The Prevalence and Evolutionary Characteristics of Bovine Coronavirus in China (preprint)

Four viral intestinal pathogens such as bovine coronavirus (BCoV), bovine rotavirus (BRV), bovine viral diarrhea virus (BVDV) and bovine astrovirus (BoAstV) are the most common causes of adult cattle diarrhea. In this study, 797 samples were collected from January 2020 to February 2023. Among them, BCoV is major pathogen we detected and the positive rate was 48.18% (471/794). Farther more, among 307 diarrhea samples and 487 asymptomatic samples, 159 and 312 were BCoV positive, respectively. The results reveal that BCoV is associated with bovine diarrhea (p=0.001). In addition, we also amplified and analyzed Hemagglutinin-esterase (HE), Spike (S) and whole genome of partially positive sample. Getting 8 HE complete sequence, 8 S complete sequence and 5 whole genomes. The molecular characterization provides reveal that 5 strains were branched Chinese strains, Japan and part of American strains in GⅡb，and Korea strains branched in GⅡa. BCoV-Neimeng S in this study was mutated 143H/A to 143R, which is uncommon in S gene. As a residue on the side chain of the core binding site of S1-NTD, this mutation changed the tertiary structure and may be possible to affect the glycoside binding spectrum. The noteworthy that BCoV-SJZ2 and BCoV-YZ1 have four amino acid insertions on HE, which is the same as SWUN/A10/2018. We also analysis 4.8kDa and 4.9kDa non-structural protein large-scale truncation and membrane protein mutation. This article will discuss epidemiology and genome analysis.

Ambient fine particulate matter and ozone pollution in China: synergy in anthropogenic emissions and atmospheric processes

Since 2013, China has taken a series of actions to relieve serious PM2.5 pollution. As a result, the annual PM2.5 concentration decreased by more than 50% from 2013 to 2021. However, ozone pollution has become more pronounced, especially in the North China Plain. Here, we review the impacts of anthropogenic emissions, meteorology, and atmospheric processes on ambient PM2.5 loading and components and O3 pollution in China. The reported influence of interannual meteorological changes on PM2.5 and O3 pollution during 2013–2019 ranged from 10%–20% and 20%–40%, respectively. During the same period, the anthropogenic emissions of NOx, SO2, primary PM2.5, NMVOC and NH3 are estimated to decrease by 38%, 51%, 35%, 11% and 17%, respectively. Such emission reduction is the main cause for the decrease in PM2.5 concentration across China. However, the imbalanced reductions in various precursors also result in the variation in nitrate gas-particle partitioning and hence an increase in the nitrate fraction in PM2.5. The increase of ozone concentration and the enhancement of atmospheric oxidation capacity can also have substantial impact on the secondary components of PM2.5, which partly explained the growth of organic aerosols during haze events and the COVID-19 shutdown period. The uneven reduction in NOx and NMVOC is suggested to be the most important reason for the rapid O3 increase after 2013. In addition, the decrease in PM2.5 may also have affected O3 formation via radiation effects and heterogeneous reactions. Moreover, climate change is expected to influence both anthropogenic emissions and atmospheric processes. However, the extent and pathways of the PM2.5-O3 interplay and how it will be impacted by the changing emission and atmospheric conditions making the synergetic control of PM2.5 and O3 difficult. Further research on the interaction of PM2.5 and O3 is needed to provide basis for a scientifically-grounded and effective co-control strategy.

