Coagulation Abnormalities in Patients with COVID-19

Coronavirus disease 2019 (COVID-19) is an emerging infectious disease. Bilateral pneumonia, acute respiratory failure, systemic inflammation, endothelial dysfunction, and coagulation activation have been described as key features of severe COVID-19. Fibrinogen and D-dimer are typically increased. Moreover, the risk for venous thromboembolism is markedly increased, especially in patients in the intensive care unit, often despite prophylactic-dose anticoagulation. Pulmonary microvascular thrombosis has also been described and the risk for arterial thrombotic diseases also appears to be increased. Bleeding is less common than thrombosis but can occur. Evaluation for venous thromboembolism may be challenging because symptoms of pulmonary embolism overlap with COVID-19, and imaging studies may not be feasible in all cases. All inpatients should receive thromboprophylaxis unless contraindicated. In hospitalized patients with COVID-19, prophylactic dosing rather than more intensive (intermediate or therapeutic) dosing are suggested. On the other hand, therapeutic dose of anticoagulation is always appropriate to treat deep venous thrombosis or pulmonary embolism, unless contraindicated. This article reviews evaluation and management of coagulation abnormalities in individuals with COVID-19. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.

Surgical clinical characteristics of acute arterial thrombosis of the extremities in the context of SARS-CoV-2 infection

Objective: To determine the clinical-surgical features of critical limb ischaemia (CLI) within the context of infection by SARS-CoV-2. Method(s): Cross-sectional, retrospective, observational, descriptive study, with clinical data obtained from printed and electronic records of patients with CLI treated by the Angiology and Vascular Surgery Service of the General Hospital of Mexico in the period between January 2020 and July 2021. Result(s): We evaluated the data of 33 patients with critical limb ischaemia of which 15 were positive for SARS-CoV-2 in the period from January 2020 to July 2021, females were the most affected representing the 53.3% of the total, patients under 60 years old accounted for 26.67%. Twenty-six percent of the patients presented critical limb ischaemia without having previous comorbidities, 60% of these presented with an advanced state of the disease and a delay in specialised medical care of more than 6 hours after the onset of symptoms, which warranted a major amputation in 37% of cases, the lower extremities represented 90% of the affected anatomical regions. Conclusion(s): the outcomes in our study show that the incidence of critical limb ischaemia during the SARS-CoV2 pandemic period occurred in an atypical way in a segment of young patients and without known event-generating comorbidities. Thromboembolic events, probably associated with the hypercoagulable state generated by this infection, also evolved rapidly and aggressively from the onset of symptoms despite prompt treatment.Copyright © 2022 Sociedad Medica del Hospital General de Mexico. Published by Permanyer.

ASSOCIATIONS OF POLYMORPHISMS OF THE ACE AND ACE2 GENES WITH CLINICAL MANIFESTATIONS AND CARDIOVASCULAR COMPLICATIONS OF THE CORONAVIRUS INFECTION

A problem of the novel coronavirus infection pandemic is the absence of specific biomarkers, the determination of which would make it possible to assess the likelihood of a severe disease course, development of complications, immediate and long-term consequences, and effective etiotropic (antiviral) therapy. The severity of the novel coronavirus infection depends on various factors such as the initial state of health, immune status, age, smoking status, concomitant cardiovascular diseases, and diabetes mellitus. However, a severe disease course is also observed in patients without the aforementioned risk factors. The development of the disease and its complications depends on sex and geographical identity. Angiotensin-converting enzyme 2 (ACE2), associated by gene-gene interaction with ACE, plays a main role in the pathogenesis of the penetration of severe acute respiratory syndrome-2 coronavirus into the cell. The main body of information on this problem is represented by systematic meta-analyses and results of single-center cohort studies, which offer insufficient information to unequivocally assert the associations of ACE and ACE2 gene polymorphisms with pathological changes in the circulatory system during and after a new coronavirus infection. Differences in the incidence of ACE and ACE2 alleles may explain the differences between susceptible populations and/or response to the severe coronavirus infection. The above studies were carried out on the effect of the coronavirus in the initial period of the pandemic. For a more complete molecular genetic picture of the influence of polymorphism, persons with different strains of the coronavirus must be considered. In addition, no data are available regarding the expressions of ACE and ACE2 genes in response to a coronavirus infection. Moreover, the identification of the polymorphic variants of the genes of the renin–angiotensin–aldosterone system and ACE2 associated with a high risk of developing and worsening cardiovascular diseases may be one of the promising areas for the early diagnosis and prevention of post-COVID-19 changes. Therefore, all scientific interest research is aimed at studying genetic factors, such as single nucleotide polymorphisms that affect susceptibility to infection, severity of the disease course, and development of circulatory system consequences. In general, polymorphic variants of ACE and ACE2 and their interaction will help us understand this problem and systematize knowledge for further research in this area. All rights reserved © Eco-Vector, 2022.

