Cross-species recognition of bat coronavirus RsYN04 and cross-reaction of SARS-CoV-2 antibodies against the virus

Following the outbreak of coronavirus disease 2019(COVID-19),several severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)-related coronaviruses have been discovered.Previous research has identified a novel lineage of SARS-CoV-2-related CoVs in bats,including RsYN04,which recognizes human angiotensin-converting enzyme 2(ACE2)and thus poses a potential threat to humans.Here,we screened the binding of the RsYN04receptor-binding domain(RBD)to ACE2 orthologs from 52animal species and found that the virus showed a narrower ACE2-binding spectrum than SARS-CoV-2.However,the presence of the T484W mutation in the RsYN04 RBD broadened its range.We also evaluated 44 SARS-CoV-2antibodies targeting seven epitope communities in the SARS-CoV-2 RBD,together with serum obtained from COVID-19 convalescents and vaccinees,to determine their cross-reaction against RsYN04.Results showed that no antibodies,except for the RBD-6 and RBD-7 classes,bound to the RsYN04 RBD,indicating substantial immune differences from SARS-CoV-2.Furthermore,the structure of the RsYN04 RBD in complex with cross-reactive antibody S43 in RBD-7 revealed a potently broad epitope for the development of therapeutics and vaccines.Our findings suggest RsYN04 and other viruses belonging to the same clade have the potential to infect several species,including humans,highlighting the necessity for viral surveillance and development of broad anticoronavirus countermeasures.

Decoding the evolution and transmissions of the novel pneumonia coronavirus(SARS-CoV-2/HCoV-19)using whole genomic data

The outbreak of COVID-19 started in mid-December2019 in Wuhan, China. Up to 29 February 2020,SARS-CoV-2(HCoV-19/2019-nCoV) had infected more than 85 000 people in the world. In this study,we used 93 complete genomes of SARS-CoV-2 from the GISAID EpiFlu TM database to investigate the evolution and human-to-human transmissions of SARS-CoV-2 in the first two months of the outbreak.We constructed haplotypes of the SARS-CoV-2 genomes, performed phylogenomic analyses and estimated the potential population size changes of the virus. The date of population expansion was calculated based on the expansion parameter tau(τ)using the formula t=τ/2 u. A total of 120 substitution sites with 119 codons, including 79 non-synonymous and 40 synonymous substitutions, were found in eight coding-regions in the SARS-CoV-2 genomes.Forty non-synonymous substitutions are potentially associated with virus adaptation. No combinations were detected. The 58 haplotypes(31 found in samples from China and 31 from outside China)were identified in 93 viral genomes under study and could be classified into five groups. By applying the reported bat coronavirus genome(bat-RaTG13-CoV)as the outgroup, we found that haplotypes H13 and H38 might be considered as ancestral haplotypes,and later H1 was derived from the intermediate haplotype H3. The population size of the SARS-CoV-2 was estimated to have undergone a recent expansion on 06 January 2020, and an early expansion on 08 December 2019. Furthermore,phyloepidemiologic approaches have recovered specific directions of human-to-human transmissions and the potential sources for international infected cases.

Acute-on-chronic liver failure in patients with severe acute respiratory syndrome coronavirus 2 infection

The coronavirus disease 2019(COVID-19)pandemic caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has had a significant impact on the lives of millions of people,especially those with other concomitant diseases,such as chronic liver diseases.To date,seven coronaviruses have been identified to infect humans.The main site of pathological action of these viruses is lung tissue.However,a substantial number of studies have proven that SARSCoV-2 shows affinity towards several organs,including the gastrointestinal tract and the liver.The current state of evidence points to several proposed mechanisms of liver injury in patients with COVID-19 and their combination.Liver impairment is considered to be the result of the direct effect of the virus on the hepatic tissue cells,a systemic reaction consisting of inflammation,hypoxia and cytokine storm,drug-induced liver injury,with the possible contribution of a perturbed gut-liver axis.Reactivation of chronic hepatic disease could be another factor for liver impairment in patients with SARS-CoV-2 infection.Acute-onchronic liver failure(ACLF)is a relatively new syndrome that occurs in 10%–30%of all hospitalized patients with chronic liver disease.It is crucial to recognize high-risk patients due to the increased morbidity and mortality in these cases.Several published studies have reported virus infection as a trigger factor for ACLF.However,to date,there are few relevant studies describing the presence of ACLF in patients with acute SARS-CoV-2 infection.In this minireview we summarize the current state of knowledge regarding the relation between ACLF and acute SARS-CoV-2 infection.

