Metformin in therapeutic applications in human diseases: its mechanism of action and clinical study.

Metformin, a biguanide drug, is the most commonly used first-line medication for type 2 diabetes mellites due to its outstanding glucose-lowering ability. After oral administration of 1 g, metformin peaked plasma concentration of approximately 20-30 µM in 3 h, and then it mainly accumulated in the gastrointestinal tract, liver and kidney. Substantial studies have indicated that metformin exerts its beneficial or deleterious effect by multiple mechanisms, apart from AMPK-dependent mechanism, also including several AMPK-independent mechanisms, such as restoring of redox balance, affecting mitochondrial function, modulating gut microbiome and regulating several other signals, such as FBP1, PP2A, FGF21, SIRT1 and mTOR. On the basis of these multiple mechanisms, researchers tried to repurpose this old drug and further explored the possible indications and adverse effects of metformin. Through investigating with clinical studies, researchers concluded that in addition to decreasing cardiovascular events and anti-obesity, metformin is also beneficial for neurodegenerative disease, polycystic ovary syndrome, aging, cancer and COVID-19, however, it also induces some adverse effects, such as gastrointestinal complaints, lactic acidosis, vitamin B12 deficiency, neurodegenerative disease and offspring impairment. Of note, the dose of metformin used in most studies is much higher than its clinically relevant dose, which may cast doubt on the actual effects of metformin on these disease in the clinic. This review summarizes these research developments on the mechanism of action and clinical evidence of metformin and discusses its therapeutic potential and clinical safety.

Hyperglycemia and blood glucose deterioration are risk factors for severe COVID-19 with diabetes: A two-center cohort study.

We aimed to assess whether blood glucose control can be used as predictors for the severity of 2019 coronavirus disease (COVID-19) and to improve the management of diabetic patients with COVID-19. A two-center cohort with a total of 241 confirmed cases of COVID-19 with definite outcomes was studied. After the diagnosis of COVID-19, the clinical data and laboratory results were collected, the fasting blood glucose levels were followed up at initial, middle stage of admission and discharge, the severity of the COVID-19 was assessed at any time from admission to discharge. Hyperglycemia patients with COVID-19 were divided into three groups: good blood glucose control, fair blood glucose control, and blood glucose deterioration. The relationship of blood glucose levels, blood glucose control status, and severe COVID-19 were analyzed by univariate and multivariable regression analysis. In our cohort, 21.16% were severe cases and 78.84% were nonsevere cases. Admission hyperglycemia (adjusted odds ratio [aOR], 1.938; 95% confidence interval [95% CI], 1.387-2.707), mid-term hyperglycemia (aOR, 1.758; 95% CI, 1.325-2.332), and blood glucose deterioration (aOR, 22.783; 95% CI, 2.661-195.071) were identified as the risk factors of severe COVID-19. Receiver operating characteristic (ROC) curve analysis, reaching an area under ROC curve of 0.806, and a sensitivity and specificity of 80.40% and 68.40%, respectively, revealed that hyperglycemia on admission and blood glucose deterioration of diabetic patients are potential predictive factors for severe COVID-19. Our results indicated that admission hyperglycemia and blood glucose deterioration were positively correlated with the risk factor for severe COVID-19, and deterioration of blood glucose may be more likely to the occurrence of severe illness in COVID-19.

Risk assessment of venous thromboembolism and bleeding in COVID-19 patients.