Hematological changes as a consequence of COVID-19 and its vaccines / Alteraciones hematológicas como consecuencia de COVID-19 y sus vacunas

El virus SARS-CoV-2 continúa infectando a millones de individuos en el mundo. Aunque los síntomas más frecuentes observados en los pacientes con COVID-19 son fiebre, fatiga y tos, en los casos severos la hipercoagulabilidad y la inflamación son dos condiciones que pueden producir complicaciones y causar daño en órganos, poniendo en riesgo la vida del paciente. Con el fin de clasificar a los pacientes durante el triaje, se han explorado diferentes marcadores hematológicos, incluidos el recuento de plaquetas, linfocitos y eosinófilos, y la relación neutrófilos/ linfocitos, entre otros. Por su parte, para la evaluación de las coagulopatías, se vienen determinando marcadores como el dímero D y el fibrinógeno. En esta revisión se abordan las coagulopatías y los parámetros hematológicos en pacientes con COVID-19, al igual que las anormalidades en la coagulación como la trombocitopenia trombótica inmune inducida por las vacunas contra el SARS-CoV-2

The SARS-CoV-2 virus continues to infect millions of individuals around the world. Although the most frequent symptoms observed in patients with COVID-19 are fever, fatigue and cough, in severe cases hypercoagulability and inflammation are two conditions that can cause complications and organ failure, putting the patient's life at risk. In order to classify patients during triage, different hematological markers have been explored, including platelet, lymphocyte, and eosinophil counts, and the neutrophil/lymphocyte ratio, among others. Furthermore, for the evaluation of coagulopathies, markers such as D-dimer and fibrinogen are being evaluated. This review addresses the coagulopathies and hematological parameters in patients with COVID-19, as well as coagulation abnormalities such as immune thrombotic thrombocytopenia induced by SARS-CoV-2 vaccines

Association of d-dimer levels with in-hospital outcomes among COVID-19 positive patients: a developing country multicenter retrospective cohort.

D-dimer levels, which originate from the lysis of cross-linked fibrin, are serially measured during coronavirus disease 2019 illness to rule out hypercoagulability as well as a septic marker. Methods: This multicenter retrospective study was carried out in two tertiary care hospitals in Karachi, Pakistan. The study included adult patients admitted with a laboratory-confirmed coronavirus disease 2019 infection, with at least one measured d-dimer within 24 h following admission. Discharged patients were compared with the mortality group for survival analysis. Results: The study population of 813 patients had 68.5% males, with a median age of 57.0 years and 14.0 days of illness. The largest d-dimer elevation was between 0.51-2.00 mcg/ml (tertile 2) observed in 332 patients (40.8%), followed by 236 patients (29.2%) having values greater than 5.00 mcg/ml (tertile 4). Within 45 days of hospital stay, 230 patients (28.3%) died, with the majority in the ICU (53.9%). On multivariable logistic regression between d-dimer and mortality, the unadjusted (Model 1) had a higher d-dimer category (tertile 3 and tertile 4) associated with a higher risk of death (OR: 2.15; 95% CI: 1.02-4.54, P=0.044) and (OR: 4.74; 95% CI: 2.38-9.46, P<0.001). Adjustment for age, sex, and BMI (Model 2) yields only tertile 4 being significant (OR: 4.27; 95% CI: 2.06-8.86, P<0.001). Conclusion: Higher d-dimer levels were independently associated with a high risk of mortality. The added value of d-dimer in risk stratifying patients for mortality was not affected by invasive ventilation, ICU stays, length of hospital stays, or comorbidities.