Zoonotic origins of human coronavirus 2019(HCoV-19/SARS-CoV-2):why is this work important?

The ongoing pandemic of coronavirus disease 2019 (COVID-19), caused by infection with human coronavirus 2019 (HCoV-19/SARS-CoV-2/2019-nCoV), is a global threat to the human population. Here, we briefly summarize the available data for the zoonotic origins of HCoV-19, with reference to the other two epidemics of highly virulent coronaviruses, SARSCoV and MERS-CoV, which cause severe pneumonia in humans. We propose to intensify future efforts for tracing the origins of HCoV-19, which is a very important scientific question for the control and prevention of the pandemic.

The 2019 novel coronavirus disease(COVID-19) pandemic: A zoonotic prospective

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),a novel coronavirus(CoV),has recently emerged as a significant pathogen for humans and the cause for the recent outbreak of the 2019 novel coronavirus disease(COVID-19)throughout the globe.For developing any preventive measure,an understanding of the zoonotic pattern for this virus is a necessity.We should have a clear knowledge of its reservoir host,its distribution pattern and spreading routes.Information about zoonotic reservoirs and its transmission among them can help to understand the COVID-19 outbreaks.In this article,we discuss about the bats as the zoonotic reservoir of several CoV strains,co-existence of bats and CoV/viruses,the sequence similarity of SARS-CoV-2 with bat SARS-like CoV,the probable source of the origin of SARS-CoV-2 strain and COVID-19 outbreak,intermediate host of CoVs and SARS-CoV-2,human to human transmission and the possibility to maintain the zoonotic barriers.Our knowledge about the zoonotic reservoir of SARS-CoV-2 and its transmission ability may help develop the preventive measures and control for the future outbreak of CoV.

Digestive system involvement of infections with SARS-CoV-2 and other coronaviruses:Clinical manifestations and potential mechanisms

Although coronavirus(CoV)infection is often characterized by respiratory symptoms,the virus can also result in extrapulmonary symptoms,especially the symptoms related to the digestive system.The outbreak of coronavirus disease 2019(COVID-19)is currently the world’s most pressing public health threat and has a significant impact on civil societies and the global economy.The occurrence of digestive symptoms in patients with COVID-19 is closely related to the development and prognosis of the disease.Moreover,thus far,there are no specific antiviral drug or vaccine approved for the treatment or prevention of COVID-19.Therefore,we elaborate on the effects of CoVs on the digestive system and the potential underlying mechanisms.

Novel coronavirus"Omicron subtype variant strain BA.2":The latest research progress

Since the outbreak of COVID-19,with the emergence of a series of novel coronavirus variants of different types,COVID-19 has continued to spread across the globe,posing a huge threat to the lives and health of people around the world and posing a severe challenge to global public health security.Recently,the World Health Organization(WHO)announced that novel coronavirus variant strain"Omicron"subtype variant strain BA.2 has been found in 57 countries and regions.It has higher vaccine and antibody tolerance and is more infectious than omicron(B.1.1.529).In this paper,we briefly review the recent studies on the omicron subtype variant strain BA.2.

Diabetes and coronavirus infections (SARS-CoV, MERS-CoV, and SARS-CoV-2)

Diabetes,as the major cause of hyperglycemia,is a chronic metabolic disease.Immune system disorders caused by diabetes can increase the risk of respiratory diseases.Thus,diabetes is considered to be a major risk factor for viral respiratory infections such as coronavirus infections.Coronaviruses are members of the Coronaviridae,which has caused three outbreaks from 2003 to 2020.Patients with coronavirus infection in the lower and upper respiratory tract could show mild to severe symptoms.In this review,we focus on the relationship between diabetes and three coronaviruses:SARS-CoV,MERS-CoV,and SARS-CoV-2.

