Ethics and Effectiveness of US COVID-19 Vaccine Mandates and Vaccination Passports: A Review.

BACKGROUND: The highest-income countries procured 50 times as many COVID-19 vaccines as low-income countries, a global health inequity that resulted in only 4.6% of the poorest 5th of the world receiving a COVID-19 vaccine. High-income countries are considering vaccine mandates and passports to contain the spread of COVID-19. This study is a curated discourse aimed at examining how vaccine mandates and passports may impact global vaccine equity from an ethics perspective. STUDY DESIGN: Narrative review adapted for a debate. METHODS: In November 2021, we conducted a review of studies examining global vaccine mandates for an upper-level global health course at Northeastern University, Boston, United States (U.S.). In total, 19 upper-level students, one research assistant, and one instructor participated in the data collection, analysis, and discussion. RESULTS: The review showed vaccine mandates are ethical and effective if autonomy-centered alternatives like soft mandates are first exhausted. Unwarranted stringent public health measures degrade public trust. In the U.S. alone, COVID-19-related deaths hovered above 300 000 before COVID-19 vaccination began in mid-December 2020. Since then, the number of COVID-19 deaths more than doubled, despite the wide availability of the vaccine. For many low- and middle-income countries (LMICs) vaccines are not available or easily accessible. Global collaboration to facilitate vaccine availability in LMICs should be a priority. CONCLUSIONS: It is essential to get as many people as possible vaccinated to return to some normality. However, vaccine mandates and passports need to be used only sparingly, especially when other options have been exhausted.

A new role for the SRC family kinase HCK as a driver of SYK activation in MYD88 mutated lymphomas.

The SRC family kinase (SFK) HCK is transcriptionally upregulated and activated by mutated MYD88 (MYD88Mut), a key adaptor for Toll-receptor signaling. HCK activates BTK, AKT, and ERK in MYD88Mut lymphomas. SYK, a B-cell receptor (BCR) component, is activated in MYD88Mut lymphoma cells. Although the SFK LYN serves as a trigger for SYK activation in MYD88Mut ABC DLBCL cells, LYN activity is muted in MYD88Mut Waldenstrom macroglobulinemia (WM) cells. We therefore investigated a role for HCK in mediating SYK activation. Overexpression of wild-type (WT) (HCKWT) or gatekeeper mutated (HCKThr333Met) HCK in MYD88Mut lymphoma cells triggered SYK activation. Conversely, HCK knockdown reduced p-SYK in MYD88Mut lymphoma cells. Coimmunoprecipitation experiments showed that HCK was complexed with p-SYK in MYD88Mut BCWM.1 and TMD8 cells, but not in MYD88 WT Ramos cells. Rescue experiments in MYD88Mut lymphoma cells expressing HCKThr333Met led to persistent HCK and SYK activation and resistance to the HCK inhibitor A419259. Treatment of primary MYD88Mut WM cells with A419259 reduced p-HCK and p-SYK expression. Taken together, our findings show that SYK is activated by HCK in MYD88Mut B-cell lymphomas cells, broaden the prosurvival signaling generated by aberrant HCK expression in response to MYD88Mut, and help define HCK as an important therapeutic target in MYD88Mut B-cell lymphomas.