COVID-19-related critical and acute illness is associated with an increased risk of venous thromboembolism (VTE). These evidence-based recommendations of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in decisions about using anticoagulation for thromboprophylaxis for patients with COVID-19-related critical illness; patients with COVID-19-related acute illness; and those being discharged from the hospital, who do not have suspected or confirmed VTE.

ASH formed a multidisciplinary panel, including patient representatives. The Michael G. DeGroote Cochrane Canada and MacGRADE Centres at McMaster University supported guideline development, including performing systematic reviews (up to June 2023). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess certainty in the evidence and make recommendations.

This is an executive summary of 3 updated recommendations that have been published, which concludes the living phase of the guidelines. For patients with COVID-19-related critical illness, the panel issued conditional recommendations suggesting (a) prophylactic-intensity over therapeutic-intensity anticoagulation and (b) prophylactic-intensity over intermediate-intensity anticoagulation. For patients with COVID-19-related acute illness, conditional recommendations were suggested (a) prophylactic-intensity over intermediate-intensity anticoagulation, and (b) therapeutic-intensity over prophylactic-intensity anticoagulation. The panel issued a conditional recommendation suggesting against the use of postdischarge anticoagulant thromboprophylaxis.

These conditional recommendations were made based on low or very low certainty in the evidence, underscoring the need for additional, high-quality, randomized controlled trials for patients with COVID-19.

Limited knowledge exists about prophylactic anticoagulation patterns in patients hospitalized for COVID-19.

We conducted a retrospective cohort study using American Heart Association COVID-19 Cardiovascular Disease Registry data from May 2020 to March 2022. We included patients without preexisting indications for or contraindications to anticoagulation, excluding those with missing anticoagulation data. Patients were categorized by the highest anticoagulation dose received. Multilevel logistic regression was used to assess the relationship between anticoagulation use/dose, patient demographics, clinical presentation, in-hospital course, institutional characteristics, and admission date, accounting for hospital clustering. Among 26 775 patients, 4157 (16%) received no anticoagulation, 15 617 (58%) low-dose, 3071 (11%) intermediate-dose, and 3930 (15%) full-dose anticoagulation. Significant hospital-level variability occurred for any anticoagulation use (range, 0%-98%; P<0.0001) and by dose (full anticoagulation range, 0%-85%; P<0.0001). Controlling for hospital variability, older age, male sex, non-White race, higher body mass index, higher platelets, corticosteroid use, and intensive care unit admission were positively associated with any anticoagulation use. Older age, male sex, higher body mass index, higher platelets, corticosteroid use, intensive care unit admission, mechanical ventilation, and admission before October 2020 were associated with higher anticoagulation dose (full versus low dose). Rates of no anticoagulation significantly increased in both intensive care unit and non-intensive care unit strata over time (P trend=0.01 and <0.0001, respectively).

In this large real-world analysis, nearly 1 in 6 patients hospitalized for COVID-19 received no prophylactic anticoagulation. Patient and disease characteristics associated with thrombotic risk and COVID-19 severity correlated with anticoagulation strategy. Importantly, substantial institutional differences emerged, highlighting gaps between clinical practice and guideline recommendations.

To examine the subclinical alterations in the retina and choroid between patients with 2019 coronavirus disease (COVID-19)-related lung involvement and the healthy control group.

In this prospective case-control study, 85 cases with lung involvement due to COVID-19 and 50 healthy cases were included. Best-corrected visual acuity, intraocular pressure measurement, and anterior and posterior segment examination were performed on both eyes for each individual. Choroidal and retinal changes were examined and recorded by optical coherence tomography angiography.

All choroidal thickness measurements of the COVID-19 group showed no statistically significant difference when compared to healthy individuals. When vascular density and perfusion density values were compared, there was a decrease in the average of these values in the COVID-19 group, although it was not statistically significant (P=0.088, P=0.065 respectively). When the fovea avascular zone (FAZ) area values were compared, the average was 0.57±0.38 in the COVID-19 group, while it was 0.54±0.24 in the control group.

Although our data are not statistically significant, the decrease in vascularity and perfusion and the accompanying FAZ expansion are detected in the acute period (1st month). These changes may anatomically alter the retina in the long term and affect functional vision. Future ischemia-related alterations in the retina caused by a prior COVID-19 infection may arise in situations without comorbidities and may require concern in the patient's systemic assessment.

Idiopathic facial nerve palsy (FNP) has devastating sequelae and is potentially linked to coronavirus disease-19 (COVID-19).

The rate of FNP was compared in the pandemic versus pre-pandemic periods. Furthermore, the risk of FNP was estimated among the COVID-19 vaccinated group.

Systematic review and meta-analysis.

An electronic search was conducted in 7 databases: Scopus, Web of Science core collection, PubMed, Cochrane Central Register of Controlled Trials, MEDLINE, Embase, and CINAHL.

English observational studies investigating an association between idiopathic FNP and COVID-19 or its vaccination were included, irrespective of patients' demographics.

COVID-19 or COVID-19 vaccine.

Change in FNP incidence between the pre-pandemic and pandemic periods; risk of developing FNP in individuals vaccinated against COVID-19 compared to those who were unvaccinated against COVID-19.

After excluding duplicates, the search yielded 906 related articles, of which 118 articles were included. The risk of FNP was statistically significantly higher during the COVID-19 pandemic than the pre-pandemic period (RR: 1.68, [95% CI: 1.16-2.43], P = .01). A nonsignificant increase in FNP risk was identified among COVID-19 vaccinated individuals compared to unvaccinated individuals (overall OR: 1.07, [95% CI: 0.85-1.35], P = .55).

A remarkable increase in FNP rates was identified during the pandemic compared to pre-pandemic, which seemed unlikely to be attributed to COVID-19 vaccination.

