021, patients admitted with a suspected Sars-CoV2 infection in the Assistance- Publique-Hopitaux de Paris network, France. Patients with confirmed COVID-19 were divided in 2 groups: a severe (ICU admission or invasive or non-invasive ventilation or ARDS or death) and a control group (no worsening). The routine blood tests and following biomarkers: troponin, C Reactive Protein (CRP), procalcitonin, Mild- Regional pro-Adrenomedulin (MR-proADM), pro-endothelin, SuPAR, NT-proBNP, calprotectin, PF4, D-dimers, were measured in plasma or serum and compared between both groups using a conditional logistic regression. Result(s): Among the 1040 first patients included in the COVIDEF cohort, we selected 512 patients having a blood sample drawn at admission before worsening, of which 60 secondarily worsened (severe group). The mean age was 59.5 (+/- 19.5) years and 50.2% were females. Among the biomarkers tested, three were independently associated with worsening: CRP (mg/l) OR 1.01 [IC 1.01-1.02], procalcitonin (ng/ml) OR 0.4428 [0.21-0.95] and MR-proADM (pg/ml) OR 3.012 [1.06-8.53]. Conclusion(s): Among a selection of biomarkers of interest, MRproADM appears to best identify at admission COVID-19 patients at risk of worsening. Future interventional studies should test the efficacy and security of this biomarker to rule-in and rule-out severe outcome and the usefulness for allocating resources.

Impacts of fungal disease on dyadic social interactions in a wild agamid lizard

Emerging infectious fungal diseases are responsible for the extinction of myriad species across a range of phyla. As recently shown by the COVID-19 pandemic, social transmission can be key to disease spread, and in this context, humans are not alone in trying to be alone. In group-living species, individuals have been shown to use social behaviour to avoid infection;diseased individuals can isolate from the group, or healthy animals can avoid diseased conspecifics. However, little is known about social behaviour as a mechanism to avoid fungal infection. In this study, we investigated the extent to which wild urban eastern water dragons, Intellagama lesueurii, a gregarious reptile, modify their social behaviour as a response to infection with a recently emerged infectious fungal disease, caused by the pathogen Nannizziopsis barbatae. Using individual data from a long-term study population inhabiting Roma Street Parkland in Brisbane's Central Business District (QLD, Australia) and focal sampling, we tested whether dragons exhibit self-isolation and social-distancing behaviours in the context of dyadic social approach events. Our results suggested that while the presence of the fungal disease had no effect on individuals' social behaviour, its severity did. Specifically, we found that (1) diseased individuals were no less social than their nondiseased conspecifics, (2) nondiseased individuals did not avoid or spend less time with diseased conspecifics, and (3) models considering the severity of skin lesions caused by N. barbatae, instead of their presence or absence, suggested that individuals avoided more severely diseased conspecifics regardless of their own disease status. © 2023 The Author(s)

2022 international clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer, including patients with COVID-19

The International Initiative on Thrombosis and Cancer is an independent academic working group of experts aimed at establishing global consensus for the treatment and prophylaxis of cancer-associated thrombosis. The 2013, 2016, and 2019 International Initiative on Thrombosis and Cancer clinical practice guidelines have been made available through a free, web-based mobile phone application. The 2022 clinical practice guidelines, which are based on a literature review up to Jan 1, 2022, include guidance for patients with cancer and with COVID-19. Key recommendations (grade 1A or 1B) include: (1) low-molecular-weight heparins (LMWHs) for the initial (first 10 days) treatment and maintenance treatment of cancer-associated thrombosis;(2) direct oral anticoagulants for the initial treatment and maintenance treatment of cancer-associated thrombosis in patients who are not at high risk of gastrointestinal or genitourinary bleeding, in the absence of strong drug-drug interactions or of gastrointestinal absorption impairment;(3) LMWHs or direct oral anticoagulants for a minimum of 6 months to treat cancer-associated thrombosis;(4) extended prophylaxis (4 weeks) with LMWHs to prevent postoperative venous thromboembolism after major abdominopelvic surgery in patients not at high risk of bleeding;and (5) primary prophylaxis of venous thromboembolism with LMWHs or direct oral anticoagulants (rivaroxaban or apixaban) in ambulatory patients with locally advanced or metastatic pancreatic cancer who are treated with anticancer therapy and have a low risk of bleeding.

