Liver injury in COVID-19: A minireview.

Coronavirus disease 2019 (COVID-19), caused by infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has escalated into a global tragedy afflicting human health, life, and social governance. Through the increasing depth of research and a better understanding of this disease, it has been ascertained that, in addition to the lungs, SARS-CoV-2 can also induce injuries to other organs including the liver. Liver injury is a common clinical manifestation of COVID-19, particularly in severe cases, and is often associated with a poorer prognosis and higher severity of COVID-19. This review focuses on the general existing information on liver injury caused by COVID-19, including risk factors and subpopulations of liver injury in COVID-19, the association between preexisting liver diseases and the severity of COVID-19, and the potential mechanisms by which SARS-CoV-2 affects the liver. This review may provide some useful information for the development of therapeutic and preventive strategies for COVID-19-associated liver injury.

A blessing in disguise-The effect of China's Covid-19 health code system on older people's mobile payment usage.

In early 2020, China launched a health code system to combat the spread of Covid-19. The required health code led to a drastic uptake of smartphone usage among older residents. This paper uses rich commercial data from the Zhejiang Province of China to track the change in consumption among the older population. The paper finds that older people significantly increased spending after switching to mobile payment. The paper contributes to the literature by identifying the unexpected windfall from the effect of the health code mandate on the older population and demonstrating that digital payment works well in the older population.

Effect of positive event recording based on positive psychology on healthy behaviors and readmission rate of patients after PCI: a study protocol for a prospective, randomized controlled trial.

BACKGROUND: Unhealthy behaviors of coronary heart disease (CHD) patients are closely related to the occurrence of major heart events, which increases the readmission rate and brings a heavy economic burden to families and society. Therefore, it is necessary for health care workers to take active preventive and therapeutic measures to keep or establish healthy behaviors of patients. Positive psychological intervention has been proved to be effective, but it has not been reported in the field of CHD in China. The purpose of this study is to explore the effects of positive event recording based on positive psychology on the healthy behaviors, readmission rate, and anxiety of patients with CHD, in order to provide new ideas for the development of secondary prevention strategies for CHD. METHODS: This is a prospective, single-center, randomized controlled trial (RCT). The subjects will be enrolled from the Department of Cardiology, the First Affiliated Hospital of Soochow University. There are 80 cases in total; according to the random number table, the subjects are randomly divided into the intervention group (n = 40) and the control group (n = 40). The patients in the intervention group will receive the intervention of recording positive events once a week for 3 months, while the patients in the control group receive conventional nursing. The primary outcomes will include healthy behaviors, readmission rate, and anxiety, and the secondary outcomes will include psychological capital, subjective well-being, and corresponding clinical laboratory indicators. The protocol was approved by the Medical Ethics Committee of Soochow University (approval no. SUDA20200604H01) and is performed in strict accordance with the Declaration of Helsinki formulated by the World Medical Association. All participants provide written informed consent. DISCUSSION: This study will verify whether positive event recording based on positive psychology can make patients maintain healthy behaviors, reduce readmission rate, and improve anxiety after PCI. Then, this study will provide new ideas and references for the development of secondary prevention strategies for patients with CHD. TRIAL REGISTRATION: Chinese Clinical Trials Registry 2000034538. Registered on 10 July 2020.

Body Mass Index and Association of Psychological Stress with Exercise Performance in Military Members: The Cardiorespiratory Fitness and Hospitalization Events in Armed Forces (CHIEF) Study.

