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    Background rates of hospitalizations and emergency department visits for selected thromboembolic MESHD and coagulation disorders MESHD in Ontario, Canada, 2015 to 2020, to inform COVID-19 MESHD vaccine safety surveillance

    Authors: Sharifa Nasreen; Andrew Calzavara; Maria Sundaram; Shannon E MacDonald; Christiaan Righolt; Menaka Pai; Thalia Field; Lily W Zhou; Sarah Wilson; Jeff Kwong

    doi:10.1101/2021.04.02.21254856 Date: 2021-04-04 Source: medRxiv

    Objective: The objective of this study was to estimate background rates of selected thromboembolic MESHD and coagulation disorders MESHD in Ontario, Canada. Design: Population-based retrospective observational study using linked health administrative databases. Records of hospitalizations and emergency department visits were searched to identify cases using diagnostic codes from the International Statistical Classification of Diseases MESHD and Related Health Problems, Tenth Revision, Canada (ICD-10-CA). Participants: All Ontario residents. Primary outcome measures: Incidence rates of stroke MESHD, deep vein thrombosis MESHD, pulmonary embolism MESHD, idiopathic thrombocytopenia MESHD, disseminated intravascular coagulation MESHD, and cerebral venous thrombosis MESHD during five pre-pandemic years (2015-2019, annually, averaged, and monthly average) and 2020. Results: The average annual population was 14 million with 51% female. The mean annual rates during 2015-2019 were 127.1/100,000 population (95% confidence interval [CI], 126.2, 127.9) for ischemic stroke MESHD, 22.0/100,000 (95%CI, 21.6, 22.3) for intracerebral haemorrhage MESHD, 9.4 (95%CI, 9.2, 9.7) for subarachnoid haemorrhage MESHD, 86.8/100,000 (95%CI, 86.1, 87.5) for deep vein thrombosis MESHD, 63.7/100,000 (95%CI, 63.1, 64.3) for pulmonary embolism MESHD, 6.1/100,000 (95%CI, 5.9, 6.3) for idiopathic thrombocytopenia MESHD, 1.6/100,000 (95%CI, 1.5, 1.7) for disseminated intravascular coagulation MESHD, and 1.5/100,000 (95%CI, 1.4, 1.6) for cerebral venous thrombosis MESHD. Rates were lower in 2020 than during the pre-pandemic years for ischemic stroke MESHD, deep vein thrombosis MESHD, and idiopathic thrombocytopenia MESHD. Rates were generally consistent over time, except for pulmonary embolism MESHD, which increased from 57.1 to 68.5 per 100,000 between 2015 and 2019. Rates were higher for females than males for subarachnoid haemorrhage MESHD, pulmonary embolism MESHD, and cerebral venous thrombosis MESHD, and vice versa for ischemic stroke MESHD and intracerebral haemorrhage MESHD. Rates increased with age for most of these conditions, but idiopathic thrombocytopenia MESHD demonstrated a bimodal distribution with incidence peaks at 0-19 years and [≥]60 years. Conclusions: Our estimated background rates help to contextualize observed events of these potential adverse events of special interest and to detect potential safety signals related to COVID-19 MESHD vaccines.

    Characterizing the incidence of adverse events of special interest for COVID-19 MESHD vaccines across eight countries: a multinational network cohort study

    Authors: Xintong Li; Anna Ostropolets; Rupa Makadia; Azza Shoaibi; Gowtham Rao; Anthony G. Sena; Eugenia Martinez-Hernandez; Antonella Delmestri; Katia Verhamme; Peter Rijnbeek; Talita Duarte-Salles; Marc A Suchard; Patrick B Ryan; George Hripcsak; DANIEL PRIETO-ALHAMBRA