Can You See Me Now?: Understanding Health Outcomesin Telehealth Among Seniors

Objective: The aim of this study is to understand how telehealth impacts the needs of the senior population in the outpatient general neurology clinic providing care for an underserved and rural population. Background: Telehealth services are increasing due to the ongoing global pandemic and overall advancement of technology. Despite the telehealth platform's ability to alleviate many obstacles, it can present new challenges for the elderly population. The senior population currently face a subset of barriers to healthcare, such as disabilities, chronic disease, healthcare costs, limited transportation, and preventing Covid-19 exposure. Design/Methods: Morehouse Healthcare in Atlanta, Georgia provides telehealth services to all of their patients in the general Neurology outpatient clinic. We implemented the IHI PDSA guidelines by assisting people greater than fifty years of age who were being evaluated for a neurological disorder were included. The level of assistance included (1) written help, (2) written and verbal help (3) no help. Written help consisted of prewritten instructions. Verbal help involved coaching participants over the phone. Notations were made if the patient received help from a family member. Patients were excluded if their account was activated on their smartphone. Patients also had the option to opt-out of using the platform. Results: The number of patients who did not require assistance with activating their accounts decreased with age: 50-59 (41%), 60-69 (23%), 70-79 (23%), 90-99 (14%). 70-79 was the large subset to accept assistance (50%). 60-69 was the largest subset to opt-out (38%). Prior to the outreach, most patients over the age of 50 had not activated their accounts. Following the phone calls, 36% successfully activated their accounts. Conclusions: This study helped identify the subsets of the aging population that need supplemental outreach for activating their telehealth accounts. Acknowledging the technological barriers that seniors may face can help improve health outcomes, especially for patients without caregivers.

Longitudinal measurement of whole blood viscoelastic properties throughout the course of extracorporeal membrane oxygenation in COVID-19 patients with severe acute respiratory distress syndrome

Background : Venovenous (vv)-extracorporeal membrane oxygenation (ECMO) support is used as rescue therapy in COVID-19 patients with severe acute respiratory distress syndrome (ARDS). However, COVID-19 is associated with a hypercoagulable state with high rates of thrombosis. Whether ECMO implantation exacerbates COVID-19-associated coagulopathy is unknown. Aims : To perform a longitudinal evaluation of whole blood viscoelastic properties throughout the course of vv-ECMO in COVID-19 ARDS patients. Methods : 20 COVID-19 patients undergoing vv-ECMO were included in this prospective study. Blood was sampled before ECMO implantation and then 24 h and 7 days after ECMO implantation. SEER Sonorheometry was performed on a Quantra ® hemostasis analyzer with the QPlus ® Cartridge (HemoSonics LLC). All patients received UFH to a target anti-Xa activity of 0.3-0.5 IU/mL. Results : The median age was 48 (42-58) years, with a median body mass index of 30.5 (28.2-38.5) Kg/m2, and 15 (71%) patients were men. The median SAPSII and SOFA scores on admission were 52.5 (44.3-65.5) and 12.0 (8.5-15.8), respectively. Baseline clot times (CT) and baseline clot times with heparinase (CTH) were within the normal range [median 150 (127-178) s and 129 (118-151) s, respectively] and did not vary throughout the course of ECMO. COVID-19 patients exhibited markedly increased baseline values of clot stiffness [CS, median 49.9 (35.5-69.2 hPA)], fibrinogen contribution to CS [FCS, median 12.80 (6.20-20.10) hPA] and platelet contribution to CS [PCS, median 38.5 (28.7-52.4) hPA]. CS, FCS and PCS decreased from baseline to day 7. CT significantly correlated with aPTT ( r = 0.75, P < 0.0001), FCS with fibrinogen levels ( r = 0.81, P < 0.0001) and PCS with platelet count ( r = 0.85, P < 0.0001) but result delivery was much faster with the Quantra ® analyzer compared to conventional tests (∼15 versus ∼60 min). Conclusions : COVID-19 patients with ARDS exhibited a pronounced baseline procoagulant state that partially resolved over the first 7 days of ECMO support.

Extracorporeal membrane oxygenation induces early alterations in coagulation and fibrinolysis profiles in COVID-19patients with acute respiratory distress syndrome

Background : Extracorporeal membrane oxygenation (ECMO) support induces complex hemostatic changes that have been yet poorly described, particularly in COVID-19 patients. Aims : To comprehensively analyze changes in coagulation and fibrinolysis profiles occurring during ECMO support in COVID-19 and non-COVID-19 patients with severe acute respiratory distress syndrome (ARDS). Methods : All consecutive patients with ARDS undergoing ECMO were eligible to participate in this prospective monocentric study. Clinical characteristics were recorded on admission. Blood was sampled before and then 24 h, 7 and 14 days after ECMO implantation for longitudinal measurement of coagulation and fibrinolysis markers. Clinical outcomes were prospectively assessed until discharge from the ICU or death. Results : We included 20 COVID-19 and 10 non-COVID-19 participants. The median age was 47 (35-56) years, with a median body mass index of 30 (27-35) kg/m, and a SOFA score of 12 (8-16). Baseline levels of von Willebrand factor, fibrinogen, factor VIII, prothrombin F1+2, thrombin-antithrombin, D-Dimers and PAI-1 were elevated in both groups, indicating that endothelial activation, endogenous thrombin generation and fibrinolysis shut-down occur in all ARDS patients before ECMO implantation. From baseline to day 7, platelet count ( P < 0.0001) and fibrinogen level ( P < 0.001) significantly decreased, resulting from increases in thrombin generation (prothrombin F1+2, P < 0.01) and fibrin formation (fibrin monomers, P < 0.001). PAI-1 levels significantly decreased from baseline to day 7 ( P < 0.0001) in all ARDS patients. These changes were more marked in COVID-19 patients, resulting in 3 fatal bleeding. Conclusions : ECMO circuit triggers early coagulation activation, resulting in significant fibrinogen and platelets consumption, with subsequent hypofibrinogenemia and thrombocytopenia, which may have contributed to the high prevalence of bleeding complications observed in COVID-19 ARDS patients rescued by ECMO. Additional studies are warranted to determine whether individualized anticoagulation might help to reduce bleeding complications during ECMO support. For now, daily monitoring of platelet count and fibrinogen should be part of ECMO management.

