BMI is Associated with Coronavirus Disease 2019 Intensive Care Unit Admission in African Americans.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) has disproportionately impacted the African American community. This study aims to identify the risk factors for severe COVID-19 disease in African American patients. METHODS: This was a retrospective cross-sectional analysis of African American patients with COVID-19 treated between March 12 and April 9, 2020, at a single tertiary center. The primary outcome of interest was severe disease defined as those requiring intensive care unit (ICU) admission. RESULTS: The study included 158 consecutive patients. The mean age was 57 years, and 61% were women. The mean (SD) of BMI was 33.2 (8.6) kg/m2 . Overall, patients admitted to the ICU were older (62 vs. 55 years, P = 0.003) and had higher BMI (36.5 kg/m2 vs. 31.9 kg/m2 , P = 0.002). In unadjusted and adjusted analysis, the factors most associated with ICU admission in this sample were age (adjusted odds ratio [aOR]: 1.073; 95% CI: 1.033-1.114), BMI (aOR: 1.115; 95% CI: 1.052-1.182), and lung disease (aOR: 3.097; 95% CI: 1.137-8.437). CONCLUSIONS: This study identified risk factors for severe disease in COVID-19, specifically in an African American population. Further inclusive research aimed at optimizing clinical care relevant to the African American population is critical to ensure an equitable response to COVID-19.

HDAC8 inhibition ameliorates pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a fibroproliferative lung disease, and fibroblast-myofibroblast differentiation (FMD) is thought to be a key event in the pathogenesis of IPF. Histone deacetylase-8 (HDAC8) has been shown to associate with α-smooth muscle actin (α-SMA; a marker of FMD) and regulates cell contractility in vascular smooth muscle cells. However, the role of HDAC8 in FMD or pulmonary fibrosis has never been reported. This study investigated the role of HDAC8 in pulmonary fibrosis with a focus on FMD. We observed that HDAC8 expression was increased in IPF lung tissue as well as transforming growth factor (TGF)ß1-treated normal human lung fibroblasts (NHLFs). Immunoprecipitation experiments revealed that HDAC8 was associated with α-SMA in TGFß1-treated NHLFs. HDAC8 inhibition with NCC170 (HDAC8-selective inhibitor) repressed TGFß1-induced fibroblast contraction and α-SMA protein expression in NHLFs cultured in collagen gels. HDAC8 inhibition with HDAC8 siRNA also repressed TGFß1-induced expression of profibrotic molecules such as fibronectin and increased expression of antifibrotic molecules such as peroxisome proliferator-activated receptor-γ (PPARγ). Chromatin immunoprecipitation quantitative PCR using an antibody against H3K27ac (histone H3 acetylated at lysine 27; a known HDAC8 substrate and a marker for active enhancers) suggested that HDAC8 inhibition with NCC170 ameliorated TGFß1-induced loss of H3K27ac at the PPARγ gene enhancer. Furthermore, NCC170 treatment significantly decreased fibrosis measured by Ashcroft score as well as expression of type 1 collagen and fibronectin in bleomycin-treated mouse lungs. These data suggest that HDAC8 contributes to pulmonary fibrosis and that there is a therapeutic potential for HDAC8 inhibitors to treat IPF as well as other fibrotic lung diseases.