COVID-19 and obesity: fighting two pandemics with intermittent fasting.

Obesity is strongly and independently associated with an increased risk of severe illness and death from coronavirus disease 2019 (COVID-19). The pathophysiological changes that result from elevated body weight lead to metabolic dysfunction, chronic inflammation, impaired immunological responses, and multisystem disorders, which increase vulnerability to severe illness from COVID-19. While vaccination strategies are under way across the world, the second and third waves of the pandemic, along with the emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains, continue to threaten the stability of medical systems worldwide. Furthermore, evidence from previous pandemics suggests that vaccines are less effective in obese individuals than in their healthy-weight counterparts over the long term. Therefore, a consideration of lifestyle changes that can boost metabolic health and immunity is critical to reduce the risk of complications and severe illness from viral infection. In this review, we discuss the potential mechanisms linking excess body weight with COVID-19 morbidity. We also present evidence that intermittent fasting (IF), a dietary program that has gained popularity in recent years, may be an effective strategy to improve metabolic health and immunity and thus reduce the impact of obesity on COVID-19 morbidity and mortality.

VEGF receptor 2 (KDR) protects airways from mucus metaplasia through a Sox9-dependent pathway.

Mucus-secreting goblet cells are the dominant cell type in pulmonary diseases, e.g., asthma and cystic fibrosis (CF), leading to pathologic mucus metaplasia and airway obstruction. Cytokines including IL-13 are the major players in the transdifferentiation of club cells into goblet cells. Unexpectedly, we have uncovered a previously undescribed pathway promoting mucous metaplasia that involves VEGFa and its receptor KDR. Single-cell RNA sequencing analysis coupled with genetic mouse modeling demonstrates that loss of epithelial VEGFa, KDR, or MEK/ERK kinase promotes excessive club-to-goblet transdifferentiation during development and regeneration. Sox9 is required for goblet cell differentiation following Kdr inhibition in both mouse and human club cells. Significantly, airway mucous metaplasia in asthmatic and CF patients is also associated with reduced KDR signaling and increased SOX9 expression. Together, these findings reveal an unexpected role for VEGFa/KDR signaling in the defense against mucous metaplasia, offering a potential therapeutic target for this common airway pathology.