Huifen Li

Bio: Huifen Li is an academic researcher from Johns Hopkins University School of Medicine. The author has contributed to research in topics: Medicine & Vaccination. The author has an hindex of 12, co-authored 19 publications receiving 892 citations. Previous affiliations of Huifen Li include Johns Hopkins University.

Frailty, Inflammation, and Immunity

Abstract: Frailty is an important geriatric syndrome that is characterized by multisystem dysregulation, leading to decreased physiological reserve and increased vulnerability for adverse health outcomes. A large number of studies have shown a heightened inflammatory state marked by elevated levels of inflammatory molecules, such as IL-6 and C-reactive protein (CRP), and increased counts of white blood cell (WBC) and WBC subpopulations in frail older adults. It has been postulated that this heightened inflammatory state, or chronic inflammation, may play an important role in the pathogenesis of frailty, directly or through its detrimental influence to other physiologic systems. Inflammatory and immune activation mediated by monocytes and macrophages demonstrated by upregulated expression of specific stress responsive inflammatory pathway genes and elevated neopterin levels may contribute, at least in part, to this chronically heightened inflammatory state in frailty. Decrease in lipopolysaccharide (LPS)-induced proliferation of the peripheral blood mononuclear cells (PBMCs), one of the functional readouts of the innate immune system, has also been observed in frail older adults. In the adaptive immune system, significant frailty-associated alterations have been identified in the T-cell compartment including expansion of CD8(+) and CCR5(+) T cells and loss of CD28 expression, above and beyond age-related senescent remodeling. Moreover, frailty is associated with impaired antibody responses to pneumococcal and influenza immunization and poor clinical protection against influenza infection in community-dwelling older adults. Taken together, these findings demonstrate significant inflammatory and immune dysregulation in frail older adults and highlight the need for strategies to improve the immune function for this vulnerable elderly population.

IL-6-independent association of elevated serum neopterin levels with prevalent frailty in community-dwelling older adults

Abstract: Background: neopterin is a monocyte/macrophage-derived immune activation marker and its levels increase with age. Frailty is an important clinical syndrome of old age. Previous studies have shown significant association between elevated interleukin-6 (IL-6) levels and frailty. The objective of this study was to evaluate IL-6-independent association of serum neopterin levels with prevalent frailty. Methods: this is a cross-sectional study in community-dwelling older adults recruited from residential and retirement communities in Baltimore, MD, USA. Frailty was determined using validated screening criteria. Serum neopterin and IL-6 levels were measured using standard enzyme-linked immunosorbent assay. Pearson correlation and multivariate linear regression analysis was performed to assess the relationship between log(neopterin) and log(IL-6). Odds ratios (ORs) for frailty were calculated using log(neopterin) and log(IL-6) as continuous measures and across tertiles of neopterin and IL-6 levels, adjusting for age, race, sex, education and body mass index. Results: one hundred and thirty-three individuals with a mean age of 84 years (range 72–97) completed the study. Neopterin levels were significantly higher in frail older adults than those in non-frail controls [median: 8.94 versus 8.35 nM, respectively, P < 0.001 t-test on log(neopterin)]. Log(neopterin) was significantly associated with prevalent frailty, adjusting for log(IL-6). Participants in the top tertile of neopterin had OR of 3.80 [95% confidence interval (CI) = 1.36–10.6, P < 0.01] for frailty. As expected, participants in the top tertile of IL-6 had OR of 3.29 (95% CI = 1.21–7.86, P < 0.05) for frailty. Log(neopterin) correlated with log(IL-6) (correlation coefficient = 0.19, P < 0.05). Moreover, OR for participants in the top neopterin tertile remained significant after adjusting for IL-6 (OR = 3.97, 95% CI = 1.15–13.72, P < 0.05). Conclusion: elevated neopterin levels had IL-6-independent association with prevalent frailty, suggesting potential monocyte/macrophage-mediated immune activation in the frail elderly.

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Abstract: Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Age-dependent dysregulation of innate immunity

Abstract: As we age, the innate immune system becomes dysregulated and is characterized by persistent inflammatory responses that involve multiple immune and non-immune cell types and that vary depending on the cell activation state and tissue context. This ageing-associated basal inflammation, particularly in humans, is thought to be induced by several factors, including the reactivation of latent viral infections and the release of endogenous damage-associated ligands of pattern recognition receptors (PRRs). Innate immune cell functions that are required to respond to pathogens or vaccines, such as cell migration and PRR signalling, are also impaired in aged individuals. This immune dysregulation may affect conditions associated with chronic inflammation, such as atherosclerosis and Alzheimer's disease.

Physical activity in older age: perspectives for healthy ageing and frailty.

Abstract: Regular physical activity helps to improve physical and mental functions as well as reverse some effects of chronic disease to keep older people mobile and independent. Despite the highly publicised benefits of physical activity, the overwhelming majority of older people in the United Kingdom do not meet the minimum physical activity levels needed to maintain health. The sedentary lifestyles that predominate in older age results in premature onset of ill health, disease and frailty. Local authorities have a responsibility to promote physical activity amongst older people, but knowing how to stimulate regular activity at the population-level is challenging. The physiological rationale for physical activity, risks of adverse events, societal and psychological factors are discussed with a view to inform public health initiatives for the relatively healthy older person as well as those with physical frailty. The evidence shows that regular physical activity is safe for healthy and for frail older people and the risks of developing major cardiovascular and metabolic diseases, obesity, falls, cognitive impairments, osteoporosis and muscular weakness are decreased by regularly completing activities ranging from low intensity walking through to more vigorous sports and resistance exercises. Yet, participation in physical activities remains low amongst older adults, particularly those living in less affluent areas. Older people may be encouraged to increase their activities if influenced by clinicians, family or friends, keeping costs low and enjoyment high, facilitating group-based activities and raising self-efficacy for exercise.