BACKGROUND: The coronavirus disease 2019 (COVID-19) is a newly recognized illness that has spread rapidly all over the world. More and more reports highlight the risk of venous thromboembolism (VTE) in COVID-19. Our study aims to identify in-hospital VTE risk and bleeding risk in COVID-19 patients. METHODS: We retrospectively studied 138 consecutively enrolled patients with COVID-19 and identified in-hospital VTE and bleeding risk by Padua Prediction Score and Improve bleed risk assessment model. The clinical data and features were analyzed in VTE patients. RESULTS: Our findings identified that 23 (16.7%) patients with COVID-19 were at high risk for VTE according to Padua prediction score and 9 (6.5%) patients were at high risk of bleeding for VTE prophylaxis according to Improve prediction score. Fifteen critically ill patients faced double high risk from thrombosis (Padua score more than 4 points in all 15 [100%] patients) and hemorrhage (Improve score more than 7 points in 9 [60.0%] patients). Thrombotic events were identified in four patients (2.9%) of all COVID-19 patients. All of them were diagnosed with deep vein thrombosis by ultrasound 3 to 18 days after admission. Three (75.0%) were critically ill patients, which means that the incidence of VTE among critically ill patients was 20%. One major hemorrhage happened in critically ill patients during VTE treatment. CONCLUSION: Critically ill patients with COVID-19 suffered both a high risk of thrombosis and bleeding risks. More effective VTE prevention strategies based on an individual assessment of bleeding risks were necessary for critically ill patients with COVID-19.

Survivors of COVID-19 exhibit altered amplitudes of low frequency fluctuation in the brain: a resting-state functional magnetic resonance imaging study at 1-year follow-up.

Although some short-term follow-up studies have found that individuals recovering from coronavirus disease 2019 (COVID-19) exhibit anxiety, depression, and altered brain microstructure, their long-term physical problems, neuropsychiatric sequelae, and changes in brain function remain unknown. This observational cohort study collected 1-year follow-up data from 22 patients who had been hospitalized with COVID-19 (8 males and 11 females, aged 54.2 ± 8.7 years). Fatigue and myalgia were persistent symptoms at the 1-year follow-up. The resting state functional magnetic resonance imaging revealed that compared with 29 healthy controls (7 males and 18 females, aged 50.5 ± 11.6 years), COVID-19 survivors had greatly increased amplitude of low-frequency fluctuation (ALFF) values in the left precentral gyrus, middle frontal gyrus, inferior frontal gyrus of operculum, inferior frontal gyrus of triangle, insula, hippocampus, parahippocampal gyrus, fusiform gyrus, postcentral gyrus, inferior parietal angular gyrus, supramarginal gyrus, angular gyrus, thalamus, middle temporal gyrus, inferior temporal gyrus, caudate, and putamen. ALFF values in the left caudate of the COVID-19 survivors were positively correlated with their Athens Insomnia Scale scores, and those in the left precentral gyrus were positively correlated with neutrophil count during hospitalization. The long-term follow-up results suggest that the ALFF in brain regions related to mood and sleep regulation were altered in COVID-19 survivors. This can help us understand the neurobiological mechanisms of COVID-19-related neuropsychiatric sequelae. This study was approved by the Ethics Committee of the Second Xiangya Hospital of Central South University (approval No. 2020S004) on March 19, 2020.

Understanding risks of refractive error among Chinese children amidst pandemic disruptions: results from a rapid survey.

BACKGROUND: Despite effectiveness in delaying the spread of the pandemic, frequent and extended disruption to children's livelihoods have fomented new norms in which learning routines encounter immense change. In particular, increased sedentary e-learning engagement with electronic screens and exposure to stressful circumstances are likely to pose adverse risks for children's vision development. METHODS: This present study examines the link between near-sighted refractive error, and sedentary exposure to electronic screens, psychosocial stress level, and outdoor activities. A Rapid Survey Methodology (RSM) design was utilized to collect information on subject's vision condition, sedentary electronic screen use, and level of psychosocial stress, in addition to detailed socio-demographic background characteristics. RESULTS: This study involves 2234 subjects enrolled in 1st to 6th grade in primary schools. Every 1 diopter hour increase in electronic screen use per day is associated with 1.036 OR (95% CI =1.024-1.047, p-value< 0.050), while every 1 h • W m- 2 sr- 1 of illuminance-weighted electronic screen use per day is associated with 2.285 OR (95% CI =1.829-2.855, p-value< 0.050) increased likelihood of near-sighted refractive error. Higher level of psychosocial stress is associated with 2.441 OR (95% CI =1.870-3.187, p-value< 0.050) and 2.403 OR (95% CI =1.839-3.141, p-value< 0.050) increased likelihood of near-sighted refractive error. Frequency of outdoor activity is not significantly associated with increased likelihood of near-sighted refractive error (p-value> 0.050). CONCLUSIONS: Findings in this study show that many factors, including grade level and prior vision condition, contribute to increased risks of near-sighted refractive error during the COVID-19 pandemic. More strikingly, pandemic-related behavioral modifications such as lengthy sedentary electronic screen use and elevated levels of psychosocial stress are two critical channels affecting children's eye health.