Moral Obligation to Follow Anti-COVID-19 Measures Strengthens the Mental Health Cost of Pandemic Fatigue (preprint)

Background: It has been observed that people became gradually exhausted about the COVID-19-related information and preventive measures as the pandemic unfolds. This phenomenon is known as pandemic fatigue. Not only is pandemic fatigue averse to the prevention of COVID-19, a small but increasing number of studies have also found that it is related to poor mental health. This study extended this line of research by examining a novel yet understudied idea that moral obligation, a crucial motivation that drives people to follow the preventive measures, would amplify the association between pandemic fatigue and mental health problems. Methods: Participants were 937 Hong Kong parents (88% mothers, 62.4% aged 31–40 years). They participated in an online survey reporting on pandemic fatigue, moral obligation, and mental health problems (i.e., depressive symptoms, anxiety, and stress). Results: Findings of moderation model analyses showed that higher levels of pandemic fatigues and moral obligation were related to more mental health problems. Importantly, these links were moderated by moral obligation, with those who felt more morally obliged to follow the preventive measures reporting poorer mental health than those who felt less morally obliged to do so.Limitations: The study was cross-sectional, which constrains the deduction of causality. Participants were only recruited from Hong Kong and females were over representative, thus limiting the generalizability of the findings. Conclusions: People who experience pandemic fatigue while feeling more morally obliged to follow the anti-COVID-19 measures are at greater risk of mental health problems. These populations need more support from practitioners.

Mental distress, quality of life and physical symptoms in Chinese women with ovarian cancer receiving olaparib treatment during the COVID-19 pandemic

Objectives Women with ovarian cancer (OC) have experienced unprecedented challenges since the novel coronavirus disease-2019 (COVID-19) outbreak in China. We aim to evaluate the experience of psychological status, physical symptoms and quality of life (QoL) and investigate the impact of COVID-19 pandemic on OC patients receiving olaparib. Methods The survey was conducted online from April 22 to May 12 in 2020. Demographic and clinical questions were listed to collect general information. The degree of insomnia, depression, anxiety, stress symptoms and QoL were assessed by the Chinese versions of the Insomnia Severity Index, the Patient Health Questionnaire-9, the Generalized Anxiety Disorder-7, the Impact of Event Scale-Revised, and the General Functional Assessment of Cancer Therapy, respectively. Multivariate logistic regression analysis was conducted to analyze the risk factors for mental distress and QoL. Results A total of 56 respondents coming from 15 various provinces in China participated in the survey. The prevalence of insomnia, depressive, anxiety, stress symptoms and reduced QoL were 37.5, 51.8, 37.5, 30.4, and 51.8%, respectively. Unfavorable disease status, shorter period of olaparib administration, adverse events of olaparib and delay in cancer care were correlated with mental health problems. Reduced QoL was also significantly associated with psychological distress. Conclusions This study emphasized that mental health problems and reduced QoL should gain more attention in women with OC who are receiving oral olaparib at home. Appropriate psychological healthcare strategies are necessary for OC patients during the COVID-19 pandemic.

Global dynamics of Porcine Epidemic Diarrhea Virus evolution and transmission (preprint)

With a possible origin from bats, the alphacoronavirus Porcine epidemic diarrhea virus (PEDV) causes significant hazards and widespread epidemics in the swine population. However, the ecology, evolution, and spread of PEDV are still unclear. Here, from 149,869 fecal and intestinal tissue samples of pigs collected in an 11-year survey, we identified PEDV as the most dominant virus in diarrheal animals. Global whole genomic and evolutionary analyses of 672 PEDV strains revealed the fast-evolving PEDV genotype 2 (G2) strains as the main epidemic viruses worldwide, which seems to correlate with the use of G2-targeting vaccines. The evolving pattern of the G2 viruses presents geographic bias as they evolve tachytely in South Korea but undergo the highest recombination in China. Therefore, we clustered six PEDV haplotypes in China, whereas South Korea held five haplotypes, including a unique haplotype G. In addition, an assessment of the spatiotemporal spread route of PEDV indicates Germany and Japan as the primary hubs for PEDV dissemination in Europe and Asia, respectively. Overall, our findings provide novel insights into the epidemiology, evolution, and transmission of PEDV, and thus may lay a foundation for the prevention and control of PEDV and other coronaviruses.

