Events In COVID-19 Patients Research Articles

Hereditary thrombophilia as a possible risk factor for severe disease in COVID-19: a case series.

The risk factors that modulate one's susceptibility for severe COVID-19 have been well documented. Despite this, hypercoagulability remains an often overlooked risk factor for severe disease for COVID-19. Because COVID-19 infection is a risk factor for hypercoagulability, a reasonable presumption/hypothesis is that patients with hereditary thrombophilia would be at a higher risk of thrombotic complications associated with COVID-19 infection. This case report details two cases where previously unknown hereditary thrombophilias likely contributed to the mortality of COVID-19 patients. The first COVID-19 patient's cause of death was pulmonary thromboemboli from deep vein thrombosis due to heterozygous MTHFR C667T and heterozygous PAI-1 4G/5G mutations. The second COVID-19 patient's cause of death was an acute myocardial infarct due to a coronary artery thrombosis in the setting of heterozygous MTHFR A1298C and homozygous PAI-1 4G/5G mutations. In each case, COVID-19 infection was also considered contributory to death. The occurrence of these fatal thrombotic events in COVID-19 patients with hereditary thrombophilias raises questions as to whether this combination of thrombotic risk factors for hypercoagulability may have placed patients at a significant enough risk to experience these fatal thrombotic complications. Thus, while not sufficient alone to prove that SARS-CoV-2 patients with hereditary thrombophilias are at increased risk for thrombotic complications, these two cases indicate that further investigation is warranted into elucidating the relationship between thrombotic risk factors as it may identify an additional high-risk medical condition for COVID-19 and have important diagnostic and therapeutic ramifications.

Effect of amubarvimab-romlusevimab for treatment of severe COVID-19 in intensive care units: A retrospective cohort study

Amubarvimab-romlusevimab is a commonly recommended antiviral treatment in China for adult patients with mild or moderate SARS-CoV-2 infections, especially for patients with a high risk factor for progression to severe COVID-19. However, its exact efficacy in patients with severe Covid-19 is not yet known.This is a single-center retrospective cohort study, in which we collected the general data, laboratory tests, radiological characteristics, viral conversion status, and prognosis of the disease from patients with COVID-19 hospitalized, from December 2022 to March 2023 in the Department of Critical Care Medicine. The amubarvimab-romlusevimab therapy can reduce the 28-day mortality (29.79 % vs 51.35 %, p = 0.02), and ICU mortality (29.79 % vs 55.41 %, p = 0.006) of severe COVID-19.A 1:1 PSM (Propensity Score Matching) was performed to reduce bias, in order to ensure the two groups were balanced and comparable. In the matched population (n = 47), there were no statistically significant differences between the mAbs (monoclonal antibody)group and the Non-antiviral group in 28-day, and thromboembolic events in COVID-19 patients. The 40-day survival analysis shows that mAbs therapy can improve patient prognosis (HR = 0.45, 95%CI = 0.26–0.76, p = 0.008). However, no significant intergroup difference in the 40-day cumulative viral conversion rate. In a univariate Cox regression analysis, The Amubarvimab - romlusevimab therapy(HR:0.464; CI:[0.252–0.853]; p:0.013) is a protective factor and CRP, PCT, PLT, Lactate, PT, PT-INR, and pt% level at admission were risk factors for clinical prognosis. After including the above covariates, Multifactorial COX regression shows that the Amubarvimab - romlusevimab therapy(HR:0.392; CI:[0.211–0.729]; p:0.003), CRP, Lactate and PT-INR at admission are independent factors for mortality of severe COVID-19. Based on the current data, we conclude that amubarvimab-romlusevimab therapy is beneficial for patients with severe COVID-19.

Hemorrhage and thrombosis in COVID-19-patients supported with extracorporeal membrane oxygenation: an international study based on the COVID-19 critical care consortium

