BACKGROUND: Reports have suggested an association between the development of myocarditis and the receipt of messenger RNA (mRNA) vaccines against coronavirus disease 2019 (Covid-19), but the frequency and severity of myocarditis after vaccination have not been extensively explored.

METHODS: We searched the database of Clalit Health Services, the largest health care organization (HCO) in Israel, for diagnoses of myocarditis in patients who had received at least one dose of the BNT162b2 mRNA vaccine (Pfizer-BioNTech). The diagnosis of myocarditis was adjudicated by cardiologists using the case definition used by the Centers for Disease Control and Prevention. We abstracted the presentation, clinical course, and outcome from the patient's electronic health record. We performed a Kaplan-Meier analysis of the incidence of myocarditis up to 42 days after the first vaccine dose.

RESULTS: Among more than 2.5 million vaccinated HCO members who were 16 years of age or older, 54 cases met the criteria for myocarditis. The estimated incidence per 100,000 persons who had received at least one dose of vaccine was 2.13 cases (95% confidence interval [CI], 1.56 to 2.70). The highest incidence of myocarditis (10.69 cases per 100,000 persons; 95% CI, 6.93 to 14.46) was reported in male patients between the ages of 16 and 29 years. A total of 76% of cases of myocarditis were described as mild and 22% as intermediate; 1 case was associated with cardiogenic shock. After a median follow-up of 83 days after the onset of myocarditis, 1 patient had been readmitted to the hospital, and 1 had died of an unknown cause after discharge. Of 14 patients who had left ventricular dysfunction on echocardiography during admission, 10 still had such dysfunction at the time of hospital discharge. Of these patients, 5 underwent subsequent testing that revealed normal heart function.

CONCLUSIONS: Among patients in a large Israeli health care system who had received at least one dose of the BNT162b2 mRNA vaccine, the estimated incidence of myocarditis was 2.13 cases per 100,000 persons; the highest incidence was among male patients between the ages of 16 and 29 years. Most cases of myocarditis were mild or moderate in severity. (Funded by the Ivan and Francesca Berkowitz Family Living Laboratory Collaboration at Harvard Medical School and Clalit Research Institute.).

BACKGROUND: Reports have suggested an association between the development of myocarditis and the receipt of messenger RNA (mRNA) vaccines against coronavirus disease 2019 (Covid-19), but the frequency and severity of myocarditis after vaccination have not been extensively explored.

METHODS: We searched the database of Clalit Health Services, the largest health care organization (HCO) in Israel, for diagnoses of myocarditis in patients who had received at least one dose of the BNT162b2 mRNA vaccine (Pfizer-BioNTech). The diagnosis of myocarditis was adjudicated by cardiologists using the case definition used by the Centers for Disease Control and Prevention. We abstracted the presentation, clinical course, and outcome from the patient's electronic health record. We performed a Kaplan-Meier analysis of the incidence of myocarditis up to 42 days after the first vaccine dose.

RESULTS: Among more than 2.5 million vaccinated HCO members who were 16 years of age or older, 54 cases met the criteria for myocarditis. The estimated incidence per 100,000 persons who had received at least one dose of vaccine was 2.13 cases (95% confidence interval [CI], 1.56 to 2.70). The highest incidence of myocarditis (10.69 cases per 100,000 persons; 95% CI, 6.93 to 14.46) was reported in male patients between the ages of 16 and 29 years. A total of 76% of cases of myocarditis were described as mild and 22% as intermediate; 1 case was associated with cardiogenic shock. After a median follow-up of 83 days after the onset of myocarditis, 1 patient had been readmitted to the hospital, and 1 had died of an unknown cause after discharge. Of 14 patients who had left ventricular dysfunction on echocardiography during admission, 10 still had such dysfunction at the time of hospital discharge. Of these patients, 5 underwent subsequent testing that revealed normal heart function.

CONCLUSIONS: Among patients in a large Israeli health care system who had received at least one dose of the BNT162b2 mRNA vaccine, the estimated incidence of myocarditis was 2.13 cases per 100,000 persons; the highest incidence was among male patients between the ages of 16 and 29 years. Most cases of myocarditis were mild or moderate in severity. (Funded by the Ivan and Francesca Berkowitz Family Living Laboratory Collaboration at Harvard Medical School and Clalit Research Institute.).

