Guang Chen

Bio: Guang Chen is an academic researcher from Huazhong University of Science and Technology. The author has contributed to research in topics: Hepatitis B virus & Hepatitis. The author has an hindex of 8, co-authored 15 publications receiving 5200 citations.

Clinical and immunological features of severe and moderate coronavirus disease 2019.

Abstract: BACKGROUNDSince December 2019, an outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, and is now becoming a global threat. We aimed to delineate and compare the immunological features of severe and moderate COVID-19.METHODSIn this retrospective study, the clinical and immunological characteristics of 21 patients (17 male and 4 female) with COVID-19 were analyzed. These patients were classified as severe (11 cases) and moderate (10 cases) according to the guidelines released by the National Health Commission of China.RESULTSThe median age of severe and moderate cases was 61.0 and 52.0 years, respectively. Common clinical manifestations included fever, cough, and fatigue. Compared with moderate cases, severe cases more frequently had dyspnea, lymphopenia, and hypoalbuminemia, with higher levels of alanine aminotransferase, lactate dehydrogenase, C-reactive protein, ferritin, and D-dimer as well as markedly higher levels of IL-2R, IL-6, IL-10, and TNF-α. Absolute numbers of T lymphocytes, CD4+ T cells, and CD8+ T cells decreased in nearly all the patients, and were markedly lower in severe cases (294.0, 177.5, and 89.0 × 106/L, respectively) than moderate cases (640.5, 381.5, and 254.0 × 106/L, respectively). The expression of IFN-γ by CD4+ T cells tended to be lower in severe cases (14.1%) than in moderate cases (22.8%).CONCLUSIONThe SARS-CoV-2 infection may affect primarily T lymphocytes, particularly CD4+ and CD8+ T cells, resulting in a decrease in numbers as well as IFN-γ production by CD4+ T cells. These potential immunological markers may be of importance because of their correlation with disease severity in COVID-19.TRIAL REGISTRATIONThis is a retrospective observational study without a trial registration number.FUNDINGThis work is funded by grants from Tongji Hospital for the Pilot Scheme Project, and partly supported by the Chinese National Thirteenth Five Years Project in Science and Technology for Infectious Disease (2017ZX10202201).

Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study.

Abstract: Objective To delineate the clinical characteristics of patients with coronavirus disease 2019 (covid-19) who died. Design Retrospective case series. Setting Tongji Hospital in Wuhan, China. Participants Among a cohort of 799 patients, 113 who died and 161 who recovered with a diagnosis of covid-19 were analysed. Data were collected until 28 February 2020. Main outcome measures Clinical characteristics and laboratory findings were obtained from electronic medical records with data collection forms. Results The median age of deceased patients (68 years) was significantly older than recovered patients (51 years). Male sex was more predominant in deceased patients (83; 73%) than in recovered patients (88; 55%). Chronic hypertension and other cardiovascular comorbidities were more frequent among deceased patients (54 (48%) and 16 (14%)) than recovered patients (39 (24%) and 7 (4%)). Dyspnoea, chest tightness, and disorder of consciousness were more common in deceased patients (70 (62%), 55 (49%), and 25 (22%)) than in recovered patients (50 (31%), 48 (30%), and 1 (1%)). The median time from disease onset to death in deceased patients was 16 (interquartile range 12.0-20.0) days. Leukocytosis was present in 56 (50%) patients who died and 6 (4%) who recovered, and lymphopenia was present in 103 (91%) and 76 (47%) respectively. Concentrations of alanine aminotransferase, aspartate aminotransferase, creatinine, creatine kinase, lactate dehydrogenase, cardiac troponin I, N-terminal pro-brain natriuretic peptide, and D-dimer were markedly higher in deceased patients than in recovered patients. Common complications observed more frequently in deceased patients included acute respiratory distress syndrome (113; 100%), type I respiratory failure (18/35; 51%), sepsis (113; 100%), acute cardiac injury (72/94; 77%), heart failure (41/83; 49%), alkalosis (14/35; 40%), hyperkalaemia (42; 37%), acute kidney injury (28; 25%), and hypoxic encephalopathy (23; 20%). Patients with cardiovascular comorbidity were more likely to develop cardiac complications. Regardless of history of cardiovascular disease, acute cardiac injury and heart failure were more common in deceased patients. Conclusion Severe acute respiratory syndrome coronavirus 2 infection can cause both pulmonary and systemic inflammation, leading to multi-organ dysfunction in patients at high risk. Acute respiratory distress syndrome and respiratory failure, sepsis, acute cardiac injury, and heart failure were the most common critical complications during exacerbation of covid-19.