[COVID-19 and mechanical circulatory support]. / COVID-19 et assistance circulatoire.

Extracorporeal membrane oxygenation (ECMO) is mainly used as a rescue therapy in COVID-19 patients with severe acute respiratory distress syndrome (ARDS). More rarely, COVID-19 can be complicated by hemodynamic failure due to fulminant myocarditis or massive pulmonary embolism necessitating the implantation of venous-arterial ECMO. The management of ECMO during the COVID-19 pandemic is challenging due to some specificities related to the disease characteristics, such as the management of anticoagulation in patients with a hypercoagulable state and an increased risk of venous thromboembolism. In large retrospective cohorts, survival of ECMO-rescued COVID-19 patients with ADRS was reported to be similar to that reported in previous studies on ECMO support for severe ARDS. Full consideration of ECMO candidacy is crucial for appropriate allocation of resources.

How to screen and diagnose deep venous thrombosis (DVT) in patients hospitalized for or suspected of COVID-19 infection, outside the intensive care units.

INTRODUCTION: The Coronavirus disease-2019 outbreak (COVID-19) has been declared a pandemic by the World Health Organization. Studies report both a severe inflammatory syndrome and a procoagulant state in severe COVID-19 cases, with an increase of venous thromboembolism, including pulmonary embolism (PE) and deep vein thrombosis (DVT). In this context, we discuss the use of doppler ultrasonography (DUS) in the screening and diagnosis of DVT in ambulatory and hospitalized patients with, or suspected of having, COVID-19, outside the intensive care unit (ICU). MATERIAL AND METHODS: Non-systematic review of the literature. RESULTS: In patients hospitalized for or suspected of COVID-19 infection with the presence of either (a) DVT clinical symptoms, (b) a strong DVT clinical probability (Wells score>2) or (c) elevated D-dimer levels without DVT clinical symptoms and without PE on lung CT angio-scan, DVT should be investigated with DUS. In the presence of PE diagnosed clinically and/or radiologically, additional systematic DVT screening using DUS is not recommended during the COVID-19 pandemic. The use of 4-points compression DUS for DVT screen and diagnosis is the most appropriate method in this context. DISCUSSION: Systematic DUS for DVT screening in asymptomatic COVID patients is not recommended unless the patient is in the ICU. This would increase the risk of unnecessarily exposing medical staff to SARS-CoV-2 and monopolizing limited resources during this period.

Association between D-Dimer levels and mortality in patients with coronavirus disease 2019 (COVID-19): a systematic review and pooled analysis.

BACKGROUND: Several observational studies have reported elevated baseline D-dimer levels in patients hospitalized for moderate to severe coronavirus disease 2019 (COVID-19). These elevated baseline D-dimer levels have been associated with disease severity and mortality in retrospective cohorts. OBJECTIVES: To review current available data on the association between D-Dimer levels and mortality in patients admitted to hospital for COVID-19. METHODS: We performed a systematic review of published studies using MEDLINE and EMBASE through 13 April 2020. Two authors independently screened all records and extracted the outcomes. A random effects model was used to estimate the standardized mean difference (SMD) with 95% confidence intervals (CI). RESULTS: Six original studies enrolling 1355 hospitalized patients with moderate to critical COVID-19 (391 in the non-survivor group and 964 in the survivor group) were considered for the final pooled analysis. When pooling together the results of these studies, D-Dimer levels were found to be higher in non-survivors than in-survivors. The SMD in D-Dimer levels between non-survivors and survivors was 3.59µg/L (95% CI 2.79-4.40µg/L), and the Z-score for overall effect was 8.74 (P<0.00001), with a high heterogeneity across studies (I2=95%). CONCLUSIONS: Despite high heterogeneity across included studies, the present pooled analysis indicates that D-Dimer levels are significantly associated with the risk of mortality in COVID-19 patients. Early integration of D-Dimer testing, which is a rapid, inexpensive, and easily accessible biological test, can be useful to better risk stratification and management of COVID-19 patients.