Abstract

BACKGROUND Pulmonary embolisms are frequently and prognostically in individuals infected by coronavirus disease 2019 (COVID-19); the incidence of pulmonary embolisms is varied across numerous studies. This study aimed to assess the pooled incidence of pulmonary embolic events and the prognostic value of such events in intensive care unit (ICU) admissions of patients with COVID-19. METHODS The Cochrane Library, PubMed, and EmBase were systematically searched for eligible studies published on or before October 20, 2021. The pooled incidence of pulmonary embolism was calculated using the random-effects model. Moreover, the prognostic value was assessed by measuring the sensitivity, specificity, positive and negative likelihood ratio (PLR and NLR), diagnostic odds ratio (DOR), and the area under the receiver operating characteristic curve (AUC). RESULTS Thirty-six studies involving 10,367 COVID-19 patients were selected for the final meta-analysis. The cumulative incidence of pulmonary embolism in patients with COVID-19 was 21% (95% confidence interval [95%CI]: 18-24%; P<0.001), and the incidence of pulmonary embolism in ICU and non-ICU patients was 26% (95%CI: 22-31%; P<0.001) and 17% (95%CI: 14-20%; P<0.001), respectively. The predictive role of pulmonary embolism in ICU admission was also assessed, and the sensitivity, specificity, PLR, NLR, DOR, and AUC were 0.31 (95%CI: 0.21-0.42), 0.84 (95%CI: 0.75-0.90), 1.88 (95%CI: 1.45-2.45), 0.83 (95%CI: 0.75-0.91), 2.25 (95%CI: 1.64-3.08), and 0.61 (95%CI: 0.57-0.65), respectively. CONCLUSION This study found that the incidence of pulmonary embolism was relatively high in COVID-19 patients, and the incidence of pulmonary embolism in ICU patients was higher than that in non-ICU patients.

Abstract

OBJECTIVES This study aimed to investigate the differences in the characteristics, management, and clinical outcomes of patients with and that of those without coronavirus disease 2019 (COVID-19) infection who had ST-segment elevation myocardial infarction (STEMI). METHODS Databases including Web of Science, PubMed, Cochrane Library, and Embase were searched up to July 2021. Observational studies that reported on the characteristics, management, or clinical outcomes and those published as full-text articles were included. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of all included studies. RESULTS A total of 27,742 patients from 13 studies were included in this meta-analysis. Significant delay in symptom onset to first medical contact (SO-to-FMC) time (mean difference = 23.42 min; 95% CI: 5.85-40.99 min; p = 0.009) and door-to-balloon (D2B) time (mean difference = 12.27 min; 95% CI: 5.77-18.78 min; p = 0.0002) was observed in COVID-19 patients. Compared to COVID-19 negative patients, those who are positive patients had significantly higher levels of C-reactive protein, D-dimer, and thrombus grade (p < 0.05) and showed more frequent use of thrombus aspiration and glycoprotein IIbIIIa (Gp2b3a) inhibitor (p < 0.05). COVID-19 positive patients also had higher rates of in-hospital mortality (OR = 5.98, 95% CI: 4.78-7.48, p < 0.0001), cardiogenic shock (OR = 2.75, 95% CI: 2.02-3.76, p < 0.0001), and stent thrombosis (OR = 5.65, 95% CI: 2.41-13.23, p < 0.0001). They were also more likely to be admitted to the intensive care unit (ICU) (OR = 4.26, 95% CI: 2.51-7.22, p < 0.0001) and had a longer length of stay (mean difference = 4.63 days; 95% CI: 2.56-6.69 days; p < 0.0001). CONCLUSIONS This study revealed that COVID-19 infection had an impact on the time of initial medical intervention for patients with STEMI after symptom onset and showed that COVID-19 patients with STEMI were more likely to have thrombosis and had poorer outcomes.