Prediction of SARS-CoV-2 hosts among Brazilian mammals and new coronavirus transmission chain using evolutionary bioinformatics

Severe acute respiratory syndrome coronavirus(SARS-CoV)and SARS-CoV-2 are thought to transmit to humans via wild mammals,especially bats.However,evidence for direct bat-to-human transmission is lacking.Involvement of intermediate hosts is considered a reason for SARS-CoV-2 transmission to humans and emergence of outbreak.Large biodiversity is found in tropical territories,such as Brazil.On the similar line,this study aimed to predict potential coronavirus hosts among Brazilian wild mammals based on angiotensin-converting enzyme 2(ACE2)sequences using evolutionary bioinformatics.Cougar,maned wolf,and bush dogs were predicted as potential hosts for coronavirus.These indigenous carnivores are philogenetically closer to the known SARS-CoV/SARS-CoV-2 hosts and presented low ACE2 divergence.A new coronavirus transmission chain was developed in which white-tailed deer,a susceptible SARS-CoV-2 host,have the central position.Cougar play an important role because of its low divergent ACE2 level in deer and humans.The discovery of these potential coronavirus hosts will be useful for epidemiological surveillance and discovery of interventions that can contribute to break the transmission chain.

Biology of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and the humoral immunoresponse:a systematic review of evidence to support global policy-level actions and research

Background Both population-level epidemiological data and individual-level biological data are needed to control the coronavirus disease 2019(COVID-19)pandemic.Population-level data are widely available and efforts to combat COVID-19 have generated proliferate data on the biology and immunoresponse to the causative pathogen,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).However,there remains a paucity of systemized data on this subject.Objective In this review,we attempt to extract systemized data on the biology and immuno-response to SARS-CoV-2 from the most up-to-date peer-reviewed studies.We will focus on the biology of the virus and immunological variations that are key for determining long-term immunity,transmission potential,and prognosis.Data Sources and Methods Peer-reviewed articles were sourced from the PubMed database and by snowballing search of selected publications.Search terms included:“Novel Coronavirus”OR“COVID-19”OR“SARS-CoV-2”OR“2019-nCoV”AND“Immunity”OR“Immune Response”OR“Antibody Response”OR“Immunologic Response”.Studies published from December 31,2019 to December 31,2020 were included.To ensure validity,papers in pre-print were excluded.Results Of 2889 identified papers,36 were included.Evidence from these studies suggests early seroconversion in patients infected with SARS-CoV-2.Antibody titers appear to markedly increase two weeks after infection,followed by a plateau.A more robust immune response is seen in patients with severe COVID-19 as opposed to mild or asymptomatic presentations.This trend persists with regard to the length of antibody maintenance.However,overall immunity appears to wane within two to three months post-infection.Conclusion Findings of this study indicate that immune responses to SARS-CoV-2 follow the general pattern of viral infection.Immunity generated through natural infection appears to be short,suggesting a need for long-term efforts to control the pandemic.Antibody testing will be essential to gauge the epidemic and inform decision-making on effective strategies for treatment and prevention.Further research is needed to illustrate immunoglobulin-specific roles and neutralizing antibody activity.

