Genomic Epidemiology of Carbapenemaseproducing Klebsiella pneumoniae in China

The rapid spread of carbapenemase-producing Klebsiella pneumoniae(cpKP)poses serious threats to public health;however,the underlying genetic basis for its dissemination is still unknown.We conducted a comprehensive genomic epidemiology analysis on 420 cpKP isolates collected from 70 hospitals in 24 provinces/autonomous regions/municipalities of China during 2009–2017 by short-/long-read sequencing.The results showed that most cpKP isolates were categorized into clonal group 258(CG258),in which ST11 was the dominant clone.Phylogenetic analysis revealed three major clades including the top one of Clade 3 for CG258 cpKP isolates.Additionally,carbapenemase gene analysis indicated that blaKPC was dominant in the cpKP isolates,and most blaKPC genes were located in five major incompatibility(Inc)groups of blaKPC-harboring plasmids.Importantly,three advantageous combinations of host–blaKPC-carrying plasmid(Clade 3.1+3.2–IncFIIpHN7A8,Clade 3.1+3.2–IncFIIpHN7A8:IncR,and Clade 3.3–IncFIIpHN7A8:IncpA1763-KPC)were identified to confer cpKP isolates the advantages in both genotypes(strong correlation/coevolution)and phenotypes(resistance/growth/competition)to facilitate the nationwide spread of ST11/CG258 cpKP.Intriguingly,Bayesian skyline analysis illustrated that the three advantageous combinations might be directly associated with the strong population expansion during 2007–2008 and subsequent maintenance of the population of ST11/CG258 cpKP after 2008.We then examined drug resistance profiles of these cpKP isolates and proposed combination treatment regimens for CG258/non-CG258 cpKP infections.Thus,the findings of our systematical analysis shed light on the molecular epidemiology and genetic basis for the dissemination of ST11/CG258 cpKP in China,and much emphasis should be given to the close monitoring of advantageous cpKP–plasmid combinations.

Genetic diversity and genomic epidemiology of SARS-CoV-2 in Morocco

Coronavirus disease 2019(COVID-19)is an infectious disease caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),declared as a pandemic due to its rapid spreadworldwide.In this study,we investigate the genetic diversity and genomic epidemiology of SARS-CoV-2,using 22 virus genome sequences reported by three different laboratories in Morocco till June 7,2020,as well as 40,366 virus genomes from all around the world.The SARSCoV-2 genomes from Moroccan patients revealed 62 mutations,of which 30weremis-sense mutations.Themutations Spike_D614G and NSP12_P323L were present in all the 22 analyzed sequences,followed by N_G204R and N_R203K,which occurred in 9 among the 22 sequences.The mutations NSP10_R134S,NSP15_D335N,NSP16_I169L,NSP3_L431H,NSP3_P1292L and Spike_V6F occurred once in Moroccan sequences,with no record in other sequences worldwide.Phylogenetic analyses revealed that Moroccan SARS-CoV-2 genomes included 9 viruses belonging to Clade 20A,9 to Clade 20B and 2 to Clade 20C,suggesting that the epidemic spread inMorocco did not display a predominant SARS-CoV-2 route.Therefore,multiple and unrelated introductions of SARS-CoV-2 into Morocco through different routes have occurred,giving rise to the diversity of virus genomes in the country.Further,in all probability,the SARS-CoV-2 circulated in a cryptic way inMorocco,starting fromJanuary 15,2020 before the first case was officially discovered on March 2,2020.

Human genome epidemiology,progress and future

Human genome epidemiology （HUGE） uses sys- tematic applications of epidemiologic methods to as- sess the impact of human genetic variation on health and disease. In the past ten years, human genome epi- demiology has made great progresses along with ad- vances in genomics technologies, which make it pos- sible for the examination of genetic variants in a large sample size at a sufficiently low cost. Genetic associa- tion study in population provides a powerful approach to identify variants or genes associated with disease of interest by comparing distributions of genetic variants between affected and unaffected individuals.