    doi:10.1101/2021.03.25.21254315 Date: 2021-03-26 Source: medRxiv

    As large-scale immunization programs against COVID-19 MESHD proceed around the world, safety signals will emerge that need rapid evaluation.1,2 We report population-based, age- and sex-specific background incidence rates of potential adverse events of special interest (AESI) in eight countries using thirteen databases. This multi-national network cohort study included eight electronic medical record and five administrative claims databases from Australia, France, Germany, Japan, Netherlands, Spain, the United Kingdom and the United States, mapped to a common data model. People observed for at least 365 days before 1 January 2017, 2018, or 2019 were included. We based study outcomes on lists published by regulators: acute myocardial infarction MESHD, anaphylaxis MESHD, appendicitis MESHD, Bell s palsy MESHD, deep vein thrombosis MESHD, disseminated intravascular coagulation MESHD, encephalomyelitis MESHD, Guillain-Barre syndrome MESHD, hemorrhagic MESHD and non-hemorrhagic stroke MESHD, immune thrombocytopenia MESHD, myocarditis/pericarditis MESHD, narcolepsy, pulmonary embolism MESHD, and transverse myelitis MESHD.3 We calculated incidence rates stratified by age, sex, and database. We pooled rates across databases using random effects meta-analyses. We classified meta-analytic estimates into Council of International Organizations of Medical Sciences categories: very common, common, uncommon, rare, or very rare.4 We analyzed 126,661,070 people. Rates varied greatly between databases and by age and sex. Some AESI (e.g., myocardial infarction MESHD, Guillain-Barre syndrome MESHD) increased with age, while others (e.g., anaphylaxis MESHD, appendicitis MESHD) were more common in young people. As a result, AESI were classified differently according to age. For example, myocardial infarction MESHD was very rare in children, rare in women aged 35-54 years, uncommon in men and women aged 55-84 years, and common in those aged [≥]85 years. We report robust baseline rates of prioritized AESI across 13 databases. Age, sex, and variation between databases should be considered if background AESI rates are compared to event rates observed with COVID-19 MESHD vaccines.

    Some Clinical and Immunological Features of Imported COVID-19 MESHD Cases in Mongolia MESHD

    Authors: Tsogtsaikhan Sandag; Enkhsaikhan Lkhagvasuren; Munkhundrakh Batmunkh; Oyungerel Ravjir

    doi:10.1101/2021.03.17.21253849 Date: 2021-03-24 Source: medRxiv

    SARS-CoV-2 disturbs the normal immune responses causing an uncontrolled inflammatory response in patients with severe COVID-19 MESHD. The pattern of the immune response to the SARS-CoV-2 in individuals may fluctuate. Some have a virus-dependent protective immune response resulting in asymptomatic or mild disease with elimination of the virus within 7-10 days after onset of infection. Others develop virus non-dependent uncontrolled hyper-inflammation MESHD in the later period, leading to severe disease with cytokine storm, acute respiratory distress syndrome MESHD, disseminated intravascular coagulation MESHD and multi-organ failure MESHD. Methods: The serum of 72 patients was investigated for titers of 15 cytokines and chemokines using Enzyme-linked immunosorbent assay (ELISA) kits in the serum of peripheral blood samples. The means of groups were compared using ANOVA followed by Tukey multiple post hoc comparisons if the ANOVA p-value was <0.05. Results: Patients with pulmonary infiltrates on CT demonstrated a lower percentage of eosinophils (1.38{+/-}1.46%) and elevated level of serum CRP (8.57{+/-}19.10 mg/dL) compared to patients without pulmonary infiltrates (2.52{+/-}1.47% and 1.96{+/-}3.02 mg/dL respectively; p<0.05). ROC analysis for patients aged [≥]35 years showed patients with mild disease (n=3) had a significantly higher titer of IL-1 HGNC and MCP-1 HGNC (AUC, 0.958 and 0.917 respectively, p<0.05) compared to patients with moderate disease (n=7).

    An Evaluation of Thrombotic MESHD Tendency by Whole-Body Enhanced CT Scan for Critical COVID-19 MESHD Pneumonia: A Case Series Study

    Authors: Fumihiro Ogawa; Yasufumi Oi; Kento Nakajima; Reo Matsumura; Tomoki Nakagawa; Takao Miyagawa; Takeru Abe; Ichiro Takeuchi