BackgroundExtracorporeal membrane oxygenation (ECMO) is a rescue therapy in patients with severe acute respiratory distress syndrome (ARDS) secondary to COVID-19. While bleeding and thrombosis complicate ECMO, these events may also occur secondary to COVID-19. Data regarding bleeding and thrombotic events in COVID-19 patients on ECMO are sparse.MethodsUsing the COVID-19 Critical Care Consortium database, we conducted a retrospective analysis on adult patients with severe COVID-19 requiring ECMO, including centers globally from 01/2020 to 06/2022, to determine the risk of ICU mortality associated with the occurrence of bleeding and clotting disorders.ResultsAmong 1,248 COVID-19 patients receiving ECMO support in the registry, coagulation complications were reported in 469 cases (38%), among whom 252 (54%) experienced hemorrhagic complications, 165 (35%) thrombotic complications, and 52 (11%) both. The hazard ratio (HR) for Intensive Care Unit mortality was higher in those with hemorrhagic-only complications than those with neither complication (adjusted HR = 1.60, 95% CI 1.28–1.99, p < 0.001). Death was reported in 617 of the 1248 (49.4%) with multiorgan failure (n = 257 of 617 [42%]), followed by respiratory failure (n = 130 of 617 [21%]) and septic shock [n = 55 of 617 (8.9%)] the leading causes.ConclusionsCoagulation disorders are frequent in COVID-19 ARDS patients receiving ECMO. Bleeding events contribute substantially to mortality in this cohort. However, this risk may be lower than previously reported in single-nation studies or early case reports.Trial registration ACTRN12620000421932 (https://covid19.cochrane.org/studies/crs-13513201).

Effectiveness and safety of rivaroxaban for anticoagulation therapy in COVID-19: A meta-analysis of randomized controlled trials.

To evaluate the effectiveness and safety of rivaroxaban anticoagulation in COVID-19 patients. PubMed, Embase, Cochrane Library electronic databases, and ClinicalTrials.gov were searched to identify all relevant randomized controlled trial studies from December 2019 to July 2023. A total of 6 randomized controlled trials, which included a total of 3323 patients, were considered for evaluation. Overall, short-term all-cause mortality and hospitalization rates were not significantly different between the rivaroxaban and control groups. Thrombotic events were significantly reduced in the rivaroxaban prophylaxis group compared to the placebo control group. However, the reduction in thrombotic events was not significantly different between rivaroxaban therapy and heparin or low-molecular-weight heparin (LMWH). Rivaroxaban prophylaxis and the therapeutic dose may be associated with a higher rate of overall bleeding rate, but major bleeding rates did not differ substantially. Rivaroxaban may reduce thrombotic events in COVID-19 patients, but it does not appear to have an advantage over heparin or LMWH, and it may increase the risk of bleeding.INPLASY Reg. No.: INPLASY 202370097.

Persistent increase of cardiovascular and cerebrovascular events in COVID-19 patients: a 3-year population-based analysis.

We evaluated the incidence and relative risk of major post-acute cardiovascular consequences of SARS-CoV-2 infection in a large real-world population from a primary care database in a region at moderate cardiovascular risk followed up in the period 2020-22. This is a retrospective cohort analysis using data from a cooperative of general practitioners in Italy. Individuals aged >18 affected by COVID-19 starting from January 2020 have been followed up for 3 years. Anonymized data from 228 266 patients in the period 2020-22 were considered for statistical analysis and included 31 764 subjects with a diagnosis of COVID-19. An equal group of subjects recorded in the same database in the period 2017-19 was used as propensity score-matched comparison as an unquestionable COVID-19-free population. Out of the 228 266 individuals included in the COMEGEN database during 2020-22, 31 764 (13.9%) were ascertained positive with SARS-CoV-2 infection by a molecular test reported to general practitioners. The proportion of individuals with a new diagnosis of major adverse cardiovascular and cerebrovascular events was higher in the 2020-22 COVID-19 group than in the 2017-19 COMEGEN propensity score-matched comparator, with an odds ratio of 1.73 (95% confidence interval: 1.53-1.94; P < 0.001). All major adverse cardiovascular and cerebrovascular events considered showed a significantly higher risk in COVID-19 individuals. Incidence calculated for each 6-month period after the diagnosis of COVID-19 in our population was the highest in the first year (1.39% and 1.45%, respectively), although it remained significantly higher than in the COVID-19-free patients throughout the 3 years. The increase of cardiovascular risk associated with COVID-19 might be extended for years and not limited to the acute phase of the infection. This should promote the planning of longer follow-up for COVID-19 patients to prevent and promptly manage the potential occurrence of major adverse cardiovascular and cerebrovascular events.