From human genome epidemiology to systems epidemiology:current progress and future perspective

The recent progress in human genome epidemiology(HuGE) is already having a profound impact on the practice of medicine and public health.First,the success of genome-wide association studies has greatly expanded the direction and content of epidemiological researches,including revealing new genetic mechanisms of complex diseases,identifying new targets for therapeutic interventions,and improving application in early screening of high-risk populations.At the same time,large-scale genomic studies make it possible to efficiently explore the gene-environment interactions,which will help better understand the biological pathways of complex diseases and identify individuals who may be more susceptible to diseases.Additionally,the emergence of systems epidemiology aims to integrate multi-omics together with epidemiological data to create a systems network that can comprehensively characterize the diverse range of factors contributing to disease development.These progress will help to apply HuGE findings into practice to improve the health of individuals and populations.

Genomic characterization of SARS-CoV-2 identified in a reemerging COVID-19 outbreak in Beijing's Xinfadi market in 2020

After 56 days without coronavirus disease 2019(COVID-19)cases,reemergent cases were reported in Beijing,China on June 11,2020.Here,we report the genetic characteristics of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)sequenced from the clinical specimens of 4 human cases and 2 environmental samples.The nucleotide similarity among six SARS-CoV-2 genomes ranged from 99.98%to 99.99%.Compared with the reference strain of SARS-CoV-2(GenBank No.NC_045512),all six genome sequences shared the same substitutions at nt241(C→T),nt3037(C→T),nt14408(C→T),nt23403(A→G),nt28881(G→A),nt28882(G→A),and nt28883(G→C),which are the characteristic nucleotide substitutions of L-lineage European branch I.This was also proved by themaximum likelihood phylogenetic tree based on the full-length genome of SARS-CoV-2.They also have a unique shared nucleotide substitution,nt6026(C→T),which is the characteristic nucleotide substitution of SARS-CoV-2 in Beijing's Xinfadi outbreak.It is noteworthy that there is an amino acid D614Gmutation caused by nt23403 substitution in all six genomes,which may enhance the virus's infectivity in humans and help it become the leading strain of the virus to spread around the world today.It is necessary to continuously monitor the genetic variation of SARS-CoV-2,focusing on the influence of key mutation sites of SARS-CoV-2 on viral transmission,clinical manifestations,severity,and course of disease.

Primary assessment of the diversity of Omicron sublineages and the epidemiologic features of autumn/winter 2022 COVID-19 wave in Chinese mainland

With the recent ongoing autumn/winter 2022 COVID-19 wave and the adjustment of public health control measures,there have been widespread SARS-CoV-2 infections in Chinese mainland.Here we have analyzed 369 viral genomes from recently diagnosed COVID-19 patients in Shanghai,identifying a large number of sublineages of the SARS-CoV-2 Omicron family.Phylogenetic analysis,coupled with contact history tracing,revealed simultaneous community transmission of two Omicron sublineages dominating the infections in some areas of China(BA.5.2 mainly in Guangzhou and Shanghai,and BF.7 mainly in Beijing)and two highly infectious sublineages recently imported from abroad(XBB and BQ.1).Publicly available data from August 31 to November 29,2022 indicated an overall severe/critical case rate of 0.035%nationwide,while analysis of 5706 symptomatic patients treated at the Shanghai Public Health Center between September 1 and December 26,2022 showed that 20 cases(0.35%)without comorbidities progressed into severe/critical conditions and 153 cases(2.68%)with COVID-19-exacerbated comorbidities progressed into severe/critical conditions.These observations shall alert healthcare providers to place more resources for the treatment of severe/critical cases.Furthermore,mathematical modeling predicts this autumn/winter wave might pass through major cities in China by the end of the year,whereas some middle and western provinces and rural areas would be hit by the upcoming infection wave in mid-to-late January 2023,and the duration and magnitude of upcoming outbreak could be dramatically enhanced by the extensive travels during the Spring Festival(January 21,2023).Altogether,these preliminary data highlight the needs to allocate resources to early diagnosis and effective treatment of severe cases and the protection of vulnerable population,especially in the rural areas,to ensure the country’s smooth exit from the ongoing pandemic and accelerate socio-economic recovery.