Multi-omics blood atlas reveals unique features of immune and platelet responses to SARS-CoV-2 Omicron breakthrough infection.

Although host responses to the ancestral SARS-CoV-2 strain are well described, those to the new Omicron variants are less resolved. We profiled the clinical phenomes, transcriptomes, proteomes, metabolomes, and immune repertoires of >1,000 blood cell or plasma specimens from SARS-CoV-2 Omicron patients. Using in-depth integrated multi-omics, we dissected the host response dynamics during multiple disease phases to reveal the molecular and cellular landscapes in the blood. Specifically, we detected enhanced interferon-mediated antiviral signatures of platelets in Omicron-infected patients, and platelets preferentially formed widespread aggregates with leukocytes to modulate immune cell functions. In addition, patients who were re-tested positive for viral RNA showed marked reductions in B cell receptor clones, antibody generation, and neutralizing capacity against Omicron. Finally, we developed a machine learning model that accurately predicted the probability of re-positivity in Omicron patients. Our study may inspire a paradigm shift in studying systemic diseases and emerging public health concerns.

Mortality burden due to ambient nitrogen dioxide pollution in China: Application of high-resolution models.

BACKGROUND: A large gap exists between the latest Global Air Quality Guidelines (AQG 2021) and Chinese air quality standards for NO2. Assessing whether and to what extent air quality standards for NO2 should be tightened in China requires a comprehensive understanding of the spatiotemporal characteristics of population exposure to ambient NO2 and related health risks, which have not been studied to date. OBJECTIVE: We predicted ground NO2 concentrations with high resolution in mainland China, explored exposure characteristics to NO2 pollution, and assessed the mortality burden attributable to NO2 exposure. METHODS: Daily NO2 concentrations in 2019 were predicted at 1-km spatial resolution in mainland China using random forest models incorporating multiple predictors. From these high-resolution predictions, we explored the spatiotemporal distribution of NO2, population and area percentages with NO2 exposure exceeding criterion levels, and premature deaths attributable to long- and short-term NO2 exposure in China. RESULTS: The cross-validation R2and root mean squared error of the NO2 predicting model were 0.80 and 7.78 µg/m3, respectively,at the daily level in 2019.The percentage of people (population number) with annual NO2 exposure over 40 µg/m3 in mainland China in 2019 was 10.40 % (145,605,200), and it reached 99.68 % (1,395,569,840) with the AQG guideline value of 10 µg/m3. NO2 levels and population exposure risk were elevated in urban areas than in rural. Long- and short-term exposures to NO2 were associated with 285,036 and 121,263 non-accidental deaths, respectively, in China in 2019. Tightening standards in steps gradually would increase the potential health benefit. CONCLUSION: In China, NO2 pollution is associated with significant mortality burden. Spatial disparities exist in NO2 pollution and exposure risks. China's current air quality standards may no longer objectively reflect the severity of NO2 pollution and exposure risk. Tightening the national standards for NO2 is needed and will lead to significant health benefits.

The Influence of Alcohol Consumption on Tobacco Use among Urban Older Adults: Evidence from Western China in 2017

Background: Tobacco use is a global public health concern due to its association with a myriad of health hazards and costs. Previous studies have found that the disinhibiting influence of alcohol consumption may lead to an increase in tobacco use. In this study, we investigated why alcohol consumption is associated with tobacco use among older adults in Western China, and we attempted to explain the mechanisms that underlie the link between alcohol consumption and tobacco use. Methods: In this cross-sectional study, we employed a representative sample of 812 urban individuals aged 60 and older in 2017 in Western China. Results: We found that alcohol consumption (OR = 2.816, 95%CI: 1.770–4.479) was positively associated with tobacco use. Additionally, other factors, including gender (OR = 0.023, 95%CI: 0.009–0.060), age (OR = 0.758, 95%CI: 0.634–0.906), health literacy (OR = 0.977, 95%CI: 0.959–0.995) and functional impairment (OR = 0.871, 95%CI: 0.767–0.988) were also strongly related to tobacco use. Conclusions: Consistent with the results of existing studies, our findings demonstrated the disinhibiting influence of alcohol consumption on tobacco use, which confirmed the theoretical mechanisms that underlie the alcohol–tobacco link and implied the co-occurrence and co-use of alcohol and tobacco, which are used as “social lubricants” in the Chinese context. The importance of other factors related to tobacco use were also discussed. As the tobacco epidemic is combatted, joint interventions tailored to concurrent control over alcohol and tobacco need to be performed, and corresponding male-specific and age-specific health education and the reinforcement of health literacy must be considered as important priorities.

Single-cell transcriptomes of peripheral blood cells indicate and elucidate severity of COVID-19.

The blood and immune system of coronavirus disease 2019 (COVID-19) infected patients are dysfunctional, and numerous studies have been conducted to resolve their characteristics and pathogenic mechanisms. Nevertheless, the variations of immune responses along with disease severity have not been comprehensively documented. Here, we profiled the single-cell transcriptomes of 96,313 peripheral blood mononuclear cells (PBMCs) derived from 12 COVID-19 patients (including four moderate, four severe and four critical cases) and three healthy donors. We showed that proliferative CD8 effector T cells with declined immune functions and cytotoxicity accumulated in the critical stage. By contrast, the quantity of natural killer (NK) cells was significantly reduced, while they exhibited enhanced immune activities. Notably, a gradually attenuated responseto COVID-19 along with disease severity was observed in monocytes, in terms of cellular composition, transcriptional discrepancy and transcription factor regulatory network. Furthermore, we identified immune cell-type dependent cytokine signatures distinguishing the severity of COVID-19 patients. In addition, cell interactions between CD8 effector T/NK cells and monocytes mediated by inflammatory cytokines were enhanced in moderate and severe stages, but weakened in critical cases. Collectively, our work uncovers the cellular and molecular players underlying the disordered and heterogeneous immune responses associated with COVID-19 severity, which could provide valuable insights for the treatment of critical COVID-19 patients.