The Efficacy of Traditional Chinese Medicine in the Treatment of the COVID-19 Pandemic in Henan Province: A Retrospective Study (preprint)

Background Since 2020, novel coronavirus disease (COVID-19) has posed serious threats to health systems and led to tremendous economic decline worldwide. Traditional Chinese medicine (TCM) is considered a promising treatment strategy for COVID-19 in China and is increasingly recognized as a key participant in the battle against COVID-19. Clinicians also need accurate evidence regarding the effectiveness of TCM treatments for COVID-19.Methods We retrospectively analyzed patients diagnosed with COVID-19 by real-time reverse transcriptase polymerase chain reaction (RT-PCR) in Henan Province from January 19, 2020, to March 2, 2020. the patients were diagnosed with COVID-19 infection confirmed assays, demographic characteristics, clinical data, frequency analysis of Chinese patent medicines (CPMs), Chinese medicine injections (CMIs), evaluation of nucleic acid negative conversion and length of hospitalization, and mortality rates were collected from the electronic medical records of the hospitals in Henan Province.Results We analyzed 1245 cases with complete basic information, and extracted information including Chinese herbal decoction, CPMs, and CMIs combined with conventional Western medicine (CWM) used for the treatment of COVID-19. The top 10 CPMs were Lianhua Qingwen capsules, Shuanghuanglian oral liquid, Pudilan Xiaoyan oral liquid, Banlangen granules, Lanqin oral liquid, compound licorice tablets, Bailing capsules, montmorillonite powder, buckwheat flakes, and Diyushengbai. The most frequently used CMIs were Xuebijing, Tanreqing, Reduning, Xiyanping, Yanhuning, Qingkai Ling, and Shenfu injection. TCM combined with CWM improved the patients’ symptom scores for fever, cough, chest tightness, shortness of breath, and fatigue. Nucleic acid negative conversion occurred at 12.06 ± 5.77 d and the average length of hospitalization was 16.56 ± 5.78 d. The mortality rate was approximately 1.76%, which is a reduction in patient mortality.Conclusion TCM combined with CWM improved clinical symptoms and reduced hospitalization and mortality rates.

Lifetime Prediction of Non-woven Face Masks in Ocean and Contributions to Microplastics and Dissolved Organic Carbon

This study explored the degradation behavior of three types of disposable face masks in simulated seawater via the accelerated aging experiments. Microplastics (MPs) and dissolved organic carbon (DOC) were monitored in UV- and thermal-treated mask suspensions and their concentrations increased slowly in the early stage at 50 ℃ and 58 ℃. Owing to the high energy supply, the release rates of MPs and DOC at 76 ℃ were much faster than the above two temperatures. The time-temperature superposition principle (TTSP) was used to superpose the MPs/DOC release kinetics from other tested temperatures to the reference temperature and its applicability was verified by the similar activation energy. Then, a release kinetics model was established and fitted well with the superposed MP data (R2 ≥ 0.96). Since less than 0.1% of carbon was leached, the superposed DOC data was roughly modelled by the exponential function (R2 ≥ 0.90). According to the TTSP and the established kinetics models, about 15 years were estimated to decompose half of a certain marine mask waste, together with leaching 0.21 ± 0.02mg∙g-mask-1 of DOC. If mask consumption remains the same before 2025, they would contribute 40000-230000 tonnes of MPs and 13-97 tonnes of DOC to the ocean by 2040.

Establishment and application of semi-nest RT-PCR for detection of Transmissible gastroenteritis virus

In order to establish an efficient, sensitive and specific semi-nest RT-PCR method for the detection of Transmissible gastroenteritis virus (TGEV), three specific primers were designed according to the N gene published by GenBank, the reaction system was established and optimized, and specificity and sensitivity were detected. The results showed that the method could successfully amplify the bands of 483 bp and 338 bp, and had good specificity to TGEV, there is no cross reaction with PEDV, PRov, PBov and PDCov, and the lowest sensitivity was 1.86 x 10-1 pg/L. The semi-nest RT-PCR shown the positive rate was 36% in 50 samples of pig diarrhea, which was higher than that of common RT-PCR, and then the positive samples coincidence rate was 100%. This semi-nest RT-PCR method has high sensitivity and specificity, and can accurately diagnose TGEV infection, which provides an effective method for clinical detection and epidemiological investigation of TGEV.