The Role of Fibrin Monomer Compared to D-dimer and CRP in Determining COVID-19 Severity

Fibrin Monomer (FM), as a product of thrombin activity in cleaving fibrinogen, can be used as an early marker of thrombotic events in COVID-19 patients. D-dimer is a commonly used marker of hemostasis as a product of plasmin activity in cleaving polymeric fibrin. D-dimer is often used to help decide whether to initiate anticoagulant administration. This study aims to know whether FM can be used as a marker for thrombotic events such as D-dimer in COVID-19 patients; CRP levels were also examined to determine how inflammation affected the two hemostatic indicators. A total of 93 patients were confirmed with COVID-19 by PCR. The median (min-max) FM in the severe stage was 4.53 (2.26-58.20)ug/mL, whereas, in the mild-moderate stage, it was 4.21 (2.19-32.35 ug/mL. There are significant differences in median D-dimer levels in severe stages to mild-moderate, respectively 0.46 (0.14–7.58) and 0.7890, and ages. The level of FM that can be used to differentiate the severe stage is &gt; 4.46 ug/mL (sensitivity 56.3%, specificity 58.0%) as in the D-dimer level is &gt; 0.58 ug/mL ((sensitivity 75.0%, specificity 65.2%). There is a moderate positive correlation between fibrin monomer and D-dimer, a weak positive correlation between D-dimer and CRP, and no correlation between FM and CRP. This study concludes that the FM median level is higher in severe COVID-19 than in D-dimer. Fibrin monomer levels have a positive correlation with D-dimer. Fibrin Monomer levels are not affected by CRP.

Descriptive Analysis of Thromboembolic Events in COVID-19 Patients in Qatar

Descriptive Analysis of Thromboembolic Events in COVID-19 Patients in Qatar

Prevalence of Thromboembolic Events, Including Venous Thromboembolism and Arterial Thrombosis, in Patients with COVID-19: A Systematic Review with Meta-Analysis.

Many studies have evaluated thromboembolic events in COVID-19 patients, and most of them have reported a high estimation of the prevalence of such events. The present study sought to evaluate the prevalence of thromboembolic events in patients with COVID-19. This study is a systematic review with meta-analysis that investigated thromboembolic events in patients with COVID-19 from the start of the pandemic to August 31, 2021. The 4 main databases for collecting articles were Medline, Scopus, Google Scholar, and Web of Science. Deep vein thrombosis, pulmonary embolism, arterial thrombosis, and the overall rate of thromboembolic events were considered primary outcomes. In a total of 63 studies (104 920 patients with COVID-19), the overall thrombosis rate was 21% (95% CI, 18% to 25%), the rate of deep vein thrombosis was 20% (95% Cl, 16% to 25%), the rate of pulmonary embolism was 8% (95% Cl, 6% to 10%), and the rate of arterial thrombosis was 5% (95% Cl, 3% to 7%). The prevalence of all primary outcomes in critically ill patients admitted to the intensive care unit (ICU) was significantly higher (P<0.05). In older patients, the prevalence of overall thrombosis, pulmonary embolism, or deep vein thrombosis was significantly higher (P<0.05). This study showed that COVID-19 increases the risk of thromboembolic events, especially in elderly and critically ill patients admitted to the ICU. Therefore, more strategies are needed to prevent thromboembolic events in patients with COVID-19, especially in ICU-admitted and elderly patients.

Pro-inflammatory sensitization of platelets after a mild course of COVID-19 infection

