This study aimed to analyze the correlation between smoking and coronavirus disease 2019 (COVID-19) severity by region and gross domestic product (GDP). The regions were categorized by continent and GDP rankings. Studies conducted between June 3, 2020 and March 27, 2023 were searched to compare the severity of COVID-19 between smokers and non-smokers according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Compared with never-smokers, the smokers’ COVID-19 severity scores were 1.48 (confidence interval [CI]: 1.25–1.75) in Asia, 1.24 (CI: 1.05–1.46) in the Middle East, 1.32 (1.21–1.45) in Europe, 1.39 (1.30–1.49) in North America, 1.69 (1.22–2.34) in South America, and 2.87 (1.82–4.53) in Africa. By GDP, the smokers’ COVID-19 severity scores were higher than those of never-smokers: 1.42 (1.32–1.53) in high-GDP countries, 1.33 (1.25–1.41) in middle-GDP countries (11th–50th), and 1.53 (0.85–2.76) in low-GDP countries. The COVID-19 severity in smokers was significantly higher in low-GDP countries than in high- and middle-income countries. The high COVID-19 death rate among smokers in the African continent and low-GDP countries is thought to stem from the lack of medical management systems compared with other countries. In addition to medical treatment, environmental or socioeconomic factors can increase the severity.

Colorectal cancer (CRC) remains a major cause of cancer-related morbidity and mortality worldwide. Metabolic disorders such as obesity, diabetes mellitus, dyslipidemia, and metabolic syndrome are associated with CRC risk. Metabolic abnormalities may contribute to colorectal tumorigenesis and reshape the tumor immune microenvironment, which in turn influence immune dysfunction and therapeutic resistance. Exhausted CD8⁺ T cells exhibit impaired effector function, sustained inhibitory receptor expression, and transcriptional and epigenetic reprogramming. Metabolic stressors within the CRC microenvironment may modulate T-cell function and exhaustion-associated states. Additionally, other immune populations (natural killer cells, macrophages, myeloid-derived suppressor cells, dendritic cells, and regulatory T cells) may develop distinct dysfunctional or immunosuppressive states. Recent single-cell and spatial studies have indicated the heterogeneity of these immunometabolic interactions in CRC. This review examines the interactions of the systemic and tumor-associated metabolic alterations with T-cell exhaustion and other forms of immune dysfunction in CRC. We discuss the influence of glucose, lipid, amino acid, and mitochondrial metabolism, hypoxia, microbiota-derived metabolites, and chronic inflammation in shaping tumor–immune interactions. Finally, we reviewed therapeutic strategies targeting immunometabolic pathways and their potential integration with immune checkpoint blockade. Overall, understanding these interactions may help identify immunometabolic vulnerabilities for informing precise therapeutic strategies for CRC.