Efficacy and safety of thrombolysis in COVID19 related ARDS.

INTRODUCTION: COVID19 causes significant pulmonary microthrombi in some individuals, which can lead to ARDS and death. Thrombolysis could be an effective approach in some patients with severe ARDS. We describe our experience with usage of thrombolytic agents in COVID19 critically ill patients, who were in worsening respiratory failure. METHODOLOGY: Retrospective chart analysis was done in patients who were thrombolysed between May 2020- Sept 2020. Analysis was done to find out factors associated with improvement in oxygenation and survival. RESULTS: Twenty seven patients with severe ARDS [all had respiratory rate >30, FiO2 >0.6(on NIV/HFNC) and PiO2/FiO2 ratio<120] were thrombolysed in our ICU for COVID19 causes. C.T. Pulmonary Angiography could not be done in any of the 27 patients due to poor general condition, but 2D echo was normal in most (5 had dilated RA,RV) and none of the patients was in shock. So there was no conventional indication of thrombolysis in these patients, yet after thrombolysis, we saw dramatic changes in oxygenation (defined by decrease in FiO2 by ≥0.2) in twenty patients. Five patients had major bleed. Eleven patients survived (survival rate of 40.7%) and survival rate was high { 66% (8/12)} in patients who were thrombolysed within 2 days of oxygen requirement. CONCLUSION: In this unprecedented pandemic with high mortality rates, efficacy of early thrombolysis needs to be further explored in randomised controlled trials.

COVID-19 Severity Shifts the Cytokine Milieu Toward a Proinflammatory State in Egyptian Patients: A Cross-Sectional Study.

Despite extensive research to decipher the immunological basis of coronavirus disease (COVID-19), limited evidence on immunological correlates of COVID-19 severity from MENA region and Egypt was reported. In a single-center cross-sectional study, we have analyzed 25 cytokines that are related to immunopathologic lung injury, cytokine storm, and coagulopathy in plasma samples from 78 hospitalized Egyptian COVID-19 patients in Tanta University Quarantine Hospital and 21 healthy control volunteers between April 2020 and September 2020. The enrolled patients were divided into 4 categories based on disease severity, namely mild, moderate, severe, and critically ill. Interestingly, interleukin (IL)-1-α, IL-2Rα, IL-6, IL-8, IL-18, tumor necrosis factor-alpha (TNF-α), FGF1, CCL2, and CXC10 levels were significantly altered in severe and/or critically ill patients. Moreover, principal component analysis (PCA) demonstrated that severe and critically ill COVID-19 patients cluster based on specific cytokine signatures that distinguish them from mild and moderate COVID-19 patients. Specifically, levels of IL-2Rα, IL-6, IL-10, IL-18, TNF-α, FGF1, and CXCL10 largely contribute to the observed differences between early and late stages of COVID-19 disease. Our PCA showed that the described immunological markers positively correlate with high D-dimer and C-reactive protein levels and inversely correlate with lymphocyte counts in severe and critically ill patients. These data suggest a disordered immune regulation, particularly in severe and critically ill Egyptian COVID-19 patients, manifested as overactivated innate immune and dysregulated T-helper1 responses. Additionally, our study emphasizes the importance of cytokine profiling to identify potentially predictive immunological signatures of COVID-19 disease severity.

Interrelationship between COVID-19 and Coagulopathy: Pathophysiological and Clinical Evidence.

