Age-related rhesus macaque models of COVID-19

Background:Since December 2019,an outbreak of the Corona Virus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus(SARS-CoV-2)in Wuhan,China,has become a public health emergency of international concern.The high fatality of aged cases caused by SARS-CoV-2 was a need to explore the possible age-related phenomena with non-human primate models.Methods:Three 3-5 years old and two 15 years old rhesus macaques were intratracheally infected with SARS-CoV-2,and then analyzed by clinical signs,viral replication,chest X-ray,histopathological changes and immune response.Results:Viral replication of nasopharyngeal swabs,anal swabs and lung in old monkeys was more active than that in young monkeys for 14 days after SARS-CoV-2 challenge.Monkeys developed typical interstitial pneumonia characterized by thickened alveolar septum accompanied with inflammation and edema,notably,old monkeys exhibited diffuse severe interstitial pneumonia.Viral antigens were detected mainly in alveolar epithelial cells and macrophages.Conclusion:SARS-CoV-2 caused more severe interstitial pneumonia in old monkeys than that in young monkeys.Rhesus macaque models infected with SARS-CoV-2 provided insight into the pathogenic mechanism and facilitated the development of vaccines and therapeutics against SARS-CoV-2 infection.

Development and evaluation of a quadruple real-time fluorescence-based quantitative reverse transcription polymerase chain reaction assay for detecting Langya, Mojiang, Nipah, and Cedar viruses

The emerging viruses within the genus Henipavirus in the family Paramyxoviridae pose a great threat to public biosafety.To develop a quadruple real-time fluorescence-based quantitative reverse transcription polymerase chain reaction(qRT-PCR)assay is pivotal for the early warning of the potential of zoonotic infectious diseases.Specific primers and probes were designed for the relatively conserved regions based on whole genome sequences of Langya virus(LayV),Mojiang virus(MojV),Nipah virus(NiV),and Cedar virus(CedV),followed by the establishment of a quadruple real-time fluorescence-based qRT-PCR detection method.No cross-reactivity was observed with other viral nucleic acids.The optimal linear detection range for LayV,MojV,NiV,and CedV was 10^(1)-10^(8)copies/μL,and the lower limit of detection was 10 copies/μL.Three different DNA concentrations of LayV,MojV,NiV,and CedV(10^(4),10^(5),and 10^(6)copies/μL)were tested 14 times,achieving good repeatability.The standard deviation of the cycle threshold values for each concentration was<0.5 and the coefficient of variation was<3%.Furthermore,the amplification efficiency of quadruple real-time fluorescence-based qRT-PCR was>90%,and the correlation coefficient was>0.99.The established quadru-ple real-time fluorescence-based qRT-PCR assay for the detection of LayV,MojV,NiV,and CedV exhibits good sensitivity,specificity,and repeatability.Therefore,it can be used to detect Henipavirus and other related clinical specimens.

An online survey among convalescents 5 months post SARS-CoV-2 infection in China

The effects of severe acute respiratory syndrome coronavirus 2(SARS‐CoV‐2)infection persist months and years after recovery.We conducted an online survey to assess the health condition of convalescents approximately 5 months following the primary infection of SARS‐CoV‐2.The study recruited 5,510 individuals who were primary infected,626 participants who had experienced reinfection,and 521 participants who were without infective history.The most common disorders after the primary infection group were fatigue(15.18%),memory issue(13.13%),post‐exertional malaise(PEM,11.68%),and brain fog(11.29%)at the time of survey.In addition,SARS‐CoV‐2 infection had an impact on the reproductive systems.In stepwise logistic regression analysis,smoking currently,with background diseases,and outpatient visits in the acute phase could be associated with moderate/severe disorders.Further analysis of different background diseases showed that allergic rhinitis,hyperlipidemia,cardiovascular disease,autoimmune diseases,neurological diseases,and asthma likely increased the risk of moderate/severe disorders.The probability of developing disorders of individuals with SARS‐CoV‐2 reinfection was higher before the secondary infection than uninfected people.Fatigue,PEM,muscle pain/spasms,chills,joint pain,excessive sweating at rest,headache/dizziness,sore throat or foreign body sensation in the throat,cough,expectoration,dry/painful/watery eyes,loss of appetite and constipation were associated with an increased risk of reinfection.It was essential to undertake further research with enhanced randomization in a larger sample in the community,and to strengthen the validation of the research conclusions.The findings of this study contribute to a deeper understanding of the health recovery process among coronavirus disease 2019(COVID‐19)convalescents.Moreover,the findings help identify characteristic health risk factors associated with convalescents and highlight the risk of moderate/severe disorders and reinfection.Furthermore,the findings also provide valuable guidance and reference for SARS‐CoV‐2 rehabilitation strategies and the prevention of reinfection,offering insights for scientific recommendations。