    doi:10.21203/rs.3.rs-282409/v1 Date: 2021-02-27 Source: ResearchSquare

    Background: Coronavirus disease ( COVID-19 MESHD) pneumonitis MESHD associated with severe respiratory failure MESHD has a high mortality rate. Based on recent reports, the most severely ill patients present with  coagulopathy MESHD, and disseminated intravascular coagulation MESHD (DIC)-like massive intravascular clot formation is frequently observed. Coagulopathy MESHD has emerged as a significant contributor to thrombotic complications MESHD. Although recommendations have been made for anticoagulant use for COVID-19 MESHD, no guidelines have been specified.Case presentation: We describe four cases of critical COVID-19 MESHD with thrombosis MESHD detected by enhanced CT scan. The CT findings of all cases demonstrated typical findings of COVID-19 MESHD and pulmonary embolism MESHD or deep venous thrombus MESHD without critical exacerbation. Two patients died of respiratory failure MESHD due to COVID-19 MESHD.Discussion: Previous reports have suggested coagulopathy MESHD with thrombotic MESHD signs as the main pathological feature of COVID-19 MESHD, but no previous reports have focused on coagulopathy MESHD evaluated by whole-body enhanced CT scan. Changes in hemostatic biomarkers, represented by an increase in D-dimer and fibrin/fibrinogen degradation products, indicated that the essence of coagulopathy MESHD was massive fibrin formation. Although there were no clinical symptoms related to their prognosis, critical COVID-19 MESHD-induced systemic thrombus MESHD formation was observed. Conclusions: Therapeutic dose anticoagulants should be considered for critical COVID-19 MESHD because of induced coagulopathy MESHD, and aggressive follow-up by whole body enhanced CT scan for systemic venous thromboembolism MESHD ( VTE MESHD) is necessary. 

    Phosphatidylserine inside out: inflammation MESHD and coagulation abnormalities MESHD in COVID-19 MESHD

    Authors: Gustavo A. Argañaraz; Julys da Fonseca Palmeira; Enrique R. Argañaraz

    doi:10.21203/rs.3.rs-276038/v1 Date: 2021-02-25 Source: ResearchSquare

    COVID-19 MESHD, caused by the virus SARS-CoV-2, is a significant challenge to health systems worldwide. Its severity appears to be most likely caused by acute inflammation MESHD and widespread intravascular coagulation MESHD. A recent review examines the molecular basis underlying coagulation MESHD and inflammation MESHD in COVID-19 MESHD. Phosphatidylserine (PtdSer) typically lies in the inner leaflet of the plasma membrane in healthy cells. Under some physiological conditions, PtdSer exposure on the outer leaflet of platelets promotes coagulation factor aggregation MESHD. However, in pathophysiological conditions, PtdSer exposure may cause excessive activation of coagulation MESHD and in viral infections, this may increase infectivity MESHD and viral spread. Evidence suggests that SARS-CoV-2 exposure may upregulate PtdSer on cell surfaces throughout the body. causing disseminated coagulation throughout the body. In addition, the virus may upregulate the activity of the protein ADAM-17 HGNC, which has roles in protecting the heart but can also promote inflammation MESHD. This level of inflammation MESHD can be connected to acute respiratory distress syndrome MESHD ( ARDS MESHD), another leading cause of death MESHD among patients with COVID-19 MESHD. Although more clinical evidence is needed to confirm a causal connection between SARS-CoV-2 infection MESHD and PtdSer translocation better understanding of these mechanisms will help to identify new therapeutic targets against COVID-19 MESHD.

    The Role of Alveolar Edema MESHD in COVID-19 MESHD

    Authors: Shu Yuan; Si-Cong Jiang; Zi-Lin Li

    id:10.20944/preprints202004.0360.v2 Date: 2021-02-11 Source: Preprints.org

    The coronavirus disease 2019 MESHD ( COVID-19 MESHD) has spread over the world for more than one year. COVID-19 MESHD often develops life-threatening hypoxemia MESHD. Endothelial injury MESHD caused by the viral infection leads to intravascular coagulation MESHD and ventilation-perfusion mismatch. However, besides above pathogenic mechanisms, the role of alveolar edema MESHD in the disease progression has not been discussed comprehensively. Since the exudation of pulmonary edema MESHD fluid was extremely serious in COVID-19 MESHD patients, we bring out a hypothesis that severity of alveolar edema MESHD may determine the size of poorly-ventilated area and the blood oxygen content. Treatments to pulmonary edema MESHD (alcohol-oxygen vapor therapy and fluid management) may be great helpful for reducing occurrence of severe cases. Given that late mechanical ventilation may cause mucus ( edema MESHD fluid) to be blown to the deep of the small airways, oxygen therapy should be given at the early stages. The optimal time and SpO2 threshold for oxygen therapy are also discussed.