Abstract

BACKGROUND Acute pulmonary embolism has been recognized as a frequent complication of COVID-19 infection influencing the clinical course and outcomes of these patients. OBJECTIVES We performed a systematic review and meta-analysis to evaluate the mortality risk in COVID-19 Italian patients complicated by acute pulmonary embolism in the short-term period. METHODS The study was performed in accordance with the Preferred Report Items for Systematic Reviews and Meta-analyses guidelines. PubMed-MEDLINE and Scopus databases were systematically searched for articles, published in the English language and enrolling Italian cohorts with confirmed COVID-19 infection from inception through 20 October 2021. Mortality risk data were pooled using the Mantel-Haenszel random effects models with odds ratio as the effect measure with 95% confidence interval. Heterogeneity among studies was assessed using Higgins and Thomson I2 statistic. RESULTS Eight investigations enrolling 1.681 patients (mean age 64.9 years, 1125 males) met the inclusion criteria and were considered for the analysis. A random-effect model showed that acute pulmonary embolism was present in 19.0% of Italian patients with COVID-19 infection. Moreover, these patients were at higher mortality risk compared with those without (odds ratio: 1.76, 95% confidence interval: 1.26-2.47, P = 0.001, I2 = 0%). Sensitivity analysis confirmed yielded results. CONCLUSION In Italian patients with COVID-19 infection, acute pulmonary embolism was present in about one out of five and significantly associated with a higher mortality risk in the short-term period. The identification of acute pulmonary embolism in these patients remains critical to promptly identify vulnerable populations who would require prioritization in treatment and prevention and close monitoring.

Abstract

BACKGROUND Previous studies demonstrate a reduced risk of thrombosis and mortality with anticoagulant treatment in patients with COVID-19 than in those without anticoagulation treatment. However, an open question regarding the efficacy and safety of therapeutic anticoagulation (T-AC) versus a lower dose, prophylaxis anticoagulation (P-AC) in COVID-19 patients is still controversial. METHODS We systematically reviewed currently available randomized clinical trials (RCTs) and observational studies (OBs) from January 8, 2019, to January 8, 2022, and compared prophylactic and therapeutic anticoagulant treatment in COVID-19 patients. The primary outcomes were risk of mortality, major bleeding, and the secondary outcomes included venous and arterial thromboembolism. Subgroup analysis was also performed between critically ill and non-critically ill patients with COVID-19 and between patients with higher and lower levels of D-dimer. Sensitivity analysis was performed to decrease the bias and the impact of population heterogeneity. RESULTS We identified 11 RCTs and 17 OBs fulfilling our inclusion criteria. In the RCTs analyses, there was no statistically significant difference in the relative risk of mortality between COVID-19 patients with T-AC treatment and those treated with P-AC (RR 0.95, 95% CI, 0.78-1.15, P = 0.60). Similar results were also found in the OBs analyses (RR 1.21, 95% CI, 0.98-1.49, P = 0.08). The pooling meta-analysis using a random-effects model combined with effect sizes showed that in the RCTs and OBs analyses, patients with COVID-19 who received T-AC treatment had a significantly higher relative risk of the major bleeding event than those with P-AC treatment in COVID-19 patients (RCTs: RR 1.76, 95% CI, 1.19-2.62, P = 0.005; OBs: RR 2.39, 95% CI, 1.56-3.68, P < 0.0001). Compared with P-AC treatment in COVID-19 patients, patients with T-AC treatment significantly reduced the incidence of venous thromboembolism (RR 0.51, 95% CI, 0.39-0.67, P<0.00001), but it is not associated with arterial thrombosis events (RR 0.97, 95% CI, 0.66-1.42, P = 0.87). The subgroup analysis of OBs shows that the mortality risk significantly reduces in critically ill COVID-19 patients treated with T-AC compared with those with P-AC treatment (RR 0.58, 95% CI, 0.39-0.86, P = 0.007), while the mortality risk significantly increases in non-critically ill COVID-19 patients treated with T-AC (RR 1.56, 95% CI, 1.34-1.80, P < 0.00001). In addition, T-AC treatment does not reduce the risk of mortality in COVID-19 patients with high d-dimer levels in RCTs. Finally, the overall sensitivity analysis after excluding two RCTs studies remains consistent with the previous results. CONCLUSIONS In our integrated analysis of included RCTs and OBs, there is no significant difference between the mortality of T-AC and P-AC treatment in unselected patients with COVID-19. T-AC treatment in COVID-19 patients significantly reduced the incidence of venous thromboembolism but showed a higher risk of bleeding than those with P-AC treatment. In addition, P-AC treatment was superior to T-AC treatment in non-critically ill COVID-19 patients, the evidence supporting the necessity for T-AC treatment in critically ill COVID-19 patients came only from OBs. TRIAL REGISTRATION Protocol registration: The protocol was registered at PROSPERO (CRD42021293294).