Enhanced potency of an IgM-like nanobody targeting conserved epitope in SARS-CoV-2 spike N-terminal domain

Almost all the neutralizing antibodies targeting the receptor-binding domain(RBD)of spike(S)protein show weakened or lost efficacy against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)emerged or emerging variants,such as Omicron and its sub-variants.This suggests that highly conserved epitopes are crucial for the development of neutralizing antibodies.Here,we present one nanobody,N235,displaying broad neutralization against the SARS-CoV-2 prototype and multiple variants,including the newly emerged Omicron and its sub-variants.Cryo-electron microscopy demonstrates N235 binds a novel,conserved,cryptic epitope in the N-terminal domain(NTD)of the S protein,which interferes with the RBD in the neighboring S protein.The neutralization mechanism interpreted via flow cytometry and Western blot shows that N235 appears to induce the S1 subunit shedding from the trimeric S complex.Furthermore,a nano-IgM construct(MN235),engineered by fusing N235 with the human IgM Fc region,displays prevention via inducing S1 shedding and cross-linking virus particles.Compared to N235,MN235 exhibits varied enhancement in neutralization against pseudotyped and authentic viruses in vitro.The intranasal administration of MN235 in low doses can effectively prevent the infection of Omicron sub-variant BA.1 and XBB in vivo,suggesting that it can be developed as a promising prophylactic antibody to cope with the ongoing and future infection.

Efficient inhibition of SARS-CoV-2 emerging EG.5,EG.5.1 and BA.2.86 variants by fusion inhibitor HY3000 peptide

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)continues to pose a significant threat to the world,as it continually evolves and gives rise to multiple variants and sub-variants.Recently,the Omicron EG.5 linage,which was first detected in Indonesia on 17 February 2023,has raised concerns due to its increased prevalence and extended immune escape properties,according to the risk analysis by the World Health Organization(WHO)[1].As of 3 October 2023,EG.5 and its sub-linages have been reported in 83 countries with shared 49,008 genome sequences in GISAID database(https://gisaid.org/hcov19-variants/).EG.5 has become the dominant strain in the United States according to Centers for Disease Control and Prevention(CDC),accounting for 29.4%of SARS-CoV-2 infections(https://covid.cdc.gov/covid-data-tracker/#variant-proportions).

A Novel Coronavirus Genome Identified in a Cluster of Pneumonia Cases--Wuhan,China 2019−2020

Emerging and re-emerging pathogens are great challenges to the public health(1).A cluster of pneumonia cases with an unknown cause occurred in Wuhan starting on December 21,2019.As of January 20,2020,a total of 201 cases of pneumonia in China have been confirmed.A team of professionals from the National Health Commission and China CDC conducted epidemiological and etiological investigations.On January 3,2020,the first complete genome of the novelβgenus coronaviruses(2019-nCoVs)was identified in samples of bronchoalveolar lavage fluid(BALF)from a patient from Wuhan by scientists of the National Institute of Viral Disease Control and Prevention(IVDC)through a combination of Sanger sequencing,Illumina sequencing,and nanopore sequencing.Three distinct strains have been identified,the virus has been designated as 2019-nCoV,and the disease has been subsequently named novel coronavirus-infected pneumonia(NCIP).

Description of the First Strain of 2019-nCoV,C-Tan-nCoV Wuhan Strain-National Pathogen Resource Center,China,2020

The recent outbreak of novel coronavirus-infected pneumonia(NCIP)in China(1)has attracted much attention domestically and internationally.As the outbreak occurred,China carried out emergency responses quickly,notified the World Health Organization(WHO)in a timely manner,and shared the viral gene sequence with international communities immediately after pathogenic identification.