新型冠状病毒肺炎与2型糖尿病炎性风暴特质的交互影响

目的 通过比较新型冠状病毒肺炎(COVID-19)患者伴或不伴2型并糖尿病(T2DM)的炎症指标、凝血功能及疾病转归的差异,讨论COVID-19合并2型糖尿病患者的炎性特质及其相互影响。方法 回顾性纳入2022年12月至2023年4月于太原市人民医院住院治疗确诊为COVID-19的轻型或普通型患者311例,其中T2DM组115例,选取同时段就诊的与之匹配的非糖尿病患者(对照组)196例。比较2组患者血细胞分析、炎症指标、凝血功能等实验室指标及核酸转阴时间、住院时间、是否使用激素等临床资料的差异。结果 T2DM组淋巴细胞计数水平低于对照组,中性粒细胞计数、C反应蛋白高于对照组(P<0.05);T2DM组D-二聚体显著升高(P<0.05);T2DM组核酸转阴时间及住院时间更长,使用激素者更多。结论 糖尿病是COVID-19发生的高危因素,新型冠状病毒感染增加了糖尿病患者的血糖调控难度。糖尿病合并COVID-19更容易发生“炎性风暴”,对患者的预后有严重的影响,住院时间更长,死亡风险大。

The origin, transmission and clinical therapies on coronavirus disease 2019(COVID-19) outbreak——an update on the status

An acute respiratory disease,caused by a novel coronavirus(SARS-CoV-2,previously known as 2019-nCoV),the coronavirus disease 2019(COVID-19)has spread throughout China and received worldwide attention.On 30 January 2020,World Health Organization(WHO)officially declared the COVID-19 epidemic as a public health emergency of international concern.The emergence of SARS-CoV-2,since the severe acute respiratory syndrome coronavirus(SARSCoV)in 2002 and Middle East respiratory syndrome coronavirus(MERS-CoV)in 2012,marked the third introduction of a highly pathogenic and large-scale epidemic coronavirus into the human population in the twenty-first century.As of 1 March 2020,a total of 87,137 confirmed cases globally,79,968 confirmed in China and 7169 outside of China,with 2977 deaths(3.4%)had been reported by WHO.Meanwhile,several independent research groups have identified that SARS-CoV-2 belongs toβ-coronavirus,with highly identical genome to bat coronavirus,pointing to bat as the natural host.The novel coronavirus uses the same receptor,angiotensin-converting enzyme 2(ACE2)as that for SARS-CoV,and mainly spreads through the respiratory tract.Importantly,increasingly evidence showed sustained human-tohuman transmission,along with many exported cases across the globe.The clinical symptoms of COVID-19 patients include fever,cough,fatigue and a small population of patients appeared gastrointestinal infection symptoms.The elderly and people with underlying diseases are susceptible to infection and prone to serious outcomes,which may be associated with acute respiratory distress syndrome(ARDS)and cytokine storm.Currently,there are few specific antiviral strategies,but several potent candidates of antivirals and repurposed drugs are under urgent investigation.In this review,we summarized the latest research progress of the epidemiology,pathogenesis,and clinical characteristics of COVID-19,and discussed the current treatment and scientific advancements to combat the epidemic novel coronavirus.

Clinical Characteristics of Children with Coronavirus Disease 2019 in Hubei, China

Since December 2019,COVID-19 has occurred unexpectedly and emerged as a health problem worldw ide.Despite the rapidly increasing number of cases in subsequent weeks,the clinical characteristics of pediatric cases are rarely described.A cross-sectional multicenter study was carried out in 10 hospitals across Hubei province.A total of 25 confirmed pediatric cases of COVID-19 were collected.The demographic data,epidemiological history,underlying discascs,clinical mani festations,laboratory and radiological data,treatments,and outcomes were analyzcd.Of 25 hospitalized patients with COVID-19,the boy to girl ratio was 1.27:1.The median age was 3 years.COVID-19 cases in children aged<3 years,3-6 years,and≥6-years patients were 10(40%),6(24%),and 9(36%),respectively.The most common symptoms at onset of ilness were fever(13[52%]),and dry cough(11[44%]).Chest CT images showed essential normal in 8 cases(33.3%),unilateral involvement of lungs in 5 cases(20.8%),and bilateral involvement in 11 cases(45.8%).Clinical diagnoses included upper respiratory tract infection(n=8),mild pneumonia(n=15),and critical cases(n=2).Two critical cases(8%)were given invasive mechanical ventilation,corticosteroids,and immunoglobulin.The symptoms in 24(96%)of 25 patients were alleviated and one patient had been discharged.It was concluded that children were susceptible to COVID-19 like adults,while the clinical presentations and outcomes were more favorable in children.However,children less than 3 years old accounted for majority cases and critical cases lied in this age group,which demanded extra attentions during home caring and hospitalization treatment.

