Prevalence of bacteria, fungi, and virus coinfections with SARS-CoV-2 Omicron variant among patients with severe COVID-19 in Guangzhou, China, winter 2022

The status of coinfection during the national outbreak of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)Omicron BA.5.2 or BF.7 in China in the winter of 2022,which is suspected to contribute substantially to the overloaded severe cases,needs to be investigated.We analyzed the coinfection status of 385 severe patients infected with the Omicron variant in Guangzhou using metagenomic sequencing.We found that 317(82.3%)patients were coinfected with at least one additional pathogen(s),including bacteria(58.7%),fungi(27.1%)and viruses(73.5%).Pseudomonas aeruginosa(P.aeruginosa)(24.2%),Staphylococcus aureus(S.aureus)(14.0%),andKlebsiella pneumoniae(K.pneumonia)(13.4%)ranked as the top three coinfected bacteria.Aspergillus fumigatus(A.fumigatus)(39.5%),Pneumocystis jirovecii(P.jirovecii)(24.4%)andCanidia albicans(C.albicans)(22.1%)were the top three coinfected fungi.Epstein-Barr virus(EBV)(63.1%),Human herpesvirus 7(HHV-7)(34.8%),and Herpes simplex virus 1(HSV-1)(32.6%)were the top three coinfected viruses.Of note,the detection of multiple coinfections of potential pathogenic bacteria,fungi,and viruses,despite lacking consistent patterns,highlighted a complicated synergistic contribution to disease severity.Our study presents the most comprehensive spectrum of bacterial,fungal,and viral coinfections in Omicron-associated severe coronavirus disease 2019(COVID-19),implying that the coinfection of conditional pathogens might synergistically deteriorate the Omicron infection outcomes.

Single-cell analysis reveals bronchoalveolar epithelial dysfunction in COVID-19 patients

Dear Editor,In 2019,a zoonotic coronavirus named severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)was identified as the causative agent of Coronavirus Disease 2019(COVID-19).As of 8 June 2020,the World Health Organization(WHO)has reported 6,912,751 globally confirmed cases with 400,469 deaths.Although generally causes mild disease,SARS-CoV-2 infection can result in serious outcomes,including acute lung injury(ALI)and acute respiratory distress syndrome(ARDS),the leading cause of mortality in patients with comorbidities.Recent autopsy studies of COVID-19 patients revealed mononuclear infiltration and excessive production of mucus in the infected lung,especially in the damaged small airways and alveoli(Bian and Team,2020;Liu et al.,2020).

Incidence and factors associated with hepatitis B surface antigen seroclearance in patients co-infected with HBV/HIV during antiretroviral therapy in Guangdong,China

Background:Hepatitis B surface antigen(HBsAg)clearance is vital for a functional cure of hepatitis B virus(HBV)infection.However,the incidence and predictors of HBsAg seroclearance in patients co-infected with HBV and human immunodeficiency virus(HIV)remain largely unknown in Guangdong,China.Methods:Between 2009 and 2019,patients co-infected with HBV/HIV undergoing antiretroviral therapy(ART)in Guangzhou Eighth People’s Hospital affiliated to Guangzhou Medical University were retrospectively reviewed with the endpoint on December 31,2020.The incidence and risk factors for HBsAg seroclearance were evaluated using Kaplan-Meier and multivariate Cox regression analyses.Results:A total of 1550 HBV/HIV co-infected patients were included in the study,with the median age of 42 years and 86.0%(1333/1550)males.Further,98.3%(1524/1550)received ART containing tenofovir disoproxil fumarate(TDF)plus lamivudine(3TC).HBV DNA was examined in 1283 cases at the last follow-up.Over the median 4.7 years of follow-up,8.1%(126/1550)patients achieved HBsAg seroclearance,among whom 50.8%(64/126)obtained hepatitis B surface antibody,28.1%(137/488)acquired hepatitis B e antigen seroconversion,and 95.9%(1231/1283)undetectable HBV DNA.Compared with patients who maintained HBsAg positive,cases achieving HBsAg seroclearance showed no differences in age,gender,CD4+T cell count,alanine aminotransferase(ALT)level,or fibrosis status;however,they presented lower HBV DNA levels,lower HBsAg levels,and higher rates of HBV genotype B at the baseline.Multivariate analysis showed that baseline HBsAg<1500 cutoff index(COI)(adjusted hazard ratio[aHR],2.74,95%confidence interval[95%CI]:1.48-5.09),ALT elevation>2×upper limit of normal during the first six months after receiving ART(aHR,2.96,95%CI:1.53-5.77),and HBV genotype B(aHR,3.73,95%CI:1.46-9.59)were independent predictors for HBsAg seroclearance(all P<0.01).Conclusions:Long-term TDF-containing ART has high anti-HBV efficacy including relatively high overall HBsAg seroclearance in HBV/HIV co-infected patients.Lower baseline HBsAg levels,HBV genotype B,and elevated ALT levels during the first six months of ART are potential predictors of HBsAg seroclearance.

