Efficacy of rapid antigen self-testing for SARS-CoV-2 screening:Real-world evidence from a prospective cohort study

Antigen rapid diagnostic tests(Ag-RDTs)have been considered and implemented as an important diagnostic and screening tool to identify SARS-CoV-2 infections in community settings.1 Ag-RDTs are less sensitive,particularly in asymptomatic populations,compared with laboratorybased viral nucleic acid amplification tests(NAATs)such as reverse transcription polymerase chain reaction(RT-PCR).2 However,taking into account the facts that Ag-RDTs are effective for identifying most contagious individuals,they are faster and less expensive than RT-PCR,as well as that RT-PCR could produce positive results for weeks to months after the infection,2 WHO recommends Ag-RDTs be offered as COVID-19 self-testing for screening purposes in addition to professionally administered testing services regardless of the community transmission level.

人体对新型冠状病毒的免疫应答

作为新发突发传染病,新型冠状病毒感染流行已经且正在对全球造成巨大影响。免疫系统是人体抵御新冠病毒感染的自然武器。研究和认识人体的免疫反应,对于我们更好地应对新冠肺炎疫情流行很重要。得益于全球研究者的投入,我们在较短时期内,对新冠病毒感染后的免疫反应有了较广泛和深入的理解,本文将对这些进展做一简述。

Development of cell-based pseudovirus entry assay to identify potential viral entry inhibitors and neutralizing antibodies against SARS-CoV-2

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is the causative virus of the coronavirus disease 2019(COVID-19)pandemic.To establish a safe and convenient assay system for studying entry inhibitors and neutralizing antibodies against SARS-CoV-2,we constructed a codon-optimized,full-length C-terminal mutant spike(S)gene of SARS-CoV-2.We generated a luciferase(Luc)-expressing pseudovirus containing the wild-type or mutant S protein of SARS-CoV-2 in the envelope-defective HIV-1 backbone.The key parameters for this pseudovirus-based assay,including the S mutants and virus incubation time,were optimized.This pseudovirus contains a Luc reporter gene that enabled us to easily quantify virus entry into angiotensin-converting enzyme 2(ACE2)-expressing 293T cells.Cathepsin(Cat)B/L inhibitor E64d could significantly block SARS-CoV-2 pseudovirus infection in 293T-ACE2 cells.Furthermore,the SARS-CoV-2 spike pseudotyped virus could be neutralized by sera from convalescent COVID-19 patients or recombinant ACE2 with the fused Fc region of human IgG1.Thus,we developed a pseudovirus-based assay for SARS-CoV-2,which will be valuable for evaluating viral entry inhibitors and neutralizing antibodies against this highly pathogenic virus.

Patients with SARS-CoV-2 and HBV coinfection are at risk of greater liver injury

To date,it remains unclear if severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)co-infection exacerbates liver injury in patients with chronic hepatitis B virus(HBV)infection.In this study,we present a retrospective study of 133 hospitalized confirmed mild coronavirus disease 2019(COVID-19)cases,including 116 patients with COVID-19 with negative serum hepatitis B antigen and 17 HBV inactive carriers with COVID-19.We found that there were no significant differences for the discharge rate or duration of hospitalization be-tween the two groups.However,inactive HBV carriers with SARS-CoV-2 co-infection are at a higher risk of abnormal liver function tests.The enhanced liver injury induced by SARS-CoV-2 and HBV co-infection was identified as the hepatocyte type rather than the cholangiocyte type.Moreover,the inflammatory response,including abnormal lactate dehydrogenase,D-dimer and interleukin-6 production,may contribute to this injury following SARS-CoV-2 co-infection.Collectively,SARS-CoV-2 and HBV co-infection exacerbates liver function of the pa-tients with COVID-19.

