Real-World Management of Pharmacological Thromboprophylactic Strategies for COVID-19 Patients in Japan: From the CLOT-COVID Study.

Background: Data on prophylactic anticoagulation are important in understanding the current issues, unmet needs, and optimal management of Japanese COVID-19 patients. Objectives: This study aimed to investigate the clinical management strategies for prophylactic anticoagulation of COVID-19 patients in Japan. Methods: The CLOT-COVID study was a multicenter observational study that enrolled 2,894 consecutive hospitalized patients with COVID-19. The study population consisted of 2,889 patients (after excluding 5 patients with missing data); it was divided into 2 groups: patients with pharmacological thromboprophylaxis (n = 1,240) and those without (n = 1,649). Furthermore, we evaluated the 1,233 patients who received prophylactic anticoagulation-excluding 7 patients who could not be classified based on the intensity of their anticoagulants-who were then divided into 2 groups: patients receiving prophylactic anticoagulant doses (n = 889) and therapeutic anticoagulant doses (n = 344). Results: The most common pharmacological thromboprophylaxis anticoagulant was unfractionated heparin (68.2%). The severity of COVID-19 at admission was a predictor of the implementation of pharmacological thromboprophylaxis in the multivariable analysis (moderate vs mild: OR: 16.6; 95% CI:13.2-21.0; P < 0.001, severe vs mild: OR: 342.6, 95% CI: 107.7-1090.2; P < 0.001). It was also a predictor of the usage of anticoagulants of therapeutic doses in the multivariable analysis (moderate vs mild: OR: 2.10; 95% CI: 1.46-3.02; P < 0.001, severe vs mild: OR: 5.96; 95% CI: 3.91-9.09; P < 0.001). Conclusions: In the current real-world Japanese registry, pharmacological thromboprophylaxis, especially anticoagulants at therapeutic doses, was selectively implemented in COVID-19 patients with comorbidities and severe COVID-19 status at admission.

Cross-immunity against SARS-COV-2 variants of concern in naturally infected critically ill COVID-19 patients.

Critically ill patients infected with SARS-CoV-2 display adaptive immunity, but it is unknown if they develop cross-reactivity to variants of concern (VOCs). We profiled cross-immunity against SARS-CoV-2 VOCs in naturally infected, non-vaccinated, critically ill COVID-19 patients. Wave-1 patients (wild-type infection) were similar in demographics to Wave-3 patients (wild-type/alpha infection), but Wave-3 patients had higher illness severity. Wave-1 patients developed increasing neutralizing antibodies to all variants, as did patients during Wave-3. Wave-3 patients, when compared to Wave-1, developed more robust antibody responses, particularly for wild-type, alpha, beta and delta variants. Within Wave-3, neutralizing antibodies were significantly less to beta and gamma VOCs, as compared to wild-type, alpha and delta. Patients previously diagnosed with cancer or chronic obstructive pulmonary disease had significantly fewer neutralizing antibodies. Naturally infected ICU patients developed adaptive responses to all VOCs, with greater responses in those patients more likely to be infected with the alpha variant, versus wild-type.

Recurrent upper extremity arterial thrombosis preceding a diagnosis of COVID-19.

Arterial thrombosis occurs when there is endothelial damage in the setting of hypercoagulability and arterial blood stasis. COVID-19 has been theorized to cause both endothelial damage and promote hypercoagulability by causing an imbalance of clotting factors. In many studies, there have been a large proportion of COVID-19 patients that suffered a thromboembolic event, in both the venous and arterial systems. Our patient, who did not have a significant past medical history, presented with a recurrent brachial artery occlusion despite medical and surgical management, and subsequently tested positive for COVID-19 late in his admission. In conclusion, there is high suspicion that there is a relationship between COVID-19 infection and recurrent arterial thrombosis.

Prevalence of bleeding secondary to anticoagulation and mortality in patients with atrial fibrillation admitted with SARS-CoV-2 infection.