Clinical and immunologic features in severe and moderate forms of Coronavirus Disease 2019

Abstract: Background Since late December, 2019, an outbreak of pneumonia cases caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, and continued to spread throughout China and across the globe. To date, few data on immunologic features of Coronavirus Disease 2019 (COVID-19) have been reported. Methods In this single-centre retrospective study, a total of 21 patients with pneumonia who were laboratory-confirmed to be infected with SARS-CoV-2 in Wuhan Tongji hospital were included from Dec 19, 2019 to Jan 27, 2020. The immunologic characteristics as well as their clinical, laboratory, radiological features were compared between 11 severe cases and 10 moderate cases. Results Of the 21 patients with COVID-19, only 4 (19%) had a history of exposure to the Huanan seafood market. 7 (33.3%) patients had underlying conditions. The average age of severe and moderate cases was 63.9 and 51.4 years, 10 (90.9%) severe cases and 7 (70.0%) moderate cases were male. Common clinical manifestations including fever (100%, 100%), cough (70%, 90%), fatigue (100%, 70%) and myalgia (50%, 30%) in severe cases and moderate cases. PaO2/FiO2 ratio was significantly lower in severe cases (122.9) than moderate cases (366.2). Lymphocyte counts were significantly lower in severe cases (0.7 × 10□/L) than moderate cases (1.1 × 10□/L). Alanine aminotransferase, lactate dehydrogenase levels, high-sensitivity C-reactive protein and ferritin were significantly higher in severe cases (41.4 U/L, 567.2 U/L, 135.2 mg/L and 1734.4 ug/L) than moderate cases (17.6 U/L, 234.4 U/L, 51.4 mg/L and 880.2 ug /L). IL-2R, TNF-α and IL-10 concentrations on admission were significantly higher in severe cases (1202.4 pg/mL, 10.9 pg/mL and 10.9 pg/mL) than moderate cases (441.7 pg/mL, 7.5 pg/mL and 6.6 pg/mL). Absolute number of total T lymphocytes, CD4+T cells and CD8+T cells decreased in nearly all the patients, and were significantly lower in severe cases (332.5, 185.6 and 124.3 × 106/L) than moderate cases (676.5, 359.2 and 272.0 × 106/L). The expressions of IFN-γ by CD4+T cells tended to be lower in severe cases (14.6%) than moderate cases (23.6%). Conclusion The SARS-CoV-2 infection may affect primarily T lymphocytes, particularly CD4+T cells, resulting in significant decrease in number as well as IFN-γ production, which may be associated with disease severity. Together with clinical characteristics, early immunologic indicators including diminished T lymphocytes and elevated cytokines may serve as potential markers for prognosis in COVID-19.

Longitudinal changes of inflammatory parameters and their correlation with disease severity and outcomes in patients with COVID-19 from Wuhan, China.