Characterization of SARS-CoV-2-specific humoral immunity and its potential applications and therapeutic prospects

Coronavirus disease 2019(COVID-19),caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),is an ongoing pandemic that poses a great threat to human health worldwide.As the humoral immune response plays essential roles in disease occurrence and development,understanding the dynamics and characteristics of virus-specific humoral immunity in SARS-CoV-2-infected patients is of great importance for controlling this disease.In this review,we summarize the characteristics of the humoral immune response after SARS-CoV-2 infection and further emphasize the potential applications and therapeutic prospects of SARSCoV-2-specific humoral immunity and the critical role of this immunity in vaccine development.Notably,serological antibody testing based on the humoral immune response can guide public health measures and control strategies;however,it is not recommended for population surveys in areas with very low prevalence.Existing evidence suggests that asymptomatic individuals have a weaker immune response to SARS-CoV-2 infection,whereas SARS-CoV-2-infected children have a more effective humoral immune response than adults.The correlations between antibody(especially neutralizing antibody)titers and protection against SARS-CoV-2 reinfection should be further examined.In addition,the emergence of cross-reactions among different coronavirus antigens in the development of screening technology and the risk of antibody-dependent enhancement related to SARS-CoV-2 vaccination should be given further attention.

O-GlcNAcylation of YTHDF2 promotes HBV-related hepatocellular carcinoma progression in an N^(6)-methyladenosine-dependent manner

Hepatitis B virus(HBV)infection is a major risk factor for hepatocellular carcinoma(HCC),but its pathogenic mechanism remains to be explored.The RNA N^(6)-methyladenosine(m^(6)A)reader,YTH(YT521-B homology)domain 2(YTHDF2),plays a critical role in the HCC progression.However,the function and regulatory mechanisms of YTHDF2 in HBV-related HCC remain largely elusive.Here,we discovered that YTHDF2 O-GlcNAcylation was markedly increased upon HBV infection.O-GlcNAc transferase(OGT)-mediated O-GlcNAcylation of YTHDF2 on serine 263 enhanced its protein stability and oncogenic activity by inhibiting its ubiquitination.Mechanistically,YTHDF2 stabilized minichromosome maintenance protein 2(MCM2)and MCM5 transcripts in an m^(6)A-dependent manner,thus promoting cell cycle progression and HBV-related HCC tumorigenesis.Moreover,targeting YTHDF2 O-GlcNAcylation by the OGT inhibitor OSMI-1 significantly suppressed HCC progression.Taken together,our findings reveal a new regulatory mechanism for YTHDF2 and highlight an essential role of YTHDF2 O-GlcNAcylation in RNA m^(6)A methylation and HCC progression.Further description of the molecular pathway has the potential to yield therapeutic targets for suppression of HCC progression due to HBV infection.

Protective Effect of Neonatal Hepatitis B Vaccine Against HBV Breakthrough Infection in Children with Leukemia:A Real-world Study

Background and Aims:Hepatitis B vaccine is the most effective preventive measure against hepatitis B virus(HBV)infection.However,the risk of HBV breakthrough infection in fully immunized children(neonatal hepatitis B immunization)who receive immunosuppressive therapy and transfusion of blood components is not well characterized.In this real-world study,we aimed to investigate the immune protection conferred by neonatal hepatitis B vaccine in children with acute lymphoblastic leukemia(ALL)who were treated with immunosuppressive therapy and blood component transfusions.Methods:Children with ALL who had received all three doses of neonatal hepatitis B vaccine were included in this study.HBV seromarkers were detected before and after the initiation of immunosuppressive therapy.Results:A total of 1,011 children with ALL who were fully vaccinated against hepatitis B in infancy before the initiation of immunosuppressive therapy were eligible for inclusion.HBV infection was detected in four of 410 children(0.98%)with an HBsAg test after the initiation of immunosuppressive therapy.The median interval from treatment initiation was 19 months.Conclusions:Three doses of neonatal hepatitis B vaccine conferred adequate protection.In endemic regions,there is a low risk of HBV breakthrough infection in fully immunized children with immunosuppressive therapy.