Risk of cardiovascular events is increased after COVID-19. However, information on cardiovascular risk trends after COVID-19 infection is lacking and estimates by sex are inconsistent. Our aim was to examine cardiovascular outcomes and mortality in a large cohort (164,346 participants) of SARS-CoV-2 positive individuals compared to non-positive individuals, stratified by sex. Data were obtained from the Spanish Health System's electronic medical records. Selected individuals were ≥ 45 years old with/without a positive SARS-CoV-2 test in the period March-May 2020. Follow-up was obtained until January 31, 2021, for cardiovascular events (angina/myocardial infarction, arrhythmias, bypass/revascularization, heart failure, peripheral artery disease, stroke/transient ischemic attack, and thrombosis), and until March 31, 2021, for mortality. Individuals were matched by propensity score. Incidence of cardiovascular events and mortality was compared with accelerated failure time models. The effect of matching and of COVID-19 severity was assessed with sensitivity analyses. In the first 3 months of follow-up, SARS-CoV-2 positive individuals had a higher risk of mortality and of all cardiovascular events. From 4-12 months, there was increased risk of mortality in SARS-CoV-2 positive individuals overall, of heart failure in SARS-CoV-2 positive females (HR= 1.26 [1.11-1.42]), and of arrhythmias and thrombosis in SARS-CoV-2 positive males (HR= 1.29 [1.14-1.47] and HR= 1.35 [1.03-1.77], respectively). When COVID-19 patients admitted to the ICU were excluded, incidence of thrombosis was similar in males regardless of positive/non-positive SARS-CoV-2 status. In the full year of follow-up, increased incidence of heart failure and of arrhythmias and thrombosis was observed in SARS-CoV-2 positive females and males, respectively.

Few epidemiological data are available for venous thromboembolism (VTE) at French national and subnational levels.

To quantify VTE events in France in 2022 and describe the features of hospital management and outcomes.

Adults hospitalized for a VTE as the primary reason for hospitalization or treatment in a medical unit in 2022 were identified from medical administrative data. Data were stratified as pulmonary embolism (PE) and deep vein thrombosis (DVT), and by French department and various sociodemographic indicators. VTE prevalence at 1 January 2023 was defined as the number of people alive at that date with a history of hospitalization for VTE or a chronic long-term disease status due to VTE (2012-2022).

VTE cases reached 896,846 adults on 1 January 2023. VTE was the primary diagnosis for a hospital stay or medical unit in 62,055 patients hospitalized in 2022. The age-standardized rate of hospitalized patients was 23.0% higher for men versus women. There were considerable variations between departments of residence, while Martinique had the highest age-standardized rate. The prevalence of triggering factors was high, with almost 30% having cancer and 20% a recent long hospitalization. One-year mortality was approximately 20% for both PE and DVT, despite rehospitalization rates <5%.

The high prevalence of cancer among patients hospitalized due to VTE partly explains the high 1-year mortality. As VTE is partially avoidable, the prevention of VTE needs to be improved in France and whether thromboprophylaxis guidance is being followed should regularly be assessed.

The Coronavirus Disease 2019 (COVID-19) pandemic, driven by the novel coronavirus and its variants, has caused over 518 million infections and 6.25 million deaths globally, leading to a significant health crisis. Beyond its primary respiratory impact, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has been implicated in various extra-pulmonary complications. Research studies reveal that the virus affects multiple organs, including the kidneys, liver, pancreas, and central nervous system (CNS), largely due to the widespread expression of Angiotensin Converting Enzyme-2 (ACE-2) receptors. Clinical evidence shows that the virus can induce diabetes by disrupting pancreatic and liver functions as well as cause acute kidney injury. Additionally, neurological complications, including cognitive impairments and neuroinflammation, have been observed in a significant number of COVID-19 patients. This review discusses the mechanisms linking SARS-CoV-2 to acute kidney injury, Type 1 and Type 2 Diabetes Mellitus (T1DM and T2DM), emphasizing its effects on pancreatic beta cells, insulin resistance, and the regulation of gluconeogenesis. We also explore how SARS-CoV-2 induces neurological complications, detailing the intricate pathways of neuro-invasion and the potential to trigger conditions such as Alzheimer's disease (AD). By elucidating the metabolic and neurological manifestations of COVID-19 and the underlying pathogenic mechanisms, this review underscores the imperative for continued research and the development of effective therapeutic interventions to mitigate the long-term and short-term impacts of SARS-CoV-2 infection.

This review aims to present current data on the course of COVID-19 in patients with Cushing syndrome (CS) and discuss treatment for CS during to the pandemic.

Literature review using PubMed (pubmed.ncbi.nlm.nih.gov). The search included the following terms: "COVID19" in combination with "Cushing syndrome", "Hypercortisolism" and "Glucocorticoid".

Chronic hypercortisolism has been reported to increase infectious risk and worsens prognostic of patients with COVID-19 potentially due to its direct impact on the immune system: lymphopenia, impairment of monocytes and neutrophils activity, diminution of complement activation. Main metabolic complications of CS - i.e. diabetes, hypertension and obesity - have been recognized as COVID-19 complications risk factors. Patients with CS treated with steroidogenesis inhibitors might experience adrenal insufficiency during COVID-19. Special attention should be paid to patients with CS and COVID-19. The pandemic has impacted - and delayed - care of chronic illnesses including CS. Specific recommendations had been provided during the pandemic: favor telemedicine consultations, limit in-hospital explorations and postpone surgery when feasible.

There are enough evidence for an increased prevalence and severity of COVID-19 to recommend a specific attention and caution in patients with CS.

The goal of this study was to assess the impact of deep local hyperthermia on oxygen (O2) saturation and infected volumes of lungs on coronavirus disease 2019 (COVID-19) cancer patients.

Fifty patients who suffered from COVID-19 (according to their computed tomography (CT) images and laboratory findings) were included in this study. The mentioned patients were divided into two groups (I and II) with thirty-five participants. The infected volumes and COVID-19 infectious locations were diagnosed using their CT images, and deep local hyperthermia was performed for group II. After three consequent days, the SPO2, D-dimer, and infected volumes of lung parenchyma of both groups were compared to each other.