Clinical Characteristics of Coronavirus Disease 2019 in China.

BACKGROUND: Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. METHODS: We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. RESULTS: The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. CONCLUSIONS: During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.).

Examining risk factors related to digital learning and social isolation: Youth visual acuity in COVID-19 pandemic.

BACKGROUND: Around the globe, various self-quarantine, social distancing, and school-closure policies were implemented during the coronavirus disease-19 (COVID-19) outbreak to reduce disease transmission. Many economies/territories were compelled to consider digital learning modalities. In particular, increased digital learning engagement with digital devices and mounting psychosocial stress due to social isolation are likely to pose adverse risks for youth visual health globally. This study examines the association between increased digital device use, psychosocial stress, and myopia symptoms among Chinese youth during the COVID-19 pandemic. METHODS: This is a retrospective observational population study consisting of 3918 participants enrolled in primary, secondary, and university in China. Participants are recruited through an online survey, which included self-reported information on daily digital device use, psychosocial stress level, condition of visual acuity, and demographic information. We utilize statistical tools including χ2 test, paired sample t test, and multiple multivariate logistic regression. RESULTS: Each hour increase in digital device use is associated with 1.25 odds ratio OR (95% confidence interval (CI) = 1.21-1.30; P < 0.001) increased risk of developing myopic symptoms, each additional hour of digital device use weighted by near-view and blue-light exposure is associated with OR = 1.04 OR (95% CI = 1.03-1.05; P < 0.001) and OR = 2.25 (95% CI = 1.94-2.60; P < 0.001) increased risk respectively. Subjects reporting under stressful conditions are between OR = 1.98 (95% CI = 1.67-2.36; P < 0.001) and OR = 2.03 (95% CI = 1.71-2.42; P < 0.001) more likely to develop myopic symptoms, relative to those citing less stress. CONCLUSIONS: The COVID-19 pandemic led to favorable conditions for myopigenic behavioral changes characterized by extended sedentary engagement with digital devices, which are significantly associated with higher risks of myopia incidence. Relatedly, psychosocial stress accompanying prolonged social isolation during the pandemic is a less noticeable, albeit significant risk factor for myopia development.

Therapeutic targets and interventional strategies in COVID-19: mechanisms and clinical studies.

Owing to the limitations of the present efforts on drug discovery against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the lack of the understanding of the biological regulation mechanisms underlying COVID-19, alternative or novel therapeutic targets for COVID-19 treatment are still urgently required. SARS-CoV-2 infection and immunity dysfunction are the two main courses driving the pathogenesis of COVID-19. Both the virus and host factors are potential targets for antiviral therapy. Hence, in this study, the current therapeutic strategies of COVID-19 have been classified into "target virus" and "target host" categories. Repurposing drugs, emerging approaches, and promising potential targets are the implementations of the above two strategies. First, a comprehensive review of the highly acclaimed old drugs was performed according to evidence-based medicine to provide recommendations for clinicians. Additionally, their unavailability in the fight against COVID-19 was analyzed. Next, a profound analysis of the emerging approaches was conducted, particularly all licensed vaccines and monoclonal antibodies (mAbs) enrolled in clinical trials against primary SARS-CoV-2 and mutant strains. Furthermore, the pros and cons of the present licensed vaccines were compared from different perspectives. Finally, the most promising potential targets were reviewed, and the update of the progress of treatments has been summarized based on these reviews.

Abnormal Indexes of Liver and Kidney Injury Markers Predict Severity in COVID-19 Patients.