Introduction and purpose: Atrial fibrillation (AF) is common in patients admitted with severe COVID-19. However, there is limited data about the management of chronic anticoagulation therapy in these patients. We assessed the anticoagulation and incidence of major cardiovascular events in hospitalized patients with AF and COVID-19. Methods: We retrospectively investigated all consecutive patients with AF admitted with COVID-19 between March and May 2020 in 9 Spanish hospitals. We selected a control group of non-AF patients consecutively admitted with COVID-19. We compared baseline characteristics, incidence of major bleeding, thrombotic events and mortality. We used propensity score matching (PSM) to minimize potential confounding variables, as well as a multivariate analysis to predict major bleeding and death. Results: 305 patients admitted with AF and COVID-19 were included. After PSM, 151 AF patients were matched with 151 control group patients. During admission, low-molecular-weight heparin was the principal anticoagulant and the incidence of major bleeding and mortality were higher in the AF group [16 (10.6%) vs 3 (2%), p = 0.003; 52 (34.4%) vs 35 (23.2%), p = 0.03, respectively]. The multivariate analysis showed the presence of AF as independent predictor of in-hospital major bleeding and mortality in COVID-19 patients. In AF group, a secondary multivariate analysis identified high levels of D-dimer as independent predictor of in-hospital major bleeding. Conclusions: AF patients admitted with COVID-19 represent a population at high risk for bleeding and mortality during admission. It seems advisable to individualize anticoagulation therapy during admission, considering patient specific bleeding and thrombotic risk.

Antecedentes y objetivos: La fibrilación auricular (FA) es frecuente en pacientes ingresados por COVID-19 grave. Sin embargo, los datos sobre el manejo de la anticoagulación crónica en estos pacientes son escasos. Analizamos la anticoagulación y la incidencia de episodios cardiovasculares mayores en pacientes con FA ingresados por la COVID-19. Métodos: Retrospectivamente, se identificaron todos los pacientes con FA ingresados por la COVID-19 entre marzo y mayo de 2020, en 9 hospitales españoles. Se seleccionó un grupo control de pacientes ingresados consecutivamente por la COVID-19 sin FA. Se compararon las características basales, incidencia de hemorragias mayores, episodios trombóticos y mortalidad. Para reducir potenciales factores de confusión se realizó un emparejamiento por puntuación de propensión, así como un análisis multivariante para predecir hemorragia mayor y mortalidad. Resultados: Se incluyeron 305 pacientes con FA ingresados por la COVID-19. Tras el emparejamiento por puntuación de propensión, 151 pacientes con FA fueron emparejados con 151 controles. Durante el ingreso, la heparina de bajo peso molecular fue el principal anticoagulante y la incidencia de hemorragia mayor y mortalidad fue mayor en el grupo de FA (16[10,6%] vs. 3[2%], p = 0,003; 52[34,4%] vs. 35[23,2%], p = 0,03, respectivamente). El análisis multivariante demostró la presencia de FA como predictor independiente de sangrados y mortalidad intrahospitalaria en los pacientes con la COVID-19. En el grupo de FA, un segundo análisis multivariante identificó valores elevados de dímero-D como predictor independiente de hemorragia mayor intrahospitalaria. Conclusiones: Los pacientes con FA ingresados por la COVID-19 representan una población de alto riesgo de sangrado y mortalidad durante el ingreso. Parece recomendable individualizar la anticoagulación durante el ingreso, considerando el riesgo específico de sangrado y trombosis.

COVID-19 in the perioperative setting: A review of the literature and the clinical landscape.

The COVID-19 pandemic has dramatically affected societies and healthcare systems around the globe. The perioperative care continuum has also been under significant strain due to the pandemic-tasked with simultaneously addressing surgical strains and backlogs, infection prevention strategies, and emerging data regarding significantly higher perioperative risk for COVID-19 patients and survivors. Many uncertainties persist regarding the perioperative risk, assessment, and management of COVID-19 survivors-and the energy to catch up on surgical backlogs must be tempered with strategies to continue to mitigate COVID-19 related perioperative risk. Here, we review the available data for COVID-19-related perioperative risk, discuss areas of persistent uncertainty, and empower the perioperative teams to pursue evidence-based strategies for high quality, patient-centered, team-based care as we enter the third year of the COVID-19 pandemic.

The Incidence of Venous Thromboembolism in Critically Ill Patients with SARS-CoV-2 Infection Compared with Critically Ill Influenza and Community-Acquired Pneumonia Patients: A Retrospective Chart Review.

