RESUMO
Immune cell dysregulation and lymphopenia characterize COVID-19 pathology in moderate to severe disease. While underlying inflammatory factors have been extensively studied, homeostatic and mucosal migratory signatures remain largely unexplored as causative factors. In this study we evaluated the association of circulating IL-6, soluble mucosal addressin cell adhesion molecule (sMAdCAM) and IL-15 with cellular dysfunction characterizing mild and hypoxemic stages of COVID-19. A cohort of SARS-CoV-2 infected individuals (n=125) at various stages of disease progression together with healthy controls (n=16) were recruited from COVID Care Centres (CCCs) across Mumbai, India. Multiparametric flow cytometry was used to perform in-depth immune subset characterization and to measure plasma IL-6 levels. sMAdCAM, IL-15 levels were quantified using ELISA. Distinct depletion profiles, with relative sparing of CD8 effector memory and CD4+ regulatory T cells was observed in hypoxemic disease within the lymphocyte compartment. An apparent increase in the frequency of intermediate monocytes characterized both mild as well as hypoxemic disease. IL-6 levels inversely correlated with those of sMAdCAM and both markers showed converse associations with observed lympho-depletion suggesting opposing roles in pathogenesis. Interestingly, IL-15, a key cytokine involved in lymphocyte activation and homeostasis, was detected in symptomatic individuals but not in healthy controls or asymptomatic cases. Further, negative association of plasma IL-15 with depleted T, B and NK subsets suggested a compensatory production of this cytokine in response to the profound lymphopenia. Finally, higher levels of plasma IL-15 and IL-6, but not sMAdCAM, were associated with longer duration of hospitalization.
RESUMO
Background@#This study was done to study the anthropometry of nonarthritic Asian knees; to determine the differences in morphology between knees of different ethnicities and to compare the knee anthropometry values with sizes of available knee implants. @*Methods@#Magnetic resonance imaging scans of 100 nonarthritic Indian knees were analyzed. Anteroposterior (AP) length, mediolateral (ML) length, and aspect ratio of the distal femur and proximal tibia, patellar length, and patellar tendon length were measured. These values were compared with values of other ethnicities from literature. The values were also compared with sizes of available knee implants and evaluated for mismatch. @*Results@#All the parameters of female knees were significantly smaller than those of male knees (p < 0.05). The distal femur of Indian knees resembled that of Chinese knees with similar AP and ML lengths and aspect ratio. The distal femur of Indian knees had a significantly smaller AP, ML, and aspect ratio than those of Hispanic knees did. In comparison to Caucasian distal femur, Indian knees had smaller AP and ML lengths and larger aspect ratio. In terms of the proximal tibia, the Indian knees were smaller than Chinese (only ML), Caucasian (AP and ML) and Hispanic (AP and ML) knees. On comparison with implant sizes, there was a mismatch between the distal femur morphology and the dimensions of all implants. For a given AP length, the ML dimensions of all implants were smaller than the measured ML length of the knee. However, the tibial components of all the studied implants correlated well with the tibial morphology. @*Conclusions@#Distinct anthropometric differences exist between knees of different ethnicities. The knees of females were smaller than the knees of males. In Indian knees, the ML-AP aspect ratio of the distal femur was higher than that of the currently available femoral components. These results suggest the need for race-specific knee implants.