For group II, the mean ± SD (standard deviation) of O2 pressure saturation (SPO2) before/after hyperthermia was 85 ± 0.0/91.3 ± 0.5, respectively, while for group I, the mean ± SD of SPO2 before/after 3 days was 85 ± 0.0/88 ± 0.2, respectively. For infected volumes of lungs before/after hyperthermia in group II, the mean ± SD was 31.36 ± 3.13/4 ± 1.53, respectively. Nonetheless, the infected volumes of lungs for group I were 34.21 ± 3.41/10 ± 2.12 before/after three days. For group II, the amount of D-dimer before/after hyperthermia was 3200 ± 106/510 ± 121, respectively. However, for group I, it was 3100/740 before/after the consequent three days, respectively.

Deep local lung hyperthermia for COVID-19 cancer patients is suggested, as a result of its positive impacts on SPO2 improvement and also D-dimer serum level, C-reactive protein, and Lactate dehydrogenaze reduction for the mentioned patients.

The Golden Syrian hamster (Mesocricetus auratus), Ferrets (Mustela putorius furo), and macaques have been described as useful laboratory animals naturally susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

To study the mechanism of lung injury, we describe the histopathological features of SARS-CoV-2 infection in Golden Syrian hamsters inoculated intranasally with the A.2 Brazilian strain.

Hamsters were intranasally inoculated with the A.2 variant and euthanised at 3-, 5-, 10- and 15-days post-inoculation. The physical examination and body weight were recorded daily. Neutralising antibodies and viral RNA load of the respiratory tract were assessed during necropsies.

The coronavirus disease 2019 (COVID-19) model presented body weight loss, high levels of respiratory viral RNA load, severe segmentary pneumonitis, and bronchial fistula besides lymphatic trapping and infiltration, like the human SARS-COV-2 pathogenesis. The presence of subepithelial lymphoeosinophilic infiltrate was highlighted in our results; it contributed to the detachment of SARS-CoV-2 nucleocapsid-positive epithelial cells resulting in the infectious cell plugs.

The SARS-CoV-2 caused segmentary pneumonia and vascular damage. In our comprehension, the infectious cell plugs, as being aspirated from the upper respiratory tract into the terminal bronchial lumen, work as a "Trojan horse", thus contributing to the dissemination of the SARS-CoV-2 infection into specific regions of the deep lung parenchyma.

Coagulopathy and thromboembolic events are associated with poor outcomes in coronavirus disease 2019 (COVID-19) patients. There is conflicting evidence on the effects of chronic anticoagulation on mortality and severity of COVID-19 disease.

To summarize the body of evidence on the effects of pre-hospital anticoagulation on outcomes in COVID-19 patients.

A Literature search was performed on LitCovid PubMed, WHO, and Scopus databases from inception (December 2019) till June 2023 for original studies reporting an association between prior use of anticoagulants and patient outcomes in adults with COVID-19. The primary outcome was the risk of thromboembolic events in COVID-19 patients taking anticoagulants. Secondary outcomes included COVID-19 disease severity, in terms of intensive care unit admission or invasive mechanical ventilation/intubation requirement in patients hospitalized with COVID-19 infection, and mortality. The random effects models were used to calculate crude and adjusted odds ratios (aORs) with 95% confidence intervals (95%CIs).

Forty-six observational studies met our inclusion criteria. The unadjusted analysis found no association between prior anticoagulation and thromboembolic event risk [n = 43851, 9 studies, odds ratio (OR)= 0.67 (0.22, 2.07); P = 0.49; I 2 = 95%]. The association between prior anticoagulation and disease severity was non-significant [n = 186782; 22 studies, OR = 1.08 (0.78, 1.49); P = 0.64; I 2 = 89%]. However, pre-hospital anticoagulation significantly increased all-cause mortality risk [n = 207292; 35 studies, OR = 1.72 (1.37, 2.17); P < 0.00001; I 2 = 93%]. Pooling adjusted estimates revealed a statistically non-significant association between pre-hospital anticoagulation and thromboembolic event risk [aOR = 0.87 (0.42, 1.80); P = 0.71], mortality [aOR = 0.94 (0.84, 1.05); P = 0.31], and disease severity [aOR = 0.96 (0.72, 1.26); P = 0.76].

Prehospital anticoagulation was not significantly associated with reduced risk of thromboembolic events, improved survival, and lower disease severity in COVID-19 patients.

COVID-19 vaccines, a cornerstone of the fight against the disease have generally proven to be safe with most commonly reported side effects being mild and self-limiting. Uncommon severe adverse effects like thromboembolism have been reported during postmarketing surveillance. Viral-based vector vaccines have been most commonly implicated in these reports. Our report however portrays a case of a 26-year-old female who developed extensive pulmonary embolism following administration of the Pfizer- BNT162b2 mRNA COVID-19 vaccine. The patient did not have any risk factors for thromboembolism. She was admitted, put on enoxaparin, and given Altaplase thrombolytic therapy. Her condition improved and she was discharged on Apixaban. The Thrombophilia screen performed on the 6-month follow-up was negative and following the resolution of thrombosis, Apixaban was stopped. Our case highlights the importance of continued surveillance of uncommon adverse effects and the need for prompt diagnosis and management of such side effects.

Systematic inflammatory response syndrome (SIRS) and the accompanying sepsis pose a huge threat to human health worldwide. Heparin is a part of the standard supportive care for the disease. However, the molecular mechanism is not fully understood yet, and the potential signaling pathways that play key roles have not yet been elucidated. In this paper, the main findings regarding the molecular mechanisms associated with the beneficial effects of heparin, including inhibiting HMGB-1-driven inflammation reactions, histone-induced toxicity, thrombo-inflammatory response control and the new emerging mechanisms are concluded. To set up the link between the preclinical research and the clinical effects, the outcomes of the clinical trials are summarized. Then, the structure and function relationship of heparin is discussed. By providing an updated analysis of the above results, the paper highlights the feasibility of heparin as a possible alternative for sepsis prophylaxis and therapy.