Traditional Chinese Medicine in Treating Children With Coronavirus Disease 2019: A Scoping Review

Coronavirus disease 2019 (COVID-19) is currently widely spread across the world. Traditional Chinese Medicine (TCM) plays an important role in the overall treatment process. As a special group of population, the treatment outcome of children with COVID-19 has attracted much attention. Our study summarizes the current situation of TCM treatment of children with COVID-19. The results showed that TCM displayed a positive role in the treatment process, and that no significant adverse reactions were found. Our findings provide analytical evidence for the efficacy and safety of TCM participation in the treatment of COVID-19 in children.

What Makes Hong Kong Parents Hesitant to Vaccinate Their Children against COVID-19? Testing Health Belief Model and Theory of Planned Behavior in a Large-Scale Survey (preprint)

COVID-19 vaccines have been authorized for use in children in many nations. Parents’ intention to vaccinate their children is context-specific. Drawing upon health belief model (HBM) and theory of planned behavior (TPB), this study contributed to a timely topic by examining the extent to which parents intended to vaccinate their children and its associated factors in Hong Kong, where the government announced children as young as five could take COVID-19 vaccines on 21-January-2022. A large-scale, online survey was conducted among 11,141 Hong Kong parents (86% mothers) of children aged 5-12 (N=14,468, 49.5% girls). They reported on measures that assessed HBM constructs (i.e., perceived susceptibility, perceived severity, perceived benefits, perceived barriers, and cues to action), TPB constructs (i.e., attitudes, subjective norms, and perceived behavioral control), and their intention to vaccinate each of their children. Multilevel regression showed that after controlling for parents’ and children’s demographic variables (e.g., sex and age), parents’ willingness to vaccinate their children was higher for parents with higher levels of perceived susceptibility, perceived benefits, positive attitudes, and subjective norms, but it was lower for parents with higher levels of perceived barriers. These findings identify health belief factors that explain Hong Kong parents’ hesitancy to vaccinate their children.

Positive Changes in Life Outcomes over the Pandemic in Chinese Adolescents: The Role of Resilience and Relation to Mental Health (preprint)

Background: Although the existing literature has well documented the negative effects of COVID-19 on multiple life outcomes in adolescents, some research has also revealed that some life outcomes have become better during COVID-19. Scant research has specifically examined to what extent and in what aspects COVID-19 is beneficial to adolescent development so far. With person-centered approach, this research addressed this gap by: (1) exploring different profiles of positive changes in life outcomes in Chinese adolescents since the outbreak of COVID-19; (2) examining the role of resilience in relation to different profiles; (3) comparing mental health across adolescents categorized into different profiles. Method Participants were 2,567 Chinese adolescents aged 12 to 24. They rated how much their lives of different domains had experienced positive changes since the outbreak of the pandemic. They also answered the questionnaires that measured their resilience and mental health. Results Results of latent profile analysis revealed three different profiles: limited positive changes (33.3%), partial positive changes (49.5%), and overall strong positive changes (17.2%). Moreover, adolescents with a higher level of resilience were more likely to be categorized into the partial positive changes profile compared to the limited positive changes profile and into the overall strong positive changes profile compared to the other two profiles, after controlling for the covariates. Finally, adolescents in the overall strong positive changes profile had better mental health than their counterparts in the other two profiles. Conclusion COVID-19 might be helpful to adolescent development to some extent, especially for those with higher resilience.

