Long-term bone and lung consequences associated with hospital-acquired severe acute respiratory syndrome:a 15-year follow-up from a prospective cohort study

The most severe sequelae after rehabilitation from SARS are femoral head necrosis and pulmonary fibrosis. We performed a 15-year follow-up on the lung and bone conditions of SARS patients. We evaluated the recovery from lung damage and femoral head necrosis in an observational cohort study of SARS patients using pulmonary CT scans, hip joint MRI examinations, pulmonary function tests and hip joint function questionnaires. Eighty medical staff contracted SARS in 2003. Two patients died of SARS, and78 were enrolled in this study from August 2003 to March 2018. Seventy-one patients completed the 15-year follow-up. The percentage of pulmonary lesions on CT scans diminished from 2003(9.40 ± 7.83)% to 2004(3.20 ± 4.78)%(P < 0.001) and remained stable thereafter until 2018(4.60 ± 6.37)%. Between 2006 and 2018, the proportion of patients with interstitial changes who had improved pulmonary function was lower than that of patients without lesions, as demonstrated by the one-second ratio(FEV1/FVC%, t = 2.21, P = 0.04) and mid-flow of maximum expiration(FEF25%–75%, t = 2.76, P = 0.01). The volume of femoral head necrosis decreased significantly from 2003(38.83 ± 21.01)% to 2005(30.38 ± 20.23)%(P = 0.000 2), then declined slowly from 2005 to 2013(28.99 ± 20.59)% and plateaued until 2018(25.52 ± 15.51)%. Pulmonary interstitial damage and functional decline caused by SARS mostly recovered, with a greater extent of recovery within 2 years after rehabilitation. Femoral head necrosis induced by large doses of steroid pulse therapy in SARS patients was not progressive and was partially reversible.

The status quo and challenges of prevention and control of chronic obstructive pulmonary disease in China

Introduction Characterized as persistent and progressive pulmonary function declining,chronic obstructive pulmonary disease (COPD) can be accompanied by a systemic inflammatory response.A variety of psychiatric and somatic comorbidities can occur to the patients,such as depression,nutritional disorders,cardiovascular disease,and lung cancer.It is imposing great impacts on the quality of patients' life.In 2010 alone,the economic burden of COPD in the world was as high as 2.1 trillion dollars [1].The high prevalence,mortality,and morbidity have made this disease a major public health problem in socio-economic development with a rapidly aging population in China.

T2T-YAO: A Telomere-to-telomere Assembled Diploid Reference Genome for Han Chinese

Since its initial release in 2001,the human reference genome has undergone continuous improvement in quality,and the recently released telomere-to-telomere(T2T)version-T2T-CHM13—reaches its highest level of continuity and accuracy after 20 years of effort by working on a simplified,nearly homozygous genome of a hydatidiform mole cell line.Here,to provide an authentic complete diploid human genome reference for the Han Chinese,the largest population in the world,we assembled the genome of a male Han Chinese individual,T2T-YAO,which includes T2T assemblies of all the 22+X+M and 22+Y chromosomes in both haploids.The quality of T2T-YAO is much better than those of all currently available diploid assemblies,and its haploid version,T2T-YAO-hp,generated by selecting the better assembly for each autosome,reaches the top quality of fewer than one error per 29.5 Mb,even higher than that of T2T-CHM13.Derived from an individual living in the aboriginal region of the Han population,T2T-YAO shows clear ancestry and potential genetic continuity from the ancient ancestors.Each haplotype of T2TYAO possesses330-Mb exclusive sequences,3100 unique genes,and tens of thousands of nucleotide and structural variations as compared with CHM13,highlighting the necessity of a population-stratified reference genome.The construction of T2T-YAO,an accurate and authentic representative of the Chinese population,would enable precise delineation of genomic variations and advance our understandings in the hereditability of diseases and phenotypes,especially within the context of the unique variations of the Chinese population.

Human Pharyngeal Microbiome May Play A Protective Role in Respiratory Tract Infections

The human pharyngeal microbiome, which resides at the juncture of digestive and respiratory tracts, may have an active role in the prevention of respiratory tract infections, similar to the actions of the intestinal microbiome against enteric infections. Recent studies have demonstrated that the pharyngeal microbiome comprises an abundance of bacterial species that interacts with the local epithelial and immune cells, and together, they form a unique micro-ecological system. Most of the microbial species in microbiomes are obligate symbionts constantly adapting to their unique surroundings. Indigenous commensal species are capable of both maintaining dominance and evoking host immune responses to eliminate invading species. Temporary damage to the pharyngeal microbiome due to the impaired local epithelia is also considered an important predisposing risk factor for infections. Therefore, reinforcement of microbiome homeostasis to prevent invasion of infection-prone species would provide a novel treatment strategy in addition to antibiotic treatment and vaccination. Hence continued research efforts on evaluating probiotic treatment and developing appropriate procedures are necessary to both prevent and treat respiratory infections.