Abstract Background Coronavirus disease-2019 (COVID-19) is a viral respiratory illness caused by the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) which can lead to an increased risk of thromboembolic events but also complications even after recovery from the disease. Multiple factors may enhance the risk of thrombotic events in COVID-19 patients including excessive inflammatory responses and increased platelet activity. To date there are hardly any data on how platelet function is affected after a mild course of infection. Purpose In this study, we investigated whether platelet function is affected after recovery from mild COVID-19 disease. Besides the response of platelets to platelet stimuli, expression of the transporter protein multidrug resistance protein 4 (MRP4) and one of its substrates, the inflammatory lipid mediator sphingosine-1-phosphate (S1P), were measured. Methods Venous blood samples were collected from patients within 2-15 weeks after recovery from a mild SARS-CoV-2 infection (recovered) and matched individuals (controls) after written informed consent. Participants were invited again at 6-9 months after infection to reexamine platelet function. Parameters of platelet aggregation were determined by light transmission aggregometry (LTA) in platelet-rich plasma (PRP). Expression of platelet activation markers were measured by Flow Cytometry (FACS). In addition, concentrations of S1P were determined by LC-MS/MS and MRP4-expression in platelets via Western blotting. Results Within 2-15 weeks after recovery, no alterations in platelet aggregation were observed after stimulation of PRP with various ADP (1, 2, and 10 µM) or collagen (1 and 2.5 µg/mL) concentrations. However, regarding FACS analysis, platelet surface expression of CD62P and PAC1 from convalescents prior activation by ADP (2 µM) and by CRP-XL (0.125 ng/mL) was significantly upregulated in comparison to samples from controls (p&amp;lt;0.05 for both). Intriguingly, S1P levels in platelet-poor plasma (PPP) from COVID-19 convalescents were significantly elevated compared to controls, i.e. 0.75±0.01 vs 0.65±0.02 nmol/mL, respectively (p&amp;lt;0.001). S1P in PRP and serum samples was not altered. Furthermore, platelet MRP4 expression was significantly elevated in COVID-19 convalescents (p&amp;lt;0.05). These differences in S1P and MRP4 levels were only present after 2-15 weeks of recovery, but not 6-9 months after infection. Conclusions While after a mild course of COVID-19 infection robust platelet functions such as aggregation determined by LTA were not affected, subtle differences in platelet activation markers occurred. Enhanced platelet MRP4 expression, which may correlate with the observed elevated S1P in PPP, are in agreement with a pro-inflammatory sensitization of platelets even after a mild COVID-19 infection. The implications of this observation concerning long-term effects of COVID-19 await further studies.

Renin-Angiotensin System and Sex Differences in COVID-19: A Critical Assessment.

The current epidemic of corona virus disease (COVID-19) has resulted in an immense health burden that became the third leading cause of death and potentially contributed to a decline in life expectancy in the United States. The severe acute respiratory syndrome-related coronavirus-2 binds to the surface-bound peptidase angiotensin-converting enzyme 2 (ACE2, EC 3.4.17.23) leading to tissue infection and viral replication. ACE2 is an important enzymatic component of the renin-angiotensin system (RAS) expressed in the lung and other organs. The peptidase regulates the levels of the peptide hormones Ang II and Ang-(1-7), which have distinct and opposing actions to one another, as well as other cardiovascular peptides. A potential consequence of severe acute respiratory syndrome-related coronavirus-2 infection is reduced ACE2 activity by internalization of the viral-ACE2 complex and subsequent activation of the RAS (higher ratio of Ang II:Ang-[1-7]) that may exacerbate the acute inflammatory events in COVID-19 patients and possibly contribute to the effects of long COVID-19. Moreover, COVID-19 patients present with an array of autoantibodies to various components of the RAS including the peptide Ang II, the enzyme ACE2, and the AT1 AT2 and Mas receptors. Greater disease severity is also evident in male COVID-19 patients, which may reflect underlying sex differences in the regulation of the 2 distinct functional arms of the RAS. The current review provides a critical evaluation of the evidence for an activated RAS in COVID-19 subjects and whether this system contributes to the greater severity of severe acute respiratory syndrome-related coronavirus-2 infection in males as compared with females.

Abstract 264: In-hospital Antiplatelet Use Is Associated With Decreased Thromboembolic Events In Covid-19 Patients

Background: COVID-19 infection has been associated with a prothrombotic state. Previous studies found conflicting results regarding the association of in-hospital antiplatelet use and mortality in patients with COVID-19. The purpose of our study was to determine whether in-hospital antiplatelet use was associated with lower morbidity or mortality in patients hospitalized with COVID-19. Methods: We conducted a two-center retrospective study of 692 adult patients hospitalized from March 2020 to October 2021 with COVID-19 confirmed by RT-PCR. Groups were stratified based on in-hospital antiplatelet use. Baseline characteristics, biomarkers, and in-hospital outcomes were described. A multivariate regression model was used to estimate the association of the primary outcome of interest with in-hospital antiplatelet use. Antiplatelet use was defined as aspirin and/or P2Y12 inhibitor therapy. Statistical analyses were performed using SPSS 28. Results: Antiplatelet use was present in 40.2% (278/692) of patients. These patients were older (68 vs. 62 years old, p&lt;0.001) and had higher rates of hypertension (74.8% vs. 59.9%, p=0.001), type 2 diabetes (48.6% vs. 34.5%, p=0.001), coronary artery disease (23% vs. 7%, p&lt;0.001), and heart failure (19.4% vs. 8.5%, &lt;0.001). There was no significant difference in peak d-dimer levels between groups. Patients with in-hospital antiplatelet use had lower adjusted odds ratios of venous thromboembolism (0.62 [0.40-0.95], p=0.03), ICU admission (0.69 [0.49-0.96], p=0.03), and intubation (0.62 [0.44-0.88], p=0.006). There was no difference in all-cause mortality. Conclusion: Hospitalized COVID-19 patients treated with antiplatelet therapy had more cardiovascular risk factors, yet they had lower adjusted odds of venous thromboembolism, ICU admission, and intubation. Antiplatelet therapy during hospitalization with COVID-19 was not associated with lower mortality risk.