While our understanding of coronavirus disease 2019 (COVID-19) has evolved, uncertainty remains regarding utility of previously established pulmonary embolism (PE) screening guidelines in patients with COVID-19. Many studies have investigated the efficacy of D-dimer (DD) screenings for patients with COVID-19 admitted to inpatient services, but few have evaluated patients in the emergency department (ED). The purpose of this study was to investigate utility of DD threshold for PE screening in patients with COVID-19 presenting to the ED.

This was a retrospective, multicenter cohort including patients presenting to three EDs between March 1, 2020 and February 1, 2021 who tested positive for COVID-19 during ED visit or in 60 days prior to presentation and had DD ordered in ED. Patients were grouped by those who underwent computed tomography pulmonary angiogram (CTPA) to evaluate for PE and those who did not, and descriptive statistics were performed. Those who underwent CTPA were further divided into PE-positive and PE-negative groups. The discriminative ability of DD in predicting PE in patients with COVID-19 was analyzed using the receiver operating characteristic (ROC) curve.

A total of 570 patients with COVID-19 were included in the study, of which 107 underwent CTPA to evaluate for PE. History of diabetes, elevated glucose, elevated lactate dehydrogenase, elevated white blood cell count, elevated platelets, elevated respiratory rate, and lower temperature were associated with increased risk for PE. Compared to those without PE, patients with PE were significantly more likely to be hospitalized (100% vs. 82%, p = 0.020) and admitted to the ICU (64% vs. 24%, p = 0.002). Those with PE had a significantly higher median DD value (21,177 ng/mL) compared to PE-negative group (952 ng/mL, p < 0.001). The ROC curve for DD in predicting PE had an area under the curve of 0.91 (95% confidence interval [0.84, 0.98]). In our study population, the optimal DD threshold for predicting PE was 1815 ng/mL (sensitivity 93% and specificity 80%). A conservative threshold of 1089 ng/mL could be used with sensitivity 100% and specificity 58%.

DD is often elevated in patients with COVID-19, regardless of PE. While the classically used DD cutoff is 500 ng/mL, our study demonstrated a threshold of 1089 ng/mL safely predicted PE in patients with COVID-19 .

Evaluate maternal and neonatal outcomes in peripartum coronavirus disease 2019 (COVID-19) positive women.

A retrospective cohort study was conducted, comparing outcomes between women with and without peripartum COVID-19. All singleton deliveries from June 2020 to January 2022 were included. Univariate analysis was followed by multivariate analysis.

Of 26,827 singleton deliveries, 563 women had peripartum COVID-19, associated with preterm deliveries both near-term and remote from term [adjusted odds ratio (aOR) 1.6 and 2.0, respectively, p = 0.007 and 0.003]. Women with peripartum COVID-19 had a significantly higher rate of disseminated intravascular coagulation (DIC) (aOR 23.0, p < 0.001). Conversely, peripartum COVID-19 peripartum COVID-19 was negatively associated with premature rupture of membranes and prolonged maternal length of stay (aOR 0.7 and 0.5, respectively, p = 0.006 and <0.001). In cesarean delivery (CDs), patients with COVID-19 had higher rate of urgent CDs (75.5 vs. 56.1%, p < 0.001), higher rate of regional anesthesia (74.5 vs. 64.9%, p = 0.049), and longer anesthesia duration (86.1 vs. 53.4 min, p < 0.001). CD rate due to non-reassuring fetal heart rate (NRFHR) was significantly higher in women with COVID-19 (29.6 vs. 17.4%, p = 0.002). Conversely, CDs rate due to history of previous single CD was significantly higher in patients without COVID-19 diagnosis (13.6 vs. 4.1%, p = 0.006). Concerning neonatal outcomes, an association has been observed between COVID-19 and low one-minute APGAR score <5, as well as neonatal COVID-19 infection (aOR 61.8 and 1.7 respectively, p < 0.001 and p = 0.037).

Peripartum COVID-19 is associated with preterm deliveries, urgent CDs and DIC, potentially aligning with the infection's pathophysiology and coagulation alterations.

COVID-19 patients experience a complex interplay involving ACE2, thrombin, D-dimer, and lipid profile, yet its full understanding remains elusive. ACE2, a pivotal regulator of the renin-angiotensin system and the primary receptor for SARS-CoV-2 undergoes downregulation upon viral binding, potentially leading to severe cases with acute respiratory distress syndrome (ARDS). A specific ACE2 gene polymorphism (rs2285666) may be associated with COVID-19 susceptibility, with the A allele potentially increasing infection risk. COVID-19 disease progression is linked to coagulation abnormalities, but the exact connection with thrombin and D-dimer remains uncertain. A study examining coagulation parameters in COVID-19 patients admitted to Al-Diwania Educational Hospital from February to May 2022 found that thrombin and D-dimer levels were directly related to disease severity. Severe cases exhibited significantly altered coagulation function compared to mild and recovered cases, with notably higher D-dimer levels and elevated thrombin serum concentrations. Moreover, dyslipidemia, particularly low HDL cholesterol, is a prevalent comorbidity in COVID-19 patients and may be linked to worse outcomes. In conclusion, COVID-19 is associated with a prothrombotic state and dysregulation of the renin-angiotensin system due to ACE2 downregulation following viral binding. The intricate interplay between ACE2, thrombin, D-dimer, and lipid profile necessitates further investigation. The multifaceted nature of the disease demands continued research to unravel its pathogenesis and identify potential therapeutic targets.