AIMS: To investigate the influence of body mass index (BMI) on the association between psychological stress and physical fitness. BACKGROUND: Both obesity and psychological stress reduce exercise performance. OBJECTIVE: It is unknown whether obesity may modify the relationship. METHODS: A population of 4,080 military subjects in Taiwan was divided to three groups according to the BMI ≥27.0 kg/m2 (obesity), 24.0-26.9 kg/m2 (overweight) and 18.5-23.9 kg/m2 (normal weight). Normal, slight, and great psychological stress was evaluated by the Brief Symptoms Rating Scale (BSRS-5) score ≤5, 6-9, and ≥10, respectively. Aerobic and anaerobic fitness were respectively evaluated by time for a 3000-meter run and numbers of 2-minute sit-ups and 2-minute push-ups. Analysis of covariance (ANCOVA) with adjustments for age and sex was used to determine the relationship. RESULTS: The mean time (sec) for a 3000-meter run (standard error) under slight and great stress differed from that under normal stress in the normal weight (881.0 (11.0) and 877.9 (5.8) vs. 862.2 (1.7), p=0.089 and 0.0088, respectively) and in the obesity (928.1 (16.8) and 921.8 (10.7) vs. 895.2 (1.6), p=0.054 and 0.016, respectively), while the differences were not significant in the overweight (877.1 (12.7) and 877.5 (7.1) vs. 867.1 (2.1), both p >0.5). The impacts of the BMI on 2-minute sit-ups had a similar pattern with that on a 3000-meter run whereas the impact of the BMI on 2-minute push-ups was insignificant. CONCLUSIONS: Mental stress may not affect physical fitness in overweight military personnel. The mechanism is not clear and should be further investigated.

Global SNP analysis of 11,183 SARS-CoV-2 strains reveals high genetic diversity.

Since first identified in December of 2019, COVID-19 has been quickly spreading to the world in few months and COVID-19 cases are still undergoing rapid surge in most countries worldwide. The causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), adapts and evolves rapidly in nature. With the availability of 16,092 SARS-CoV-2 full genomes in GISAID as of 13 May, we removed the poor-quality genomes and performed mutational profiling analysis for the remaining 11,183 viral genomes. Global analysis of all sequences identified all single nucleotide polymorphisms (SNPs) across the whole genome and critical SNPs with high mutation frequency that contributes to five-clade classification of global strains. A total of 119 SNPs were found with 74 non-synonymous mutations, 43 synonymous mutations and two mutations in intergenic regions. Analysis of geographic pattern of mutational profiling for the whole genome reveals differences between each continent. A transition mutation from C to T represents the most mutation types across the genome, suggesting rapid evolution and adaptation of the virus in host. Amino acid (AA) deletions and insertions found across the genome results in changes in viral protein length and potential function alteration. Mutational profiling for each gene was analysed, and results show that nucleocapsid gene demonstrates the highest mutational frequency, followed by Nsp2, Nsp3 and Spike gene. We further focused on non-synonymous mutational distributions on four key viral proteins, spike with 75 mutations, RNA-dependent-RNA-polymerase with 41 mutations, 3C-like protease with 22 mutations and Papain-like protease with 10 mutations. Results show that non-synonymous mutations on critical sites of these four proteins pose great challenge for development of anti-viral drugs and other countering measures. Overall, this study provides more understanding of genetic diversity/variability of SARS-CoV-2 and insights for development of anti-viral therapeutics.

Consistent weekly cycles of atmospheric NO2, CO, and CO2 in a North American megacity from ground-based, mountaintop, and satellite measurements