A Meta-Analysis on the Neurovascular Complications Of Extracorporeal Membrane Oxygenation In Critically Ill COVID-19 Patients (S4.004)

<h3>Objective:</h3> To determine the incidence and type of neurovascular complications in adult COVID-19 patients requiring veno-venous extracorporeal membrane oxygenation (VV-ECMO). <h3>Background:</h3> ECMO is a high-stakes intervention for patients with acute respiratory failure from severe COVID-19 infections. Introduction of extracorporeal circuit, COVID-19 associated endothelial injury and anticoagulation can predispose these patients to neurovascular complications, but the incidence of these adverse events in COVID-19 patients remains unknown. <h3>Design/Methods:</h3> We performed a systematic review and meta-analysis using MEDLINE, Embase, PsycINFO, and Cochrane databases to identify studies that reported neurological complications in adult COVID-19 patients receiving ECMO for respiratory failure. Among 840 identified studies, 28 studies (n = 3147) were included in the systematic review. Studies that had ≥95% of patients on VV-ECMO were pooled for meta-analyses. <h3>Results:</h3> The incidence of intracranial hemorrhages was 11% [95% CI, 8–15%], and the incidence of ischemic strokes was 2% [9%% CI, 1–3%] in patients with COVID-19 requiring VV-ECMO. Intraparenchymal and subarachnoid hemorrhages accounted for 73% and 8% of all intracranial hemorrhages, respectively. Higher anticoagulation targets did not influence the incidence of intracranial hemorrhages (p = 0.22). One study reported the occurrence of cerebral venous sinus thrombosis. <h3>Conclusions:</h3> Patients with COVID-19 requiring ECMO have a higher incidence of intracranial hemorrhage compared to historical data in non-COVID-19 patients (11% vs. 8%), while the incidence of ischemic stroke is similar (2%) in both cohorts. Intraparenchymal hemorrhage occurred most frequently. Despite earlier observations of higher thrombotic rates in COVID-19 patients, cerebral venous sinus thrombosis was rarely reported in COVID-19 patients requiring ECMO. Healthcare providers should be aware of these increased risks and maintain a high index of suspicion for intracranial hemorrhage in this patient population. <b>Disclosure:</b> Dr. Li has nothing to disclose. Miss Deng has nothing to disclose. Ms. Ma has nothing to disclose. Ms. Li has nothing to disclose. Ms. Dawson has nothing to disclose. Ms. Huong has nothing to disclose. Dr. Wang has nothing to disclose. The institution of Dr. Gofton has received research support from Government of Canada. The institution of Dr. Gofton has received research support from Canadian Institutes of Health Research. The institution of Dr. Gofton has received research support from Academic Medical Organisation of Southwestern Ontario. Dr. Gofton has a non-compensated relationship as a Medical Advisory Board Member with NORSE Institute that is relevant to AAN interests or activities. Dr. Nagpal has nothing to disclose. The institution of Dr. Slessarev has received research support from Carestream health . Dr. Slessarev has received intellectual property interests from a discovery or technology relating to health care.

A massive stroke in a pregnant woman following COVID-19 infection: A case report

Background and aims: COVID-19 infection increases the risk of pathological thrombotic events in venous and arterial circulation. COVID-19 patients are reported, a wide range of neurovascular symptoms is highlighted, such as cerebral vascular accidence. This study aimed to report a massive stroke in a pregnant woman with COVID-19 infection. Case Report: We report a 41-year-old pregnant woman, gravid 5 para 2 living 2 abortion 2 at gestational age 22 weeks and 4 days with Covid-19 infection, which developed into a massive stroke in the Basilar artery despite receiving a therapeutic dosage of Enoxaparin Sodium. Conclusion: The possibility of thrombosis should be considered in COVID-19 patients with symptoms indicating an increase in intracranial pressure (ICP) such as decreased consciousness, strabismus, and agitation. Considering the higher risk of thrombotic events in COVID-19 patients, cerebral venous sinus thrombosis (CVST) could be a possible consequence. Thus, the precise observation of neurologic manifestations in covid-19 patients, especially in pregnant women, is recommended.

