ABSTRACT
Objective: This is the first prospective cohort study in Singapore to investigate the COVID-19 vaccine-associated myocarditis to understand its pathophysiology. Introduction: Acute myocarditis and other cardiovascular symptoms have been observed to be associated with the two mRNA-based coronavirus disease 2019 (COVID-19) vaccines-namely Pfizer-BioNTech BNT162b2 and Moderna mRNA-1273)-currently in-use in Singapore. The mechanisms through which myocarditis occurs are unknown, hence our study aims to understand the pathophysiology of myocarditis associated with COVID-19 vaccines. Method(s): Patients with onset of cardiac manifestations were recruited from multiple hospital outpatient clinics between November 2021 and September 2022. Clinical history and physical examination data was collected with blood sample collection, echocardiography, 12-lead electrocardiogram (ECG), coronary angiography and magnetic resonance imaging (MRI) at recruitment and 6-month follow-up. Analysis of biomarkers, genetic, serological and MRI data was conducted. Result(s): As of 6 September 2022, a total of 5 patients have been enrolled (4 males, 1 female). The most commonly reported symptoms across all patients were chest pain/discomfort (80%), followed by palpitations (40%). MRI evidence of myocarditis has been detected in 2 (50%) of the male patients, of which both reported two or more symptoms occurring 1-2 days post-vaccination. Both patients have each received at least two doses of either the Pfizer-BioNTech BNT162b2 vaccine or Moderna mRNA-1273 vaccine. Their MRI findings were consistent with myocarditis. On late gadolinium enhancement (LGE) imaging, epicardial enhancement at the basal inferolateral segment and mid-wall enhancement at the apical anterior, lateral and inferior walls were observed in one patient. Patchy, mid-wall LGE in the basal inferior/inferolateral wall was observed in the other patient. No MRI evidence of myocarditis was available for the sole female patient. Conclusion(s): While more data is needed to definitively prove the association of the two mRNA-based Pfizer-BioNTech BNT162b2 and Moderna mRNA-1273 COVID-19 vaccines with post-vaccination myocarditis, we believe our findings may support further investigations to enable risk stratification for vaccine-associated myocarditis and identify potential preventative strategies accordingly.
ABSTRACT
INTRODUCTION: Despite reports suggesting an association between COVID-19 mRNA vaccination and pericarditis and myocarditis, detailed nationwide population-based data are sparsely available. We describe the incidence of pericarditis and myocarditis by age categories and sex after COVID-19 mRNA vaccination from a nationwide mass vaccination programme in Singapore. METHODS: The incidence of adjudicated cases of pericarditis and myocarditis following COVID-19 mRNA vaccination that were reported to the vaccine safety committee between January to July 2021 was compared with the background incidence of myocarditis in Singapore. RESULTS: As of end July 2021, a total of 34 cases were reported (9 pericarditis only, 14 myocarditis only, and 11 concomitant pericarditis and myocarditis) with 7,183,889 doses of COVID-19 mRNA vaccine administered. Of the 9 cases of pericarditis only, all were male except one. The highest incidence of pericarditis was in males aged 12-19 years with an incidence of 1.11 cases per 100,000 doses. Of the 25 cases of myocarditis, 80% (20 cases) were male and the median age was 23 years (range 12-55 years) with 16 cases after the second dose. A higher-than-expected number of cases were seen in males aged 12-19 and 20-29 years, with incidence rates of 3.72 and 0.98 case per 100,000 doses, respectively. CONCLUSION: Data from the national registry in Singapore indicate an increased incidence of pericarditis and myocarditis in younger men after COVID-19 mRNA vaccination.
ABSTRACT
Background : Critically-ill COVID-19 patients demonstrate a hypercoagulable state, hence necessitating thromboprophylaxis. However, in non-critically ill COVID-19 patients, the haemostatic profile is unknown. Aims : A prospective, observational study was performed to evaluate coagulation parameters, and thrombotic outcomes in critically and non-critically ill COVID-19 patients. Methods : Informed consent was obtained from 10 critically ill (oxygen dependent, PaO2/FiO2 ratio<300) PCR positive COVID-19 patients matched for age and gender with 10 non-critically ill patients (nonoxygen dependent). On recruitment, laboratory (FBC/LDH/CRP/ procalcitonin) and coagulation tests (PT/APTT/D-Dimer/Fibrinogen/ TCT/Factors II,V,VII,VIII,IX,X,XI/vWF/anti-thrombinIII/ProteinC/ ProteinS/antiphospholipid antibodies), Thromboelastography(TEG), Clot Waveform Analysis(CWA) were performed, with repeat TEG/ CWA every 3 days, till 21 days of admission or discharge. This study was DSRB approved and supported by an NHG-NCID grant. Results : The median age was 60 years(49.5, 64.5) with 16 males and 4 females. Median Padua score of critically ill patients was 5 with PaO2/FiO2 ratio 194.5 (174, 241). Hypercoagulability was present in critically ill patients with elevated median levels of Fibrinogen 5.6 g/L(4.9, 6.6), D-dimer 1.0 μg/ml(0.6, 1.4), Factor VIII 206%(171, 230), von Willebrand Factor 265%(206, 321) as compared with lower levels in non-critically ill patients. Hypercoagulability was shown in TEG with increased CRT Angle 78.9°(78.3, 80.0), CFF MA 34.6 mm(27.4, 38.6) and CFF A10 30.9 s (25.5, 34.0);and CWA had increased clot velocity, aPTT Min1 7.7%/s(6.4, 8.3). CK K, CK Angle, CK MA, CRT MA were higher in critically ill patients (Table 1). In noncritically ill patients, D-dimer levels were normal, 0.3 μg/mL(0.3, 0.4) while Factor VIII levels of 176%(157, 192) and vWF levels of 225%(158, 237) were mildly elevated, with TEG and CWA demonstrating no hypercoagulability. 2 critically-ill patients developed thromboembolism(stroke, DVT) while no non-critically ill patients (not on thromboprophylaxis) had thrombosis. Conclusions : Critically ill COVID-19 patients demonstrate a hypercoagulable state with raised fibrinogen and Factor VIII levels correlating with raised CK, CRT, CFF maximal amplitude and increased CWA clot velocity(min1), while non-critical patients showed an absence of hypercoagulability in global tests of haemostasis.
ABSTRACT
Coronavirus disease 2019 (COVID-19) is associated with an increased risk of thromboembolic events in the acute setting. However, the abnormal thrombotic diathesis is not known to persist into the recovery phase of COVID-19 infection. We described 3 cases of ST-segment elevation myocardial infarction in healthy male patients who recovered from COVID-19 with no prior cardiovascular risk factors. They shared features of elevated von Willebrand factor antigen, factor VIII and D-dimer level. One patient had a borderline positive lupus anticoagulant. Intravascular ultrasound of culprit vessels revealed predominantly fibrotic plaque with minimal necrotic core. Clot waveform analysis showed parameters of hypercoagulability. They were treated with dual antiplatelet therapy, angiotensin-converting-enzyme inhibitor, beta blocker and statin. These cases highlight the strong thrombogenic nature of COVID-19 that persisted among patients who recovered from infection. Several suspected mechanisms could explain the association between vascular thrombosis in the convalescent period (endothelial dysfunction, hypercoagulability, systemic inflammatory response and vasculopathy). Additional studies on "long COVID" are essential for identifying endotheliopathy and thrombotic sequalae.