Risks of Myocarditis and Pericarditis Following Vaccination with SARS-CoV-2 mRNA Vaccines in Japan: An Analysis of Spontaneous Reports of Suspected Adverse Events.

OBJECTIVE: To identify the risks of myocarditis or pericarditis after vaccination with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines in Japan. METHODS: We conducted an observed-to-expected analysis (OE analysis) of spontaneous reports of suspected adverse events from pharmaceutical companies, calculating rate ratios with myocarditis and pericarditis after the vaccination of the mRNA vaccines Comirnaty (BNT162b2) and Spikevax (mRNA-1273) and expected rate of myocarditis and pericarditis in the population before the COVID-19 pandemic. These reports dated from 17/2/2021 to 14/11/2021 and from 22/5/2021 to 14/11/2021 for Comirnaty and Spikevax, respectively. The observed-to-expected ratios (OE ratios) for each vaccine were estimated by age groups and sex. RESULTS: We identified 281 and 195 cases of myocarditis or pericarditis for Comirnaty and Spikevax, respectively, which were administrated 163,059,502 and 31,768,352 doses for Comirnaty and Spikevax until the 14th of November 2021, respectively. The OE ratios were statistically significantly higher in adolescent and young adult males in their age of teens and twenties after the second dose in a two-dose series [Comirnaty in teens male: 6.15 (95% CI, 2.26-21.98), Comirnaty in twenties male: 2.86 (95% CI, 1.13-8.38), Spikevax in teens male: 41.59 (95% CI, 5.64-43,281.94), Spikevax in twenties male: 16.84 (95%CI, 6.77-57.49)]. CONCLUSIONS: Risks of myocarditis and pericarditis following SARS-CoV-2 mRNA vaccines in Japan seems to be significantly elevated for adolescent and young adult males.

The specific Na(+)/Ca(2+) exchange inhibitor SEA0400 prevents nitric oxide-induced cytotoxicity in SH-SY5Y cells.

The Na(+)/Ca(2+) exchanger (NCX) plays a role in the regulation of intracellular Ca(2+) levels, and nitric oxide (NO) is involved in many pathological conditions including neurodegenerative disorders. We have previously found that sodium nitroprusside (SNP), an NO donor, causes apoptotic-like cell death in cultured glial cells via NCX-mediated pathways and the mechanism for NO-induced cytotoxicity is cell type-dependent. The present study examined using the specific NCX inhibitor 2-[4-[(2,5-difluorophenyl)methoxy]phenoxy]-5-ethoxyaniline (SEA0400) whether NCX is involved in NO-induced injury in cultured neuronal cells. The treatment of neuroblastoma SH-SY5Y cells with SNP resulted in apoptosis and the cytotoxicity was blocked by the mitogen-activated protein (MAP)/extracellular signal-regulated kinase (ERK) kinase inhibitor U0126 and the p38 MAP kinase (MAPK) inhibitor SB203580, but not by the c-Jun N-terminal kinase (JNK) inhibitor SP60012. SNP increased Ca(2+) influx and intracellular Ca(2+) levels. In addition, SNP increased ERK and p38 MAPK phosphorylation, and production of reactive oxygen species (ROS) in an extracellular Ca(2+)-dependent manner. These effects of SNP were prevented by SEA0400. SNP-induced cytotoxicity was not affected by inhibitors of the Ca(2+), Na(+) and store-operated/capacitative channels. Moreover, SNP-induced increase in intracellular Ca(2+) levels, ROS production and decrease in cell viability were blocked by a cGMP-dependent protein kinase (PKG) inhibitor. These results suggest that Ca(2+) influx via the reverse of NCX is involved in the cascade of NO-induced neuronal apoptosis and NO activates the NCX through guanylate cyclase/PKG pathway.