DuCN: Dual-children Network for Medical Diagnosis and Similar Case Recommendation towards COVID-19 (preprint)

Early detection of the coronavirus disease 2019 (COVID-19) helps to treat patients timely and increase the cure rate, thus further suppressing the spread of the disease. In this study, we propose a novel deep learning based detection and similar case recommendation network to help control the epidemic. Our proposed network contains two stages: the first one is a lung region segmentation step and is used to exclude irrelevant factors, and the second is a detection and recommendation stage. Under this framework, in the second stage, we develop a dual-children network (DuCN) based on a pre-trained ResNet-18 to simultaneously realize the disease diagnosis and similar case recommendation. Besides, we employ triplet loss and intrapulmonary distance maps to assist the detection, which helps incorporate tiny differences between two images and is conducive to improving the diagnostic accuracy. For each confirmed COVID-19 case, we give similar cases to provide radiologists with diagnosis and treatment references. We conduct experiments on a large publicly available dataset (CC-CCII) and compare the proposed model with state-of-the-art COVID-19 detection methods. The results show that our proposed model achieves a promising clinical performance.

Early Treatment Effect of Chinese Herbal Medicine Formula Huashibaidu Granule on Mild COVID-19 Patients in Fangcang Hospital: An Unblinded, Cluster-Randomized Clinical Trial (preprint)

BACKGROUND: Previous study suggested that Chinese Herbal Medicine (CHM) Formula Huashibaidu granule might shorten disease course of Corona Virus Disease 2019 (COVID-19) patients. Our research aims to investigate the early treatment effect of Huashibaidu granule in mild COVID-19 patients under well clinical management.METHODS: An unblended cluster-randomized clinical trial was conducted at the Dongxihu FangCang hospital. 2 cabins were randomly allocated to CHM or control group, with 204 randomly sampled mild COVID-19 patients in each cabin. All participants received a 7-day conventional treatment, and CHM group cabin used additional Huashibaidu granule 10g twice daily. Participants were followed up until they met clinical endpoint. The primary outcome was patient become worsening before clinical endpoint occurred. The secondary outcomes was discharge with cure before clinical endpoint occurred and relief of composite symptoms after 7 days treatment.FINDINGS: All 408 participants were followed up to meet clinical endpoint and included in statistical analysis. The baseline characteristics were comparable between 2 groups. The number of worsening patients in the CHM group was 5 (2.5%), and that in the control group was 16 (7.8%). There was a significant difference between groups (P=0.014). 8 foreseeable mild adverse events occurred without statistical difference between groups.INTERPRETATION: 7-day early treatment with Huashibaidu granule reduced worsening conversion of mild COVID-19 patients. Our study supports Huashibaidu Granule as an active option for early treatment of mild COVID-19 in similar medical locations with well management.TRIAL REGISTRATION: The Chinese Clinical Trial Registry: ChiCTR2000029763.FUNDING: This study was supported by “National Key R&D Program of China” (No.2020YFC0841500).DECLARATION OF INTERESTS: The authors guaranteed that there existed no competing interest in this paper.ETHICS APPROVAL STATEMENT: Ethics Review Committee of Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences Approval of Ethical Review Acceptance Number: S2020-001; Approval Number: P20001/PJ01.

Chinese medicine (Q-14) in the Treatment of Patients with Coronavirus Disease 2019 (COVID-19): A Single-center, Open label, Randomised Controlled Trial (preprint)