一株靶向沙贝病毒高度保守的S2亚基的广谱中和纳米抗体

新型冠状病毒感染给人类健康和全球公共安全带来了巨大威胁,但是病毒仍在持续变异产生新的变异毒株,尤其OmicronBQ.1.1和XBB变异株,完全逃逸现有抗体药物,疫苗保护效力也严重降低。此外,多种动物源新冠相关冠状病毒(沙贝病毒)具有感染人的危险。

Low levels of neutralizing antibodies against XBB Omicron subvariants after BA.5 infection

The COVID-19 response strategies in Chinese mainland were recently adjusted due to the reduced pathogenicity and enhanced infectivity of Omicron subvariants.In Chengdu,China,an infection wave was predominantly induced by the BA.5 subvariant.It is crucial to determine whether the hybrid anti-SARS-CoV-2 immunity following BA.5 infection.

A pan-coronavirus peptide inhibitor prevents SARS-CoV-2 infection in mice by intranasal delivery

Coronaviruses(Co Vs)have brought serious threats to humans,particularly severe acute respiratory syndrome coronavirus 2(SARS-Co V-2),which continually evolves into multiple variants.These variants,especially Omicron,reportedly escape therapeutic antibodies and vaccines,indicating an urgent need for new antivirals with pan-SARS-Co V-2 inhibitory activity.We previously reported that a peptide fusion inhibitor,P3,targeting heptad repeated-1(HR1)of SARS-Co V-2 spike(S)protein,could inhibit viral infections.Here,we further designed multiple derivatives of the P3 based on structural analysis and found that one derivative,the P315V3,showed the most efficient antiviral activity against SARS-Co V-2 variants and several other sarbecoviruses,as well as other human-Co Vs(HCo Vs).P315V3 also exhibited effective prophylactic efficacy against the SARS-Co V-2 Delta and Omicron variants in mice via intranasal administration.These results suggest that P315V3,which is in PhaseⅡclinical trial,is promising for further development as a nasal pan-SARS-Co V-2 or pan-Co Vs inhibitor to prevent or treat CoV diseases.

Immunological and metabolic characteristics of the Omicron variants infection

The Omicron variants of SARS-CoV-2,primarily authenticated in November 2021 in South Africa,has initiated the 5th wave of global pandemics.Here,we systemically examined immunological and metabolic characteristics of Omicron variants infection.We found Omicron resisted to neutralizing antibody targeting receptor binding domain(RBD)of wildtype SARS-CoV-2.Omicron could hardly be neutralized by sera of Corona Virus Disease 2019(COVID-19)convalescents infected with the Delta variant.Through mass spectrometry on MHC-bound peptidomes,we found that the spike protein of the Omicron variants could generate additional CD8+T cell epitopes,compared with Delta.These epitopes could induce robust CD8+T cell responses.Moreover,we found booster vaccination increased the cross-memory CD8+T cell responses against Omicron.Metabolic regulome analysis of Omicron-specific T cell showed a metabolic profile that promoted the response of memory T cells.Consistently,a greater fraction of memory CD8+T cells existed in Omicron stimulated peripheral blood mononuclear cells(PBMCs).In addition,CD147 was also a receptor for the Omicron variants,and CD147 antibody inhibited infection of Omicron.CD147-mediated Omicron infection in a human CD147 transgenic mouse model induced exudative alveolar pneumonia.Taken together,our data suggested that vaccination booster and receptor blocking antibody are two effective strategies against Omicron.

Safety and immunogenicity of a mosaic vaccine booster against Omicron and other SARS-CoV-2 variants:a randomized phase 2 trial

An ongoing randomized,double-blind,controlled phase 2 trial was conducted to evaluate the safety and immunogenicity of a mosaic-type recombinant vaccine candidate,named NVSI-06-09,as a booster dose in subjects aged 18 years and older from the United Arab Emirates(UAE),who had administered two or three doses of inactivated vaccine BBIBP-CorV at least 6 months prior to enrollment.The participants were randomly assigned with 1:1 to receive a booster dose of NVSI-06-09 or BBIBP-CorV.The primary outcomes were immunogenicity and safety against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)Omicron variant,and the exploratory outcome was cross-immunogenicity against other circulating strains.Between May 25 and 30,2022,516 adults received booster vaccination with 260 in NVSI-06-09 group and 256 in BBIBP-CorV group.Interim results showed a similar safety profile between two booster groups,with low incidence of adverse reactions of grade 1 or 2.For immunogenicity,by day 14 post-booster,the fold rises in neutralizing antibody geometric mean titers(GMTs)from baseline elicited by NVSI-06-09 were remarkably higher than those by BBIBP-CorV against the prototype strain(19.67 vs 4.47-fold),Omicron BA.1.1(42.35 vs 3.78-fold),BA.2(25.09 vs 2.91-fold),BA.4(22.42 vs 2.69-fold),and BA.5 variants(27.06 vs 4.73-fold).Similarly,the neutralizing GMTs boosted by NVSI-06-09 against Beta and Delta variants were also 6.60-fold and 7.17-fold higher than those by BBIBP-CorV.Our findings indicated that a booster dose of NVSI-06-09 was well-tolerated and elicited broad-spectrum neutralizing responses against divergent SARS-CoV-2 variants,including Omicron and its sub-lineages.