Since the first description of COVID-19 infection, among clinical manifestations of the disease, including fever, dyspnea, cough, and fatigue, it was observed a high incidence of thromboembolic events potentially evolving towards acute respiratory distress syndrome (ARDS) and COVID-19-associated-coagulopathy (CAC). The hypercoagulation state is based on an interaction between thrombosis and inflammation. The so-called CAC represents a key aspect in the genesis of organ damage from SARS-CoV-2. The prothrombotic status of COVID-19 can be explained by the increase in coagulation levels of D-dimer, lymphocytes, fibrinogen, interleukin 6 (IL-6), and prothrombin time. Several mechanisms have been hypothesized to explain this hypercoagulable process such as inflammatory cytokine storm, platelet activation, endothelial dysfunction, and stasis for a long time. The purpose of this narrative review is to provide an overview of the current knowledge on the pathogenic mechanisms of coagulopathy that may characterize COVID-19 infection and inform on new areas of research. New vascular therapeutic strategies are also reviewed.

NLRP3 inflammasome and interleukin-1 contributions to COVID-19-associated coagulopathy and immunothrombosis.

Immunothrombosis - immune-mediated activation of coagulation - is protective against pathogens, but excessive immunothrombosis can result in pathological thrombosis and multiorgan damage, as in severe Coronavirus Disease 2019 (COVID-19). The NACHT-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome produces major proinflammatory cytokines of the interleukin (IL)-1 family, IL-1ß and IL-18, and induces pyroptotic cell death. Activation of the NLRP3 inflammasome pathway also promotes immunothrombotic programs including release of neutrophil extracellular traps and tissue factor by leukocytes, and prothrombotic responses by platelets and the vascular endothelium. NLRP3 inflammasome activation occurs in patients with COVID-19 pneumonia. In preclinical models, NLRP3 inflammasome pathway blockade restrains COVID-19-like hyperinflammation and pathology. Anakinra, recombinant human IL-1 receptor antagonist, showed safety and efficacy, and is approved for the treatment of hypoxemic COVID-19 patients with early signs of hyperinflammation. The non-selective NLRP3 inhibitor colchicine reduced hospitalization and death in a subgroup of COVID-19 outpatients, but is not approved for the treatment of COVID-19. Additional COVID-19 trials testing NLRP3 inflammasome pathway blockers are inconclusive or ongoing. We herein outline the contribution of immunothrombosis to COVID-19-associated coagulopathy, and review preclinical and clinical evidence suggesting an engagement of the NLRP3 inflammasome pathway in the immunothrombotic pathogenesis of COVID-19. We also summarize current efforts to target the NLRP3 inflammasome pathway in COVID-19, and discuss challenges, unmet gaps and the therapeutic potential that inflammasome-targeted strategies may provide for inflammation-driven thrombotic disorders including COVID-19.

Circulating Extracellular Vesicle Levels in Patients with Coronavirus Disease 2019 Coagulopathy: A Prospective Cohort Study.

Coronavirus disease 2019 (COVID-19) is associated with coagulopathy. However, the underlying mechanisms are not completely understood. We evaluated the association between COVID-19 coagulopathy and extracellular vesicle (EV) levels. We hypothesized that several EV levels would be higher in COVID-19 coagulopathy patients than in non-coagulopathy patients. This prospective observational study was conducted in four tertiary care faculties in Japan. We enrolled 99 COVID-19 patients (48 with coagulopathy and 51 without coagulopathy) aged ≥20 years who required hospitalization, and 10 healthy volunteers; we divided the patients into coagulopathy and non-coagulopathy groups according to the D-dimer levels (≥1 µg/mL and <1 µg/mL, respectively). We used flow cytometry to measure the tissue-factor-bearing, endothelium-derived, platelet-derived, monocyte-derived, and neutrophil-derived EV levels in platelet-free plasma. The EV levels were compared between the two COVID-19 groups as well as among the coagulopathy patients, non-coagulopathy patients, and healthy volunteers. No significant difference was found in EV levels between the two groups. Meanwhile, the cluster of differentiation (CD) 41 + EV levels were significantly higher in COVID-19 coagulopathy patients than in healthy volunteers (549.90 [255.05-984.65] vs. 184.3 [150.1-254.1] counts/µL, p = 0.011). Therefore, CD41+ EVs might play an essential role in COVID-19 coagulopathy development.