Hepatobiliary system and intestinal injury in new coronavirus infection(COVID-19):A retrospective study

BACKGROUND An important area of effective control of the coronavirus disease 19(COVID-19)pandemic is the study of the pathogenic features of severe acute respiratory syndrome coronavirus 2 infection,including those based on assessing the state of the intestinal microbiota and permeability.AIM To study the clinical features of the new COVID-19 in patients with mild and moderate severity at the stage of hospitalization,to determine the role of hepatobiliary injury,intestinal permeability disorders,and changes in the qualitative and quantitative composition of the microbiota in the development of systemic inflammation in patients with COVID-19.METHODS The study was performed in 80 patients with COVID-19,with an average age of 45 years,19 of whom had mild disease,and 61 had moderate disease severity.The scope of the examination included traditional clinical,laboratory,biochemical,instrumental,and radiation studies,as well as original methods for studying microbiota and intestinal permeability.RESULTS The clinical course of COVID-19 was studied,and the clinical and biochemical features,manifestations of systemic inflammation,and intestinal microbiome changes in patients with mild and moderate severity were identified.Intestinal permeability characteristics against the background of COVID-19 were evaluated by measuring levels of proinflammatory cytokines,insulin,faecal calprotectin,and zonulin.CONCLUSION This study highlights the role of intestinal permeability and microbiota as the main drivers of gastroenterological manifestations and increased COVID-19 severity.

Leveraging immunoliposomes as nanocarriers against SARS-CoV-2 and its emerging variants

The global COVID-19 pandemic arising from SARS-CoV-2 has impacted many lives,gaining interest worldwide ever since it was first identified in December 2019.Till 2023,752 million cumulative cases and 6.8 million deaths were documented globally.COVID-19 has been rapidly evolving,affecting virus transmissibility and properties and contributing to increased disease severity.The Omicron is themost circulating variant of concern.Although success in its treatment has indicated progress in tackling the virus,limitations in delivering the current antiviral agents in battling emerging variants remain remarkable.With the latest advancements in nanotechnology for controlling infectious diseases,liposomes have the potential to counteract SARS-CoV-2 because of their ability to employ different targeting strategies,incorporating monoclonal antibodies for the active and passive targeting of infected patients.This review will present a concise summary of the possible strategies for utilizing immunoliposomes to improve current treatment against the occurrence of SARSCoV-2 and its variants.

The coronavirus disease 2019 (COVID-19) pandemic: A review and an update on cases in Africa

The world has experienced several epidemics posing serious threat to global public health,including the 2002 severe acute respiratory syndrome(SARS)epidemic that caused 800 deaths out of about 8000 cases,the 2009 H1N1 pandemic with 18500 deaths,the 2012 Middle East respiratory syndrome(MERS)epidemic that caused 800 deaths out of 2500 cases,the 2014 Ebola outbreak with 28616 cases and 11310 deaths,and the current coronavirus disease(COVID-19)pandemic with more than 35000 deaths out of over 730000 confirmed cases till now.Emerging infectious diseases continue to infect and reduce human populations.The COVID-19 pandemic has spread to more than 114 countries before it was officially declared as a pandemic by the WHO on the 11th March 2020.Here,the first set of index cases inAfrica,and the differences between SARS-CoV-2 and other coronaviruses in addition to the preventive strategies on the emergence of COVID-19 were reviewed.