The weekday-weekend effect of anthropogenic emissions in cities, driven by the associated weekly changes in human activities, provides a unique opportunity to assess the sensitivity of observation networks (e.g., ground-based and space-borne instruments) on urban emissions. In this study, we focus on the weekly cycle amplitudes of nitrogen dioxide (NO2), carbon monoxide (CO), and carbon dioxide (CO2) in the Los Angeles (LA) megacity, where a significant weekly cycle of human activities exists. In addition, abundant observations are being produced continuously from existing ground-based, mountaintop, and satellite platforms to monitor carbon emissions and air quality in LA. From our analysis, significant agreement can be found in observations from different platforms. For NO2, a 30%–35% Sunday decline relative to mid-week mixing ratios can be observed from both ground-based and satellite observations. For CO, the Sunday drops from ground-based, mountain-top and satellite observations are 13%–20%. The TROPOMI instrument with its high spatial resolution provides detailed spatial information on the reduction of tropospheric NO2 and CO columns on Sundays. The spatial pattern is in good agreement with traffic density in LA. Impact due to the prevailing winds from the coast in the afternoon can also be observed. For anthropogenic CO2, we show that the weekly cycle of XCO2 enhancement above background from OCO-2 observations has a Sunday decline (15%–20%) consistent with ground-based observations and TCCON. This weekly pattern of CO2 in a megacity directly detected by OCO-2 is reported for the first time. In addition, we also investigate the weekly cycles in the stable carbon isotopic composition of CO2 (δ13C) from ground-based observations, which demonstrates the weekly variation in fossil fuel usage in LA. Finally, using the COVID-19 lockdown period as an example of a short-term perturbation on anthropogenic emissions, we found that the weekly cycle amplitude became larger during the lockdown period primarily because of the traffic volume changes in light-duty vehicles. This study highlights the consistencies and effectiveness of existing observing platforms in monitoring the anthropogenic emissions of the LA megacity.

The size and culturability of patient-generated SARS-CoV-2 aerosol.

BACKGROUND: Aerosol transmission of COVID-19 is the subject of ongoing policy debate. Characterizing aerosol produced by people with COVID-19 is critical to understanding the role of aerosols in transmission. OBJECTIVE: We investigated the presence of virus in size-fractioned aerosols from six COVID-19 patients admitted into mixed acuity wards in April of 2020. METHODS: Size-fractionated aerosol samples and aerosol size distributions were collected from COVID-19 positive patients. Aerosol samples were analyzed for viral RNA, positive samples were cultured in Vero E6 cells. Serial RT-PCR of cells indicated samples where viral replication was likely occurring. Viral presence was also investigated by western blot and transmission electron microscopy (TEM). RESULTS: SARS-CoV-2 RNA was detected by rRT-PCR in all samples. Three samples confidently indicated the presence of viral replication, all of which were from collected sub-micron aerosol. Western blot indicated the presence of viral proteins in all but one of these samples, and intact virions were observed by TEM in one sample. SIGNIFICANCE: Observations of viral replication in the culture of submicron aerosol samples provides additional evidence that airborne transmission of COVID-19 is possible. These results support the use of efficient respiratory protection in both healthcare and by the public to limit transmission.

Oropharyngeal Probiotic ENT-K12 Prevents Respiratory Tract Infections Among Frontline Medical Staff Fighting Against COVID-19: A Pilot Study.

Healthcare workers at the frontline are facing a substantial risk of respiratory tract infection during the COVID-19 outbreak due to an extremely stressful work schedule and public health event. A well-established first-line defense on oropharyngeal microbiome could be a promising strategy to protect individuals from respiratory tract infections including COVID-19. The most thoroughly studied oropharyngeal probiotic product which creates a stable upper respiratory tract microbiota capable of preventing upper respiratory tract infections was chosen to evaluate the safety and efficacy on reducing episodes of upper respiratory tract infections for COVID-19 healthcare workers. To our knowledge to date, this is the very first study describing the beneficial effects of oropharyngeal probiotic been administered by healthcare workers during the COVID-19 pandemic. In this randomized controlled trial, we provided the probiotics to frontline medical staff who work in the hospitals in Wuhan and had been in close contact with hospitalized COVID-19 patients for prophylactic use on a daily basis. Our finding suggests that oropharyngeal probiotic administration significantly reduced the incidence of respiratory tract infections by 64.8%, reduced the time experiencing respiratory tract infections and oral ulcer symptoms by 78%, shortened the days absent from work by 95.5%, and reduced the time under medication where there is no record of antibiotic and anti-viral drug intake in the probiotic group. Furthermore, medical staff treated with Bactoblis experienced sustained protection from respiratory tract infections since the 10th day of oropharyngeal probiotic administration resulting in an extremely low incidence rate of respiratory tract infections.