Platelet-neutrophil interaction in COVID-19 and vaccine-induced thrombotic thrombocytopenia.

Coronavirus disease 2019 (COVID-19) is known to commonly induce a thrombotic diathesis, particularly in severely affected individuals. So far, this COVID-19-associated coagulopathy (CAC) has been partially explained by hyperactivated platelets as well as by the prothrombotic effects of neutrophil extracellular traps (NETs) released from neutrophils. However, precise insight into the bidirectional relationship between platelets and neutrophils in the pathophysiology of CAC still lags behind. Vaccine-induced thrombotic thrombocytopenia (VITT) is a rare autoimmune disorder caused by auto-antibody formation in response to immunization with adenoviral vector vaccines. VITT is associated with life-threatening thromboembolic events and thus, high fatality rates. Our concept of the thrombophilia observed in VITT is relatively new, hence a better understanding could help in the management of such patients with the potential to also prevent VITT. In this review we aim to summarize the current knowledge on platelet-neutrophil interplay in COVID-19 and VITT.

Common Coagulopathies Associated With COVID-19 Patients.

The coronavirus disease 2019 (COVID-19) outbreak, which first appeared in the Chinese province of Hubei city of Wuhan, has been spreading internationally since December 2019. The World Health Organization (WHO) declared the coronavirus illness from 2019 to be a pandemic on March 11, 2020. Patients hospitalised with severe coronavirus or comorbid conditions (like cardiovascular disease and obesity) are linked to a worse prognosis. The rise in D-dimer and its relationship to prognosis are the most often documented aberrations in coagulation/fibrinolysis in COVID-19. However, the D-dimer assessment's utility is not limitless. Since the coagulation/fibrinolytic state might occasionally change over a short period of time, routine exams are also advantageous in understanding the relevance of the inquiry. Both thrombotic and hemorrhagic diseases should be taken into consideration, despite the fact that the pathophysiology of disseminated intravascular coagulation (DIC) linked with coronavirus disease 19 differs significantly from that of septic disseminated intravascular coagulation. Coagulation as well as fibrinolysis indicators are used to make the diagnosis of COVID-19 thrombosis, which encompasses both macro- and micro-thrombosis. Compared to bacterial-sepsis-associated coagulopathy/DIC, COVID-19 has a lower prevalence of prolonged prothrombin time, activated partial thromboplastin time, and decreased antithrombin activity. However, the causes of coagulopathy remain poorly understood. Hypoxia, endothelial injury, dysregulated immunological responses mediated by inflammatory cytokines, and lymphocyte cell death are thought to be implicated. While blood loss tends to be rare, it is uncertain if COVID-19 suffers from thrombosis or whether the current recommendations for regular venous thromboembolic dose are appropriate. It is important to decide on the COVID-19 therapy phases. Antiviral therapy, cytokine storm therapy, and thrombosis therapy are the steps. Future advancements are predicted, such as a therapy that combines heparin and nafamostat.

Impact of SARS-CoV-2 Infection on Unvaccinated Pregnant Women: Non-Reassuring Fetal Heart Rate Tracing Because of Placentitis.