Comprehensive Humoral and Cellular Immune Responses to SARS-CoV-2 Variants in Diverse Chinese Population

The SARS-CoV-2 variants have been emerging and have made great challenges to current vaccine and pandemic control strategies.It is urgent to understand the current immune status of various Chinese populations given that the preexisting immunity has been established by national vaccination or ex posure to past variants.Using sera from 85 individuals(including 21 convalescents of natural infection,15 cases which suffered a breakthrough infection after being fully vaccinated,and 49 healthy vaccinees),we showed signifcantly enhanced neutralizing activities against SRAS-CoV-2 variants in convalescent sera,especially those who had been fully vaccinated.The neut ralizing antibodies against Omicron were detectable in 75%of convalescents and 4.9%of healthy vaccinees(p=0.006),with a GMT of 289.5,180.9-463.3,and 42.6,31.3-59,respetively.However,the neutralizing activities were weaker in young convalescents(aged<18y),with a detectable rate of 50%and a GMT of 46.4 against Omicron.We also examined and found no pan.sarbecovirus neutralizing activities in vaccinated SARS-CoV-I survivors.A booster dose could further increase the breadth and magnitude of neutralization against WT and variants of concern(VOCs)to different degrees.In addition,we showed that COVID-19-inactivated vaccines can elicit Omicron-specific T-cell responses.The positive rates of ELISpot reactions were 26.7%(4/15)and 43.8%(7/16)in the full vaccination group and the booster vaccination group,respectively,although without statistically significant difference.The neutralizing antibody titers declined while T-cell responses remain consistent over 6 months.These findings will inform the optimization of public health vaccination and intervention strategies to protect diverse populations against SARS-CoV-2 variants.Advances.Breakthrough infection significantly boosted neutralizing activities against SARS-CoV-2 variants a compared to booster immunization with inaclivated vaccine.Vaccine-induced vir us-specific T-cell immunity,on the other hand,may compensate for the shortall.Furthermore,the public health system should target the most vulnerable group due to a poorer protective serological response in both infected and vaccinated adolescents.

Meta-analysis Reveals Potential Influence of Oxidative Stress on the Airway Microbiomes of Cystic Fibrosis Patients

The lethal chronic airway infection of the cystic fibrosis(CF) patients is predisposed by colonization of specific CF-philic pathogens or the CF microbiomes, but key processes and reasons of the microbiome settlement in the patients are yet to be fully understood, especially their survival and metabolic dynamics from normal to diseased status under treatment. Here, we report our meta-analysis results on CF airway microbiomes based on metabolic networks reconstructed from genome information at species level. The microbiomes of CF patients appear to engage much more redox-related activities than those of controls, and by constructing a large dataset of anti-oxidative stress(anti-OS) genes, our quantitative evaluation of the anti-OS capacity of each bacterial species in the CF microbiomes confirms strong conservation of the anti-OS responses within genera and also shows that the CF pathogens have significantly higher anti-OS capacity than commensals and other typical respiratory pathogens. In addition, the anti-OS capacity of a relevant species correlates with its relative fitness for the airways of CF patients over that for the airways of controls.Moreover, the total anti-OS capacity of the respiratory microbiome of CF patients is collectively higher than that of controls, which increases with disease progression, especially after episodes of acute exacerbation and antibiotic treatment. According to these results, we propose that the increased OS in the airways of CF patients may play an important role in reshaping airway microbiomes to a more resistant status that favors the pre-infection colonization of the CF pathogens for a higher anti-OS capacity.

Characteristics of staphylococcal cassette chromosome mec and lugdunin operon genes in the complete genome of Staphylococcus lugdunensis

Staphylococcus lugdunensis(S.lugdunensis)is a coagulase-negative Staphylococcus comprising the normal skin microbiota,primarily colonizing the lower abdomen and extremities.[1]S.lugdunensis has attracted substantial attention in recent years since the discovery of lugdunin by Zipperer et al[2]in 2016.Lugdunin is a secondary metabolite synthesized by non-ribosomal peptide synthetase(NRPS)that inhibits the growth of various grampositive bacteria,including methicillin-resistant S.aureus(MRSA),[2]suggesting its potential as an antibiotic.

Efficacy and safety of hospital-based group medical quarantine for dialysis patients exposed to coronavirus disease 2019

To the Editor:The coronavirus disease2019(COVID-19)outbreak developedinto a pandemic.Patientsundergoing hemodialysis(HD)are more susceptible to COVID-19,and isolating patients undergoing HD after exposure are extremely challenging since they frequently travel between their homes and dialysis centers,during which they share a hall for dialysis sessions that may last for hours.We successfully quarantined one infected HD patient and other potentially exposed patients.This experience might serve as an important reference for dialysis centers or for people in similar situations across the country to reduce the spread of COVID-19.

Enhancing Variant Calling in Whole-exome Sequencing Data Using Population-matched Reference Genomes

Whole-exome sequencing(WES)data are frequently used for cancer diagnosis and genome-wide association studies(GWAS),based on high-coverage read mapping,informative variant calling,and high-quality reference genomes.The center position of the currently used genome assembly,GRCh38,is now challenged by two newly published telomere-to-telomere(T2T)genomes,T2T-CHM13 and T2T-YAO,and it becomes urgent to have a comparative study to test population specificity using the three reference genomes based on real case WES data.Here,we report our analysis along this line for 19 tumor samples collected from Chinese patients.The primary comparison of the exon regions among the three references reveals that the sequences in up to∼1%of target regions in T2T-YAO are widely diversified from GRCh38 and may lead to off-target in sequence capture.However,T2T-YAO still outperforms GRCh38 by obtaining 7.41%of more mapped reads.Due to more reliable read-mapping and closer phylogenetic relationship with the samples than GRCh38,T2T-YAO reduces half of variant calls of clinical significance which are mostly benign,while maintaining sensitivity in identifying pathogenic variants.T2T-YAO also outperforms T2T-CHM13 in reducing calls of Chinese-specific variants.Our findings highlight the critical need for employing population-specific reference genomes in genomic analysis to ensure accurate variant analysis and the significant benefits of tailoring these approaches to the unique genetic background of each ethnic group.