BACKGROUND: SARS-CoV-2 can damage not only the lungs but also the liver and kidney. Most critically ill patients with coronavirus disease 2019 (COVID-19) have liver and kidney dysfunction. We aim to investigate the levels of liver and kidney function indexes in mild and severe COVID-19 patients and their capability to predict the severity of the disease. METHODS: The characteristics and laboratory indexes were compared between patients with different conditions. We applied binary logistic regression to find the independent risk factors of severe patients. Receiver operating characteristic (ROC) analysis was used to predict the severity of COVID-19 using the liver and kidney function indexes. RESULTS: This study enrolled 266 COVID-19 patients, including 235 mild patients and 31 severe patients. Compared with mild patients, severe patients had lower albumin (ALB) and higher alanine aminotransferase (ALT), aspartate aminotransferase (AST), and urea nitrogen (BUN) (all p<0.001). Binary logistic regression analysis also identified ALB [OR=0.273 (0.079-0.947), p=0.041] and ALT [OR=2.680 (1.036-6.934), p=0.042] as independent factors of severe COVID-19 patients. Combining ALB, ALT, BUN, and LDH exhibited the area under ROC at 0.914, with a sensitivity of 86.7% and specificity of 83.0%. CONCLUSION: COVID-19 patients, especially severe patients, have damage to liver and kidney function. ALT, AST, LDH, and BUN could be independent factors for predicting the severity of COVID-19. Combining the ALB, ALT, BUN, and LDH could predict the transition from mild to severe in COVID-19 patients.

Multiplex Real-Time Reverse Transcription PCR for Influenza A Virus, Influenza B Virus, and Severe Acute Respiratory Syndrome Coronavirus 2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019, and the outbreak rapidly evolved into the current coronavirus disease pandemic. SARS-CoV-2 is a respiratory virus that causes symptoms similar to those caused by influenza A and B viruses. On July 2, 2020, the US Food and Drug Administration granted emergency use authorization for in vitro diagnostic use of the Influenza SARS-CoV-2 Multiplex Assay. This assay detects influenza A virus at 102.0, influenza B virus at 102.2, and SARS-CoV-2 at 100.3 50% tissue culture or egg infectious dose, or as few as 5 RNA copies/reaction. The simultaneous detection and differentiation of these 3 major pathogens increases overall testing capacity, conserves resources, identifies co-infections, and enables efficient surveillance of influenza viruses and SARS-CoV-2.

Adolescent Vision Health During the Outbreak of COVID-19: Association Between Digital Screen Use and Myopia Progression.

The coronavirus (COVID-19) pandemic has impacted education systems globally, making digital devices common arrangements for adolescent learning. However, vision consequences of such behavioral changes are not well-understood. This study investigates the association between duration of daily digital screen engagement and myopic progression among 3,831 Chinese adolescents during the COVID-19 pandemic. Study subjects report an average of 2.70 (SD = 1.77), 3.88 (SD = 2.23), 3.58 (SD = 2.30), and 3.42 (SD = 2.49) hours of television, computer, and smartphone for digital learning use at home, respectively. Researchers analyzed the association between digital screen use and myopic symptoms using statistical tools, and find that every 1 h increase in daily digital screen use is associated with 1.26 OR [Odds Ratio] (95% CI [Confidence Interval: 1.21-1.31, p < 0.001]) higher risks of myopic progression. Using computers (OR = 1.813, 95% CI = 1.05-3.12, p = 0.032) and using smartphones (OR = 2.02, 95% CI = 1.19-3.43, p = 0.009) are shown to be associated with higher risks of myopic progression than television use. Results from additional sensitivity tests that included inverse probability weights which accounted for heterogeneous user profile across different device type categories confirm that these findings are robust. In conclusion, this study finds that daily digital screen use is positively associated with prevalence of myopic progression and holds serious vision health implications for adolescents.

Clinical course of patients on maintenance hemodialysis and COVID-19: a retrospective longitudinal study.

