Understanding metabolic alterations after SARS-CoV-2 infection: insights from the patients' oral microenvironmental metabolites.

BACKGROUND: Coronavirus disease 2019 is a type of acute infectious pneumonia and frequently confused with influenza since the initial symptoms. When the virus colonized the patient's mouth, it will cause changes of the oral microenvironment. However, few studies on the alterations of metabolism of the oral microenvironment affected by SARS-CoV-2 infection have been reported. In this study, we explored metabolic alterations of oral microenvironment after SARS-CoV-2 infection. METHODS: Untargeted metabolomics (UPLC-MS) was used to investigate the metabolic changes between oral secretion samples of 25 COVID-19 and 30 control participants. To obtain the specific metabolic changes of COVID-19, we selected 25 influenza patients to exclude the metabolic changes caused by the stress response of the immune system to the virus. Multivariate analysis (PCA and PLS-DA plots) and univariate analysis (students' t-test) were used to compare the differences between COVID-19 patients and the controls. Online hiplot tool was used to perform heatmap analysis. Metabolic pathway analysis was conducted by using the MetaboAnalyst 5.0 web application. RESULTS: PLS-DA plots showed significant separation of COVID-19 patients and the controls. A total of 45 differential metabolites between COVID-19 and control group were identified. Among them, 35 metabolites were defined as SARS-CoV-2 specific differential metabolites. Especially, the levels of cis-5,8,11,14,17-eicosapentaenoic acid and hexanoic acid changed dramatically based on the FC values. Pathway enrichment found the most significant pathways were tyrosine-related metabolism. Further, we found 10 differential metabolites caused by the virus indicating the body's metabolism changes after viral stimulation. Moreover, adenine and adenosine were defined as influenza virus-specific differential metabolites. CONCLUSIONS: This study revealed that 35 metabolites and tyrosine-related metabolism pathways were significantly changed after SARS-CoV-2 infection. The metabolic alterations of oral microenvironment in COVID-19 provided new insights into its molecular mechanisms for research and prognostic treatment.

Rates of Antipsychotic Drug Prescribing Among People Living With Dementia During the COVID-19 Pandemic.

Importance: Concerns have been raised that the use of antipsychotic medication for people living with dementia might have increased during the COVID-19 pandemic. Objective: To examine multinational trends in antipsychotic drug prescribing for people living with dementia before and during the COVID-19 pandemic. Design, Setting, and Participants: This multinational network cohort study used electronic health records and claims data from 8 databases in 6 countries (France, Germany, Italy, South Korea, the UK, and the US) for individuals aged 65 years or older between January 1, 2016, and November 30, 2021. Two databases each were included for South Korea and the US. Exposures: The introduction of population-wide COVID-19 restrictions from April 2020 to the latest available date of each database. Main Outcomes and Measures: The main outcomes were yearly and monthly incidence of dementia diagnosis and prevalence of people living with dementia who were prescribed antipsychotic drugs in each database. Interrupted time series analyses were used to quantify changes in prescribing rates before and after the introduction of population-wide COVID-19 restrictions. Results: A total of 857 238 people with dementia aged 65 years or older (58.0% female) were identified in 2016. Reductions in the incidence of dementia were observed in 7 databases in the early phase of the pandemic (April, May, and June 2020), with the most pronounced reduction observed in 1 of the 2 US databases (rate ratio [RR], 0.30; 95% CI, 0.27-0.32); reductions were also observed in the total number of people with dementia prescribed antipsychotic drugs in France, Italy, South Korea, the UK, and the US. Rates of antipsychotic drug prescribing for people with dementia increased in 6 databases representing all countries. Compared with the corresponding month in 2019, the most pronounced increase in 2020 was observed in May in South Korea (Kangwon National University database) (RR, 2.11; 95% CI, 1.47-3.02) and June in the UK (RR, 1.96; 95% CI, 1.24-3.09). The rates of antipsychotic drug prescribing in these 6 databases remained high in 2021. Interrupted time series analyses revealed immediate increases in the prescribing rate in Italy (RR, 1.31; 95% CI, 1.08-1.58) and in the US Medicare database (RR, 1.43; 95% CI, 1.20-1.71) after the introduction of COVID-19 restrictions. Conclusions and Relevance: This cohort study found converging evidence that the rate of antipsychotic drug prescribing to people with dementia increased in the initial months of the COVID-19 pandemic in the 6 countries studied and did not decrease to prepandemic levels after the acute phase of the pandemic had ended. These findings suggest that the pandemic disrupted the care of people living with dementia and that the development of intervention strategies is needed to ensure the quality of care.