ErbB2 interacting protein (Erbin) is a widely expressed protein and participates in inhibition of several intracellular signaling pathways. Its mRNA has been found to be present in relatively high levels in the heart. However, its physiological role in the heart has not been explored. In the present work, we elucidated the role of Erbin in cardiac hypertrophy. Cardiac hypertrophy was induced in mice either by isoproterenol administration or by aortic constriction. The level of Erbin was significantly decreased in both models. Erbin(-/-) mice rapidly develop decompensated cardiac hypertrophy, and following severe pressure overload all Erbin(-/-) mice died from heart failure. Down-regulation of Erbin expression was also observed in biopsies derived from human failing hearts. It is known that Erbin inhibits Ras-mediated activation of the extracellular signal-regulated kinase (ERK) by binding to Soc-2 suppressor of clear homolog (Shoc2). Our data clearly show that ERK phosphorylation is enhanced in the heart tissues of Erbin(-/-) mice. Furthermore, we clearly demonstrate here that Erbin associates with Shoc2 in both whole hearts and in cardiomyocytes, and that in the absence of Erbin, Raf is phosphorylated and binds Shoc2, resulting in ERK phosphorylation. In conclusion, Erbin is an inhibitor of pathological cardiac hypertrophy, and this inhibition is mediated, at least in part, by modulating ERK signaling.

BACKGROUND: COVID-19 continues to spread throughout the world. Real-time reverse transcriptase polymerase chain reaction (RT-PCR) is used to diagnose COVID-19, with its cycle threshold (Ct) value inversely related to the viral load. The association between Ct values and COVID-19 related outcomes has been studied in the hospital setting but less so in the community. We aimed to estimate the association between Ct values and the severity of community-diagnosed COVID-19 to provide evidence on the utility of Ct testing in this setting.

METHODS: This was a retrospective cohort study based on data from Israel's largest health organization. The study population included 34,658 individuals who tested positive for COVID-19 by RT-PCR and had available Ct values between June 1st and December 21st, 2020. Outcomes included COVID-19 related symptoms, hospitalization, severe disease, and death. Ct values were modelled both as discrete and continuous exposures.

RESULTS: After adjusting for known risk factors for severe COVID-19, low Ct values were associated with symptomatic disease (odds ratio [OR]: 1.51; 95% confidence interval [CI]:1.21-1.84), hospitalization (OR: 1.27; 95%CI: 1.12-1.49), severe disease (OR: 1.80; 95%CI: 1.43-2.27), and death (OR: 1.64; 95%CI: 1.06-2.59). By modelling the exposure as continuous, we noticed a dose-response relationship, with the risk gradually rising with lower Ct values.

CONCLUSIONS: This study found a significant association between low Ct values and severe COVID-19 related outcomes, with a dose-response relationship. This suggests that Ct values could be helpful in identifying high-risk patients diagnosed in the community.

BACKGROUND: COVID-19 continues to spread throughout the world. Real-time reverse transcriptase polymerase chain reaction (RT-PCR) is used to diagnose COVID-19, with its cycle threshold (Ct) value inversely related to the viral load. The association between Ct values and COVID-19 related outcomes has been studied in the hospital setting but less so in the community. We aimed to estimate the association between Ct values and the severity of community-diagnosed COVID-19 to provide evidence on the utility of Ct testing in this setting.

METHODS: This was a retrospective cohort study based on data from Israel's largest health organization. The study population included 34,658 individuals who tested positive for COVID-19 by RT-PCR and had available Ct values between June 1st and December 21st, 2020. Outcomes included COVID-19 related symptoms, hospitalization, severe disease, and death. Ct values were modelled both as discrete and continuous exposures.

RESULTS: After adjusting for known risk factors for severe COVID-19, low Ct values were associated with symptomatic disease (odds ratio [OR]: 1.51; 95% confidence interval [CI]:1.21-1.84), hospitalization (OR: 1.27; 95%CI: 1.12-1.49), severe disease (OR: 1.80; 95%CI: 1.43-2.27), and death (OR: 1.64; 95%CI: 1.06-2.59). By modelling the exposure as continuous, we noticed a dose-response relationship, with the risk gradually rising with lower Ct values.

CONCLUSIONS: This study found a significant association between low Ct values and severe COVID-19 related outcomes, with a dose-response relationship. This suggests that Ct values could be helpful in identifying high-risk patients diagnosed in the community.

