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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.
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Background: Regional variations in the impact of the coronavirus disease-2019 (COVID-19) pandemic on out-of-hospital cardiac arrest (OHCA) have been reported. We aimed to examine differences in the community response, emergency medical services (EMS) interventions, and outcomes of OHCA, in Singapore (population 5.7 million) and Atlanta (population 4.16 million), before and during the pandemic. Methods: Using prospectively collected Singapore Pan-Asian Resuscitation Outcomes Study (PAROS) and Atlanta Cardiac Arrest Registry to Enhance Survival (CARES) data, we compared EMS-treated adult OHCAs (≥18 years) during the pandemic period (17weeks from the date of first confirmed COVID-19 case) and pre-pandemic period (corresponding weeks in 2019). The primary outcome was pre-hospital return of spontaneous circulation (ROSC). We reported adjusted odds ratios (aOR) for OHCA characteristics, pre-hospital interventions, and outcomes using binary logistic regression. Results: Of the 3987 EMS-treated OHCAs (overall median age 69 years, 60.1% males) in Singapore and Atlanta, 2084 occurred during the pandemic and 1903 during the pre-pandemic period. Compared with Atlanta, OHCA cases in Singapore were older (median age 72 vs 66 years), received more bystander interventions (65.1% vs 41.4% received cardiopulmonary resuscitation (CPR) and 28.4% vs 10.1% had automated external defibrillator application), yet observed less pre-hospital ROSC (11.3% vs 27.1%). When compared with the pre-pandemic period, the likelihood of residential OHCAs doubled in both cities during the pandemic;in Singapore, OHCAs were more likely to be witnessed (aOR 1.95, 95% confidence interval (CI), 1.59-2.39) yet less likely to receive CPR (aOR 0.81, 95% CI, 0.65-0.99) during the pandemic. OHCAs occurring during the pandemic, compared with pre-pandemic, were less likely to be transported in Singapore and Atlanta (aOR 0.50, 95% CI, 0.42%-0.85%, and 0.36, 95% CI, 0.26-0.50, respectively), without significant differences in overall pre-hospital ROSC. Conclusion: Changes in OHCA characteristics and pre-hospital interventions during the pandemic were likely collateral consequences, with regional variations partly reflecting differences in systems of care and other sociocultural factors. These highlight opportunities for public education and the need for further study into lower transport rates during the pandemic.
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BACKGROUND Bortezomib-based induction (V-IND) approaches are used in >90% of Australian newly diagnosed transplant eligible multiple myeloma (NDTE MM) patients (pts) with a maximum of 4 cycles of V-IND therapy available via the pharmaceutical benefits scheme (PBS) prior to a planned autologous stem cell transplantation (ASCT). However, NDTE MM patients failing V-IND (defined as best response < partial response [PR]) demonstrate shortened survival and continue to represent a sub-group of MM where a clear unmet medical need persists. The ALLG MM21 was designed to evaluate the efficacy of an early response adapted approach with a switch to an intensive Daratumumab-lenalidomide-dexamethasone (DRd)-based salvage-ASCT- consolidation strategy in patients failing V-IND. METHOD We present the results of a planned interim analysis of the multi-centre single arm study MM21 (ACTRN12618001490268). Eligible pts were NDTE MM who had received V-IND pre-ASCT and demonstrated either a sub-optimal response (SOR - defined as <minimal response [MR] after 2 cycles or <PR after 4 cycles of V-IND) or primary refractoriness (1REF - defined as disease progression while on or within 60 days of completing V-IND). Pre-ASCT DRd was DARA 16mg/kg IV days 1, 8, 15 and 22 for cycles 1 (C1) and 2, and on days 1 and 15 of C3 and C4;Lenalidomide 25mg OD D1-21;and, dexamethasone 40mg PO on D 1, 8, 15 and 22 of each 28-day cycle for C1 to C4. Anti-thrombotic and anti-viral prophylaxis was as per individual institutional practice. Between C3 and C4, patients underwent a G-CSF mobilised PBSC collection with a melphalan 200mg/m2 conditioned ACST after C4. Patients underwent D100 post-ASCT disease response assessment including EuroFlow minimal residual disease (MRD) testing. In the absence of disease progression, patients then received 12, 28-day cycles of consolidation comprising DARA IV 16mg/kg on D1, 15 of C1 and C2 and on D1 of C3 to C12, lenalidomide 25mg PO on D1-21 of C1 and C2 and 10mg OD on days 1-28 of C3 to C12;dexamethasone 40mg was weekly from C1 to C12. RESULTS Fifty patients were recruited from 7 Australian sites between March 2019 and July 2020. Median age was 61 years with 66% males. Disease status at study entry was SOR in 72% (<MR n = 9, <PR n = 27) and 1REF in 28%. Data cut-off date was June 30 2021. 45 patients (90%) received 4 complete cycles of salvage DRd. 11/50 (22%) patients did not undergo ASCT and 4 patients failed stem cell collection. Two pts were withdrawn due to treatment related gastrointestinal toxicity - persistent oesophagitis (n =1) and recurrent colitis (n=1). There were two deaths, due to COVID-19 pneumonia (n =1) and septic shock (n =1). Pre-ASCT response was evaluable in 43 patients, overall response rate (ORR) was 70% - complete response (CR) 6%, very good partial response (VGPR) 18%, partial response (PR) 46%, clinical benefit rate (CBR) 83% - MR 11% and stable disease (SD) 2% on Intention to Treat (ITT n = 50) analysis. 33 patients were assessed for MRD - MRD negative 6% on ITT (3/33 9%). Pre-consolidation disease assessment was evaluable in 37 pts, both ORR and CBR were 72% - stringent complete response (sCR) 4%, CR 14%, VGPR 24%, PR 30% ITT analysis. 31 pts were evaluated for MRD - MRD negative 28% ITT (14/31 45%). In 6 patients, MRD was omitted or could not be performed due to pre-analytical issues. Post-C2 consolidation assessment was evaluable in 37 pts, ORR 72% - sCR 2%, CR 24%, VGPR 26%, PR 20%, CBR 74% - SD 2% ITT analysis. To date, 22 patients have been evaluated for MRD with 4 patients awaiting results, MRD negative rate of 38% ITT (10/22 45%). MRD sample collection at this time-point was omitted in 7 patients, potentially skewing MRD negativity on ITT analysis. CONCLUSION Preliminary analysis of the MM21 trial demonstrates early response-adaptive escalation to DRd facilitated ASCT in the majority patients with robust ORR post-autologous stem cell transplant and substantial improvement in disease control, as reflected in improved rates of MRD and disease response to treatment. At both post-ASCT time-p ints there was significant drop off in MRD testing due to testing omission, potential skewing results of MRD analysis. MRD and duration of response analysis following C12 consolidation is planned and will be of interest. Current data suggests this drug combination shows potential for substantial benefit in the study population. (Figure Presented).