Bystander effect of SARS-CoV-2 spike protein on human monocytic THP-1 cell activation and initiation of prothrombogenic stimulus representing severe COVID-19

BackgroundHypercoagulable state and thromboembolic complications are potential life-threatening events in COVID-19 patients. Our previous studies demonstrated that SARS-CoV-2 infection as well as viral spike protein expressed epithelial cells exhibit senescence with the release of inflammatory molecules, including alarmins.FindingsWe observed extracellular alarmins present in the culture media of SARS-CoV-2 spike expressing cells activate human THP-1 monocytes to secrete pro-inflammatory cytokines to a significant level. The release of THP-1 derived pro-inflammatory cytokine signature correlated with the serum of acute COVID-19 patient, but not in post-COVID-19 state. Our study suggested that the alarmins secreted by spike expressing cells, initiated phagocytosis property of THP-1 cells. The phagocytic monocytes secreted complement component C5a and generated an autocrine signal via C5aR1 receptor. The C5a-C5aR1 signal induced formation of monocyte mediated extracellular trap resulted in the generation of a prothrombogenic stimulus with activating platelets and increased tissue factor activity. We also observed an enhanced C5a level, platelet activating factor, and high tissue factor activity in the serum of acute COVID-19 patients, but not in recovered patients.ConclusionOur present study demonstrated that SARS-CoV-2 spike protein modulates monocyte responses in a paracrine manner for prothrombogenic stimulus by the generation of C5a complement component.

194: CHRONIC ANTICOAGULANT USE PRIOR TO COVID-19 DIAGNOSIS: A SYSTEMATIC REVIEW AND META-ANALYSIS

Introduction: Coagulopathy and thromboembolic events are poor prognostic indicators of COVID-19 disease. There is a discrepancy in the results of different studies regarding the effects of chronic anticoagulation on clinical outcomes. This systematic review aims to summarize the evidence on the impact of chronic anticoagulation on clinical outcomes in COVID-19. Methods: A Literature search was performed on LitCovid PubMed, WHO, and Embase databases from inception (December 2019) till May 2022. Our eligibility criteria included original studies that reported the association between prior use of anticoagulants for unrelated indications at the time of COVID-19 diagnosis and the patient outcomes in adults suffering from COVID-19. The risk of thromboembolic events in COVID-19 infected patients on chronic anticoagulation is the primary outcome and severity of COVID-19 disease in terms of ICU admission or invasive mechanical ventilation/intubation requirements, and all-cause mortality were the secondary outcomes. Random effects models were used to compute crude ODDs ratios (OR) and adjusted odds ratios (aOR) with 95% confidence intervals (CIs). Results: A total of 44 observational studies met our inclusion criteria. In unadjusted analysis, prior anticoagulation was not associated with reduced risk of thromboembolic events in COVID-19 patients (N=43851, 9 studies, OR 0.67 [0.22, 2.07]; p= 0.49; I2= 95%). However, pre-hospital use of anticoagulants significantly increase the risk of all-cause mortality in COVID-19 patients (N= 580601; 37 studies, OR 1.56 [1.22, 2.01]; p=0.0005; I2= 97%). There was no statistically significant association between pre-hospital anticoagulants usage and COVID-19 disease severity (N=186239; 20 studies, OR 0.96 [0.70, 1.33]; p= 0.82; I2= 88%). Pooling adjusted estimates revealed no statistically significant association between pre-hospital use of anticoagulants and risk of Thromboembolic events in COVID-19 patients (aOR= 0.85 [0.34, 2.12]; p= 0.72), COVID-19 related mortality (aOR= 0.93 [0.82, 1.07]; p= 0.32), and the severity of COVID-19 infection (aOR= 0.96 [0.72, 1.30]; p= 0.81). Conclusions: Prehospital use of anticoagulation was not significantly associated with reduced risk of thromboembolic events, improved survival, and lower severity of disease in COVID-19 patients.