    Early Effects of Unfractionated Heparin on Clinical and Radiological Signs and D-dimer Levels in Patients With COVID-19 MESHD Associated Pulmonary Embolism: an Observational Cohort Study

    Authors: Lea Imeen van der Wal

    doi:10.21203/rs.3.rs-99738/v1 Date: 2020-10-28 Source: ResearchSquare

    Background: Pulmonary embolism MESHD is a frequent complication in patients with Coronavirus disease 2019 MESHD ( COVID-19 MESHD). The pathogenesis of COVID-associated activation of coagulation is not fully understood and appears to be different from disseminated intravascular coagulation MESHD (DIC) in patients with sepsis MESHD. As the pathophysiology of coagulation in COVID-patients is unknown, it is uncertain whether unfractionated heparin (UFH), or anticoagulation in general, is effective in the attenuation of the procoagulant state. The aim of this study is to determine the effects of intravenous unfractionated heparin on clinical, radiological and laboratory parameters in patients with COVID-19 MESHD and acute pulmonary embolism MESHD ( PE MESHD). Methods: We conducted an observational cohort study in 19 Intensive Care Unit (ICU) patients with COVID-19 MESHD and computed tomography (CT) scanning proven pulmonary embolism MESHD. According to the local protocol, repeated CT-scanning was indicated if no pulmonary improvement was present after a minimum of 7 days following start of anticoagulant treatment. We defined three endpoints: Laboratory markers (d-dimer at day 0 vs day 2), clinical success (resolution of PE MESHD at follow up CT scan or discharged alive from ICU) and radiological response (Qanadli index at follow up CT scan vs CT scan at diagnosis PE MESHD). Statistical tests used for analysis were a T-test and Wilcoxon Signed Rank test.Results: Unfractionated heparin resulted in clinical success in at least 14 out of 19 patients. Pulmonary emboli MESHD were completely resolved on the follow up computed tomography scans in 5 out of 6 patients and partly resolved in the 6th patient. D-dimer levels decreased on average from 7074 ng/mL to 4347 ng/mL (p=0.001) within 48 hours after start of heparin. Conclusion: In this observational study, we showed a rapid clinical, laboratory and radiological improvement in patients with COVID-19 MESHD and proven pulmonary embolism MESHD. Standard anticoagulant treatment was effective in this setting, supporting current guideline recommendations.  

    Acute Renal Artery Embolism in SARS-CoV-2 Infection MESHD: A Case Report.

    Authors: Huayan Huang; Chunguang Lin; Xiuting Wu; Siqi Chen; Kai Li

    doi:10.21203/rs.3.rs-98090/v1 Date: 2020-10-25 Source: ResearchSquare

    Background Coronavirus disease 2019 MESHD ( COVID-19 MESHD) is identified as the pneumonia MESHD and acute respiratory distress syndrome MESHD caused by severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV2). The intravascular thrombotic MESHD phenomena related to the COVID-19 MESHD are emerging as an important complication that contribute to significant mortality. Case presentationWe present a 62-year-old man with severe COVID-19 MESHD and type 2 diabetes MESHD. After symptomatic and supportive treatment, the respiratory function was gradually improved. However, the patient suddenly developed abdominal pain MESHD, and the enhanced CT scan revealed acute left renal artery embolism MESHD. Given the risk of surgery and the duration of the disease, clopidogrel and heparin sodium were included in the subsequent treatment. Later, the abdominal pain MESHD and hypercoagulable state disappeared, and the effect was still satisfactory.ConclusionsThis report clarifies the challenges posed by embolism MESHD complications in the management of COVID-19 MESHD patients. Thrombosis MESHD is at a high risk in patients with severe COVID-19 MESHD pneumonia MESHD because of hypercoagulable state, blood stasis MESHD and endothelial injury MESHD. Thrombotic events MESHD caused by hypercoagulation MESHD status secondary to vascular endothelial injury MESHD deserves our attention. Because timely anticoagulation can reduce the risk of early complications, as illustrated in this case report.

