Purpose There are growing signs that the COVID‐19 virus has started to spread to rural areas and can impact the rural health care system that is already stretched and lacks resources. To aid in the legislative decision process and proper channelizing of resources, we estimated and compared the county‐level change in prevalence rates of COVID‐19 by rural‐urban status over 3 weeks. Additionally, we identified hotspots based on estimated prevalence rates. Methods We used crowdsourced data on COVID‐19 and linked them to county‐level demographics, smoking rates, and chronic diseases. We fitted a Bayesian hierarchical spatiotemporal model using the Markov Chain Monte Carlo algorithm in R‐studio. We mapped the estimated prevalence rates using ArcGIS 10.8, and identified hotspots using Gettis‐Ord local statistics. Findings In the rural counties, the mean prevalence of COVID‐19 increased from 3.6 per 100,000 population to 43.6 per 100,000 within 3 weeks from April 3 to April 22, 2020. In the urban counties, the median prevalence of COVID‐19 increased from 10.1 per 100,000 population to 107.6 per 100,000 within the same period. The COVID‐19 adjusted prevalence rates in rural counties were substantially elevated in counties with higher black populations, smoking rates, and obesity rates. Counties with high rates of people aged 25‐49 years had increased COVID‐19 prevalence rates. Conclusions Our findings show a rapid spread of COVID‐19 across urban and rural areas in 21 days. Studies based on quality data are needed to explain further the role of social determinants of health on COVID‐19 prevalence.

Background Subanesthetic doses of (R,S)-ketamine are used in the treatment of neuropathic pain and depression. In the rat, the antidepressant effects of (R,S)-ketamine are associated with increased activity and function of mammalian target of rapamycin (mTOR); however, (R,S)-ketamine is extensively metabolized and the contribution of its metabolites to increased mTOR signaling is unknown. Methods Rats (n = 3/time point) were given (R,S)-ketamine, (R,S)-norketamine and (2S,6S)-hydroxynorketamine and their effect on the mTOR pathway determined after 20, 30, and 60 minutes. PC-12 pheochromocytoma cells (n = 3/experiment) were treated with escalating concentrations of each compound and the impact on the mTOR pathway was determined. Results The phosphorylation of mTOR and its downstream targets was significantly increased in rat pre-frontal cortex tissue by more than ~2.5-, ~25- and ~2-fold, respectively, in response to a 60-min post-administration of (R,S)-ketamine, (R,S)-norketamine, and (2S,6S)-hydroxynorketamine (p<0.05, ANOVA analysis). In PC-12 pheochromocytoma cells, the test compounds activated the mTOR pathway in a concentration-dependent manner, which resulted in a significantly higher expression of serine racemase with ~2-fold increases at 0.05nM (2S,6S)-hydroxynorketamine, 10nM (R,S)-norketamine and 1000nM (R,S)-ketamine. The potency of the effect reflected antagonistic activity of the test compounds at the α7-nicotinic acetylcholine receptor. Conclusions The data demonstrate that (R,S)-norketamine and (2S,6S)-hydroxynorketamine have potent pharmacological activity both in vitro and in vivo and contribute to the molecular effects produced by sub-anesthetic doses of (R,S)-ketamine. The results suggest that the determination of the mechanisms underlying the antidepressant and analgesic effects of (R,S)-ketamine requires a full study of the parent compound and its metabolites.