Transcriptome analysis of CD4^(+)T cells from HIV-infected individuals receiving ART with LLV revealed novel transcription factors regulating HIV-1 promoter activity

Some HIV-infected individuals receiving ART develop low-level viremia(LLV),with a plasma viral load of 50-1000 copies/mL.Persistent low-level viremia is associated with subsequent virologic failure.The peripheral blood CD4^(+)T cell pool is a source of LLV.However,the intrinsic characteristics of CD4^(+)T cells in LLV which may contribute to low-level viremia are largely unknown.We analyzed the transcriptome profiling of peripheral blood CD4^(+)T cells from healthy controls(HC)and HIV-infected patients receiving ART with either virologic sup-pression(VS)or LLV.To identify pathways potentially responding to increasing viral loads from HC to VS and to LLV,KEGG pathways of differentially expressed genes(DEGs)were acquired by comparing VS with HC(VS-HC group)and LLV with VS(LLV-VS group),and overlapped pathways were analyzed.Characterization of DEGs in key overlapping pathways showed that CD4^(+)T cells in LLV expressed higher levels of Th1 signature transcription factors(TBX21),toll-like receptors(TLR-4,-6,-7 and-8),anti-HIV entry chemokines(CCL3 and CCL4),and anti-IL-1βfactors(ILRN and IL1R2)compared to VS.Our results also indicated activation of the NF-κB and TNF signaling pathways that could promote HIV-1 transcription.Finally,we evaluated the effects of 4 and 17 tran-scription factors that were upregulated in the VS-HC and LLV-VS groups,respectively,on HIV-1 promoter activity.Functional studies revealed that CXXC5 significantly increased,while SOX5 markedly suppressed HIV-1 tran-scription.In summary,we found that CD4^(+)T cells in LLV displayed a distinct mRNA profiling compared to that in VS,which promoted HIV-1 replication and r+eactivation of viral latency and may eventually contribute to virologic failure in patients with persistent LLV.CXXC5 and SOX5 may serve as targets for the development of latency-reversing agents.

Molecular phylogenomic analysis reveals a single origin of monkeypox virus transmission in Guangzhou,China in June 2023

The monkeypox(mpox)virus has caused worldwide transmission since its initial report in England in early May 2022.Available data from the World Health Organization(WHO)show that Europe and the Americas experienced a huge wave of mpox virus infection.Now the number of infected cases is on the rise in Asia.Several sporadic infections have been reported in China.In this study,we obtained high‐quality whole viral genomic sequences using a mpox virus‐specific amplicon‐based sequencing strategy.Our analysis of the phylogenomic characteristics indicated that all eight mpox virus sequences from Guangzhou belonged to the clade IIb lineage B.1.3 cluster.However,we could not locate the exact origins where the virus was imported,based on all the available mpox virus sequences from the Global Initiative on Sharing Avian Influenza Data(GISAID)database(https://gisaid.org/),except for their closest sequence similarity to that was reported from Japan.Novel amino acid mutations were found among the eight cases,suggesting that a local transmission may have occurred in Guangzhou,China.