A potent neutralizing antibody provides protection against SARS-CoV-2 Omicron and Delta variants via nasal delivery

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is still rapidly spreading worldwide.Many drugs and vaccines have been approved for clinical use show efficacy in the treatment and prevention of SARS-CoV-2 infections.However,the emergence of SARS-CoV-2 variants of concern(VOCs),such as Delta(B.1.617.2)and the recently emerged Omicron(B.1.1.529),has seriously challenged the application of current therapeutics.Therefore,there is still a pressing need for identification of new broad-spectrum antivirals.Here,we further characterized a human antibody(58G6),which we previously isolated from a patient,with a broadly authentic virus-neutralizing activity that inhibits the Delta and Omicron variants with half-maximal inhibitory concentrations(ICso)of 1.69 ng/ml and 54.31 ng/ml,respectively.58G6 shows prophylactic and therapeutic effcacy in hamsters challenged with the Delta and Omicron variants through nasal delivery.Notably,a very low dosage(2 mg/kg daily)of 58G6 efficiently prevented Omicron variant replication in the lungs.These advantages may overcome the efficacy limitation of currently approved neutralizing antibodies that can be administered only by intravenous injection.In general,58G6 is a promising prophylactic and therapeutic candidate against current circulating VOCs and even future emerging mutants.To the best of our knowledge,58G6 is one of the most potent neutralizing antibodies against Omicron,with a broader spectrum than those approved for clinical use.58G6 could be developed as a nebulized therapy,which would be more cost effective and user friendly and enhance the clinical outcome comparedto thatobtainedwithdirect nasaldelivery.

Dynamics of neutralizing antibody responses to SARS-CoV-2 in patients with COVID-19: an observational study

Our understanding of the protective immunity,particularly the long-term dynamics of neutralizing antibody(NAbs)response to SARS-CoV-2,is currently limited.We enrolled a cohort of 545 COVID-19 patients from Hubei,China,who were followed up up to 7 months,and determined the dynamics of NAbs to SARS-CoV-2 by using a surrogate virus neutralization test(sVNT).In our validation study,sVNT IC50 titers and the neutralization rate measured at a single dilution(1:20)were well correlated with FRNT titers(r=0.85 and 0.84,respectively).The median time to seroconversion of NAbs was 5.5 days post onset of symptoms.The rate of positive sVNT was 52% in the first week,reached 100% in the third week,and remained above 97% till 6 months post onset.Quantitatively,NAbs peaked in the fourth week and only a quarter of patients had an estimated peak titer of>1000.NAbs declined with a half-time of 61 days(95%CI:49-80 days)within the first two months,and the decay deaccelerated to a half-time of 104 days(95%CI:86-130 days)afterward.The peak levels of NAbs were positively associated with severity of COVID-19 and age,while negatively associated with serum albumin levels.The observation that the low-moderate peak neutralizing activity and fast decay of NAbs in most naturally infected individuals called for caution in evaluating the feasibility of antibody-based therapy and vaccine durability.NAbs response positively correlated with disease severity,warning for the possibility of repeat infection in patients with mild COVID-19.

Towards robust immune responses after heterologous COVID-19 vaccination and its application perspectives

The coronavirus disease 2019(COVID-19)pandemic,caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)[1],has seriously impacted the global health and economy.Effective vaccination,with homologous or heterologous prime-boost strategies,is the key to controlling the ongoing COVID-19 pandemic[2].Homologous vaccinations,which are the administration of the same type of COVID-19 vaccine,have been shown to be highly efficient in inducing robust immune responses[3–7].

Durability of Hepatitis B surface antigen seroclearance in patients experienced nucleoside analogs or interferon monotherapy: A real-world data from Electronic Health Record

Little is known about the difference in durability of HBsAg seroclearance induced by nucleoside analogs (NAs) or by interferon (IFN). A real-world, retrospective cohort study was conducted. Patients were assigned into two groups: NAs monotherapy-induced HBsAg seroclearance subjects and IFN monotherapy induced-HBsAg seroclearance subjects. A total of 198 subjects, comprised by 168 NAs monotherapy-induced and 30 IFN monotherapy-induced, who achieved HBsAg seroclearance were included in this study. The one-year probabilities of confirmed HBsAg seroclearance were significantly different in patients with NAs monotherapy and IFN monotherapy (0.960 (with 95% CI 0.922–0.999) vs. 0.691 (with 95% CI 0.523–0.913), log-rank-P = 4.04e-4). 73.3% (11 of 15) HBsAg recurrence occurred within one year after HBsAg seroclearance. The one-year probabilities of confirmed HBsAg seroclearance were higher in IFN monotherapy patients with anti-HBs than in IFN monotherapy patients without anti-HBs (0.839 (with 95% CI 0.657–1.000) vs. 0.489 (with 95% CI 0.251–0.953), log-rank test, P = 0.024). Our study thus provided novel insights into the durability of HBsAg seroclearance induced by NAs or IFN monotherapy. In particular, the HBsAg seroreversion rate was relatively high in IFN monotherapy subjects. The presence of anti-HBs was significantly correlated with a longer durability of functional cure induced by IFN treatment. And one-year follow-up in HBsAg seroclearance achieved individuals is proper for averting HBsAg seroreversion and other liver disease.