The rate of venous thromboembolism in COVID-19 patients has been reported to be 30% (deep vein thrombosis 20% and pulmonary embolism 18%). This has been shown to be higher in COVID-19 patients admitted to the ICU. Prophylactic anticoagulation may be sufficient at ward level, but not in intensive care. A retrospective chart review was undertaken in a large university hospital. The review included 276 patients from COVID-19 Wave 1, COVID-19 Wave 2, influenza, and community-acquired pneumonia groups. The timeframe included patients admitted between 23 February 2014 and 12 May 2021. Clinical characteristics, outcomes, blood results, rates of venous thromboembolism, and anticoagulation status were recorded. The incidence of venous thromboembolism in COVID-19 Wave 1, COVID-19 Wave 2, influenza, and community-acquired pneumonia was 10.91%, 13.69%, 13.33%, and 6.81%, respectively (p = 0.481). The incidence of pulmonary embolism was 7.27%, 10.95%, 3.33%, and 5.68%, respectively (p = 0.350). The incidence of deep vein thrombosis was 5.45%, 5.48%, 10.00%, and 1.14%, respectively (p = 0.117). Although most patients were prophylactically anticoagulated, venous thromboembolism still occurred. Venous thromboembolism remains an important differential to consider in critically ill COVID-19 patients. The current literature does not advise therapeutic anticoagulation for thromboprophylaxis in the ICU.

Cardiovascular complications in the Post-Acute COVID-19 syndrome (PACS).

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV 2) or coronavirus disease 2019 (COVID-19) initially surfaced in December 2019 from Wuhan, China, sweeping the world with various strains, forcing the WHO to declare a pandemic epidemic in March 2020. Furthermore, COVID-19 manifests with a wide array of presentations from fever and fatigue to severe respiratory and cardiovascular complications. Post-COVID-19 syndrome is poorly understood affecting COVID-19 survivors at all levels of disease severity. The disease is most associated with post-discharge dyspnea and fatigue. However, other persistent symptoms as chest pains, palpitations, smell, and taste dysfunctions. Patients with high concentrations of CRP and creatinine in the acute phase of Covid-19 are more prone to cardiac sequelae. Therefore, high levels of cardiac-sensitive troponin and hypokalaemia can also be used for risk stratification. Furthermore, Cardiac damage can manifest as myocarditis, pericarditis, rhythm abnormalities. The use of different diagnostic modalities like electrocardiogram (ECG), echocardiogram, and cardiac magnetic resonance imaging (MRI)(CMR) to evaluate the myocardial damage were studied. However, Cardiovascular complications are a common manifestation of PASC, classification of severity of cardiac symptoms and the emergence of CMR as a diagnostic tool needs more evidence.

A retrospective analysis of 902 hospitalized COVID-19 patients in Lebanon: clinical epidemiology and risk factors.

BACKGROUND: The clinical epidemiology of hospitalized COVID-19 patients has never been described before in Lebanon. Moreover, the hospital admission and PCR positivity rates have not been assessed and compared yet. OBJECTIVES: To describe the characteristics and outcomes of hospitalized patients with coronavirus induced disease 2019 (COVID-19) in Lebanon and identify risk factors for severe disease or death. STUDY DESIGN: This is a retrospective mono-center cohort study in which we used patients' files to extract and analyse data on demographic and clinical characteristics, as well as mortality. Moreover, we tracked the pandemic by recording the daily total and ICU inpatient census and the PCR positivity rate for admitted and outpatients. RESULTS: Although the total admission rate increased from September to April, the ICU census switched this trend in December to stabilize at an average of around 10 patients/day until April. The case fatality rate was 19% for the 902 hospitalized patients, of which the majority (80%) had severe COVID-19. The severity odds ratio is significantly decreased in immunosuppressed cases (OR, 0.18; CI, 0.05-0.67; p=0.011). Additionally, the odds of COVID-19 related death are significantly greater if consolidations are found in the chest computed tomography (CT) scan (OR, 12; CI, 2.63-55.08; p=0.0013). CONCLUSION: Consolidations in the lungs significantly increase the COVID-19 death risk. Risk factors identification is important to improve patients' management and vaccination strategies. In addition, hospital statistics are good indicators of a pandemic's track.

Comparison between standard Vs. Escalated dose venous thromboembolism (VTE) prophylaxis in critically ill patients with COVID-19: A two centers, observational study.