Significantly reduced abilities to cross-neutralize SARS-CoV-2 variants by sera from convalescent COVID-19 patients infected by Delta or early strains

The worldwide pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has resulted in more than 4.5 million deaths.Although coronaviruses have a proofreading mechanism to maintain the stability of their long genomic RNAs,mutations emerge continuously,and new variants conferring advantages rapidly become the dominant lineages[1].Strategies to fight the COVID-19 pandemic using either vaccines or nonpharmaceutical interventions have specifically been threatened by the emergence of SARS-CoV-2 variants of concern(VOCs)[2].

COVID-19 induces new-onset insulin resistance and lipid metabolic dysregulation via regulation of secreted metabolic factors

Abnormal glucose and lipid metabolism in COVID-19 patients were recently reported with unclear mechanism.In this study,we retrospectively investigated a cohort of COVID-19 patients without pre-existing metabolic-related diseases,and found new-onset in suli n resista nee,hyperglycemia,and decreased HDL-C in these patie nts.Mecha nistically,SARS-CoV-2 infecti on in creased the expression of RE1-silencing transcription factor(REST),which modulated the expression of secreted metabolic factors including myeloperoxidase,apelin,and myostatin at the transcriptional level,resulting in the perturbation of glucose and lipid metabolism.Furthermore,several lipids,including(±)5-HETE,(±)12-HETE,propionic acid,and isobutyric acid were identified as the potential biomarkers of COVID-19-induced metabolic dysregulation,especially in insulin resistance.Taken together,our study revealed insulin resistance as the direct cause of hyperglycemia upon COVID-19,and further illustrated the underlying mechanisms,providing potential therapeutic targets for COVID-19-induced metabolic complications.

Pre-treatment Drug Resistance Could Impact the 96-Week Antiretroviral Efficacy in Treatment-Naive HIV-1–Infected Patients in Guangdong,China

Background:With the high prevalence of pre-treatment drug resistance(PDR)and the potential impact to the virological inhibition,the detection of PDR was particularly necessary.This study aimed to determine the prevalence of PDR in Guangdong,China,and its impact on antiretroviral therapy(ART)in treatment-naive HIV patients.Methods:A retrospective cohort study was conducted.A total of 1936 HIV-1-infected treatment-naive patients in the clinic of the infectious department,Guangzhou Eighth People’s Hospital,between August 2018 and December 2019 were assayed for PDR mutations before initiating ART.Patients with PDR mutations(PDR arm)were screened and compared with those without drug-resistant mutations(non-PDR arm).The rate of HIV-1 virologic failure(VF)and CD4^(+)T-cell counts of the 2 arms were compared at the 96th week after ART to evaluate the impact of PDR on the efficacy of ART.Results:Pretreatment drug resistance was detected in 125 cases(6.46%)from the 1936 enrolled participants,most of which were resistant to non-nucleoside reverse transcriptase inhibitors(64.00%,80/125).One hundred and eight of 125 completed the follow-up of 96 weeks(PDR arm).In this cohort,52 patients whose ART regimen containing the resistant drug were grouped as con-PDR arm,and the remaining 56 patients whose ART regimen did not contain the resistant drug were grouped as non-con-PDR arm.A total of 125 patients without PDR were randomly selected as the control group(non-PDR arm),112 of whom had completed the 96-week followup.At the 96th week after ART initiation,7 patients(6.5%,7/108)in the PDR arm and 1 patient(0.9%,1/112)in the non-PDR arm developed VF,exhibiting a significant difference(χ^(2)=4.901,P=0.029).Meanwhile,3 patients(5.8%,3/52)in the con-PDR arm developed VF;the rate was also higher than that in the non-PDR arm,but without a significant difference(χ^(2)=3.549,P=0.095).The CD4^(+)T-cell count in the non-PDR arm increased more than the PDR arm(386.6 vs.319.1 cells/μL,t=2.448,P=0.015)or the con-PDRarm(386.6 vs.325.1 cells/μL,t=1.821,P=0.070)at 12weeks afterART.However,no significant differenceswere observed in the CD4^(+)T-cell count from the 24th week after ART onward.Conclusions:Pretreatment drug resistance was moderately prevalent in Guangdong,China,and could affect the antiretroviral efficacy during a 96-week observation period,indicating the need to closely monitor PDR before ART initiation.