Patients with multiple myeloma (MM) were among the groups impacted more severely by the COVID-19 pandemic, with higher rates of severe disease and COVID-19-related mortality. MM and COVID-19, plus post-acute sequelae of SARS-CoV-2 infection, are associated with endothelial dysfunction and injury, with overlapping inflammatory pathways and coagulopathies. Existing treatment options for MM, notably high-dose therapy with autologous stem cell transplantation and novel chimeric antigen receptor (CAR) T-cell therapies and bispecific T-cell engaging antibodies, are also associated with endothelial cell injury and mechanism-related toxicities. These pathologies include cytokine release syndrome (CRS) and neurotoxicity that may be exacerbated by underlying endotheliopathies. In the context of these overlapping risks, prophylaxis and treatment approaches mitigating the inflammatory and pro-coagulant effects of endothelial injury are important considerations for patient management, including cytokine receptor antagonists, thromboprophylaxis with low-molecular-weight heparin and direct oral anticoagulants, and direct endothelial protection with defibrotide in the appropriate clinical settings.

Patients with hematologic malignancies (HMs) are at a significantly higher risk of contracting COVID-19 and experiencing severe outcomes compared to individuals without HMs. This heightened risk is influenced by various factors, including the underlying malignancy, immunosuppressive treatments, and patient-related factors. Notably, immunosuppressive regimens commonly used for HM treatment can lead to the depletion of B cells and T cells, which is associated with increased COVID-19-related complications and mortality in these patients. As the pandemic transitions into an endemic state, it remains crucial to acknowledge and address the ongoing risk for individuals with HMs. In this review, we aim to summarize the current evidence to enhance our understanding of the impact of HMs on COVID-19 risks and outcomes, identify particularly vulnerable individuals, and emphasize the need for specialized clinical attention and management. Furthermore, the impaired immune response to COVID-19 vaccination observed in these patients underscores the importance of implementing additional mitigation strategies. This may include targeted prophylaxis and treatment with antivirals and monoclonal antibodies as indicated. To provide practical guidance and considerations, we present two illustrative cases to highlight the real-life challenges faced by physicians caring for patients with HMs, emphasizing the need for individualized management based on disease severity, type, and the unique circumstances of each patient.

Background and Objectives: The concurrent occurrence of tuberculosis and COVID-19 coinfection poses significant clinical complexities, warranting a nuanced approach to diagnosis, management, and patient care. Materials and Methods: A retrospective, cross-sectional study was conducted on two groups: one comprising 32 patients with pulmonary TB (PTB) and COVID-19 co-infection, and one including 100 patients with COVID-19 alone. Data was collected from medical records, including patient history, clinical parameters, laboratory, imaging results, and patient outcome. Results: A lower BMI emerges as a significant marker suggesting underlying PTB in patients with SARS-CoV-2 co-infection. Type 2 diabetes mellitus increases the risk of death in PTB-SARS-CoV-2 co-infection. Co-infected patients show lymphocytopenia and higher neutrophil levels, CRP, transaminases, and D-dimer levels. Elevated CRP and ALT levels are linked to increased co-infection likelihood. Certain parameters like SpO2, CRP, ALT, AST, and D-dimer effectively differentiate between co-infected and COVID-19 patients. Platelet-to-lymphocyte ratio is notably higher in co-infected individuals. Lesion severity on imaging is significantly associated with co-infection, highlighting imaging's diagnostic importance. Longer hospital stays are linked to co-infection but not significantly to death risk. Conclusions: Certain clinical and biological factors may serve as potential indicators of PTB co-infection in patients with SARS-CoV-2.

Coagulation activation in immunothrombosis involves various pathways distinct from classical hemostasis, offering potential therapeutic targets to control inflammation-induced hypercoagulability while potentially sparing hemostasis. The Angiopoietin/Tie2 pathway, previously linked to embryonic angiogenesis and sepsis-related endothelial barrier regulation, was recently associated with coagulation activation in sepsis and COVID-19. This study explores the connection between key mediators of the Angiopoietin/Tie2 pathway and coagulation activation. The study included COVID-19 patients with hypoxia and healthy controls. Blood samples were processed to obtain platelet-free plasma, and frozen until analysis. Extracellular vesicles (EVs) in plasma were characterized and quantified using flow cytometry, and their tissue factor (TF) procoagulant activity was measured using a kinetic chromogenic method. Several markers of hemostasis were assessed. Levels of ANGPT1, ANGPT2, and soluble Tie2 correlated with markers of coagulation and platelet activation. EVs from platelets and endothelial cells were increased in COVID-19 patients, and a significant increase in TF+ EVs derived from endothelial cells was observed. In addition, ANGPT2 levels were associated with TF expression and activity in EVs. In conclusion, we provide further evidence for the involvement of the Angiopoietin/Tie2 pathway in the coagulopathy of COVID-19 mediated in part by release of EVs as a potential source of TF activity.

COVID-19 disrupts the balance between coagulation and fibrinolysis. Especially in the clinical course of serious disease, plasminogen activator inhibitor-1 (PAI-1), thrombin activatable fibrinolysis inhibitor (TAFI), and tissue plasminogen activator levels increase in association with hypercoagulable state and hypofibrinolysis. This explains the increased incidence of thrombosis seen in COVID-19 infection. In this study, we aimed to examine the changes in PAI-1 and TAFI levels of COVID-19 patients. Department of Infectious Diseases and Clinical Microbiology, University of Health Sciences, Dişkapi Yildirim Beyazit Training and Research Hospital-Ankara Turkey, between April 1 and May 7, 2021. Patients who were diagnosed with COVID-19 were included in this retrospective study. TAFI and PAI-1 levels were analyzed from the samples that had been stored at -80 °C formerly. One hundred thirty-five patients diagnosed with COVID-19 and followed up in the service or intensive care unit were included in the study. Thirty-four (25.2%) patients required follow-up in the intensive care unit. Mortality rate was 10.4%, the coagulation tests of these patients were also compared. PA1-1 levels were found to be statistically significantly higher in intensive care unit patients (median: 133 pg/mL vs 31 pg/mL; P < .001), and there was no significant difference in TAFI levels (median:7.31 ng/mL vs 9.80 ng/mL; P = .171) between the 2 groups. TAFI levels were found to be higher in patients who died. In COVID-19 infection, as the severity of the disease increases, the coagulation balance deteriorates and eventually a hypercoagulable state occurs with an increase in PAI-1 and TAFI levels. Markers such as PAI and TAFI can be illuminating in further studies in determining prognosis and mortality and developing new treatment options.

