Soluble factors in COVID-19 mRNA vaccine-induced myocarditis causes cardiomyoblast hypertrophy and cell injury: a case report.

BACKGROUND: Inflammation affecting the heart and surrounding tissues is a clinical condition recently reported following COVID-19 mRNA vaccination. Assessing trends of these events related to immunization will improve vaccine safety surveillance and best practices for forthcoming vaccine campaigns. However, the causality is unknown, and the mechanisms associated with cardiac myocarditis are not understood. CASE PRESENTATION: After the first dose, we reported an mRNA vaccine-induced perimyocarditis in a young patient with a history of recurrent myocardial inflammation episodes and progressive loss of cardiac performance. We tested this possible inflammatory cytokine-mediated cardiotoxicity after vaccination in the acute phase (ten days), and we found a significant elevation of MCP-1, IL-18, and IL-8 inflammatory mediators. Still, these cytokines decreased considerably at the recovery phase (42 days later). We used the cardiomyoblasts cell line to test the effect of serum on cell viability, observing that serum from the acute phase reduced the cell viability to 75%. We did not detect this toxicity in cells when we tested serum from the patient in the recovery phase. We also tested serum-induced hypertrophy, a phenomenon in myocarditis and heart failure. We found that acute phase-serum has hypertrophy effects, increasing 25% of the treated cardiac cells' surface and significantly increasing B-type natriuretic peptide. However, we did not observe the hypertrophic effect in the recovery phase or sera from healthy controls. CONCLUSION: Our results opened the possibility of the inflammatory cytokines or serum soluble mediators as key factors for vaccine-associated myocarditis. In this regard, identifying anti-inflammatory molecules that reduce inflammatory cytokines could help avoid vaccine-induced myocardial inflammation.

Risk Factors, Clinical Presentation, Therapeutic Trends, and Outcomes in Arterial Thrombosis Complicating Unvaccinated COVID-19 Patients: A Systematic Review.

Data on characteristics and outcomes of coronavirus (COVID)-19 patients complicated with arterial thrombosis (AT) are scarce. Therefore, we carried out a systematic review (PRISMA, PROSPERO statements; PubMed, Scopus, and Web of Science) to identify risk factors, clinical presentation, treatment, and outcomes. We included publications from December 2019 to October 2020. Groups: (a) ischemic stroke, (b) thrombotic storm, (c) peripheral vascular thrombosis, (d) myocardial infarction, and (e) left cardiac thrombus or in-transit thrombus (venous system thrombus floating or attaching to the right heart). We considered 131 studies. The most frequent cardiovascular risk factors were: hypertension, diabetes, and dyslipidemia. A high proportion presented with asymptomatic, mild, or moderate COVID-19 (n = 91, 41.4%). We identified a high percentage of isolated ischemic stroke and thrombotic storm. Groups with higher mortality rate: intracardiac thrombus (1/2, 50.0%), thrombotic storm (18/49, 36.7%), and ischemic stroke (48/131, 36.6%). A small number received thromboprophylaxis. Most patients received antithrombotic treatment. The most frequent bleeding complication was intracranial hemorrhage, primarily with isolated stroke. Overall mortality was 33.6% (74/220). Despite a wide range of COVID-19 severity, a high proportion had AT as a complication of non-severe disease. AT can affect different vascular territories; mortality is associated with stroke, intensive care unit stay, and severe COVID-19.

Venous Thromboembolism in Hospitalized COVID-19 Patients Treated in a Single Academic Center in Mexico: A Case Series Study.

BACKGROUND: The increasing prevalence of venous thromboembolism (VTE) among patients with coronavirus disease 2019 (COVID-19) is a matter of concern as it contributes significantly to patients' morbidity and mortality. Data regarding the optimal anticoagulation regimen for VTE prevention and treatment remain scarce. This study describes the characteristics, treatment, and outcomes of COVID-19 patients with VTE treated in a single academic center in Mexico. METHODS: We conducted a retrospective study of all patients with a positive PCR test for SARS-CoV-2 hospitalized in a single academic center in Monterrey, Mexico, between March 2020 and February 2021, with a radiologically confirmed VTE, including deep venous thrombosis (DVT) and pulmonary embolism (PE). Informed consent was obtained from each patient before reviewing their medical records. RESULTS: Of the 2000 COVID-19 hospitalized patients, 36 (1.8%) developed VTE and were included in the analysis. The median age was 60 years (range 32-88 years), and up to 78% (n = 28) were males. Most patients (n = 34, 94%) had an underlying comorbidity and 47% (n = 17) had a BMI ≥ 30 kg/m2. In most cases (n=28, 78%), VTE presented as a PE, whereas the remaining 22% (n = 8) had a DVT. The median time between hospital admission and VTE was 8 days (range 0-33 days). Regarding the thromboprophylaxis regimen, 35/36 patients received low molecular weight heparin enoxaparin on admission, most commonly at a dose of 60 mg daily (n = 19, 53%). Other complications presented were superinfection (n = 19, 53%), acute kidney injury (n = 11, 31%), and septic shock (n = 5, 14%). A total of 69% of patients (n = 25) required intensive care unit admission, and patients' overall mortality was 55.6%. CONCLUSION: VTE remains a significant cause of increased morbidity and mortality among patients with COVID-19. The strikingly high mortality among patients with VTE highlights the need for further investigation regarding the best preventive, diagnostic, and treatment approaches.