Evidence regarding the effectiveness of covid-19 vaccine in patients with impaired immunity, is limited. Initial observations suggest a lower humoral response in these patients. We evaluated the relative effectiveness of the mRNA BNT162b2 vaccine in patients with hematological neoplasms compared to matched controls. Data on patients with hematological neoplasms after two vaccine doses were extracted and matched 1:1 with vaccinated controls. Subpopulation analyses focused on patients receiving therapy for the hematological neoplasm, patients without treatment who are only followed, and recipients of specific treatments. The analysis focused on covid-19 outcomes from day 7 through 43 following the second vaccine dose: Documented covid-19 infection by PCR; Symptomatic infection; Hospitalizations; Severe covid-19 disease and covid-19-related death. Of a population of 4.7 million insured people, 32,516 patients with hematological neoplasms were identified, of whom 5,017 were receiving therapy for an active disease. Vaccinated patients with hematological neoplasms, compared with vaccinated matched controls, had an increased risk of documented infections (RR 1.60, 95% confidence interval [CI] 1.12-2.37), symptomatic covid-19 (RR 1.72, 95% CI 1.05-2.85), covid-19 related hospitalizations (RR 3.13, 95% CI 1.68-7.08), severe covid-19 (RR 2.27, 95% CI 1.18-5.19) and covid-19 related death (RR 1.66, 95% CI 0.72-4.47). Limiting the analysis to patients on hematological treatments showed a higher increased risk. This analysis shows that vaccinated patients with hematological neoplasms, in particular patients on treatment, suffer from covid-19 outcomes more than vaccinated individuals with intact immune system. Ways to enhance covid-19 immunity in this patient population, such as additional doses, should be explored.

Evidence regarding the effectiveness of covid-19 vaccine in patients with impaired immunity, is limited. Initial observations suggest a lower humoral response in these patients. We evaluated the relative effectiveness of the mRNA BNT162b2 vaccine in patients with hematological neoplasms compared to matched controls. Data on patients with hematological neoplasms after two vaccine doses were extracted and matched 1:1 with vaccinated controls. Subpopulation analyses focused on patients receiving therapy for the hematological neoplasm, patients without treatment who are only followed, and recipients of specific treatments. The analysis focused on covid-19 outcomes from day 7 through 43 following the second vaccine dose: Documented covid-19 infection by PCR; Symptomatic infection; Hospitalizations; Severe covid-19 disease and covid-19-related death. Of a population of 4.7 million insured people, 32,516 patients with hematological neoplasms were identified, of whom 5,017 were receiving therapy for an active disease. Vaccinated patients with hematological neoplasms, compared with vaccinated matched controls, had an increased risk of documented infections (RR 1.60, 95% confidence interval [CI] 1.12-2.37), symptomatic covid-19 (RR 1.72, 95% CI 1.05-2.85), covid-19 related hospitalizations (RR 3.13, 95% CI 1.68-7.08), severe covid-19 (RR 2.27, 95% CI 1.18-5.19) and covid-19 related death (RR 1.66, 95% CI 0.72-4.47). Limiting the analysis to patients on hematological treatments showed a higher increased risk. This analysis shows that vaccinated patients with hematological neoplasms, in particular patients on treatment, suffer from covid-19 outcomes more than vaccinated individuals with intact immune system. Ways to enhance covid-19 immunity in this patient population, such as additional doses, should be explored.

BACKGROUND: Emerging data suggest increased arterial thrombosis risk in the months preceding a cancer diagnosis.

OBJECTIVES: To assess whether patients without documented vascular risk factors or pre-existing cardiovascular disease have a higher relative risk of cancer 12 months after arterial thrombotic events (ATE), compared to unselected patients.

PATIENTS/METHODS: A population-based cohort study of Clalit Health Services (CHS) database included CHS members ≥25 years without prior cancer or ATE (n = 2 804 584). An iterative matching process selected 10 potential controls chronologically for each consecutive exposed, age- and sex-matched (actual controls drawn 1:1 from a lot). Study exposure, ATE, was defined as ischemic stroke, transient ischemic attack, myocardial infarction or systemic arterial thromboembolism during hospitalization. The outcome was newly-diagnosed cancer within 12 months, based on Israeli national cancer registry. Cox proportional hazards multivariate regression calculated hazard ratio (HR) for outcomes, adjusted for cancer risk factors. Analysis also performed for three subgroups: age ≤50 years; no cardiovascular risk factors; no prior cardiovascular disease.

RESULTS: The full ATE and matched control cohorts included 43 108 patients. The 12-month cumulative incidence of cancer (95% confidence interval) was 0.020 (0.019-0.022) in the ATE cohort and 0.012 (0.011-0.013) in controls, corresponding to an adjusted HR of 1.665 (1.489-1.862). The relative risk of cancer was high in all subgroups up to a HR of 3.754 (1.912-7.372) in patients without cardiovascular risk factors.

CONCLUSION: There is an increased risk of previously undiagnosed cancer at 12 months after ATE, especially in patients without documented vascular risk factors or pre-existent cardiovascular disease.