INTRODUCTION: The risk of mortality in patients with COVID-19 was found to be significantly higher in patients who experienced thromboembolic events. Thus, several guidelines recommend using prophylactic anticoagulants in all COVID-19 hospitalized patients. However, there is uncertainty about the appropriate dosing regimen and safety of anticoagulation in critically ill patients with COVID-19. Thus, this study aims to compare the effectiveness and safety of standard versus escalated dose pharmacological venous thromboembolism (VTE) prophylaxis in critically ill patients with COVID-19. METHODS: A two-center retrospective cohort study including critically ill patients aged ≥ 18-years with confirmed COVID-19 admitted to the intensive care unit (ICU) at two tertiary hospitals in Saudi Arabia from March 1st, 2020, until January 31st, 2021. Patients who received either Enoxaparin 40 mg daily or Unfractionated heparin 5000 Units three times daily were grouped under the "standard dose VTE prophylaxis and patients who received higher than the standard dose but not as treatment dose were grouped under "escalated VTE prophylaxis dose". The primary outcome was the occurance of thrombotic events, and the secondary outcomes were bleeding, mortality, and other ICU-related complications. RESULTS: A total of 758 patients were screened; 565 patients were included in the study. We matched 352 patients using propensity score matching (1:1). In patients who received escalated dose pharmacological VTE prophylaxis, any case of thrombosis and VTE were similar between the two groups (OR 1.22;95 %CI 0.52-2.86; P = 0.64 and OR 0.75; 95% CI 0.16-3.38; P = 0.70 respectively). However, the odds of minor bleeding was higher in patients who received escalated VTE prophylaxis dose (OR 3.39; 95% CI 1.08-10.61; P = 0.04). There was no difference in the 30-day mortality nor in-hospital mortality between the two groups (HR 1.17;95 %CI0.79-1.73; P = 0.43 and HR 1.08;95 %CI 0.76-1.53; P = 0.83, respectively). CONCLUSION: Escalated-dose pharmacological VTE prophylaxis in critically ill patients with COVID-19 was not associated with thrombosis, or mortality benefits but led to an increased risk of minor bleeding. This study supports previous evidence regarding the optimal dosing VTE pharmacological prophylaxis regimen for critically ill patients with COVID-19.

Effect of Crizanlizumab, a P-Selectin Inhibitor, in COVID-19: A Placebo-Controlled, Randomized Trial.

COVID-19 is characterized by vascular inflammation and thrombosis, including elevations in P-selectin, a mediator of inflammation released by endothelial cells. We tested the effect of P-selectin inhibition on biomarkers of thrombosis and inflammation in patients with COVID-19. Hospitalized patients with moderate COVID-19 were randomly assigned to receive either placebo or crizanlizumab, a P-selectin inhibitor, in a double-blind fashion. Crizanlizumab reduced P-selectin levels by 89%. Crizanlizumab increased D-dimer levels by 77% and decreased prothrombin fragment. There were no significant differences between crizanlizumab and placebo for clinical endpoints. Crizanlizumab was well tolerated. Crizanlizumab may induce thrombolysis in the setting of COVID-19. (Crizanlizumab for Treating COVID-19 Vasculopathy [CRITICAL]; NCT04435184).

Outpatient and inpatient anticoagulation therapy and the risk for hospital admission and death among COVID-19 patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with a hypercoagulable state. Limited data exist informing the relationship between anticoagulation therapy and risk for COVID-19 related hospitalization and mortality. METHODS: We evaluated all patients over the age of 18 diagnosed with COVID-19 in a prospective cohort study from March 4th to August 27th, 2020 among 12 hospitals and 60 clinics of M Health Fairview system (USA). We investigated the relationship between (1) 90-day anticoagulation therapy among outpatients before COVID-19 diagnosis and the risk for hospitalization and mortality and (2) Inpatient anticoagulation therapy and mortality risk. FINDINGS: Of 6195 patients, 598 were immediately hospitalized and 5597 were treated as outpatients. The overall case-fatality rate was 2•8% (n = 175 deaths). Among the patients who were hospitalized, the inpatient mortality was 13%. Among the 5597 COVID-19 patients initially treated as outpatients, 160 (2.9%) were on anticoagulation and 331 were eventually hospitalized (5.9%). In a multivariable analysis, outpatient anticoagulation use was associated with a 43% reduction in risk for hospital admission, HR (95% CI = 0.57, 0.38-0.86), p = 0.007, but was not associated with mortality, HR (95% CI=0.88, 0.50 - 1.52), p = 0.64. Inpatients who were not on anticoagulation (before or after hospitalization) had an increased risk for mortality, HR (95% CI = 2.26, 1.17-4.37), p = 0.015. INTERPRETATION: Outpatients with COVID-19 who were on outpatient anticoagulation at the time of diagnosis experienced a 43% reduced risk of hospitalization. Failure to initiate anticoagulation upon hospitalization or maintaining outpatient anticoagulation in hospitalized COVID-19 patients was associated with increased mortality risk. FUNDING: No funding was obtained for this study.