In 2020, a new coronavirus, called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in China. SARS-CoV-2 infection has been shown to be highly morbid in pregnant women, being a risk factor for several obstetric conditions leading to increased maternal and neonatal mortality. A few studies since 2020 have shown SARS-CoV-2 maternal-fetal transmission and noted placental abnormalities grouped under the term placentitis. We hypothesized that these placental lesions could be responsible for abnormalities in placental exchange and therefore abnormalities in cardiotocographic monitoring, leading to premature fetal extraction. The objective is to identify the clinical, biochemical, and histological determinants associated with the occurrence of non-reassuring fetal heart rate (NRFHR) outside labor in fetuses of SARS-CoV-2-infected mothers. We conducted a retrospective multicenter case series of the natural history of maternal SARS-CoV-2 infections resulting in fetal delivery outside labor due to NRFHR. Collaboration was sought with the maternity hospitals in the CEGORIF, the APHP and Brussels hospitals. The investigators were contacted by e-mail on three successive occasions over a period of one year. Data from 17 mothers and 17 fetuses were analyzed. Most women had a mild SARS-CoV-2 infection; only two women presented severe infection. No woman was vaccinated. We found a substantial proportion of maternal coagulopathy at birth: elevation of APTT ratio (62%), thrombocytopenia (41%) and liver cytolysis (58.3%). Iatrogenic prematurity was noted in 15 of 17 fetuses, and 100% were born by cesarean delivery due to emergency criteria. One male neonate died on the day of birth due to peripartum asphyxia. Three cases of maternal-fetal transmission were recorded following WHO criteria. Placental analysis in 15 cases revealed eight cases of SARS-CoV-2 placentitis, causing placental insufficiency. In total, 100% of the placentas analyzed showed at least one lesion suggestive of placentitis. SARS-CoV-2 maternal infection during pregnancy is likely to generate neonatal morbidity in relation to placental damage resulting in placental insufficiency. This morbidity may be the consequence of induced prematurity as well as acidosis in the most severe situations. Placental damage occurred in unvaccinated women and in women with no identified risk factor, in contrast to severe maternal clinical forms.

Is post-COVID osteonecrosis of jaw (PCONJ) Masquerading as osteomyelitis ? A largest unicentric report of 13 cases

Objective The purpose of this study was to ascertain the correlation between COVID-19 infection and jaw osteonecrosis, along with the identification of risk factors that could be associated with the development of the condition. Another aim of our study is to establish whether maxillofacial osteonecrosis is an early or late complication seen in COVID-19 patients. Material and method This was a retrospective study conducted over a period of two years. Case records of patients with a history of severe COVID and steroid treatment who later developed jaw osteonecrosis were evaluated. Result 13 patients with an age range from 8 years to 70 years were identified. Osteonecrosis was seen as late as 21 months after COVID-19. The majority of the cases involved maxilla, one case was of bi-jaw involvement, and one case presented with isolated mandibular involvement. 6 patients were diabetic and 11 patients gave a history of provocative dental treatment like extraction. Conclusion A triad of post-COVID coagulopathy, steroid administration, and a provocative dental treatment may contribute to jaw osteonecrosis which may be seen in patients without pre-existing systemic illness and may present as late as 21 months after COVID-19.

The Effects of 10,000 IU Vitamin D Supplementation on Improvement of Clinical Outcomes, Inflammatory and Coagulation Markers in Moderate COVID-19 Patients: A Randomized-Controlled Trial