Comparison of machine learning methods with logistic regression analysis in creating predictive models for risk of critical in-hospital events in COVID-19 patients on hospital admission

BackgroundMachine learning (ML) algorithms have been trained to early predict critical in-hospital events from COVID-19 using patient data at admission, but little is known on how their performance compares with each other and/or with statistical logistic regression (LR). This prospective multicentre cohort study compares the performance of a LR and five ML models on the contribution of influencing predictors and predictor-to-event relationships on prediction model´s performance.MethodsWe used 25 baseline variables of 490 COVID-19 patients admitted to 8 hospitals in Germany (March–November 2020) to develop and validate (75/25 random-split) 3 linear (L1 and L2 penalty, elastic net [EN]) and 2 non-linear (support vector machine [SVM] with radial kernel, random forest [RF]) ML approaches for predicting critical events defined by intensive care unit transfer, invasive ventilation and/or death (composite end-point: 181 patients). Models were compared for performance (area-under-the-receiver-operating characteristic-curve [AUC], Brier score) and predictor importance (performance-loss metrics, partial-dependence profiles).ResultsModels performed close with a small benefit for LR (utilizing restricted cubic splines for non-linearity) and RF (AUC means: 0.763–0.731 [RF–L1]); Brier scores: 0.184–0.197 [LR–L1]). Top ranked predictor variables (consistently highest importance: C-reactive protein) were largely identical across models, except creatinine, which exhibited marginal (L1, L2, EN, SVM) or high/non-linear effects (LR, RF) on events.ConclusionsAlthough the LR and ML models analysed showed no strong differences in performance and the most influencing predictors for COVID-19-related event prediction, our results indicate a predictive benefit from taking account for non-linear predictor-to-event relationships and effects. Future efforts should focus on leveraging data-driven ML technologies from static towards dynamic modelling solutions that continuously learn and adapt to changes in data environments during the evolving pandemic.Trial registration number: NCT04659187.

Cardiovascular Adverse Events Associated with Monoclonal Antibody Products in Patients with COVID-19.

Little is known about cardiovascular safety profiles for monoclonal antibody products that received the FDA Emergency Use Authorization for COVID-19. In this study, data from the FDA Adverse Event Reporting System from the first quarter of 2020 to the second quarter of 2022 were used to investigate cardiovascular safety signals associated with seven monoclonal antibody products (casirivimab + imdevimab, bamlanivimab, bamlanivimab + etesevimab, sotrovimab, tocilizumab, bebtelovimab, tixagevimab + cilgavimab) in COVID-19 patients. Disproportionality analyses were conducted using reporting odds ratio and information component to identify safety signals. About 10% of adverse events in COVID-19 patients were cardiovascular adverse events. Four monoclonal antibody products (casirivimab + imdevimab, bamlanivimab, bamlanivimab + etesevimab, and bebtelovimab) were associated with higher reporting of hypertension. Tocilizumab was associated with higher reporting of cardiac failure and embolic and thrombotic event. Casirivimab + imdevimab and bamlanivimab were also associated with higher reporting of ischemic heart disease. No cardiovascular safety signals were identified for sotrovimab and tixagevimab + cilgavimab. The results indicate differential cardiovascular safety profiles in monoclonal antibodies. Careful monitoring of cardiovascular events may be considered for certain COVID-19 patients at risk when they are treated with monoclonal antibodies.

Analysis of Azithromycin adverse events in COVID-19 Patients reported to Iraqi Pharmacovigilance center in 2020

