CRP Monitoring in Early Hospitalization: Implications for Predicting Outcomes in Patients with COVID-19.

Elevated C-reactive protein (CRP) levels have been associated with poorer COVID-19 outcomes. While baseline CRP levels are higher in women, obese individuals, and older adults, the relationship between CRP, sex, body mass index (BMI), age, and COVID-19 outcomes remains unknown. To investigate, we performed a retrospective analysis on 824 adult patients with COVID-19 admitted during the first pandemic wave, of whom 183 (22.2%) died. The maximum CRP value over the first five hospitalization days better predicted hospitalization outcome than the CRP level at admission, as a maximum CRP > 10 mg/dL independently quadrupled the risk of death (p < 0.001). Males (p < 0.001) and patients with a higher BMI (p = 0.001) had higher maximum CRP values, yet CRP levels did not impact their hospitalization outcome. While CRP levels did not statistically mediate any relation between sex, age, or BMI with clinical outcomes, age impacted the association between BMI and the risk of death. For patients 60 or over, a BMI < 25 kg/m2 increased the risk of death (p = 0.017), whereas the reverse was true for patients <60 (p = 0.030). Further impact of age on the association between BMI, CRP, and the risk of death could not be assessed due to a lack of statistical power but should be further investigated.

Predicting COVID-19 prognosis in hospitalized patients based on early status.

IMPORTANCE: COVID-19 remains the fourth leading cause of death in the United States. Predicting COVID-19 patient prognosis is essential to help efficiently allocate resources, including ventilators and intensive care unit beds, particularly when hospital systems are strained. Our PLABAC and PRABLE models are unique because they accurately assess a COVID-19 patient's risk of death from only age and five commonly ordered laboratory tests. This simple design is important because it allows these models to be used by clinicians to rapidly assess a patient's risk of decompensation and serve as a real-time aid when discussing difficult, life-altering decisions for patients. Our models have also shown generalizability to external populations across the United States. In short, these models are practical, efficient tools to assess and communicate COVID-19 prognosis.

Both NPY-Expressing and CART-Expressing Neurons Increase Energy Expenditure and Trabecular Bone Mass in Response to AP1 Antagonism, But Have Opposite Effects on Bone Resorption.

Energy metabolism and bone homeostasis share several neuronal regulatory pathways. Within the ventral hypothalamus (VHT), the orexigenic neurons co-express Agouti-related peptide (AgRP) and neuropeptide Y (NPY) and the anorexigenic neurons co-express, α-melanocyte stimulating hormone derived from proopiomelanocortin (POMC), and cocaine and amphetamine-regulated transcript (CART). These neurons regulate both processes, yet their relative contribution is unknown. Previously, using genetically targeted activator protein (AP1) alterations as a tool, we showed in adult mice that AgRP or POMC neurons are capable of inducing whole-body energy catabolism and bone accrual, with different effects on bone resorption. Here, we investigated whether co-residing neurons exert similar regulatory effects. We show that AP1 antagonists targeted to NPY-producing or CART-producing neurons in adult mice stimulate energy expenditure, reduce body weight gain and adiposity and promote trabecular bone formation and mass, yet again via different effects on bone resorption, as measured by serum level of carboxy-terminal collagen type I crosslinks (CTX). In addition, AP1 antagonists promote neurite expansion, increasing neurite number, length, and surface area in primary hypothalamic neuronal cultures. Overall, our data demonstrate that the orexigenic NPY and anorexigenic CART neurons both have the capacity to stimulate energy burning state and increase bone mass. © 2020 American Society for Bone and Mineral Research.