Back to Science in Searching for SARS-CoV-2 Origins

In recent decades,emerging and re-emerging human-infecting pathogens have been represented as huge threats to public health and have become a global concern(1).After outbreaks of two coronaviruses(CoVs),severe acute respiratory syndrome coronavirus(SARS-CoV)and Middle East respiratory syndrome coronavirus(MERS-CoV),severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)became the first-known pandemic hastening CoV with tremendous wrecking to the world(2).The origin tracing of these emerging pathogens is of great significance in infectious disease prevention and control(3–4).The origin of SARS-CoV-2 remains elusive after the more than 3-year pandemic,though scientists around the world are making great efforts.From the experience of studying many other infectious pathogens,origin tracing is systematic and time-consuming work.The supposed origins of many infectious pathogens are still in debate,including SARS-CoV and human immunodeficiency virus,etc(5).

Cold-chain transportation in the frozen food industry may have caused a recurrence of COVID-19 cases in destination:Successful isolation of SARS-CoV-2 virus from the imported frozen cod package surface

Coronavirus disease 2019(COVID-19)pandemic has spread in 220 countries/regions towreak havoc to human beings around theworld.At present,the second wave of COVID-19 has begun in many European countries.The complete control of COVID-19 is very urgent.Although China quickly brought the virus under control,there have been eight sporadic outbreaks in China since then.Both in Xinfadi of Beijing and Dalian outbreak of COVID-19,environmental swab samples related to imported cold chain food were tested nucleic acid positive for SARS-CoV-2.In this outbreak in Qingdao,we directly isolated SARS-CoV-2 from the cod outer package's surface swab samples.This is the first time worldwide,SARS-CoV-2 were isolated from the imported frozen cod outer package's surface,which showed that imported frozen food industry could import SARS-CoV-2 virus.

Biosafety chemistry and biosafety materials:A new perspective to solve biosafety problems

Coronavirus disease 2019(COVID‐19)has rapidly swept around the globe since its emergence near 2020.However,people have failed to fully understand its origin or mutation.Defined as an international biosafety incident,COVID‐19 has again encouraged worldwide attention to reconsider the importance of biosafety due to the adverse impact on personal well‐being and social stability.Most countries have already taken measures to advocate progress in biosafety‐relevant research,aiming to prevent and solve biosafety problems with more advanced techniques and products.Herein,we propose a new concept of biosafety chemistry and reiterate the notion of biosafety materials,which refer to the interdisciplinary integration of biosafety and chemistry or materials.We attempt to illustrate the exquisite association that chemistry and materials science possess with biosafety‐science,and we hope to provide a pragmatic perspective on approaches to utilize the knowledge of these two subjects to handle specific biosafety issues,such as detection and disinfection of pathogenic microorganisms,personal protective equipment,vaccine adjuvants and specific drugs,etc..In addition,we hope to promote multidisciplinary cooperation to strengthen biosafety research and facilitate the development of biosafety products to defend national security in the future.

CD147 antibody specifically and effectively inhibits infection and cytokine storm of SARS-CoV-2 and its variants delta,alpha,beta,and gamma