Background & aims: Vitamin D supplementation as an immunomodulator has been identified as a potential strat-egy to prevent and treat Coronavirus disease 2019 (COVID-19). We aimed to analyze the effect of 10,000 IU vitamin D3 supplementation on 25(OH)D levels on primary clinical out-comes (conversion length), inflammatory markers (Total Lymphocyte Count (TLC), Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR)) and coagulation marker (D-Dimer) in moderate COVID-19 patients at Wahidin Sudirohusodo Hospital, Makassar, Indonesia.Methods: We conducted a single-blind randomized -con-trolled trial on the confirmed moderate COVID-19 patients above 18 years old and low vitamin D status. Each of inter-vention and control groups were supplemented of 10,000 IU and 1000 IU cholecalciferol that taken daily for 2 weeks. Levels of 25(OH)D were analyzed for the primary endpoint (conversion length), then correlated to secondary endpoints (Length of Stay (LOS)), clinical manifestations improvement, and markers TLC, NLR, PLR, and D-Dimer serum, handgrip strength (HGS) as functional capacity measurement, after ad-justed to age, sex, nutritional status based on body mass in- dex (BMI) and Subjective Global Assessment (SGA) tool, co -morbidities, and anti-coagulant administration. Medical nutri-tional therapy was given and presented as energy, protein, carbohydrate, and fat achievement, and vitamin D intake was also calculated.Results: A significant effects was found in 60 samples with pre-intervention vitamin D deficiency (61.7%) and insuffi-ciency (38.3%) status, and 10,000 IU of vitamin D3 supple-mentation could increase 25(OH)D levels within 2 weeks to reach sufficiency status (16.7%). The Vitamin D3 supplemen-tation of 10,000 IU and 1000 IU could significantly increase 25(OH)D levels compared to the control group of 1000 IU (4.61 +/- 5.43 vs.-0.29 +/- 2.72;P <0.0001) and it was correlated to primary clinical outcome, which is length of conversion (6.53 +/- 1.17 vs 10.47 +/- 2.56;P < 0.0001). The increase in HGS (6.61 +/- 3.01 vs. 4.04 +/- 4.44;P = 0.011), LOS (11.63 +/- 2.5 vs. 14.73 +/- 3.45;P = 0.001), and improvement in clinical mani-festations were found to be significant in both groups. We an-alyzed changes the effect of vitamin D supplementation in TLC, NLR, and D-Dimer as marker of coagulopathy associated COVID-19 on both groups that showed were not significant. Positive and significant correlation was only showed on PLR levels after intervention (r=0.368;P=0.045).Conclusion: Supplementation of vitamin D3 10,000 IU in moderate COVID-19 patients had a significant effect on 25(OH)D level, length of conversion, LOS, functional capacity, and PLR levels, but it has negative correlation in TLC, NLR, and D-Dimer levels.This study has been registered in the ClinicalTrial.gov data-base with the identification number NCT05126602.

COVID-19 associated coagulopathy: A bibliometric investigation.

Infection with SARS-CoV-2 initiates an immune-hemostatic response. While both systems are intimately connected and necessary for an efficient immune response to contain the infection, excessive coagulation activation might exceed the valuable benefits by causing thrombotic consequences and excessive inflammation. This biological response is new to clinicians and researchers, and accordingly, tremendous studies have been conducted on coagulopathy and its relationship to COVID-19 disease during this pandemic. Therefore, it takes a research insight from a bibliometric perspective to determine research hotspots and trends of COVID-19 associated coagulopathy (C19-CA). The analysis relies on the Scopus database for bibliographic content and Visualization of Similarities viewer software to map bibliometric data of C19-CA. Our study finds the most eminent authors, journals, institutions, funding organizations, and countries that publish in the C19-CA. Additionally; this research employs bibliometric analysis of co-authorship, co-citations, bibliographic coupling, and co-occurrence of keywords. A total of 2242 studies were retrieved, and the number of annual publications of C19-CA showed remarkable growth. The top-publishing authors on C19-CA are Smadja, D.M., Diehl, J.L., and Gendron, N (France). The total number of articles published in English in these three years was 1241, with the original article accounting for 99.8% and conference papers accounting for 0.2%. Huazhong University of Science and Technology (China) is the top-productive institution, with the US being the top-publishing country. Journal of Thrombosis and Thrombolysis received the highest number of original articles. The research results were mainly published in the fields of Medicine, Biochemistry, Genetics, and Molecular Biology, Immunology and Microbiology. Yuanyuan Li, who is (China), is the top-collaborating author. China and its authors have the highest number of citations. Keywords' co-occurrence analyses of the authors and all keywords revealed the following themes in C19-CA; abnormal coagulation parameters, pulmonary coagulopathy, venous and arterial thrombotic disorders, distinct features of coagulopathy, inflammation, and thrombosis in COVID-19, and anticoagulants and thrombolytic therapies. By combining bibliometric analysis with VOSviewer software, we identified C19-CA's leaders, collaborating institutions, and research hotspots, as well as give references for future research paths.