Coronavirus Disease 2019 (COVID-19) emerges as a global pandemic and there is a lack of evidence about the clinical course and outcome of patients on maintenance hemodialysis (MHD). Here we conducted a retrospective longitudinal study aimed to analyze the clinical features and outcome of MHD patients hospitalized with COVID-19. Of 3126 inpatients with COVID-19 at 3 Branches of Wuhan Tongji Hospital from Jan 18th to Mar 9th, 2020, 19 patients were undergoing maintenance hemodialysis. Among the 19 MHD patients with COVID-19, 6 patients (31.6%) died, and 13 patients (68.4%) were able to be discharged. Baseline characteristics, clinical courses, laboratory findings, and dynamic trajectories of major laboratory markers were compared between survivors and nonsurvivors. According to our findings, MHD patients with COVID-19 who experienced non-surviving outcome had more elevated CRP, IL6 and procalcitonin as well as fibrinogen levels at various points compared to survivors. Thus the dysregulation of immune response as well as coagulation abnormalities might be highly involved in the pathological process of COVID-19, contributing to the poor prognosis in MHD patients.

Student Health Implications of School Closures during the COVID-19 Pandemic: New Evidence on the Association of e-Learning, Outdoor Exercise, and Myopia.

The coronavirus disease 2019 (COVID-19) pandemic forced many education systems to consider alternative remote e-learning modalities, which have consequential behavioral and health implications for youth. In particular, increased e-learning engagement with digital screens and reduction in outdoor activities are two likely channels posing adverse risks for myopia development. This study investigated the association between e-learning screen use, outdoor activity, lighting condition, and myopia development among school-age children in China, during the first wave of the COVID-19 pandemic. Data were collected from 3405 school-age children attending primary, lower-secondary, and upper-secondary schools in China. Univariate parametric and nonparametric tests, and multivariate logistic regression analysis were used. Findings show that each diopter hour increase in daily e-learning screen use is significantly associated with progression of myopia symptoms (OR: 1.074, 95% CI: 1.058-1.089; p < 0.001), whereas engaging in outdoor exercise four to six times per week (OR: 0.745, 95% CI: 0.568-0.977; p = 0.034) and one to three times per week (OR: 0.829, 95% CI: 0.686-0.991; p = 0.048) is associated with a lower likelihood of myopia progression than none at all. In addition, we found that indoor lighting that is either "too dim" (OR: 1.686, 95% CI: 1.226-2.319; p = 0.001) or "too bright" (OR: 1.529, 95% CI: 1.007-2.366; p = 0.036) is significantly associated higher likelihood of myopic symptoms. Findings in this study uncover the less observable vision consequences of the COVID-19 pandemic on youths through digital online learning and highlight the importance of considering appropriate mitigation strategies to deal with this emerging public health challenge.

How do social media and individual behaviors affect epidemic transmission and control?

In the outbreak of infectious diseases such as COVID-19, social media channels are important tools for the public to obtain information and form their opinions on infection risk, which can affect their disease prevention behaviors and the consequent disease transmission processes. However, there has been a lack of theoretical investigation into how social media and human behaviors jointly affect the spread of infectious diseases. In this study, we develop an agent-based modeling framework that couples (1) a general opinion dynamics model that describes how individuals form their opinions on epidemic risk with various information sources, (2) a behavioral adoption model that simulates the adoption of disease prevention behaviors, and (3) an epidemiological SEIR model that simulates the spread of diseases in a host population. Through simulating the spread of a coronavirus-like disease in a hypothetical residential area, the modeling results show that social media can make a community more sensitive to external drivers. Social media can increase the public's awareness of infection risk, which is beneficial for epidemic containment, when high-quality epidemic information exists at the early stage of pandemics. However, fabricated and fake news on social media, after a "latent period", can lead to a significant increase in infection rate. The modeling results provide scientific evidence for the intricate interplay between social media and human behaviors in epidemic dynamics and control, and highlight the importance of public education to promote behavioral changes and the need to correct misinformation and fake news on social media in a timely manner.

Association of liver abnormalities with in-hospital mortality in patients with COVID-19.