The range of clinical manifestations associated with the infection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) encompasses a broad spectrum, ranging from flu-like symptoms to the occurrence of multiple organ failure and death. The severity of the coronavirus disease 2019 (COVID-19) is categorized based on clinical presentation and is divided into three distinct levels of severity identified as non-severe, severe, and critical. Although individuals of all age groups are susceptible to SARS-CoV-2 infection, middle-aged and older adults are more frequently impacted, with the latter being more likely to develop severe illness. Various laboratory characteristics observed in hospitalized COVID-19 patients have been correlated with adverse outcomes. These include elevated levels of D-dimer, liver enzymes, lactate dehydrogenase, C-reactive protein, ferritin, prothrombin time, and troponin, as well as decreased lymphocyte and platelets counts. This review investigated the relationship between baseline clinical characteristics, initial laboratory parameters upon hospital admission, and the severity of illness and mortality rates among COVID-19 patients. Although the COVID-19 pandemic has concluded, understanding the laboratory predictors of virus severity and mortality remains crucial, and examining these predictors can have long-term effects. Such insights can help healthcare systems manage resources more effectively and deliver timely and appropriate care by identifying and targeting high-risk individuals. This knowledge can also help us better prepare for future pandemics. By examining these predictors, we can take steps to protect public health and mitigate the impact of future pandemics.

Despite the progressive decline in the virulence of the novel coronavirus, there has been no corresponding reduction in its associated hospital mortality. Our aim was to redefine an accurate predictor of mortality risk in COVID-19 patients, enabling effective management and resource allocation. We conducted a retrospective analysis of 2917 adult Chinese patients diagnosed with COVID-19 who were admitted to our hospital during two waves of epidemics, involving the Beta and Omicron variants. Upon admission, NT-proBNP levels were measured, and we collected demographic, clinical, and laboratory data. We introduced a new concept called the NT-proBNP ratio, which measures the NT-proBNP level relative to age-specific maximum normal values. The primary outcome was all-cause in-hospital mortality. Our analysis revealed a higher in-hospital mortality rate in 2022, as shown by the Kaplan-Meier Survival Curve. To assess the predictive value of the NT-proBNP ratio, we employed the time-dependent receiver operating characteristic (ROC) curve. Notably, the NT-proBNP ratio emerged as the strongest predictor of mortality in adult Chinese hospitalized COVID-19 patients (area under the curve, AUC = 0.826; adjusted hazard ratio [HR], 3.959; 95% confidence interval [CI] 3.001-5.221; P < 0.001). This finding consistently held true for both the 2020 and 2022 subgroups. The NT-proBNP ratio demonstrates potential predictive capability compared to several established risk factors, including NT-proBNP, hsCRP, and neutrophil-to-lymphocyte ratio, when it comes to forecasting in-hospital mortality among adult Chinese patients with COVID-19.Trial registration Clinical Trial Registration: www.clinicaltrials.gov NCT05615792.

Multisystemic inflammatory syndrome in adults is a hyperinflammatory condition following (within 4-12 weeks) SARS-CoV-2 infection. Here, the dysregulation of the immune system leads to a multiorgan involvement often affecting the heart. Cardiac involvement in multisystemic inflammatory syndrome in adults has been described mainly in young men without other comorbidities and may present with different clinical scenarios, including acute heart failure, life-threatening arrhythmias, pericarditis, and myocarditis, with a nonnegligible risk of mortality (up to 7% of all cases). The heterogeneity of its clinical features and the absence of a clear case definition make the differential diagnosis with other postinfectious (eg, infective myocarditis) and hyperinflammatory diseases (eg, adult Still disease and macrophage activation syndrome) challenging. Moreover, the evidence on the efficacy of specific treatments targeting the hyperinflammatory response underlying this clinical condition (eg, glucocorticoids, immunoglobulins, and other immunomodulatory agents) is sparse and not supported by randomized clinical trials. In this review article, we aim to provide an overview of the clinical features and the diagnostic workup of multisystemic inflammatory syndrome in adults with cardiac involvement, highlighting the possible pathogenetic mechanisms and the therapeutic management, along with remaining knowledge gaps in this field.

Coronavirus disease 2019 (COVID-19) has infected over 700 million people, with up to 30% developing neurological manifestations, including dementias. However, there is a lack of understanding of common molecular brain markers causing Alzheimer's disease (AD). COVID-19 has etiological cofactors with AD, making patients with AD a vulnerable population at high risk of experiencing more severe symptoms and worse consequences. Both AD and COVID-19 have upregulated several shared kinases, leading to the repositioning of kinase inhibitors (KIs) for the treatment of both diseases. This review provides an overview of the interactions between the immune system and the nervous system in relation to receptor tyrosine kinases, including epidermal growth factor receptors, vascular growth factor receptors, and non-receptor tyrosine kinases such as Bruton tyrosine kinase, spleen tyrosine kinase, c-ABL, and JAK/STAT. We will discuss the promising results of kinase inhibitors in pre-clinical and clinical studies for both COVID-19 and Alzheimer's disease (AD), as well as the challenges in repositioning KIs for these diseases. Understanding the shared kinases between AD and COVID-19 could help in developing therapeutic approaches for both.