Treatment of coronavirus disease 2019: Timing determines prognosis

The global epidemic of coronavirus disease 2019 (COVID-19) is still growing. The response to this emerging disease should be considered with the context of its clinical characteristics and pathophysiological mechanisms. Although available therapeutic options are still very limited, current experience has suggested that the choice of clinical strategies should be based upon the disease stage and immune functions of the patients. The present article reviews the clinical characteristics of COVID-19 and current evidence of various treatment approaches. Combined with first-line experience, we summarize the current clinical strategies for COVID-19 management based on disease progress and staging.Copyright © 2021, Peking Union Medical College Hospital. All rights reserved.

Morphological Changes in Blood Cells as Indicators for Disease Progression in COVID-19

BACKGROUND: COVID-19 as a pandemic has caused an alarming increase in mortality and morbidity. Viral-induced morphologic changes in the peripheral blood cells are well characterized in certain infections and can direct diagnostic workup to ensure timely therapeutic intervention. This study describes the morphological changes of blood cells in various stages of COVID disease. MATERIALS AND METHODS: A total of thousand COVID-positive patients admitted in the tertiary care center were taken for the study. They were classified as mild, moderate, and severe based on the clinical criteria suggested by World Health Organization. Peripheral smears of the patients were analyzed, and the morphological changes in various blood cells were correlated with the disease stage and coagulation parameters. RESULT(S): The study demonstrated significant morphological changes in the blood cells of COVID patients during the course of disease progression and during the onset of COVID-associated coagulopathy. Leukocytosis, neutrophilia, and toxic changes in neutrophils were seen in the severe stage of the disease and in COVID coagulopathy suggesting these are important indicators of disease severity. Activated lymphocyte was found to be the most common morphological presentation seen in all patients irrespective of the disease stage, whereas plasmacytoid lymphocytes were an important finding in severe-stage disease. Schistocytes an important finding in any other coagulopathy was present only in 1% of cases of COVID coagulopathy. CONCLUSION(S): The study demonstrated significant morphological changes in the blood cells of COVID-positive patients during the course of disease progression. Comprehensive daily complete blood count and peripheral smear examination should be undertaken in patients hospitalized with COVID-19 to predict potential clinical deterioration and signs of disease progression. These morphological changes in peripheral smear can be used as one of the factors indicating disease progression which can formulate for further evaluation. Since follow-up and post-COVID morphological examination were not done, additional research in this aspect can shed light on the clinical categorization of COVID patients based on the morphological findings.Copyright © 2023 Journal of Applied Hematology Published by Wolters Kluwer - Medknow.

COVID-19-Associated Coagulopathy: Ascending Aortic Thrombus.

The mechanism of arterial thrombosis in coronavirus disease 2019 (COVID-19) is not completely understood and is attributed to the complex interactions of endothelial injury, platelet hyperactivation, and activated pro-inflammatory cytokines. Management strategies may include a combination of surgery and anticoagulation, or anticoagulation alone. A 56-year-old woman with recent COVID-19 infection presented with chest pain and dyspnea. Chest CT angiography (CTA) and aortic magnetic resonance imaging revealed an intraluminal thrombus in the mid ascending aorta. A multidisciplinary team decided on heparin infusion. She was transitioned to apixaban and a three-month interval outpatient CTA revealed complete resolution of the aortic thrombus.

Therapeutic approaches for intravascular microthrombi-induced acute respiratory distress syndrome (ARDS) in COVID-19 infection.

The COVID-19 pandemic has overwhelmed our health care capacity in an unprecedented way due to the sheer number of critically infected patients admitted to hospitals during the last two years. Endothelial injury is seen as one of the central hallmarks of COVID-19 infection that is the starting point in the generation of microthrombi and sepsis eventually leading to acute respiratory distress syndrome (ARDs) and multi-organ failure. The dramatic fall in lung function during ARDs is attributed to the microthrombi-induced coagulopathy primed by a hyperactive immune system. Due to the lack of effective antiviral agents, the line of treatment is limited to the management of two key risk factors i.e., immune activation and coagulopathy. In the present review, we describe the mechanistic role, therapeutic targets and opportunities to control immune activation and coagulopathy during the pathogenesis of COVID-19-induced ARDs.