Impacts of SARS-CoV-2 on diabetes mellitus:A pre and post pandemic evaluation

The coronavirus disease 2019(COVID-19)pandemic caused by the novel beta coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)crippled the whole world and has resulted in large number of morbidity and mortality.The origin of the SARS-CoV-2 is still disputed.The risk of infection with SARS-CoV-2 is dependent on several risk factors as observed in many studies.The severity of the disease depends on many factors including the viral strain,host immunogenetics,environmental factors,host genetics,host nutritional status and presence of comorbidities like hypertension,diabetes,Chronic Obstructive Pulmonary Disease,cardiovascular disease,renal impairment.Diabetes is a metabolic disorder mainly characterized by hyperglycemia.Diabetic individuals are intrinsically prone to infections.SARS-CoV-2 infection in patients with diabetes result inβ-cell damage and cytokine storm.Damage to the cells impairs the equilibrium of glucose,leading to hyperglycemia.The ensuing cytokine storm causes insulin resistance,especially in the muscles and liver,which also causes a hyperglycemic state.All of these increase the severity of COVID-19.Genetics also play pivotal role in disease pathogenesis.This review article focuses from the probable sources of coronaviruses and SARS-CoV-2 to its impacts on individuals with diabetes and host genetics in pre-and post-pandemic era.

Effect of SARS-CoV-2 infection on the liver

There have been numerous concerns about the disease and how it affects the human body since the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)pandemic began in December 2019.The impact of SARS-CoV-2 on the liver is being carefully investigated due to an increase in individuals with hepatitis and other liver illnesses,such as alcoholic liver disease.Additionally,the liver is involved in the metabolism of numerous drugs used to treat comorbidities and coronavirus disease 2019(COVID-19).Determining how SARS-CoV-2 affects the liver and what factors place individuals with COVID-19 at a higher risk of developing liver problems are the two main objectives of this study.This evaluation of the literature included research from three major scientific databases.To provide an update on the current impact of COVID-19 on the liver,data was collected and relevant information was incorporated into the review.With more knowledge about the effect of the disease on the liver,better management and therapeutics can be developed,and education can ultimately save lives and reduce the long-term impact of the pandemic on our population.

Clinical features and potential mechanism of coronavirus disease 2019-associated liver injury

Coronavirus disease 2019(COVID-19),caused by severe acute respiratory syndrome coronavirus 2,has posed a serious threat to global public health security.With the increase in the number of confirmed cases globally,the World Health Organization has declared the outbreak of COVID-19 an international public health emergency.Despite atypical pneumonia as the primary symptom,liver dysfunction has also been observed in many clinical cases and is associated with the mortality risk in patients with COVID-19,like severe acute respiratory syndrome and Middle East respiratory syndrome.Here we will provide a schematic overview of the clinical characteristics and the possible mechanisms of liver injury caused by severe acute respiratory syndrome coronavirus 2 infection,which may provide help for optimizing the management of liver injury and reducing mortality in COVID-19 patients.

Extracorporeal membrane oxygenation for coronavirus disease 2019-associated acute respiratory distress syndrome:Report of two cases and review of the literature

BACKGROUND Coronavirus disease 2019(COVID-19),caused by severe acute respiratory syndrome coronavirus-2,is a worldwide pandemic.Some COVID-19 patients develop severe acute respiratory distress syndrome and progress to respiratory failure.In such cases,extracorporeal membrane oxygenation(ECMO)treatment is a necessary life-saving procedure.CASE SUMMARY Two special COVID-19 cases—one full-term pregnant woman and one elderly(72-year-old)man—were treated by veno-venous(VV)-ECMO in the Second People’s Hospital of Zhongshan,Zhongshan City,Guangdong Province,China.Both patients had developed refractory hypoxemia shortly after hospital admission,despite conventional support,and were therefore managed by VV-ECMO.Although both experienced multiple ECMO-related complications on top of the COVID-19 disease,their conditions improved gradually.Both patients were weaned successfully from the ECMO therapy.At the time of writing of this report,the woman has recovered completely and been discharged from hospital to home;the man remains on mechanical ventilation,due to respiratory muscle weakness and suspected lung fibrosis.As ECMO itself is associated with various complications,it is very important to understand and treat these complications to achieve optimal outcome.CONCLUSION VV-ECMO can provide sufficient gas exchange for COVID-19 patients with acute respiratory distress syndrome.However,it is crucial to understand and treat ECMO-related complications.