Network analysis between neuron dysfunction and neuroimmune response based on neural single-cell transcriptome of COVID-19 patients.

Despite global vaccination efforts, COVID-19 breakthrough infections caused by variant virus continue to occur frequently, long-term sequelae of COVID-19 infection like neuronal dysfunction emerge as a noteworthy issue. Neuroimmune disorder induced by Inflammatory factor storm was considered as a possible reason, however, little was known about the functional factors affecting neuroimmune response to this virus. Here, using medial prefrontal cortex single cell data of COVID-19 patients, expression pattern analysis indicated that some immune-related pathway genes expressed specifically, including genes associated with T cell receptor, TNF signaling in microglia and Cytokine-cytokine receptor interaction and HIF-1 signaling pathway genes in astrocytes. Besides the well-known immune-related cell type microglia, we also observed immune-related factors like IL17D, TNFRSF1A and TLR4 expressed in Astrocytes. Based on the ligand-receptor relationship of immune-related factors, crosstalk landscape among cell clusters were analyzed. The findings indicated that astrocytes collaborated with microglia and affect excitatory neurons, participating in the process of immune response and neuronal dysfunction. Moreover, subset of astrocytes specific immune factors (hinged neuroimmune genes) were proved to correlate with Covid-19 infection and ventilator-associated pneumonia using multi-tissue RNA-seq and scRNA-seq data. Function characterization clarified that hinged neuroimmune genes were involved in activation of inflammation and hypoxia signaling pathways, which could lead to hyper-responses related neurological sequelae. Finally, a risk model was constructed and testified in RNA-seq and scRNA data of peripheral blood.

Decisive role of ozone formation control in winter PM2.5 mitigation in Shenzhen, China.

During the COVID-19 lockdown, atmospheric PM2.5 in the Pearl River Delta (PRD) showed the highest reduction in China, but the reasons, being a critical question for future air quality policy design, are not yet clear. In this study, we analyzed the relationships among gaseous precursors, secondary aerosols and atmospheric oxidation capacity in Shenzhen, a megacity in the PRD, during the lockdown period in 2020 and the same period in 2021. The comprehensive observational datasets showed large lockdown declines in all primary and secondary pollutants (including O3). We found that, however, the daytime concentrations of secondary aerosols during the lockdown period and normal period were rather similar when the corresponding odd oxygen (Ox≡O3+NO2, an indicator of photochemical processing avoiding the titration effect of O3 by freshly emitted NO) were at similar levels. Therefore, reduced Ox, rather than the large reduction in precursors, was a direct driver to achieve the decline in secondary aerosols. Moreover, Ox was also found to determine the spatial distribution of intercity PM2.5 levels in winter PRD. Thus, an effective strategy for winter PM2.5 mitigation should emphasize on control of winter O3 formation in the PRD and other regions with similar conditions.

Global characterization of B cell receptor repertoire in COVID-19 patients by single-cell V(D)J sequencing.

The world is facing a pandemic of Corona Virus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Adaptive immune responses are essential for SARS-CoV-2 virus clearance. Although a large body of studies have been conducted to investigate the immune mechanism in COVID-19 patients, we still lack a comprehensive understanding of the BCR repertoire in patients. In this study, we used the single-cell V(D)J sequencing to characterize the BCR repertoire across convalescent COVID-19 patients. We observed that the BCR diversity was significantly reduced in disease compared with healthy controls. And BCRs tend to skew toward different V gene segments in COVID-19 and healthy controls. The CDR3 sequences of heavy chain in clonal BCRs in patients were more convergent than that in healthy controls. In addition, we discovered increased IgG and IgA isotypes in the disease, including IgG1, IgG3 and IgA1. In all clonal BCRs, IgG isotypes had the most frequent class switch recombination events and the highest somatic hypermutation rate, especially IgG3. Moreover, we found that an IgG3 cluster from different clonal groups had the same IGHV, IGHJ and CDR3 sequences (IGHV4-4-CARLANTNQFYDSSSYLNAMDVW-IGHJ6). Overall, our study provides a comprehensive characterization of the BCR repertoire in COVID-19 patients, which contributes to the understanding of the mechanism for the immune response to SARS-CoV-2 infection.