Although type 2 diabetes (T2D) is a major comorbidity of novel coronavirus disease 2019 (COVID-19), the impact of blood glucose control on the degree of medical interventions required and on all-cause mortality of patients with COVID-19 and pre-existing T2D remains unclear. Here, Zhu et al. report that among $7,300 individuals with COVID-19 (among which nearly 1,000 had T2D) in Hubei Province, China, those with T2D had significantly increased medical interventions and mortality risk. But among the patients with T2D, those with well-controlled blood glucose regulation (upper limit % 10 mmol/L) fared much better than those with poorly controlled blood glucose (upper limit > 10 mmol/L). These findings provide clinical evidence correlating more proper blood glucose control with improved outcomes in patients with COVID-19.

The upcoming flu season in the Northern Hemisphere merging with the current COVID-19 pandemic raises a potentially severe threat to public health. Through experimental coinfection with influenza A virus (IAV) and either pseudotyped or live SARS-CoV-2 virus, we found that IAV preinfection significantly promoted the infectivity of SARS-CoV-2 in a broad range of cell types. Remarkably, in vivo, increased SARS-CoV-2 viral load and more severe lung damage were observed in mice coinfected with IAV. Moreover, such enhancement of SARS-CoV-2 infectivity was not observed with several other respiratory viruses, likely due to a unique feature of IAV to elevate ACE2 expression. This study illustrates that IAV has a unique ability to aggravate SARS-CoV-2 infection, and thus, prevention of IAV infection is of great significance during the COVID-19 pandemic.

Highlights d Bhlhe40 is required for Trm cell and TIL fitness and function d Bhlhe40 is critical for TIL reinvigoration following anti-PD-L1 blockade d Bhlhe40 programs Trm cell and TIL mitochondrial metabolism and active chromatin state d Epigenetic targeting Trm cell and TIL functional program promotes tumor control

IgE has a key role in the pathogenesis of allergic responses through its ability to activate mast cells via the receptor FcεR1. In addition to mast cells, many cell types implicated in atherogenesis express FcεR1, but whether IgE has a role in this disease has not been determined. Here, we demonstrate that serum IgE levels are elevated in patients with myocardial infarction or unstable angina pectoris. We found that IgE and the FcεR1 subunit FcεR1α were present in human atherosclerotic lesions and that they localized particularly to macrophagerich areas. In mice, absence of FcεR1α reduced inflammation and apoptosis in atherosclerotic plaques and reduced the burden of disease. In cultured macrophages, the presence of TLR4 was required for FcεR1 activity. IgE stimulated the interaction between FcεR1 and TLR4, thereby inducing macrophage signal transduction, inflammatory molecule expression, and apoptosis. These IgE activities were reduced in the absence of FcεR1 or TLR4. Furthermore, IgE activated macrophages by enhancing Na + /H + exchanger 1 (NHE1) activity. Inactivation of NHE1 blocked IgE-induced macrophage production of inflammatory molecules and apoptosis. Cultured human aortic SMCs (HuSMCs) and ECs also exhibited IgE-induced signal transduction, cytokine expression, and apoptosis. In human atherosclerotic lesions, SMCs and ECs colocalized with IgE and TUNEL staining. This study reveals what we believe to be several previously unrecognized IgE activities that affect arterial cell biology and likely other IgE-associated pathologies in human diseases.