Earlier diagnosis improves COVID-19 prognosis: a nationwide retrospective cohort analysis.

BACKGROUND: Risk of adverse outcomes in COVID-19 patients by stratifying by the time from symptom onset to confirmed diagnosis status is still uncertain. METHODS: We included 1,590 hospitalized COVID-19 patients confirmed by real-time RT-PCR assay or high-throughput sequencing of pharyngeal and nasal swab specimens from 575 hospitals across China between 11 December 2019 and 31 January 2020. Times from symptom onset to confirmed diagnosis, from symptom onset to first medical visit and from first medical visit to confirmed diagnosis were described and turned into binary variables by the maximally selected rank statistics method. Then, survival analysis, including a log-rank test, Cox regression, and conditional inference tree (CTREE) was conducted, regarding whether patients progressed to a severe disease level during the observational period (assessed as severe pneumonia according to the Chinese Expert Consensus on Clinical Practice for Emergency Severe Pneumonia, admission to an intensive care unit, administration of invasive ventilation, or death) as the prognosis outcome, the dependent variable. Independent factors included whether the time from symptom onset to confirmed diagnosis was longer than 5 days (the exposure) and other demographic and clinical factors as multivariate adjustments. The clinical characteristics of the patients with different times from symptom onset to confirmed diagnosis were also compared. RESULTS: The medians of the times from symptom onset to confirmed diagnosis, from symptom onset to first medical visit, and from first medical visit to confirmed diagnosis were 6, 3, and 2 days. After adjusting for age, sex, smoking status, and comorbidity status, age [hazard ratio (HR): 1.03; 95% CI: 1.01-1.04], comorbidity (HR: 1.84; 95% CI: 1.23-2.73), and a duration from symptom onset to confirmed diagnosis of >5 days (HR: 1.69; 95% CI: 1.10-2.60) were independent predictors of COVID-19 prognosis, which echoed the CTREE models, with significant nodes such as time from symptom onset to confirmed diagnosis, age, and comorbidities. Males, older patients with symptoms such as dry cough/productive cough/shortness of breath, and prior COPD were observed more often in the patients who procrastinated before initiating the first medical consultation. CONCLUSIONS: A longer time from symptom onset to confirmed diagnosis yielded a worse COVID-19 prognosis.

Transdermal drug delivery systems for fighting common viral infectious diseases.

Transdermal drug delivery systems (TDDS) have many advantages and represent an excellent alternative to oral delivery and hypodermic injections. TDDS are more convenient and less invasive tools for disease and viral infection treatment, prevention, detection, and surveillance. The emerging development of microneedles for TDDS has facilitated improved skin barrier penetration for the delivery of macromolecules or hydrophilic drugs. Microneedle TDDS patches can be fabricated to deliver virus vaccines and potentially provide a viable alternative vaccine modality that offers improved immunogenicity, thermostability, simplicity, safety, and compliance as well as sharp-waste reduction, increased cost-effectiveness, and the capacity for self-administration, which could improve vaccine distribution. These advantages make TDDS-based vaccine delivery an especially well-suited option for treatment of widespread viral infectious diseases including pandemics. Because microneedle-based bioassays employ transdermal extraction of interstitial fluid or blood, they can be used as a minimally invasive approach for surveying disease markers and providing point-of-care (POC) diagnostics. For cutaneous viral infections, TDDS can provide localized treatment with high specificity and less systemic toxicity. In summary, TDDS, especially those that employ microneedles, possess special attributes that can be leveraged to reduce morbidity and mortality from viral infectious diseases. In this regard, they may have considerable positive impact as a modality for improving global health. In this article, we introduce the possible role and summarize the current literature regarding TDDS applications for fighting common cutaneous or systemic viral infectious diseases, including herpes simplex, varicella or herpes zoster, warts, influenza, measles, and COVID-19.

