No abstract

Background: Obesity may contribute to adverse outcomes in coronavirus disease 2019 (COVID-19). However, studies of large, broadly generalizable patient populations are lacking, and the effect of body mass index (BMI) on COVID-19 outcomes— particularly in younger adults—remains uncertain. Methods: We analyzed data from patients hospitalized with COVID-19 at 88 US hospitals enrolled in the American Heart Association’s COVID-19 Cardiovascular Disease Registry with data collection through July 22, 2020. BMI was stratified by World Health Organization obesity class, with normal weight prespecified as the reference group. Results: Obesity, and, in particular, class III obesity, was overrepresented in the registry in comparison with the US population, with the largest differences among adults ≤50 years. Among 7606 patients, in-hospital death or mechanical ventilation occurred in 2109 (27.7%), in-hospital death in 1302 (17.1%), and mechanical ventilation in 1602 (21.1%). After multivariable adjustment, classes I to III obesity were associated with higher risks of in-hospital death or mechanical ventilation (odds ratio, 1.28 [95% CI, 1.09–1.51], 1.57 [1.29–1.91], 1.80 [1.47–2.20], respectively), and class III obesity was associated with a higher risk of in-hospital death (hazard ratio, 1.26 [95% CI, 1.00–1.58]). Overweight and class I to III obese individuals were at higher risk for mechanical ventilation (odds ratio, 1.28 [95% CI, 1.09–1.51], 1.54 [1.29–1.84], 1.88 [1.52–2.32], and 2.08 [1.68–2.58], respectively). Significant BMI by age interactions were seen for all primary end points ( P -interaction<0.05 for each), such that the association of BMI with death or mechanical ventilation was strongest in adults ≤50 years, intermediate in adults 51 to 70 years, and weakest in adults >70 years. Severe obesity (BMI ≥40 kg/m 2 ) was associated with an increased risk of in-hospital death only in those ≤50 years (hazard ratio, 1.36 [1.01–1.84]). In adjusted analyses, higher BMI was associated with dialysis initiation and with venous thromboembolism but not with major adverse cardiac events. Conclusions: Obese patients are more likely to be hospitalized with COVID-19, and are at higher risk of in-hospital death or mechanical ventilation, in particular, if young (age ≤50 years). Obese patients are also at higher risk for venous thromboembolism and dialysis. These observations support clear public health messaging and rigorous adherence to COVID-19 prevention strategies in all obese individuals regardless of age.

In the growth plate, stem-like cells in the resting zone differentiate into rapidly dividing chondrocytes of the proliferative zone and then terminally differentiate into the nondividing chondrocytes of the hypertrophic zone. To explore the molecular switches responsible for this two-step differentiation program, we developed a microdissection method to isolate RNA from the resting (RZ), proliferative (PZ), and hypertrophic zones (HZ) of 7-day-old male rats. Expression of approximately 29 000 genes was analyzed by microarray and selected genes verified by real-time PCR. The analysis identified genes whose expression changed dramatically during the differentiation program, including multiple genes functionally related to bone morphogenetic proteins (BMPs). BMP-2 and BMP-6 were upregulated in HZ compared with RZ and PZ (30-fold each, P!0 . 01 and 0 . 001 respectively). In contrast, BMP signaling inhibitors were expressed early in the differentiation pathway; BMP-3 and gremlin were differentially expressed in RZ (100-and 80-fold, compared with PZ, P! 0 . 001 and 0 . 005 respectively) and growth differentiation factor (GDF)-10 in PZ (160-fold compared with HZ, P!0 . 001). Our findings suggest a BMP signaling gradient across the growth plate, which is established by differential expression of multiple BMPs and BMP inhibitors in specific zones. Since BMPs can stimulate both proliferation and hypertrophic differentiation of growth plate chondrocytes, these findings suggest that low levels of BMP signaling in the resting zone may help maintain these cells in a quiescent state. In the lower RZ, greater BMP signaling may help induce differentiation to proliferative chondrocytes. Farther down the growth plate, even greater BMP signaling may help induce hypertrophic differentiation. Thus, BMP signaling gradients may be a key mechanism responsible for spatial regulation of chondrocyte proliferation and differentiation in growth plate cartilage.

No abstract