SARS-CoV-2 mutations contribute to increased viral transmissibility and immune escape,compromising the effectiveness of existing vaccines and neutralizing antibodies.An in-depth investigation on COVID-19 pathogenesis is urgently needed to develop a strategy against SARS-CoV-2 variants.Here,we identified CD147 as a universal receptor for SARS-CoV-2 and its variants.Meanwhile,Meplazeumab,a humanized anti-CD147 antibody,could block cellular entry of SARS-CoV-2 and its variants-alpha,beta,gamma,and delta,with inhibition rates of 68.7,75.7,52.1,52.1,and 62.3%at 60μg/ml,respectively.Furthermore,humanized CD147 transgenic mice were susceptible to SARS-CoV-2 and its two variants,alpha and beta.When infected,these mice developed exudative alveolar pneumonia,featured by immune responses involving alveoli-infiltrated macrophages,neutrophils,and lymphocytes and activation of IL-17 signaling pathway.Mechanistically,we proposed that severe COVID-19-related cytokine storm is induced by a"spike protein-CD147-CyPA signaling axis":Infection of SARS-CoV-2 through CD147 initiated the JAK-STAT pathway,which further induced expression of cyclophilin A(CyPA);CyPA reciprocally bound to CD147 and triggered MAPK pathway.Consequently,the MAPK pathway regulated the expression of cytokines and chemokines,which promoted the development of cytokine storm.Importantly,Meplazumab could effectively inhibit viral entry and inflammation caused by SARS-CoV-2 and its variants.Therefore,our findings provided a new perspective for severe COVID-19-related pathogenesis.Furthermore,the validated universal receptor for SARS-CoV-2 and its variants can be targeted for COVID-19 treatment.

Laboratory biosafety in China: past, present, and future

The launch of the new journal,Biosafety and Health,presents me with a unique opportunity to recount the progress of laboratory biosafety(LB)in China and my contribution to this area over the past 30 years.Since the severe acute respiratory syndrome epidemic in 2003,China has constructed a primary network of high-level biosafety laboratories at different levels and established an expert team on LB.Furthermore,a series of LB management documents,including laws,regulations,standards,and guidelines,have been developed and published.This gradually maturing LB system has played a pivotal role in emerging infectious disease control and prevention,as well as in research,which in turn contributes to public health.In recent years,international collaboration between China and other countries has also been accelerated.Despite these achievements,we are still facing many challenges and opportunities in the field of LB.Sustainable LB development requires the joint efforts of the entire society and continuous international cooperation to safeguard global public health.

Genetic tracing of HCoV-19 for the re-emerging outbreak of COVID-19 in Beijing, China

The ongoing pandemic of coronavirus disease 2019(COVID-19)caused by a novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2,also named as 2019-nCoV or HCoV-19)poses an unprecedented threat to public health(Zhu et al.,2020;Wang et al.,2020;Jiang et al.,2020).The novel HCoV-19 virus has rapidly spread into multiple countries across the world since it was first reported in December 2019.The World Health Organization(WHO)declared COVID-19 as a pandemic on 11th March 2020.As of 4th July,over 10 million confirmed COVID-19 cases have been reported in over 200 countries/regions with more than 0.5 million deaths,including 85,287 documented cases and 4,648 deaths in China(WHO,2020a).

First Imported Case of SARS-CoV-2 Omicron Subvariant BA.5—Shanghai Municipality,China,May 13,2022

On April 27,2022,an international flight KL857 from Amsterdam,the Netherlands arrived at Pudong International Airport,Shanghai Municipality.Passengers were transferred to the quarantine hotel for a routine 14-day medical observation in Songjiang District and regularly tested for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).One of the passengers(a 37-year-old Chinese male)was reported positive and diagnosed as a mild case on April 29.The case set out from Uganda(flight KL535)on April 25 and transferred at Amsterdam,the Netherlands on April 26 and Seoul,the Republic of Korea(KL857)on April 27.The patient has been vaccinated in four doses against coronavirus disease 2019(COVID-19)(Beijing Institute of Biological Products Co.,Ltd)in China and Uganda.After diagnosis,he was transferred to Shanghai Public Health Clinical Center for treatment.He recovered after treatment and was discharged on May 12.

Isolation of 2019-nCoV from a Stool Specimen of a Laboratory- Confirmed Case of the Coronavirus Disease 2019 (COVID-19)

The novel coronavirus(2019-nCoV)is spreading very fast in Hubei Province of China.As of February 14,2020,51,986 confirmed cases(including laboratory-confirmed cases and clinically-confirmed cases)were reported in Hubei Province,and 1,318 of them died.Respiratory droplets and contact transmission are considered to be the most important routes of transmission of 2019-nCoV,but do not fully account for the occurrence of all coronavirus disease 2019(COVID-19)cases,previously known as novel coronavirus pneumonia(NCP),and the reasons for the rapid spread of this virus(1).