Blood plasma is a large reservoir of circulating mediators of inflammation and its expansion has been associated with unfavorable outcomes in patients with inflammatory and cardiovascular diseases. The aim of this study was to determine clinical and prognostic value of estimated plasma volume status (ePVS) in hospitalized patients with COVID-19. We retrospectively investigated 5871 consecutive COVID-19 patient hospitalized in our tertiary-level institution in period 3/2020-6/2021. ePVS was determined using the Strauss-derived Duarte formula and was correlated with clinical characteristics and unwanted outcomes. Median ePVS was 4.77 dl/g with interquartile range 4.11-5.74. Higher ePVS was significantly associated with older age, female sex, higher comorbidity burden, worse functional status, less severe COVID-19 clinical presentation with lower severity and longer duration of symptoms, but more pronounced inflammatory profile with higher C-reactive protein, interleukin-6 and D-dimer levels (P < 0.05 for all analyses). In the multivariate regression analysis U shaped relationship of ePVS with mortality was revealed, present independently of age, sex, COVID-19 severity and comorbidity burden. In addition, higher ePVS was independently associated with higher tendency for mechanical ventilation, intensive care unit treatment, venous thromboembolism, major bleeding and bacteriemia and lower ePVS was independently associated with tendency for arterial thrombotic events. Higher ePVS, indicative of plasma volume expansion and inflammatory cytokine accumulation, may predispose respiratory deterioration and venous thromboembolism, despite less severe initial clinical presentation. Lower ePVS, indicative of hemoconcentration, may predispose arterial thrombotic events. Both may be associated with higher mortality in hospitalized COVID-19 patients.

Acute pulmonary embolism (PE) is a common cardiovascular disorder, potentially associated with high morbidity and mortality rates.

Herein, we report on a patient with COVID-19 infection and bilateral PE, who presented after cardiovascular resuscitation with return of spontaneous circulation. Initially, an acute coronary syndrome was suspected but bedside echocardiography showed dilatation of the right ventricle (RV) and RV dysfunction, helping to establish the diagnosis of acute intermediate-to-high-risk PE, which was subsequently confirmed by contrast-enhanced computed tomography pulmonary angiography. The patient was successfully treated using low-dose (12 mg of tissue plasminogen) ultrasound-assisted catheter-directed thrombolysis, which resulted in prompt clinical improvement and reversal of RV dysfunction without bleeding complications.

This case demonstrates the importance of echocardiography for the differential diagnosis of PE and of catheter-directed thrombolysis for its treatment in patients with intermediate-to-high-risk and high-risk PEs.

Coronavirus disease 2019 (COVID-19) carries a high risk of vascular thrombosis. However, whether a specific anticoagulation intensity strategy may prevent clinical worsening in severe COVID-19 patients is still debated. We conducted a joint analysis of two randomized controlled trials, COVID-19 HD (NCT044082359) and EMOS-COVID (NCT04646655), to assess the efficacy and safety of two anticoagulant regimens in hospitalized severe COVID-19 patients. Subjects with COVID-19-associated respiratory compromise and/or coagulopathy were randomly assigned to low (4000 IU qd) or high (70 IU Kg-1 every 12 h) enoxaparin dose. The primary efficacy endpoint was clinical worsening within 30 days, defined as the occurrence of at least one of the following events, whichever came first: in-hospital death, evidence of arterial or venous thromboembolism, acute myocardial infarction, need for either continuous positive airway pressure (CPAP) or non-invasive ventilation (NIV) in patients receiving standard oxygen therapy or none at randomization, and need for mechanical ventilation in any patient. The safety endpoint was major bleeding. We estimated the relative risk (RR) and its 95% confidence interval (CI) for the outcomes. Among 283 patients included in the study (144 in the low-dose and 139 in the high-dose group), 118 (41.7%) were on NIV or CPAP at randomization. 23/139 (16.5%) patients in the high-dose group reached the primary endpoint compared to 33/144 (22.9%) in the low-dose group (RR 0.72, 95% CI 0.45-1.17). No major bleeding was observed. No significant differences were found in the clinical worsening of hospitalized COVID-19 patients treated with high versus low doses of enoxaparin.

Background: Coronavirus disease 2019, caused by SARS-CoV-2 (SCV-2) was stated as a pandemic on March 11 2020 by World Health Organization (WHO), and since then, it has become a major health issue worldwide. It mainly attacks the respiratory system with various accompanying complications, including cardiac injury, renal failure, encephalitis and Stroke.Materials and Methods: The current systematic review has been compiled to summarize the available literature on SCV-2 induced ischemic Stroke and its subtypes. Further, the mechanisms by which the virus crosses the blood-brain barrier (BBB) to enter the brain have also been explored. The role of CRP and D-dimer as potent prognostic markers was also explored. The literature search was carried out comprehensively on Google scholar, PubMed, SCOP US, Embase and Cochrane databases by following guidelines.Results: All the studies were reviewed thoroughly by authors and disagreements were resolved by consensus and help of the senior authors. The most common subtype of the IS was found to be large artery atherosclerosis in SCV-2 induced IS. Hypertension emerged as the most significant risk factor. The mechanism resulting in elevated levels of CRP and D-dimer have also been discussed. However, there is a scarcity of definitive evidence on how SCV-2 enters the human brain. The available literature based on various studies demonstrated that SCV-2 enters through the nasopharyngeal tract via olfactory cells to olfactory neurons, astrocytes and via choroid plexus through endothelial cells. Further, disruption of gut-brain axis has been also discussed.Conclusion: Data available in the literature is not adequate to come to a conclusion. Therefore, there is a need to carry out further studies to delineate the possible association between SCV-2 induced IS.

Our study aimed to explore the association between serum C-reactive protein (CRP) and COVID-19 mortality. This is a retrospective cohort study of all patients admitted to 4 hospitals within the Montefiore Health System between March 1 and April 16, 2020, with SARS-CoV-2 infection. All-cause mortality were collected in 7 May 2020. The mortality risk was estimated using Cox proportional hazards models. Of the 3545 patients with a median age of 63.7 years, 918 (25.9%) died within the time of cohort data collection after admission. When the CRP was < 15.6 mg/L, the mortality rate increased with an adjusted HR of 1.57 (95% CI 1.30-1.91, P < 0.0001) for every 10 mg/L increment in the CRP. When the CRP was ≥ 15.6 mg/L, the mortality rate increased with an adjusted HR of 1.11 (95% CI 0.99-1.24, P = 0.0819) for every 10 mg/L increment in the CRP. For patients with COVID-19, the association between the CRP and the mortality risk was curve and had a saturation effect. When the CRP was small, the mortality rate increased significantly with the increase of CRP. When CRP > 15.6 mg/L, with the increase of CRP, the mortality rate increases relatively flat.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and acute pulmonary embolism (APE) present a diagnostic challenge in the emergency department (ED) setting. We aimed to identify key clinical characteristics and D-dimer thresholds associated with APE in SARS-CoV-2 positive ED patients.