Abstract: Coronavirus disease 2019 (COVID-19) is a newly emerging infectious disease and rapidly escalating epidemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The pathogenesis of COVID-19 remains to be elucidated. We aimed to clarify correlation of systemic inflammation with disease severity and outcomes in COVID-19 patients. In this retrospective study, baseline characteristics, laboratory findings, and treatments were compared among 317 laboratory-confirmed COVID-19 patients with moderate, severe, or critically ill form of the disease. Moreover, the longitudinal changes of serum cytokines, lactate dehydrogenase (LDH), high-sensitivity C-reactive protein (hsCRP), and hsCRP to lymphocyte count ratio (hsCRP/L) as well as their associations with disease severity and outcomes were investigated in 68 COVID-19 patients. Within 24 h of admission, the critically ill patients showed higher concentrations of inflammatory markers including serum soluble interleukin (IL)-2 receptor, IL-6, IL-8, IL-10, tumor necrosis factor alpha (TNF-α), ferritin, procalcitonin, LDH, hsCRP, and hsCRP/L than patients with severe or moderate disease. The severe cases displayed the similar response patterns when compared with moderate cases. The longitudinal assays showed the levels of pro-inflammatory cytokines, LDH, hsCRP, and hsCRP/L gradually declined within 10 days post admission in moderate, severe cases or those who survived. However, there was no significant reduction in cytokines, LDH, hsCRP, and hsCRP/L levels in critically ill or deceased patients throughout the course of illness. Compared with female patients, male cases showed higher serum concentrations of soluble IL-2R, IL-6, ferritin, procalcitonin, LDH, and hsCRP. Multivariate logistic regression analysis revealed that IL-6 > 50 pg/mL and LDH > 400 U/L on admission were independently associated with disease severity in patients with COVID-19. Exuberant inflammatory responses within 24 h of admission in patients with COVID-19 may correlate with disease severity. SARS-CoV-2 infection appears to elicit a sex-based differential immune response. IL-6 and LDH were independent predictive parameters for assessing the severity of COVID-19. An early decline of these inflammation markers may be associated with better outcomes.

Clinical characteristics and risk factors of liver injury in COVID-19: a retrospective cohort study from Wuhan, China

Abstract: Coronavirus disease 2019 (COVID-19) has rapidly become a major international public health concern. This study was designed to evaluate the clinical characteristics and risk factors of COVID-19-associated liver injury. A fraction of 657 COVID-19 patients were retrospectively analyzed. Clinical and laboratory data were derived from electronic medical records and compared between patients with or without liver injury. Multivariate logistic regression method was used to analyze the risk factors for liver injury. Among 657 patients, 303 (46.1%) patients had liver injury with higher rate in severe/critically ill patients [148/257 (57.6%)] than those in moderate cases [155/400 (38.8%)]. The incidence of liver injury was much higher in male [192/303 (63.4%)] than female [111/303 (36.6%)], and in severe/critical patients [148/303 (48.8%)] with percutaneous oxygen saturation ≤ 93% [89/279 (31.9%)] or peak body temperature ≥ 38.5 °C [185/301 (61.5%)] on admission. Liver injury-related inflammations included increased white blood cells, neutrophils and decreased lymphocytes. More patients with liver injury than without had increased serum IL-2R, TNFα, ferritin, hsCRP, PCT, ESR, γ-GT, and LDH. Multivariate regression analysis revealed that increasing odds of liver injury were related to male, higher serum hsCRP (≥ 10 mg/L), and neutrophil-to-lymphocyte ratio (NLR) (≥ 5). Moreover, more deceased patients (14/82 (17%)) had significantly elevated serum TBIL than discharged patients [25/532 (4.7%)]. Liver injury is a common complication in COVID-19 patients. The potential risk factors of liver injury include male, hsCRP and NLR score. A close monitor of liver function should be warned in COVID-19 patients, especially in severe/critical individuals.

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.

The trinity of COVID-19: immunity, inflammation and intervention.

Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Alongside investigations into the virology of SARS-CoV-2, understanding the fundamental physiological and immunological processes underlying the clinical manifestations of COVID-19 is vital for the identification and rational design of effective therapies. Here, we provide an overview of the pathophysiology of SARS-CoV-2 infection. We describe the interaction of SARS-CoV-2 with the immune system and the subsequent contribution of dysfunctional immune responses to disease progression. From nascent reports describing SARS-CoV-2, we make inferences on the basis of the parallel pathophysiological and immunological features of the other human coronaviruses targeting the lower respiratory tract - severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Finally, we highlight the implications of these approaches for potential therapeutic interventions that target viral infection and/or immunoregulation.