Abstract

OBJECTIVES Venous thrombosis has been widely described in the setting of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection; however, arterial thrombosis has rarely been reported. This study aims to assess the incidence, risk factors, interventions, and outcomes of acute aortoiliac arterial thrombosis in patients with active SARS-CoV-2 infections. METHODS We present seven SARS-CoV-2-positive patients from our institution who acutely developed thrombi in the aortoiliac arterial system (7/2020-1/2021). A systematic review of the literature on aortoiliac arterial thrombosis in patients with SARS-CoV-2 infections in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was also performed. The available data from all reported cases in the literature and at our institution were analyzed. RESULTS Thirty published articles and journal correspondences, including 52 patients, were reviewed and analyzed in addition to our institution's 7 cases. In total, 59 SARS-CoV-2-positive patients were found to have acute aortoiliac thrombosis. The abdominal aorta was the most frequent location for the development of a thrombus. Baseline demographics and medical comorbidities were not significantly different between the symptomatic and asymptomatic cohorts. Seventy-one percent of patients were symptomatic (lower limb ischemia: 75.0%, renal infarction: 20.0%, stroke: 12.5%, mesenteric ischemia: 10.0%). All patients with thrombus involving the ascending aorta, aortic bifurcation, or iliac artery developed thromboembolic or ischemic complications. All patients received systemic anticoagulation. Fifty-three percent of all patients were managed medically. Ninety-four percent of the asymptomatic patients were managed medically. One asymptomatic patient underwent endovascular aspiration of a mobile thrombus. Three (23.1%) deaths occurred in the asymptomatic cohort from hypoxic respiratory failure. Fourteen (36.8%) deaths occurred in the symptomatic cohort. The in-hospital mortality rate was 33.3% overall and 43.8% for patients with thrombi involving more than one aortoiliac segment. CONCLUSIONS The presence of thrombi in the aortoiliac arterial system appears to be a poor prognostic indicator for patients with active SARS-CoV-2 infections. Medical management of patients with asymptomatic aortoiliac thrombi may be considered. The presence of thrombi involving the ascending aorta, aortic bifurcation, or iliac artery may warrant consideration for operative intervention due to the risk for thromboembolic or ischemic complications. Further study is needed to fully delineate the risk factors, optimal treatment, and outcomes of arterial thrombosis in the setting of SARS-CoV-2 infection.