Differences between surviving and non-surviving venous thromboembolism COVID-19 patients: a systematic review.

BACKGROUND: To our knowledge, the treatment, outcome, clinical presentation, risk stratification of patients with venous thromboembolism and COVID-19 have not been well characterized. METHODS: We searched for systematic reviews, cohorts, case series, case reports, editor letters, and venous thromboembolism COVID-19 patients' abstracts following PRISMA and PROSPERO statements. We analyzed therapeutic approaches and clinical outcomes of venous thromboembolism COVID-19 patients. Inclusion: COVID-19 patients with venous thromboembolism confirmed by an imaging method (venous doppler ultrasound, ventilation-perfusion lung scan, computed tomography pulmonary angiogram, pulmonary angiography). We assessed and reported the original Pulmonary Embolism Severity Index for each pulmonary embolism patient. In addition, we defined major bleedings according to the International Society of Thrombosis and Haemostasis criteria. RESULTS: We performed a systematic review from August 9 to August 30, 2020. We collected 1,535 papers from PubMed, Scopus, Web of Science, Wiley, and Opengrey. We extracted data from 89 studies that describe 143 patients. Unfractionated and low-molecular-weight heparin was used as parenteral anticoagulation in 85/143 (59%) cases. The Food and Drug Administration-approved alteplase regimen guided the advanced treatment in 39/143 (27%) patients. The mortality was high (21.6%, CI 95% 15.2-29.3). The incidence of major bleeding complications was 1 (0.9%) in the survival group and 1 (3.2%) in the death group. Pulmonary Embolism Severity Index was class I in 11.6% and II in 22.3% in survivors compared to 0% and 6.5% in non-survivors, respectively. Patients who experienced venous thromboembolism events at home were more likely to live than in-hospital events. CONCLUSIONS: We determined a high mortality incidence of pulmonary embolism and a low rate of bleeding. Unfractionated and low-molecular-weight heparin drove parenteral anticoagulation and alteplase the advanced treatment in both groups. The original Pulmonary Embolism Severity Index could be helpful in the risk stratification.

Clinical outcomes of very elderly patients treated with ultrasound-assisted catheter-directed thrombolysis for pulmonary embolism: a systematic review.

Pulmonary embolism (PE) is a significant cause of death in the very elderly (≥ 75 years) population. Ultrasound-assisted catheter-directed thrombolysis (USCDT) emerges to improve thrombolysis safety and efficacy. However, outcomes in very elderly patients are unknown, as randomized controlled trials exclude this population. Recently, we demonstrated acute kidney injury (AKI) and ischemic hepatitis in an octogenarian intermediate-risk PE patient treated with USCDT. Considering the lack of evidence, we undertook a systematic review to evaluate the clinical outcomes in very elderly PE patients treated with USCDT. We searched for very elderly PE patients treated with USCDT from 2008 to 2019. Additionally, we conducted another systematic review without age restriction to update previous evidence and compare both populations. We also did an exploratory analysis to determine if thrombolysis was followed based on current guidelines or impending clinical deterioration factors. We identified 18 very elderly patients (age 79.2, 75-86), mostly female and with intermediate-risk PE. We found an intracranial hemorrhage (ICH), and a right pulmonary artery rupture. Additionally, two significant bleedings complicated with transient AKI, and one case of AKI and ischemic hepatic injury. The patients who survived all had clinical and echocardiographic in-hospital improvement. Despite low rt-PA doses, ICH and major bleeding remain as feared complications. Thrombolysis decision was driven by impending clinical deterioration factors instead of international guideline recommendations. Our data do not suggest prohibitive risk associated with USCDT in very elderly intermediate and high-risk PE patients. Despite long-term infusions and right ventricular dysfunction, AKI and ischemic hepatic injury were infrequent.

Systemic thrombolysis and anticoagulation improved biomarker measurements in massive-like pulmonary embolism and severe COVID-19 pneumonia: a case report.

BACKGROUND: From asymptomatic patients to severe acute respiratory distress syndrome, COVID-19 has a wide range of clinical presentations, and venous thromboembolism has emerged as a critical and frequent complication. CASE SUMMARY: We present a case of a 69-year-old man with a clinical presentation of massive-like pulmonary embolism (PE) overlapping with severe COVID-19 pneumonia. The diagnosis was made based on hypotension, severe oxygen desaturation (33%), and right ventricular dysfunction (RVD). We used alteplase and low-molecular-weight heparin, obtaining immediate clinical improvement. Also, we identified an extremely elevated D-dimer (31.2 mcg/mL), and computed tomography pulmonary angiography (CTPA) revealed an unexpected low thrombus burden and a crazy-paving pattern. Considering this, we decided to discontinue the alteplase. Therefore, the mechanisms of pulmonary hypertension and RVD could be multifactorial. Despite the patient's respiratory status worsening and ongoing mechanical ventilation, biomarkers kept lowering to normal ranges. It appears a favourable outcome was related to early PE diagnosis and a multimodal therapeutic approach. DISCUSSION: Physicians in the ER should be warned about extremely high D-dimer measurements and severe oxygen desaturation as possible markers of severe COVID-19 pneumonia in patients with high-clinical suspicion of PE. Although ESC guidelines recommend immediate reperfusion in cardiogenic shock secondary to PE, we suggest initial CTPA in patients with high-clinical suspicion of severe COVID-19.