Seasonality of COVID-19 incidence in the United States.

Background: The surges of Coronavirus Disease 2019 (COVID-19) appeared to follow a repeating pattern of COVID-19 outbreaks regardless of social distancing, mask mandates, and vaccination campaigns. Objectives: This study aimed to investigate the seasonality of COVID-19 incidence in the United States of America (USA), and to delineate the dominant frequencies of the periodic patterns of the disease. Methods: We characterized periodicity in COVID-19 incidences over the first three full seasonal years (March 2020 to March 2023) of the COVID-19 pandemic in the USA. We utilized a spectral analysis approach to find the naturally occurring dominant frequencies of oscillation in the incidence data using a Fast Fourier Transform (FFT) algorithm. Results: Our study revealed four dominant peaks in the periodogram: the two most dominant peaks show a period of oscillation of 366 days and 146.4 days, while two smaller peaks indicate periods of 183 days and 122 days. The period of 366 days indicates that there is a single COVID-19 outbreak that occurs approximately once every year, which correlates with the dominant outbreak in the early/mid-winter months. The period of 146.4 days indicates approximately 3 peaks per year and matches well with each of the 3 annual outbreaks per year. Conclusion: Our study revealed the predictable seasonality of COVID-19 outbreaks, which will guide public health preventative efforts to control future outbreaks. However, the methods used in this study cannot predict the amplitudes of the incidences in each outbreak: a multifactorial problem that involves complex environmental, social, and viral strain variables.

The mitochondrial NAD kinase functions as a major metabolic regulator upon increased energy demand.

OBJECTIVE: The mitochondrial nicotinamide adenine dinucleotide (NAD) kinase (MNADK) mediates de novo mitochondrial NADP biosynthesis by catalyzing the phosphorylation of NAD to yield NADP. In this study, we investigated the function and mechanistic basis by which MNADK regulates metabolic homeostasis. METHODS: Generalized gene set analysis by aggregating human patient genomic databases, metabolic studies with genetically engineered animal models, mitochondrial bioenergetic analysis, as well as gain- and loss- of-function studies were performed to address the functions and mechanistic basis by which MNADK regulates energy metabolism and redox state associated with metabolic disease. RESULTS: Human MNADK common gene variants or decreased expression of the gene are significantly associated with the occurrence of type-2 diabetes, non-alcoholic fatty liver disease (NAFLD), or hepatocellular carcinoma (HCC). Ablation of the MNADK gene in mice led to decreased fat oxidation, coincident with increased respiratory exchange ratio (RER) and decreased energy expenditure upon energy demand triggered by endurance exercise or fasting. On an atherogenic high-fat diet (HFD), MNADK-null mice exhibited hepatic insulin resistance and glucose intolerance, indicating a type-2 diabetes-like phenotype in the absence of MNADK. MNADK deficiency led to a decrease in mitochondrial NADP(H) but an increase in cellular reactive oxygen species (ROS) in mouse livers. Consistently, protein levels of the major metabolic regulators or enzymes were decreased, while their acetylation modifications were increased in the livers of MNADK-null mice. Feeding mice with a HFD caused S-nitrosylation (SNO) modification, a posttranslational modification that represses protein activities, on MNADK protein in the liver. Reconstitution of an SNO-resistant MNADK variant, MNADK-S193, into MNADK-null mice mitigated hepatic steatosis induced by HFD. CONCLUSION: MNADK, the only known mammalian mitochondrial NAD kinase, plays important roles in preserving energy homeostasis to mitigate the risk of metabolic disorders.

The links of fine airborne particulate matter exposure to occurrence of cardiovascular and metabolic diseases in Michigan, USA.

Air pollutants, particularly airborne particulate matter with aerodynamic diameter < 2.5µm (PM2.5), have been linked to the increase in mortality and morbidity associated with cardiovascular and metabolic diseases. In this study, we investigated the dose-risk relationships between PM2.5 concentrations and occurrences of cardiovascular and metabolic diseases as well as the confounding socioeconomic factors in Michigan, USA, where PM2.5 levels are generally considered acceptable. Multivariate linear regression analyses were performed to investigate the relationship between health outcome and annual ground-level PM2.5 concentrations of 82 counties in Michigan. The analyses revelated significant linear dose-response associations between PM2.5 concentrations and cardiovascular disease (CVD) hospitalization. A 10 µg/m3 increase in PM2.5 exposure was found to be associated with a 3.0% increase in total CVD, 0.45% increase in Stroke, and a 0.3% increase in Hypertension hospitalization rates in Medicare beneficiaries. While the hospitalization rates of Total Stroke, Hemorrhagic Stroke, and Hypertension in urbanized counties were significantly higher than those of rural counties, the death rates of coronary heart disease and ischemic stroke in urbanized counties were significantly lower than those of rural counties. These results were correlated with the facts that PM2.5 levels in urbanized counties were significantly higher than that in rural counties and that the percentage of the population with health insurance and the median household income in rural counties were significantly lower. While obesity prevalence showed evidence of a weak positive correlation (ρ = 0.20, p-value = 0.078) with PM2.5 levels, there was no significant dose-response association between county diabetes prevalence rates and PM2.5 exposure in Michigan. In summary, this study revealed strong dose-response associations between PM2.5 concentrations and CVD incidence in Michigan, USA. The socioeconomic factors, such as access to healthcare resources and median household income, represent important confounding factors that could override the impact of PM2.5 exposure on CVD mortality.