Azithromycin is an antibiotic that belongs to the macrolide family used in a wide variety of bacterial diseases. However, it has been proposed as a potential therapy for the treatment of SARS-CoV-2 pneumonia (off-label use) given for its antiviral and&#x0D; &#x0D; immunomodulatory activity. Never-theless, its role in the treatment of COVID-19 remains unclear. Azithromycin has a well-characterized safety profile. However, its use outside the approved indication needs further follow up to ensure that the benefit-risk balance remains positive. One method to look for new/ changed safety information is through using the information component (IC025) value. IC025 is the lower limit of a 95% credibility interval for the IC. The credibility interval provides information about the stability of a particular IC value: the narrower the interval, the higher the stability.&#x0D; Objective:&#x0D; Study the submitted adverse events reports of Azithromycin to the Iraqi Pharmacovigilance center and compare the occurrence of these reported adverse events in Iraq to the internationally reported cases during 2020COVID-19 pandemic using IC025.&#x0D; &#x0D; Methodology:&#x0D; The reported adverse events of Azithromycin to the national Pharmacovigilance database were studied qualitatively (age, gender and seriousness) and quantitatively (using IC025) as a measure of presence of a new/changed safety information related to Azithromycin.&#x0D; &#x0D; Results:&#x0D; The total number of reports for Azithromycin were 419, female represent (43%) and male represent (55.8%), and the predominant age groups was from 45-64 years representing (41.1%). The most widely reported adverse events were gastrointestinal disorders (68%), cardiac disorders (14.1%), general disorders and administration site effect (6.9%), and investigations (Interfere with Lab tests) (5.7%). There were 96 drug-adverse reaction combinations. The IC025 value for the most widely reported adverse events showed a comparable value for ECG-QT prolonged (3.6/3.7), Arrhythmia (0.6/0.7). There was a decreased value for palpitation (0.5/0.9) and dyspnea (0.3/0.6). Tachycardia and increased liver enzymes showed an increased value of (2.0/0.1) and (0.5/0.1) respectively.&#x0D; &#x0D; Conclusion:&#x0D; Using the IC025 was helpful in finding the increased reporting rate of adverse events compared to the background rate.

Impact of corticosteroids on the procoagulant profile of critically ill COVID-19 patients: a before-after study.

Several studies have reported an increased risk of thrombotic events in COVID-19 patients, but the pathophysiology of this procoagulant phenotype remains poorly understood. We hypothesized that corticosteroids may attenuate this procoagulant state through their anti-inflammatory effects. The aim of this study was to evaluate the impact of dexamethasone (DXM) on the coagulation profile of severely ill COVID-19 patients. We conducted a retrospective, observational before/after bi-centric cohort study among ICU patients hospitalized for severe COVID-19 and receiving therapeutic anticoagulation by unfractionated heparin (UFH). Before and after the standardized use of DXM, we compared inflammatory and coagulation profiles, as well as the kinetics of heparin requirement, adjusted for weight and anti-Xa activity. Eighty-six patients were included, 35 in the no-DXM group, and 51 in the DXM group. At admission, CRP and fibrinogen levels were not different between groups, neither were UFH infusion rates. At day 3 after ICU admission, CRP (178±94 mg/L vs. 99±68 mg/L, P<0.001) and fibrinogen (7.2±1.4 g/L vs. 6.1±1.4 g/L, P=0.001) significantly decreased in the DXM group, but not in the no-DXM group. Over time, UFH infusion rates were lower in the DXM group (P<0.001) without any significant difference in plasma anti-Xa activity. CRP variations correlated with heparin dose variations between Day 0 and Day 3 (r=0.39, P=0.009). Finally, the incidence of venous thromboembolic events during in-ICU stay was significantly reduced in the DXM group (4 vs. 43%, P<0.0001). In critically ill COVID-19 patients, dexamethasone use was associated with a decrease in both pro-inflammatory and procoagulant profile.

Plasma Endocan as a Biomarker of Thrombotic Events in COVID-19 Patients.

(1) Background: Endocan is a marker of endothelial dysfunction that may be associated with thrombotic events. The aim of the study was to investigate the performance of endocan as a marker of thrombotic events in COVID-19 patients. (2) Methods: We measured endocan in plasma from 79 documented COVID-19 patients classified according to disease severity (from mild to critical). Thrombotic events were recorded. (3) Results: Endocan concentrations at admission were significantly increased according to COVID-19 severity. Levels of endocan were significantly increased in patients experiencing thrombotic events in comparison with those without (16.2 (5.5–26.7) vs. 1.81 (0.71–10.5) ng/mL, p < 0.001). However, endocan concentrations were not different between pulmonary embolism and other thrombotic events. The Receiver Operating Characteristic (ROC) analysis for the identification of thrombotic events showed an area under the ROC curve (AUC) of 0.776 with an optimal threshold at 2.83 ng/mL (93.8% sensitivity and 54.7% specificity). When combining an endocan measurement with D-dimers, the AUC increased to 0.853. When considering both biomarkers, the Kaplan–Meier survival curves showed that the combination of endocan and D-dimers better discriminated patients with thrombotic events than those without. The combination of D-dimers and endocan was independently associated with thrombotic events. (4) Conclusions: Endocan might be a useful and informative biomarker to better identify thrombotic events in COVID-19 patients.