OBJECTIVE To evaluate the efficacy and safety of Chinese medicine (Q-14) plus standard care compared with standard care alone in adult with coronavirus disease 2019 (COVID-19). Study DESIGN Single-center, open label, randomised controlled trial. SETTING Wuhan Jinyintan Hospital, Wuhan, China, February 27 to March 27, 2020. PARTICIPANTS 204 patients with laboratory confirmed COVID-19 were randomised in to treatment group and control group, which was 102 patients each group. INTERVENTIONS In treatment group, Q-14 was administrated at 10g (granules), twice daily for 14 days and plus standard care. In control group, patients were given standard care alone for 14 days. MAIN OUTCOME MEASURE The primary outcome was conversion time of SARS-CoV-2 viral assay. Adverse events were analyzed in the safety population. RESULTS Among 204 patients, 195 were analyzed according to the intention to treat principle. There were 149 patients (71 vs. 78 in treatment group and control group respectively) turning to negative via SARS-CoV-2 viral assay. No statistically significance showed in conversion time between treatment group and control group (FAS: Median (IQR): 10.00 (9.00-11.00) vs. 10.00 (9.00-11.00); Mean rank: 67.92 vs. 81.44; P=0.051.). Time to recovery of fever was shorter in treatment group as compared in control group. The disappearance rate of symptom in cough, fatigue, chest discomfort was significantly higher in treatment group. In chest computed tomography (Chest CT) examinations, overall evaluation of chest CT examination after treatment compared with baseline showed more patients improved in treatment group .There were no significant differences in the other outcomes. CONCLUSION Administration of Q-14 on standard care for COVID-19 was useful for improvement of symptoms (such as fever, cough, fatigue and chest discomfort), while did not result in a significantly higher probability of negative conversion of SARS-CoV-2 viral assay. No serious adverse events were reported. TRIAL REGISTRATION ChiCTR2000030288

Chinese Public’s Knowledge, Perceived Severity, and Perceived Controllability of COVID-19 and Their Associations with Emotional and Behavioural Reactions, Social Participation, and Precautionary Behaviour: A National Survey (preprint)

Background: The outbreak of the coronavirus disease-19 (COVID-19) has caused enormous stress among the public in China. Intellectual input from various aspects is needed to fight against COVID-19, including understanding of the public’s emotion and behaviour and their antecedents from the psychological perspectives. Drawing upon the cognitive appraisal theory, this study examined three cognitive appraisals (i.e., perceived severity, perceived controllability, and knowledge of COVID-19) and their associations with a wide range of emotional and behavioural outcomes among the Chinese public. Methods: : Participants were 4607 citizens (age range: 17–90 years, Mage=23.71 years) from 31 provinces in China and they took part in a cross-sectional survey online. Results: : The results showed that the public’s emotional and behavioural reactions were slightly affected by the outbreak of COVID-19. Moreover, the public had limited participation in the events regarding COVID-19 but actively engaged in precautionary behaviour. In addition, results of structural equation model with latent variables revealed that the three appraisals were differentially related to the outcome variables (i.e., negative emotion, positive emotion, sleep problems, aggression, substance use, mobile phone use, social participation, and precautionary behaviour). Conclusions: : The findings highlight the utility of cognitive appraisal, as a core process of coping stress, in explaining the public’s emotion and behaviour in the encounter of public health concern. Practically, the findings facilitate the government and practitioners to design and deliver targeted intervention programs to the public.

Reanalysis of MERS, SARS and COVID-19 Infection Datasets using VirOmics Playground Reveals Common Patterns in Gene and Protein Expression (preprint)

Three lethal lower respiratory tract coronavirus epidemics have occurred over the past 20 years. This coincided with major developments in genome-wide gene and protein expression analysis, resulting in a wealth of datasets in the public domain. Seven such in vitro studies were selected for comparative bioinformatic analysis through the VirOmics Playground, a user-friendly visualisation and exploration platform we recently developed. Despite the heterogeneous nature of the data sets, several commonalities could be observed across studies and species. Differences, on the other hand, reflected not only variations between species, but also other experimental variables, such as cell lines used for the experiments, infection protocols and potential discrepancies between transcriptome and proteome data. The results presented here are available online and can be replicated through the VirOmics Playground.