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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.
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Background: COVID-19 pandemic has been devastating not only medically but also socially and economically. Selangor, an urbanised state in Malaysia, has been severely affected by COVID19. There is concern that patients with rheumatic diseases (RD) may have higher risk of infection, with increased mortality1. Objectives: To investigate patients' characteristics which are associated with 'feeling stressed' among patients with RD during the second wave of COVID19 infection in Selangor. Methods: This is a cross-sectional study conducted over 3 weeks during the second wave of COVID19 infection in Malaysia. Patients with RD, scheduled for rheumatology clinic appointment in a rheumatology referral centre were invited to participate in this study. Personal and clinical data were collected by phone interview and from patients' medical records respectively. Patients were asked to grade their disease activity by giving a score from 0 (not active) to 10 (active). All patients were asked 'are you feeling stressed' and the answer was recorded as yes or no. Reasons explored for a yes answer, included financial, social disruption, physical illness and future uncertainties. Categorical and continuous data were analysed using chi-squared test and student t-test, respectively. A p-value of <0.05 is considered statistically significant. Results: Three hundred and sixty-one patients with various RD participated in this study. The mean age of these was 48.2 years (range between 16-80 years). More than half (54.3%) were Malay and other ethnicities were Chinese (25.5%), Indian (18.2%) and others (2%). A quarter of patients (24.7%) were not working (unemployed, retired and students) and a third of patients (32.1%) had unpaid work (mainly housewife). The other patients' characteristics are shown in Table 1. Eighty-three (23%) admitted to 'feeling stressed' and the stressors identified were physical illness in 34 (40.9%), social disruption in 23 (27.7%), financial problems in 23 (27.7%) and future uncertainties in 19 (22.9%). Patients' characteristics that were significantly different between patients who were 'feeling stressed' and not 'feeling stressed' were age, employment status and perceived disease activity (Table 1). Conclusion: The COVID19 pandemic has caused mental distress in a significant number of RD patients and associations were found with older age, having paid work and perceived disease activity. Issues that may influence patients' responses, including access to rheumatology care, medication and fear of getting infection were not explored in this study.
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Background: COVID-19 is a major global pandemic. Since the first case reported in Wuhan, China, COVID-19 has spread across the globe with more than 7.6 million individuals affected worldwide. Several studies have tried to investigate the risk factors for mortality but there has bot been a definitive study in patients with ESRD. Herein, we aimed to investigate whether ESRD is associated with mortality as compared to age, gender and comorbidities matched cohorts. Methods: A retrospective case control study was performed on patients 18-yearold with confirmed SARS-CoV-2 admitted to our hospital during the study period (03/15/2020 to 05/15/2020). Demographic, characteristics and clinical outcome were retrieved and reviewed. We found 39 ESRD patients, we matched them for 5 variables: Age, gender, diabetes mellitus (DM), hypertension (HTN), and body mass index (BMI). Age was stratified into 3 groups (< 30, 30 to 60, >60), history of DM and HTN were defined by reviewing the admission medications, and BMI was divided into 2 categories (< 30 and 30 kg/m2). The primary endpoint was percentage of inpatient mortality. Results: We had 39 ESRD patients with COVID-19 out of the 400 patients admitted during the study period with known clinical outcome. Nineteen patients (49%) were between 30 to 60 years old while the rest (51%) were older than 60 years old. As for gender, 25 (64%) were males and 14 (36%) females. Additional comorbidities were present in 38 patients with hypertension (92%) being the most common, followed by DM (64%) and BMI >30 kg/m2 (49%). With the 5 variables, we were able to match with 177 controls. Nineteen individuals expired out of the 39 ESRD patients (49%), as compared to 46 patients from the 177 matched cohort (26%) (z-score 2.80, p=0.0051;odds ratio [OR], 2.71;95% confidence interval [CI], 1.28-5.41). Conclusion: Our results suggest that ESRD patients is an independent risk factor for increased mortality in patients with COVID 19 disease. Larger prospective studies will need to confirm this finding and try to find ways to mitigate this very high mortality in this vulnerable population.