Complementary Presence of HBV Humoral and T-cell Response Provides Protective Immunity after Neonatal Immunization

Background and Aims:Hepatitis B vaccination is the most cost effective way to prevent hepatitis B virus(HBV)infection.Hepatitis B vaccine(HepB)efficacy is usually assessed by an-ti-hepatitis B surface antigen(HBsAg)level,but there are few reports of humoral and cellular immune responses to HepB in children after neonatal vaccination.Methods:A group of 100 children with a history of primary hepatitis B immunization were included in this study to evaluate the efficacy of HepB.Blood samples were obtained from 80 children before,and 41 children after,a single HepB booster dose.Children with low anti-HBsAg(HBs)titers of<100 mIU/mL received a booster dose after giving their informed consent.Anti-HBsAg,T-cell re-sponse and percentage of B-cell subsets were assayed before and after the booster.Results:Of the 80 children,81.36%had positive T cell and anti-HBsAg responses at baseline.After the booster dose,the anti-HBsAg titer(p<0.0001),positive HBsAg-specific T-cell response(p=0.0036),and spot-form-ing cells(p=0.0003)increased significantly.Compared with pre-existing anti-HBsAg titer<10 mIU/mL,the anti-HBsAg(p=0.0005)and HBsAg-specific T-cell responses(p<0.0001)increased significantly in preexisting anti-HBsAg titer between 10 and 100 mIU/mL group.Change of the HBV-specific hu-moral response was the reverse of the T-cell response with age.Peripheral blood lymphocytes,B cells,and subset fre-quency decreased.Conclusions:HBV immunization protec-tion persisted at least 13 years after primary immunization because of the complementary presence of HBV-specific hu-moral antibodies and a T-cell immune response.One dose of a HepB booster induced protective anti-HBsAg and promoted an HBsAg-specific T-cell response.In HBV endemic regions,a HepB booster is recommended to children without anti-HBsAg because of effectiveness in HBV prevention.

Real-world effectiveness of an intranasal spray A8G6 antibody cocktail in the post-exposure prophylaxis of COVID-19

Previously,we identified an antibody combination A8G6 that showed promising efficacy in COVID-19 animal models and favorable safety profile in preclinical models as well as in a first-in-human trial.To evaluate the real-word efficacy of A8G6 neutralizing antibody nasal spray in post-exposure prophylaxis of COVID-19,an open-label,non-randomized,two-arm,blank-controlled,investigator-initiated trial was conducted in Chongqing,China(the register number:ChiCTR2200066416).High-risk healthy participants(18–65 years)within 72 h after close contact to COVID-19 patients were recruited and received a three-dose(1.4 mg/dose)A8G6 treatment daily or no treatment(blank control)for 7 consecutive days.SARS-CoV-2 infection occurred in 151/340(44.4%)subjects in the blank control group and 12/173(6.9%)subjects in the A8G6 treatment group.The prevention efficacy of the A8G6 treatment within 72 h exposure was calculated to be 84.4%(95%CI:74.4–90.4%).Moreover,compared to the blank-control group,the time from the SARS-CoV-2 negative to the positive COVID-19 conversion was significantly longer in the AG86 treatment group(mean time:3.4 days vs 2.6 days,p=0.019).In the secondary end-point analysis,the A8G6 nasal treatment had no effects on the viral load at baseline SARS-CoV-2 RT-PCR positivity and the time of the negative COVID-19 conversion.Finally,except for 5 participants(3.1%)with general adverse effects,we did not observe any severe adverse effects related to the A8G6 treatment.In this study,the intranasal spray AG86 antibody cocktail showed potent efficacy for prevention of SARS-CoV-2 infection in close contacts of COVID-19 patients.