Abstract

BACKGROUND Coronavirus disease 2019 (COVID-19) is associated with increased thrombosis prevalence. However, there are insufficient data supporting the appropriate anticoagulation dose in COVID-19. OBJECTIVE We aim to systematically assess the currently available data regarding the effects of different dosing regimens of low molecular weight heparin and/or fondaparinux (LMWH/F) on mortality risk as well as the risk of arterial/venous thrombotic events and hemorrhagic complications in confirmed COVID-19 cases. DESIGN We conducted a living systematic review and meta-analysis on the effects of different LMWH/F doses on mortality, thrombotic and hemorrhagic events in COVID-19 patients. DATA SOURCES AND METHODS MEDLINE, Scopus, Embase, Cochrane Library, Cochrane COVID-19 study register, European Union Drug Regulating Authorities Clinical Trials Database, and ClinicalTrials.gov were searched to detect observational cohort studies and randomized-controlled clinical trials (RCTs) comparing difference doses of LMWH/F among confirmed COVID-19 cases. RESULTS Thirty-one eligible studies (6 RCTs and 25 cohort studies) with 11,430 hospitalized patients were included. No association was found between LMWH/F and mortality during the following comparisons: (1) no LMWH/F versus any LMWH/F; (2) prophylactic versus higher than prophylactic LMWH/F; (3) prophylactic versus therapeutic LMWH/F; (4) intermediate versus therapeutic LMWH/F; and (5) lower than therapeutic versus therapeutic LMWH/F. Mortality was higher in patients receiving prophylactic versus intermediate LMWH/F (OR = 2.01; 95% CI: 1.19-3.39). However, this effect was mostly driven by observational data. No associations were detected between the intensity of LMWH/F and the risk of thrombotic and hemorrhagic events, except the lower risk for hemorrhage in patients on prophylactic compared to higher LMWH/F doses. CONCLUSION The risk for all-cause mortality was higher in patients receiving prophylactic LMWH/F compared to those on an intermediate dose of LMWH/F, based on observational data. These results should be interpreted in light of the moderate quality and heterogeneity of the included studies. REGISTRATION The study protocol has been registered in the International Prospective Register of Ongoing Systematic Reviews PROSPERO (Registration number: CRD42021229771).

Abstract

AIMS: To update our previously reported systematic review and meta-analysis of observational studies on cardiovascular drug exposure and COVID-19 clinical outcomes by focusing on newly published randomized controlled trials (RCTs). METHODS More than 500 databases were searched between 1-Nov-2020 and 2-Oct-2021 to identify RCTs that were published after our baseline review. One reviewer extracted data with other reviewers verifying the extracted data for accuracy and completeness. RESULTS After screening 22,414 records, we included 24 and 21 RCTs in the qualitative and quantitative syntheses, respectively. The most investigated drug classes were angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blocker (ARBs) and anticoagulants, investigated by 10 and 11 studies respectively. In meta-analyses, ACEI/ARBs did not affect hospitalization length (mean difference/MD -0.42, 95% CI -1.83; 0.98 days, n=1183), COVID-19 severity (risk ratio/RR 0.90, 95% CI 0.71; 1.15, n=1661) and mortality (RR 0.92, 95% CI 0.58; 1.47, n=1646). Therapeutic anticoagulation also had no effect (hospitalization length MD -0.29, 95% CI -1.13 to 0.56 days, n=1449; severity RR 0.86, 95% CI 0.70; 1.04, n=2696; and, mortality RR 0.93, 95% CI 0.77; 1.13, n=5689). Other investigated drug classes were antiplatelets (aspirin, 2 trials), antithrombotics (sulodexide, 1 trial), calcium channel blockers (amlodipine, 1 trial) and lipid modifying drugs (atorvastatin, 1 trial). CONCLUSION Moderate- to high-certainty RCT evidence suggests that cardiovascular drugs such as ACEIs/ARBs are not associated with poor COVID-19 outcomes, and should therefore not be discontinued. These cardiovascular drugs should also not be initiated to treat or prevent COVID-19 unless they are needed for an underlying currently approved therapeutic indication.