We performed a multicenter, retrospective cohort study for adult patients who were diagnosed with coronavirus 2019 (COVID-19) and had computed tomography pulmonary angiogram (CTPA) performed between March 17, 2020-January 31, 2021. We performed univariate analysis to determine numeric medians, chi-square values for association between clinical characteristic and positive CTPA. Logistic regression was used to determine the odds of a clinical characteristic being associated with a diagnosis of APE.

Of 408 patients who underwent CTPA, 29 (7.1%) were ultimately found to have APE. In multivariable analysis, patients with a body mass index greater than 32 (odds ratio [OR] 4.4, 95% confidence interval [CI] 1.0 -19.3), a heart rate greater than 90 beats per minute (bpm) (OR 5.0, 95% CI 1.0-24.9), and a D-dimer greater than 1,500 micrograms per liter (μg/L) (OR 5.6, 95% CI 1.6-20.2) were significantly associated with pulmonary embolism. In our population that received a D-dimer and was SARS-CoV-2 positive, limiting CTPA to patients with a heart rate over 90 or a D-dimer value over 1500 μg/L would reduce testing 27.2% and not miss APE.

In patients with acute COVID-19 infections, D-dimer at standard cutoffs was not usable. Limiting CTPA using a combination of heart rate greater than 90 bpm or D-dimer greater than 1,500 μg/L would significantly decrease imaging in this population.

The coronavirus disease 2019 (COVID-19) pandemic is responsible for huge morbidity and mortality throughout the world. Several serious complications of this disease have been reported. It can cause hypercoagulability, which may lead to venous and arterial thromboembolic diseases. This hypercoagulability state is also associated with high morbidity and mortality. Arterial thrombosis in COVID-19 is poorly described compared to venous thrombosis and pulmonary embolism. We report a case of an extensive arterial thrombosis leading to a limb ischemia with extremely high D-dimer in a COVID-19 patient. A 69-year-old man was hospitalized for febrile dyspnea. He is a hypertensive and diabetic patient. On admission, pulse oxygen saturation was 72% on room air. He had cyanosis of the left foot up to the mid-thigh. The left pedal, posterior tibial, popliteal and femoral pulses were abolished. Chest CT scan was in favor of COVID-19. He has a high D-dimer level of 257,344 ng/mL. Arterial Echo-Doppler found an extensive intraluminal thrombus along the arterial axes of the left lower limb, completely obstructing them, starting from the primitive iliac artery just after its bifurcation with the aorta, and extending distally (external iliac; common femoral; superficial femoral; popliteal; anterior tibial; posterior tibial; fibular and pedal). The patient was diagnosed with COVID-19 critical form, associated with ischemia of the left lower limb secondary to an extensive arterial thrombosis. He was receiving anticoagulation, and underwent surgical amputation of the ischemic limb. The patient survived the event; however, he was on long-term oxygen therapy at home. Arterial thrombosis may occur during COVID-19 and may be responsible for peripheral or central ischemia aggravating morbidity and mortality. The occurrence of these events is related to the D-dimer value. Anticoagulation is an important part of the management of COVID-19, especially in severe forms in order to limit the occurrence of these thromboembolic diseases.

The impact of plasma biomarkers on diagnosis and prognosis of patients with acute pericarditis (AP) has been poorly investigated. This study aims to assess the diagnostic and prognostic role of d-dimer (DD), an easily obtainable biomarker, in patients with AP.

This is a prospective clinical study enrolling 265 consecutive patients hospitalized between September 2010 and May 2019 with a first episode of AP. At baseline, demographics, clinical features, laboratory and imaging findings were recorded. All patients were followed-up for a minimum of 18 months. Endpoints included cardiac tamponade, new-onset atrial fibrillation, pericardial drainage, recurrent/constrictive pericarditis and death.

DD was measured in 165 out of 265 patients (62.3%, median levels 1456 ng/mL) Among them, 121 patients (73.3%) presented with elevated age-adjusted DD levels. Patients with elevated DD depicted a higher rate of pleural (69.4%, vs 38.6%, p<0.001) and pericardial effusions (89.3% vs 72.7%, p = 0.009). Elevated DD correlated with admission (rho=0.37) and peak (rho=0.36) C-reactive protein values. Patients with elevated DD depicted a trend towards a greater prevalence of pericardial tamponade vs those without (14.9% vs 4.5% respectively, p = 0.07). In the 43.8% of patients with elevated DD who underwent computed tomography pulmonary angiography (CTPA), no case of pulmonary embolism or aortic syndrome was unveiled.

DD elevation is detected in the majority of AP cases at presentation and may herald cardiac tamponade. In patients with chest pain not attributable to alternative causes, elevated DD denotes an inflammatory condition and should not prompt unnecessary investigations, such as CTPA.

An unprecedented global social and economic impact as well as a significant number of fatalities have been brought on by the coronavirus disease 2019 (COVID-19), produced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Acute SARS-CoV-2 infection can, in certain situations, cause immunological abnormalities, leading to an anomalous innate and adaptive immune response. While most patients only experience mild symptoms and recover without the need for mechanical ventilation, a substantial percentage of those who are affected develop severe respiratory illness, which can be fatal. The absence of effective therapies when disease progresses to a very severe condition coupled with the incomplete understanding of COVID-19's pathogenesis triggers the need to develop innovative therapeutic approaches for patients at high risk of mortality. As a result, we investigate the potential contribution of promising combinatorial cell therapy to prevent death in critical patients.