Genes & Diseases: Moving molecular and translational medicine forward

Welcome to the inaugural issue of Genes&Diseases,a peerreviewed international journal that aims to facilitate a rapid dissemination and exchange of scientific advances about human diseases between basic science investigators and physicians worldwide.Genes&Diseases focuses on publishing investigations on the molecular bases and experimental therapeutics of human diseases.Human medicine is undoubtedly a rapidly evolving field.The journal’s emphasis is placed on hypothesis-driven,mechanistic studies relevant to the pathogenesis and/or experimental therapeutics of human diseases.Thus,Genes&Diseases has a broad scope in basic and translational biomedical research related to molecular biology,molecular genetics,cell biology,and experimental medicine.The current publication formats include full length research article,review article,short communication,correspondence,perspectives,commentary,views on news,and research watch.

Realization of humoral immunity against SARS-CoV-2 infections

The coronavirus disease 2019(COVID-19)pandemic,caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),is a major ongoing challenge to global health.After being infected by SARS-CoV-2,a specific humoral immune response may be rapidly induced in the host to restrain the viral infection via the production of neutralizing antibodies(NAbs),which are also useful for preventing reinfection[1,2].However,there is a lack of comprehensive understanding of the mechanisms underlying SARS CoV-2 specifc humoral immunity and alterations in immunoglobulin M(1gM)and G(1gG)levels in humans during viral infection.

Characterization of Specific Humoral Immunity in Asymptomatic SARS-CoV-2 Infection

The outbreak of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection in December 2019 caused a huge blow to both global public health and global economy.At the early stage of the coronavirus disease 2019(COVID-19)epidemic,asymptomatic individuals with SARS-CoV-2 infection were ignored,without appropriate identification and isolation.However,asymptomatic individuals proved to comprise a high proportion of all SARS-CoV-2-infected individuals,which greatly contributed to the rapid and wide spread of this disease.In this review,we summarize the latest advances in epidemiological characteristics,diagnostic assessment methods,factors related to the establishment of SARS-CoV-2 asymptomatic infection,as well as humoral immune features after SARS-CoV-2 infection or vaccination in asymptomatic individuals,which would contribute to effective control of ongoing COVID-19 epidemic.

Opinion on the Policy of Lifting Restrictions to Entry Under the Circumstance of the COVID-19 Pandemic

One of the serious consequences of the coronavirus disease 2019(COVID-19)pandemic is the extreme restriction on international contacts.Communication between some countries has almost been frozen for a period of time,which is a manifestation of“social distancing”,a strategy for epidemic prevention and control,among countries.In the context of economic globalization,“social distancing”has caused serious adverse effects,including poor communication in society,the economy and personnel,reduced efficiency of resource allocation,and increased costs.Therefore,people should take necessary measures to restore international contact and eliminate these adverse effects as soon as possible.

The proteasome activator subunit PSME1 promotes HBV replication by inhibiting the degradation of HBV core protein

Chronic hepatitis B virus(HBV)infection is a leading cause of liver cirrhosis and he-patocellular carcinoma,representing a global health problem for which a functional cure is difficult to achieve.The HBV core protein(HBc)is essential for multiple steps in the viral life cycle.It is the building block of the nucleocapsid in which viral DNA reverse transcription oc-curs,and its mediation role in viral-host cell interactions is critical to HBV infection persis-tence.However,systematic studies targeting HBc-interacting proteins remain lacking.Here,we combined HBc with the APEX2 to systematically identify HBc-related host proteins in living cells.Using functional screening,we confirmed that proteasome activator subunit 1(PSME1)is a potent HBV-associated host factor.PSME1 expression was up-regulated upon HBV infection,and the protein level of HBc decreased after PSME1 knockdown.Mechanistically,the interac-tion between PSME1 and HBc inhibited the degradation of HBc by the 26S proteasome,thereby improving the stability of the HBc protein.Furthermore,PSME1 silencing inhibits HBV tran-scription in the HBV infection system.Our findings reveal an important mechanism by which PSME1 regulates HBc proteins and may facilitate the development of new antiviral therapies targeting PSME1 function.