Abstract

Implementation of higher dose (HD) thromboprophylaxis has been considered in patients infected with coronavirus disease 2019 (COVID-19). Our aim was to compare HD to standard dose (SD) thromboprophylaxis in COVID-19 patients. The protocol is registered on PROSPERO (CRD42021284808). We searched for randomised controlled studies (CENTRAL, Embase, Medline and medRxviv) that compared HD to SD anticoagulation in COVID-19 and analysed outcomes such as mortality, thrombotic events, bleedings, and disease progression. The statistical analyses were made using the random effects model. Fourteen articles were included (6253 patients). HD compared with SD showed no difference in mortality (OR 0.83 [95% CI 0.54-1.28]). The use of HD was associated with a decreased risk of thrombosis (OR 0.58 [95% CI 0.44-0.76]), although with an increased risk of major bleeding (OR 1.64 [95% CI 1.25-2.16]). The cohort with D-dimer < 1 mg/mL showed no effect (OR 1.19 [95% CI 0.67-2.11]), but in the case of D-dimer > 1 mg/mL, a tendency of lower risk in the HD group was observed (OR 0.56 [95% CI 0.31-1.00]). The need for intubation in moderately ill patients showed a nonsignificant lower likelihood in the HD group (OR 0.82 [95% CI 0.63-1.08]). We cannot advocate for HD in all COVID-19 patients, although it shows some nonsignificant benefits on disease progression in those with elevated D-dimer who do not need ICU admission.

Abstract

We aimed to conduct the current meta-analysis to provide better insight into the efficacy of mechanical thrombectomy (MT) in managing COVID-19 patients suffering from a stroke. An electronic search was conducted through eight databases for collecting the current evidence about the efficacy of MT in stroke patients with COVID-19 until 18 December 2021. The results were reported as the pooled prevalence rates and the odds ratios (ORs), with their corresponding 95% confidence intervals (CI). Out of 648 records, we included nine studies. The prevalence of stroke patients with COVID-19 who received MT treatment was with TICI ≥2b 79% (95%CI: 73-85), symptomatic intracranial haemorrhage 6% (95%CI: 3-11), parenchymal haematoma type 1, 11.1% (95%CI: 5-23), and mortality 29% (95%CI: 24-35). On further comparison of MT procedure between stroke patients with COVID 19 to those without COVID-19, we found no significant difference in terms of TICI ≥2b score (OR: 0.85; 95%CI: 0.03-23; p = 0.9). However, we found that stroke patients with COVID-19 had a significantly higher mortality rate than stroke patients without COVID-19 after MT procedure (OR: 2.99; 95%CI: 2.01-4.45; p < 0.001). Stroke patients with COVID-19 can be safely and effectively treated with MT, with comparable reperfusion and complication rates to those without the disease.

Abstract

Background: Hypercoagulability and thromboembolic events are associated with poor prognosis in coronavirus disease 2019 (COVID-19) patients. Whether chronic oral anticoagulation (OAC) improve the prognosis is yet controversial. The present study aimed to investigate the association between the chronic OAC and clinical outcomes in COVID-19 patients. Methods: PubMed, Embase, Web of Science, and the Cochrane Library were comprehensively searched to identify studies that evaluated OAC for COVID-19 until 24 July 2021. Random-effects model meta-analyses were performed to pool the relative risk (RR) and 95% confidence interval (CI) of all-cause mortality and intensive care unit (ICU) admission as primary and secondary outcomes, respectively. According to the type of oral anticoagulants [direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs)], subgroup and interaction analyses were performed to compare DOACs and VKAs. Meta-regression was performed to explore the potential confounders on all-cause mortality. Results: A total of 12 studies involving 30,646 patients met the inclusion criteria. The results confirmed that chronic OAC did not reduce the risk of all-cause mortality (RR: 0.92; 95% CI 0.82-1.03; p = 0.165) or ICU admission (RR: 0.65; 95% CI 0.40-1.04; p = 0.073) in patients with COVID-19 compared to those without OAC. The chronic use of DOACs did not reduce the risk of all-cause mortality compared to VKAs (P (interaction) = 0.497) in subgroup and interaction analyses. The meta-regression failed to detect any potential confounding on all-cause mortality. Conclusion: COVID-19 patients with chronic OAC were not associated with a lower risk of all-cause mortality and ICU admission compared to those without OAC, and the results were consistent across DOACs and VKA subgroups. Systematic Review Registration: clinicaltrials.gov, identifier CRD42021269764.