BACKGROUND & AIMS: The evolution and clinical significance of abnormal liver chemistries and the impact of hepatitis B infection on outcome in patients with COVID-19 is not well characterized. This study aimed to explore these issues. METHODS: This large retrospective cohort study included 2,073 patients with coronavirus disease 2019 (COVID-19) and definite outcomes in Wuhan, China. Longitudinal liver function tests were conducted, with associated factors and risk of death determined by multivariate regression analyses. A prognostic nomogram was formulated to predict the survival of patients with COVID-19. The characteristics of liver abnormalities and outcomes of patients with COVID-19, with and without hepatitis B, were compared after 1:3 propensity score matching. RESULTS: Of the 2,073 patients, 1,282 (61.8%) had abnormal liver chemistries during hospitalization, and 297 (14.3%) had a liver injury. The mean levels of aspartate aminotransferase (AST) and direct bilirubin (D-Bil) increased early after symptom onset in deceased patients and showed disparity compared to levels in discharged patients throughout the clinical course of the disease. Abnormal AST (adjusted hazard ratio [HR] 1.39; 95% CI 1.04-1.86, p = 0.027) and D-Bil (adjusted HR 1.66; 95% CI 1.22-2.26; p = 0.001) levels at admission were independent risk factors for mortality due to COVID-19. A nomogram was established based on the results of multivariate analysis and showed sufficient discriminatory power and good consistency between the prediction and the observation. HBV infection in patients did not increase the risk of poor COVID-19-associated outcomes. CONCLUSIONS: Abnormal AST and D-Bil levels at admission were independent predictors of COVID-19-related mortality. Therefore, monitoring liver chemistries, especially AST and D-Bil levels, is necessary in hospitalized patients with COVID-19. LAY SUMMARY: Liver test abnormalities (in particular elevations in the levels of aspartate aminotransferase [AST] and direct bilirubin [D-Bil]) were observed after symptom onset in patients who went on to die of coronavirus disease 2019 (COVID-19). Abnormal levels of AST and D-Bil at admission were independent predictors of COVID-19-related mortality. HBV infection in patients did not increase the risk of poor COVID-19-associated outcomes.

Increased circulating level of interleukin-6 and CD8+ T cell exhaustion are associated with progression of COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is pandemic. It is critical to identify COVID-19 patients who are most likely to develop a severe disease. This study was designed to determine the clinical and epidemiological features of COVID-19 patients associated with the development of pneumonia and factors associated with disease progression. METHODS: Seventy consecutive patients with etiologically confirmed COVID-19 admitted to PLA General Hospital in Beijing, China from December 27, 2019 to March 12, 2020 were enrolled in this study and followed-up to March 16, 2020. Differences in clinical and laboratory findings between COVID-19 patients with pneumonia and those without were determined by the χ2 test or the Fisher exact test (categorical variables) and independent group t test or Mann-Whitney U test (continuous variables). The Cox proportional hazard model and Generalized Estimating Equations were applied to evaluate factors that predicted the progression of COVID-19. RESULTS: The mean incubation was 8.67 (95% confidence interval, 6.78-10.56) days. Mean duration from the first test severe acute respiratory syndrome coronavirus 2-positive to conversion was 11.38 (9.86-12.90) days. Compared to pneumonia-free patients, pneumonia patients were 16.5 years older and had higher frequencies of having hypertension, fever, and cough and higher circulating levels of neutrophil proportion, interleukin-6, low count (< 190/µl) of CD8+ T cells, and neutrophil/lymphocyte ratio. Thirteen patients deteriorated during hospitalization. Cox regression analysis indicated that older age and higher serum levels of interleukin-6, C-reactive protein, procalcitonin, and lactate at admission significantly predicted the progression of COVID-19. During hospitalization, circulating counts of T lymphocytes, CD4+ T cells, and CD8+ T cells were lower, whereas neutrophil proportion, neutrophil/lymphocyte ratio, and the circulating levels of interleukin-6, C-reactive protein, and procalcitonin were higher, in pneumonia patients than in pneumonia-free patients. CD8+ lymphocyte count in pneumonia patients did not recover when discharged. CONCLUSIONS: Older age and higher levels of C-reactive protein, procalcitionin, interleukin-6, and lactate might predict COVID-19 progression. T lymphocyte, especially CD8+ cell-mediated immunity is critical in recovery of COVID-19. This study may help in predicting disease progression and designing immunotherapy for COVID-19.

Clinical characteristics and outcomes of hospitalised patients with COVID-19 treated in Hubei (epicentre) and outside Hubei (non-epicentre): a nationwide analysis of China.