Toward a new normality in Via Paolo Sarpi (Milan, Italy)? Social behaviors and spatial transitions during and after the lockdown

During the COVID-19 crisis (February–September 2020), Lombardy—the most populous region in Italy—suffered more than 101,705 contagions with more than 16,880 deaths. Such an amount of cases (38,9% over the total Italian COVID-19 patients and 47,8% over Italian deaths) imposed a severe lockdown that affected ten million inhabitants in one of the larger urban regions of Europe that includes the cities of Milan, Bergamo, and Brescia. Social contact where forbidden, and civil rights and mobility dramatically reduced. Therefore, over two months, three urban values (the density, the proximity, and the continuous interaction) that shaped the European lifestyle in cities were considered dangerous. The urban space itself turned in a risky environment for its inhabitants. The disruptive result has been a general decline of urban public life, and this reduction has been evident in high streets and other public spaces. Hoping that the current situation will change rapidly, we recognize that we must adapt to a new normality, where public spaces and social encounters will still have a crucial role in cities. Regarding the rapid and profound transformation of social behaviors in Milan during the COVID-19 crisis, the research will be picking the focus on the street space as a suitable environment for converting more sociable anwctd healthy public spaces. Starting from the case of a multiethnic consolidated neighborhood in Milan (around Via Paolo Sarpi, a pedestrian-oriented street marked by the presence of the Chinese community), the proposed chapter explores how social behaviors and their spatial impacts changed—and adapted—during the lockdown. We will involve the analysis of the changes in the living practices of the street during the pandemic not only physically but also performed as booming social media connections. In the conclusions, we will point out how several reflections about the new normality that is rising out after this extra-ordinary situation at the local level, and how this original knowledge must support a new approach to the urban planning and territorial governance in the next years.

Risk Factors and Prognosis in Patients with COVID-19 and Liver Injury: A Retrospective Analysis.

PURPOSE: COVID-19 is a new infectious disease with global spread. The aim of the present study was to explore possible risk factors and evaluate prognosis in COVID-19 with liver injury. METHODS: A retrospective study was conducted on 356 COVID-19 patients in the Third People's Hospital of Yichang, Hubei, China. Clinical characteristics and laboratory tests between patients with and without liver injury were compared, while risk factors of COVID-19-related liver injury were analyzed. Univariate and multivariate Cox regression analyses were conducted to identify risk factors of in-hospital death. RESULTS: Of the patients with liver injury, severe and critical types of COVID-19 comprised 12.43% and 14.69%, respectively, higher than in patients without liver injury (both P<0.05). CRP and male sex were independent risk factors for for patients with liver injury, while decreased lymphocyte count (HR 0.024, 95% CI 0.001-0.821) and elevated monocytes (HR 1.951, 95% CI 1.040-3.662) and CRP (HR 1.028, 95% CI 1.010-1.045) were independent risk factors of prognosis of death in COVID-19 patients with liver injury. CONCLUSION: Liver injury is a common complication in severe COVID-19 patients. Male sex and elevated CRP were independent risk factors in COVID-19 complicated by liver damage. Liver damage with increased CRP and monocyte count and decreased lymphocyte count may imply a poor prognosis.

SARS-CoV-2 hijacks folate and one-carbon metabolism for viral replication.

The recently identified Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the cause of the COVID-19 pandemic. How this novel beta-coronavirus virus, and coronaviruses more generally, alter cellular metabolism to support massive production of ~30 kB viral genomes and subgenomic viral RNAs remains largely unknown. To gain insights, transcriptional and metabolomic analyses are performed 8 hours after SARS-CoV-2 infection, an early timepoint where the viral lifecycle is completed but prior to overt effects on host cell growth or survival. Here, we show that SARS-CoV-2 remodels host folate and one-carbon metabolism at the post-transcriptional level to support de novo purine synthesis, bypassing viral shutoff of host translation. Intracellular glucose and folate are depleted in SARS-CoV-2-infected cells, and viral replication is exquisitely sensitive to inhibitors of folate and one-carbon metabolism, notably methotrexate. Host metabolism targeted therapy could add to the armamentarium against future coronavirus outbreaks.