SARS-CoV-2 and Malayan pangolin coronavirus infect human endoderm, ectoderm and induced lung progenitor cells (preprint)

Since the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in several somatic cells, little is known about the infection of SASRS-CoV-2 and its related pangolin coronavirus (GX_P2V). Here we present for the first time that SARS-CoV-2 pseudovirus and GX_P2V could infect lung progenitor and even anterior foregut endoderm cells causing these cells death, which differentiated from human embryonic stem cells (hESCs). The infection and replication of SARS-CoV-2 and GX_P2V were inhibited when treated with whey protein of breastmilk and Remdesivir, confirming that these two viruses could infect lung progenitor and even anterior foregut endoderm. Moreover, we found that SARS-CoV-2 pseudovirus could infect endoderm and ectoderm. We found that whey protein blocked SARS-CoV-2 infecting these cells. In line with the SARS-CoV-2 results, GX_P2V could also infected endoderm and ectoderm, and also was inhibited by Remdesivir treatment. Although expressing coronavirus related receptor such as ACE2 and TMPRSS2, mesoderm cells are not permissive for SARS-CoV-2 and GX_P2V infection, which needed further to study the mechanisms. Interestingly, we also found that hESCs, which also express ACE2 and TMPRSS2 markers, are permissive for GX_P2V but not SARS-CoV-2 pseudovirus infection and replication, indicating the widespread cell types for GX_P2V infection. Heparin treatment blocked efficiently viral infection. These results provided insight that these stem cells maybe provided a stable repository of coronavirus function or genome. The potential consequence of SARS-CoV-2 and animal coronavirus such as GX_P2V infection in hESCs, germ layer and induced progenitors should be closely monitored.

Nitazoxanide and JIB-04 have broad-spectrum antiviral activity and inhibit SARS-CoV-2 replication in cell culture and coronavirus pathogenesis in a pig model (preprint)

Pathogenic coronaviruses represent a major threat to global public health. Here, using a recombinant reporter virus-based compound screening approach, we identified several small-molecule inhibitors that potently block the replication of the newly emerged severe acute respiratory syndrome virus 2 (SARS-CoV-2). Two compounds, nitazoxanide and JIB-04 inhibited SARS-CoV-2 replication in Vero E6 cells with an EC50 of 4.90 M and 0.69 M, respectively, with specificity indices of greater than 150. Both inhibitors had in vitro antiviral activity in multiple cell types against some DNA and RNA viruses, including porcine transmissible gastroenteritis virus. In an in vivo porcine model of coronavirus infection, administration of JIB-04 reduced virus infection and associated tissue pathology, which resulted in improved body weight gain and survival. These results highlight the potential utility of nitazoxanide and JIB-04 as antiviral agents against SARS-CoV-2 and other viral pathogens.

Baseline Interleukin-6 Level Predicts Risk of Severe COVID-19: A Two-Center, Retrospective Study (preprint)

Background:The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic has affected almost every country. Interleukin-6 (IL-6), a cytokine secreted by CD4+ T cell, has been shown to be a reliable marker of disease severity and a useful parameter for monitoring progression of coronavirus disease-2019 (COVID-19). However its value as a predictor of severe disease has not been assessed.Methods:A total of 160 laboratory-confirmed COVID-19 patients admitted to two hospitals were enrolledand separated into two groups according to whether or not they progressed to develop severe illness. Demographic and clinical characteristics at admission were compared between the groups.Results: Patients who developed severe COVID-19 had significantly higher baseline IL-6 levels than patients who had mild disease course in hospital (P< 0.001). Patients were further grouped according to quartiles of IL-6 level. The cumulative incidence of severe illnesswas significantly higher in the third and fourth quartiles groups than in the first quartile group (55% vs. 15% and 80% vs. 15%, respectively;bothP< 0.001). In multivariate logistic regression analysis, the risk for developing severe disease was markedly higher in the highest IL-6 quartile than in the lowest quartile (odds ratio: 14.95; 95% confidence interval: 3.65–61.30; P< 0.001). Receiver operating characteristic curve analysis of potential predictive variables showed the area under the curve to be largest for baseline IL-6, with the value of 5.20 pg/mL having the best balance of sensitivity and specificity for predicting risk of severe COVID-19.Conclusion: Serum baseline IL-6 appears to be a reliable predictor of risk of severe COVID-19. Early intervention may be advisable in patients with serum IL-6 levels >5.20 pg/mL, even if initial symptoms are mild.