Background The role of diet on COVID-19 is emerging. Methods We included 42,935 participants aged 55 to 99 years in two ongoing cohort studies, Nurses’ Health Study II and Health Professionals Follow-up Study, who completed a series of COVID-19 surveys in 2020 and 2021. Using data from food frequency questionnaires prior to COVID-19, we assessed diet quality using the Alternative Healthy Eating Index (AHEI)-2010, the alternative Mediterranean Diet (AMED) score, an Empirical Dietary Index for Hyperinsulinemia (EDIH), and an Empirical Dietary Inflammatory Pattern (EDIP). We calculated multivariable adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for SARS-CoV-2 infection and severity of COVID-19 after controlling for demographic, medical, and lifestyle factors. Results Among 19,754 participants tested for SARS-CoV-2, 1,941 participants reported a positive result. Of these, 1,327 reported symptoms needing assistance and another 109 were hospitalized. Healthier diet, represented by higher AHEI-2010 and AMED scores and lower EDIH and EDIP scores, were associated with lower likelihood of SARS-CoV-2 infection (ORs Q (quartile) 4 vs. Q1 (95%CI) were 0.80 (0.69, 0.92) for AHEI-2010; 0.78 (0.67, 0.92) for AMED; 1.36 (1.16, 1.57) for EDIH; and 1.13 (0.99, 1.30) for EDIP; all p for trend ≤ 0.01). In the analysis of COVID-19 severity, participants with healthier diet had lower likelihood of severe infection and were less likely to be hospitalized due to COVID-19. However, associations were no longer significant after controlling for BMI and pre-existing medical conditions. Conclusion Diet may be an important modifiable risk factor for SARS-CoV-2 infection, as well as for severity of COVID-19. This association is partially mediated by BMI and pre-existing medical conditions.

Understanding how cells acquire genetic mutations is a fundamental biological question with implications for many different areas of biomedical research, ranging from tumor evolution to drug resistance. While karyotypic heterogeneity is a hallmark of cancer cells, few mutations causing chromosome instability have been identified in cancer genomes, suggesting a nongenetic origin of this phenomenon. We found that in vitro exposure of karyotypically stable human colorectal cancer cell lines to environmental stress conditions triggered a wide variety of chromosomal changes and karyotypic heterogeneity. At the molecular level, hyperthermia induced polyploidization by perturbing centrosome function, preventing chromosome segregation, and attenuating the spindle assembly checkpoint. The combination of these effects resulted in mitotic exit without chromosome segregation. Finally, heat-induced tetraploid cells were on the average more resistant to chemotherapeutic agents. Our studies suggest that environmental perturbations promote karyotypic heterogeneity and could contribute to the emergence of drug resistance.

Polyploidization, a common event during the evolution of different tumours, has been proposed to confer selective advantages to tumour cells by increasing the occurrence of mutations promoting cancer progression and by conferring chemotherapy resistance. While conditions leading to polyploidy in cancer cells have been described, a general mechanism explaining the incidence of this karyotypic change in tumours is still missing. In this study, we tested whether a widespread tumour microenvironmental condition, low pH, could induce polyploidization in mammalian cells. We found that an acidic microenvironment, in the range of what is commonly observed in tumours, together with the addition of lactic acid, induced polyploidization in transformed and non-transformed human cell lines in vitro. In addition, we provide evidence that polyploidization was mainly driven through the process of endoreduplication, i.e. the complete skipping of mitosis in-between two S-phases. These findings suggest that acidic environments, which characterize solid tumours, are a plausible path leading to polyploidization of cancer cells.