From People to Panthera: Natural SARS-CoV-2 Infection in Tigers and Lions at the Bronx Zoo.

Despite numerous barriers to transmission, zoonoses are the major cause of emerging infectious diseases in humans. Among these, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and ebolaviruses have killed thousands; the human immunodeficiency virus (HIV) has killed millions. Zoonoses and human-to-animal cross-species transmission are driven by human actions and have important management, conservation, and public health implications. The current SARS-CoV-2 pandemic, which presumably originated from an animal reservoir, has killed more than half a million people around the world and cases continue to rise. In March 2020, New York City was a global epicenter for SARS-CoV-2 infections. During this time, four tigers and three lions at the Bronx Zoo, NY, developed mild, abnormal respiratory signs. We detected SARS-CoV-2 RNA in respiratory secretions and/or feces from all seven animals, live virus in three, and colocalized viral RNA with cellular damage in one. We produced nine whole SARS-CoV-2 genomes from the animals and keepers and identified different SARS-CoV-2 genotypes in the tigers and lions. Epidemiologic and genomic data indicated human-to-tiger transmission. These were the first confirmed cases of natural SARS-CoV-2 animal infections in the United States and the first in nondomestic species in the world. We highlight disease transmission at a nontraditional interface and provide information that contributes to understanding SARS-CoV-2 transmission across species.IMPORTANCE The human-animal-environment interface of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an important aspect of the coronavirus disease 2019 (COVID-19) pandemic that requires robust One Health-based investigations. Despite this, few reports describe natural infections in animals or directly link them to human infections using genomic data. In the present study, we describe the first cases of natural SARS-CoV-2 infection in tigers and lions in the United States and provide epidemiological and genetic evidence for human-to-animal transmission of the virus. Our data show that tigers and lions were infected with different genotypes of SARS-CoV-2, indicating two independent transmission events to the animals. Importantly, infected animals shed infectious virus in respiratory secretions and feces. A better understanding of the susceptibility of animal species to SARS-CoV-2 may help to elucidate transmission mechanisms and identify potential reservoirs and sources of infection that are important in both animal and human health.

Complete Genome Sequence of SARS-CoV-2 in a Tiger from a U.S. Zoological Collection.

This report describes the identification and characterization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a Malayan tiger in a U.S. zoo.

A comparative-descriptive analysis of clinical characteristics in 2019-coronavirus-infected children and adults.

Acute respiratory disease caused by 2019 novel coronavirus (2019-nCoV) has rapidly spread throughout China. Children and adults show a different clinical course. The purpose of the current study is to comparatively analyze the clinical characteristics of 2019-nCoV infection in children and adults and to explore the possible causes for the discrepancies present. The medical records of 25 adults and 7 children confirmed cases of 2019-2019-nCoV acute respiratory diseases were reviewed retrospectively. All children were family clusters. The total adult patients were differentiated into the local residents of Wuhan, a history of travel to Wuhan and direct contact with people from Wuhan. The numbers were 14 (56%), 10 (40%), and 1 (4%), respectively. The median incubation period of children and adults was 5 days (ranged, 3-12 days) and 4 days (ranged, 2-12 days), respectively. Diarrhoea and/or vomiting (57.1%) were demic by World Health Organiza more common in children, whereas for adults it was myalgia or fatigue (52%). On admission, the percentage of children having pneumonia (5%, 71.4%) was roughly the same as adults (20%, 80%). A total of 20% of adults had leucopoenia, but leukocytosis was more frequently in children (28.6%, P=.014). A higher number of children had elevated creatine kinase isoenzyme (57.1% vs 4%, P=.004). Antiviral therapy was given to all adult patients but to none of the children. In summary, knowledge of these differences between children and adults will not only be helpful for the clinical diagnosis of 2019-nCoV disease, but also for a future discussion on age-specific coronavirus infection.