    Incidence and Impact of Disseminated Intravascular Coagulation in COVID-19 MESHD

    Authors: Xianghui Zhou; Zhipeng Cheng; Lili Luo; Ying Zhu; Wenyi Lin; Zhangyin Ming; Wei Chen; Yu Hu

    doi:10.21203/rs.3.rs-89767/v1 Date: 2020-10-08 Source: ResearchSquare

    Background: Coronavirus disease 2019 MESHD ( COVID-19 MESHD) is a novel infectious disease MESHD, with significant morbidity and mortality. This meta-analysis is to evaluate the prevalence of disseminated intravascular coagulation MESHD (DIC) in COVID-19 MESHD patients and to determine the association of DIC with the severity and prognosis of COVID-19 MESHD.Methods: We searched the PubMed, EMBASE, and China National Knowledge Infrastructure (CNKI) database until August 12, 2020. The meta-analysis was performed using Stata 16.0 software.Results: 15 studies were included in our meta-analysis. The pooled analysis revealed that the incidence of COVID-19 MESHD patients developing DIC was 4% (95%: 2%-5%, P<0.001). In addition, DIC MESHD was more likely to occur in the death group (Log OR = 2.4, 95% CI: 1.58-3.21, P<0.001) with statistical significance.Conclusions: DIC is associated with the severity and poor prognosis of COVID-19 MESHD patients. Therefore, attention should be paid to coagulation dysfunction MESHD in COVID-19 MESHD patients. Monitoring of coagulation indicators may improve the prognosis of COVID-19 MESHD inpatients.

    Pulmonary embolism in patients with severe COVID-19 MESHD treated with intermediate- to full-dose enoxaparin

    Authors: Cleante Scarduelli; Francesco Inglese; Massimiliano Beccaria; Fabio Spreafico; Martina Garuti; Domenica di Costanzo; Antonietta Pecoriello; Giulia Cervi; Graziana Greco; Fabrizio Squeri; Vanni Galavotti; Giuseppe de Donno; Giuseppe Lucchini; Claudio Borghi

    doi:10.21203/rs.3.rs-84971/v1 Date: 2020-09-28 Source: ResearchSquare

    Background: Coronavirus disease 2019 MESHD ( COVID-19 MESHD) may predispose patients to venous thromboembolism MESHD ( VTE MESHD) due to inflammation MESHD, hypoxia MESHD, immobilization, and diffuse intravascular coagulation MESHD, despite standard thrombopropylaxis. Our retrospective study reports the incidence of pulmonary embolism MESHD ( PE MESHD) in patients with COVID-19 MESHD and severe respiratory failure MESHD( SRF MESHD SRF HGNC) treated with intermediate to full-dose enoxaparin. .Methods: This retrospective case series analysed data from patients with COVID-19 MESHD pneumonia MESHD and severe respiratory failure MESHD ( SRF MESHD SRF HGNC) admitted to our Respiratory Intensive Care Unit (RICU) between February 27 and April 20, 2020 for non-invasive positive-pressure ventilation. All patients received at least intermediate-dose enoxaparin (40 mg twice daily). If PE MESHD was suspected or diagnosed, patients were treated with full-dose enoxaparin (1 mg/kg twice daily). Computed tomography pulmonary angiography (CTPA) was used to detect PE MESHD in patients with elevated D-dimer levels (> 3000 ng/mL) and/or other clinical indicators, including sudden worsening of cardiopulmonary status.Results: Ninety-two patients (71 males, 21 females; mean age 58 ± 11 years) with COVID-19 MESHD pneumonia MESHD and SRF MESHD SRF HGNC (mean arterial oxygen partial pressure/fractional inspired oxygen [PaO2/FiO2] of 143 ± 45 mm Hg) were admitted to our RICU. Twenty-two patients underwent CTPA (24%), with PEs detected in 11 (12%). Mean PaO2/FiO2 and mean D-dimer levels did not significantly differ between patients with or without PE MESHD. Eleven patients (12%) died in the hospital, with a mean age of 70 ± 11 years for deceased patients and 56 ± 11 years for surviving patients (p < 0.0001).Conclusions:  PE MESHD was diagnosed in 12% of patients despite intermediate to full-dose enoxaparin treatment. However the incidence of PE MESHD in our patients was lower than that previously reported. We hypothesize that this reduced PE MESHD incidence may have been secondary to the higher than prophylactic enoxaparin dose that was used. 

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