BACKGROUND: During the outbreak of coronavirus disease 2019 (COVID-19), consistent and considerable differences in disease severity and mortality rate of patients treated in Hubei province compared to those in other parts of China have been observed. We sought to compare the clinical characteristics and outcomes of patients being treated inside and outside Hubei province, and explore the factors underlying these differences. METHODS: Collaborating with the National Health Commission, we established a retrospective cohort to study hospitalised COVID-19 cases in China. Clinical characteristics, the rate of severe events and deaths, and the time to critical illness (invasive ventilation or intensive care unit admission or death) were compared between patients within and outside Hubei. The impact of Wuhan-related exposure (a presumed key factor that drove the severe situation in Hubei, as Wuhan is the epicentre as well the administrative centre of Hubei province) and the duration between symptom onset and admission on prognosis were also determined. RESULTS: At the data cut-off (31 January 2020), 1590 cases from 575 hospitals in 31 provincial administrative regions were collected (core cohort). The overall rate of severe cases and mortality was 16.0% and 3.2%, respectively. Patients in Hubei (predominantly with Wuhan-related exposure, 597 (92.3%) out of 647) were older (mean age 49.7 versus 44.9 years), had more cases with comorbidity (32.9% versus 19.7%), higher symptomatic burden, abnormal radiologic manifestations and, especially, a longer waiting time between symptom onset and admission (5.7 versus 4.5 days) compared with patients outside Hubei. Patients in Hubei (severe event rate 23.0% versus 11.1%, death rate 7.3% versus 0.3%, HR (95% CI) for critical illness 1.59 (1.05-2.41)) have a poorer prognosis compared with patients outside Hubei after adjusting for age and comorbidity. However, among patients outside Hubei, the duration from symptom onset to hospitalisation (mean 4.4 versus 4.7 days) and prognosis (HR (95%) 0.84 (0.40-1.80)) were similar between patients with or without Wuhan-related exposure. In the overall population, the waiting time, but neither treated in Hubei nor Wuhan-related exposure, remained an independent prognostic factor (HR (95%) 1.05 (1.01-1.08)). CONCLUSION: There were more severe cases and poorer outcomes for COVID-19 patients treated in Hubei, which might be attributed to the prolonged duration of symptom onset to hospitalisation in the epicentre. Future studies to determine the reason for delaying hospitalisation are warranted.

Comorbidity and its impact on 1590 patients with COVID-19 in China: a nationwide analysis.

BACKGROUND: The coronavirus disease 2019 (COVID-19) outbreak is evolving rapidly worldwide. OBJECTIVE: To evaluate the risk of serious adverse outcomes in patients with COVID-19 by stratifying the comorbidity status. METHODS: We analysed data from 1590 laboratory confirmed hospitalised patients from 575 hospitals in 31 provinces/autonomous regions/provincial municipalities across mainland China between 11 December 2019 and 31 January 2020. We analysed the composite end-points, which consisted of admission to an intensive care unit, invasive ventilation or death. The risk of reaching the composite end-points was compared according to the presence and number of comorbidities. RESULTS: The mean age was 48.9 years and 686 (42.7%) patients were female. Severe cases accounted for 16.0% of the study population. 131 (8.2%) patients reached the composite end-points. 399 (25.1%) reported having at least one comorbidity. The most prevalent comorbidity was hypertension (16.9%), followed by diabetes (8.2%). 130 (8.2%) patients reported having two or more comorbidities. After adjusting for age and smoking status, COPD (HR (95% CI) 2.681 (1.424-5.048)), diabetes (1.59 (1.03-2.45)), hypertension (1.58 (1.07-2.32)) and malignancy (3.50 (1.60-7.64)) were risk factors of reaching the composite end-points. The hazard ratio (95% CI) was 1.79 (1.16-2.77) among patients with at least one comorbidity and 2.59 (1.61-4.17) among patients with two or more comorbidities. CONCLUSION: Among laboratory confirmed cases of COVID-19, patients with any comorbidity yielded poorer clinical outcomes than those without. A greater number of comorbidities also correlated with poorer clinical outcomes.