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.

KRAS Ubiquitination at Lysine 104 Retains Exchange Factor Regulation by Dynamically Modulating the Conformation of the Interface.

RAS proteins function as highly regulated molecular switches that control cellular growth. In addition to regulatory proteins, RAS undergoes a number of posttranslational modifications (PTMs) that regulate its activity. Lysine 104, a hot spot for multiple PTMs, is a highly conserved residue that forms key interactions that stabilize the RAS helix-2(H2)/helix-3(H3) interface. Mutation at 104 attenuates interaction with guanine nucleotide exchange factors (GEFs), whereas ubiquitination at lysine 104 retains GEF regulation. To elucidate how ubiquitination modulates RAS function, we generated monoubiquitinated KRAS at 104 using chemical biology approaches and conducted biochemical, NMR, and computational analyses. We find that ubiquitination promotes a new dynamic interaction network and alters RAS conformational dynamics to retain GEF function. These findings reveal a mechanism by which ubiquitination can regulate protein function.