Coagulopathies in novel coronavirus (SARS-CoV-2) pandemic: Emerging evidence for hematologists.

The coronavirus disease (COVID-19), which is also known as acute respiratory syndrome coronavirus-2 (SARS-CoV2) is a transmissible disease, has phenotypes varying from asymptomatic to Acute Respiratory Distress Syndrome (ARDS) or multiple organ dysfunction syndrome (MODS) and ultimately death in certain cases. Coagulation disorders are being frequently reported amongst these patients and the pathogenesis is still not completely understood. Proposed mechanisms for these coagulopathies comprise a hypercoagulable state with micro- and/or macro-thrombosis in the vessels. A number of changes have been reported or proposed in circulating prothrombotic factors in COVID-19 patients and includes elevation in both factor VIII and fibrinogen, circulating prothrombotic microparticles and hyperviscosity. The COVID-19 patients are showing varied coagulopathies and are at high risk for venous thromboembolism (VTE) which demands an early intervention. This paper reviews the evolving data regarding the evaluation and managing of coagulopathies in patients with COVID-19.

Acute high-risk pulmonary embolism requiring thrombolytic therapy in a COVID-19 pneumonia patient despite intermediate dosing deep vein thromboprophylaxis.

Cytokine storm induced by the coronavirus 19 (COVID-19) profoundly activates the coagulation cascade causing venous thromboembolism (VTE). Initial studies from Wuhan, China showed increased incidence of VTE in patients with no standard deep vein thrombosis (DVT) prophylaxis in COVID-19 pneumonia patients. Few have argued for high intensity or intermediate DVT prophylaxis in COVID-19 patients with the incidence of VTE ranging from 16 to 27% despite standard DVT prophylaxis. However, no guideline recommendations presently exist to prescribe augmented DVT prophylaxis in these patients due to lack of evidence although the risk of VTE was clearly demonstrated. While there are ongoing trials to demonstrate the efficacy of intermediate dosing against standard DVT prophylaxis in the prevention of VTE, we present a 36-year-old male admitted with COVID-19 pneumonia who developed acute high-risk pulmonary embolism (PE) requiring emergent thrombolytic therapy despite intermediate dosing DVT prophylaxis.

Coronavirus disease 2019 and cardiovascular system: A narrative review.

At the end of 2019, a viral pneumonia disease called coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV2), emerged in Wuhan, China. This novel disease rapidly spread at an alarming rate that as a result, it has now been declared pandemic by the World Health Organization. Although this infective disease is mostly characterized by respiratory tract symptoms, increasing numbers of evidence had shown considerable amounts of patients with cardiovascular involvements and these were associated with higher mortality among COVID-19 patients. Cardiac involvement as a possible late phenomenon of the viral respiratory infection is an issue that should be anticipated in patients with COVID-19. Cardiovascular manifestation in COVID-19 patients include myocardial injury (MI), arrhythmias, cardiac arrests, heart failure and coagulation abnormality, ranging from 7.2% up to 33%. The mechanism of cardiac involvement in COVID-19 patients involves direct injury to myocardial cells mediated by angiotensin-converting enzyme 2 (ACE2) receptors as suggested by some studies, while the other studies suggest that systemic inflammation causing indirect myocyte injury may also play a role. Combination of proper triage, close monitoring, and avoidance of some drugs that have cardiovascular toxicity are important in the management of cardiovascular system involvement in COVID-19 patients. The involvement of the cardiovascular system in COVID-19 patients is prevalent, variable, and debilitating. Therefore, it requires our attention and comprehensive management.

Right Ventricular Clot in Transit in COVID-19: Implications for the Pulmonary Embolism Response Team.

Severe acute respiratory syndrome coronavirus 2 is associated with a prothrombotic state in infected patients. After presenting a case of right ventricular thrombus in a patient with coronavirus disease-2019 (COVID-19), we discuss the unique challenges in the evaluation and treatment of COVID-19 patients, highlighting our COVID-19-modified pulmonary embolism response team algorithm. (Level of Difficulty: Beginner.).