Variation in synonymous evolutionary rates in the SARS-CoV-2 genome.

Introduction: Coronavirus disease 2019 is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Influential variants and mutants of this virus continue to emerge, and more effective virus-related information is urgently required for identifying and predicting new mutants. According to earlier reports, synonymous substitutions were considered phenotypically silent; thus, such mutations were frequently ignored in studies of viral mutations because they did not directly cause amino acid changes. However, recent studies have shown that synonymous substitutions are not completely silent, and their patterns and potential functional correlations should thus be delineated for better control of the pandemic. Methods: In this study, we estimated the synonymous evolutionary rate (SER) across the SARS-CoV-2 genome and used it to infer the relationship between the viral RNA and host protein. We also assessed the patterns of characteristic mutations found in different viral lineages. Results: We found that the SER varies across the genome and that the variation is primarily influenced by codon-related factors. Moreover, the conserved motifs identified based on the SER were found to be related to host RNA transport and regulation. Importantly, the majority of the existing fixed-characteristic mutations for five important virus lineages (Alpha, Beta, Gamma, Delta, and Omicron) were significantly enriched in partially constrained regions. Discussion: Taken together, our results provide unique information on the evolutionary and functional dynamics of SARS-CoV-2 based on synonymous mutations and offer potentially useful information for better control of the SARS-CoV-2 pandemic.

A network view of human immune system and virus-human interaction.

The immune system is highly networked and complex, which is continuously changing as encountering old and new pathogens. However, reductionism-based researches do not give a systematic understanding of the molecular mechanism of the immune response and viral pathogenesis. Here, we present HUMPPI-2022, a high-quality human protein-protein interaction (PPI) network, containing > 11,000 protein-coding genes with > 78,000 interactions. The network topology and functional characteristics analyses of the immune-related genes (IRGs) reveal that IRGs are mostly located in the center of the network and link genes of diverse biological processes, which may reflect the gene pleiotropy phenomenon. Moreover, the virus-human interactions reveal that pan-viral targets are mostly hubs, located in the center of the network and enriched in fundamental biological processes, but not for coronavirus. Finally, gene age effect was analyzed from the view of the host network for IRGs and virally-targeted genes (VTGs) during evolution, with IRGs gradually became hubs and integrated into host network through bridging functionally differentiated modules. Briefly, HUMPPI-2022 serves as a valuable resource for gaining a better understanding of the composition and evolution of human immune system, as well as the pathogenesis of viruses.

[An Overview and Interpretation of Important Clinical Studies 
on Non-small Cell Lung Cancer in 2021].

Though the coronavirus disease is still raging in 2021, clinical research on non-small cell lung cancer (NSCLC) did not stop. However, benefiting from advances in lung cancer treatment modality, NSCLC patients have experienced significant improvements in overall survival and quality of life. Currently, research advances on targeted therapy and immunotherapy have together transformed the status of postoperative adjuvant therapy and established a new standard treatment modality for resectable NSCLC. There are equally important research advances in locally advanced and advanced NSCLC, including new treatment modalities, new therapeutic agents, etc., all of which bringing more options for clinical treatment. These therapies will bring changes to NSCLC and will gradually lead to the chronicity of lung cancer in the foreseeable future. Therefore, this paper reviews important studies that will change clinical practice in NSCLC treatment and noteworthy research advances in 2021.
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COVID-19 vaccine uptake and hesitancy among HIV-infected men who have sex with men in mainland China: a cross-sectional survey.

BACKGROUND: Men who have sex with men (MSM), a population bearing the greatest HIV burden in many countries, may also be vulnerable to COVID-19. COVID-19 vaccines are essential to containing the pandemic. However, vaccine hesitancy may compromise vaccine coverage. We aimed to understand the uptake of COVID-19 vaccine and factors associated with COVID-19 vaccine hesitancy among HIV-infected MSM in mainland China. METHODS: A cross-sectional online survey among HIV-infected MSM was conducted between 13 and 21 February 2021 in mainland China. Variables including demographics, mental health status, HIV characteristics, and knowledge of and attitudes toward COVID-19 pandemic and COVID-19 vaccine were collected. Chi-square tests and multivariable logistic regression were used to analyze factors associated with COVID-19 vaccine hesitancy. RESULTS: A total of 1295 participants were included. The median age was 29.3 years (interquartile range [IQR] 25.2-34.0 years). The uptake of COVID-19 vaccine was 8.7%. Two main reasons for receiving vaccines were "regarded vaccination as self-health protection" (67.3%) and "trust in domestic medical technology" (67.3%). Among participants who did not initiate vaccination, concern about side effects (46.4%) and disclosure of HIV infection (38.6%) were top two reasons, and 47.2% had higher vaccine hesitancy. Men who had with high antiretroviral therapy (ART) adherence (adjusted odds ratio [aOR] 0.53, 95% confidence interval [CI] 0.35-0.80), often (0.26, 0.17-0.40) or sometimes (0.46, 0.31-0.67) paid attention to information about the COVID-19 vaccine, preferred domestic vaccines (0.37, 0.24-0.59), thought the pandemic had moderate (0.58, 0.38-0.90) and moderately severe or severe impact (0.54, 0.38-0.78) on immunity, who were waiting for vaccination programs organized at workplace (0.60, 0.44-0.81) and who were unaware of where to get COVID-19 vaccine (0.61, 0.45-0.82) had lower degree of COVID-19 vaccine hesitancy. Men who were concerned about the efficacy (1.72, 1.16-2.54) and side effects (2.44, 1.78-3.35) had higher degree of COVID-19 vaccine hesitancy. CONCLUSION: COVID-19 vaccine uptake among HIV-infected MSM is still suboptimal. Understanding influencing factors of vaccine hesitancy among this group and making tailored measures to alleviate hesitancy would help improve the coverage of COVID-19 vaccination in this population.

A Chinese host genetic study discovered IFNs and causality of laboratory traits on COVID-19 severity.

The COVID-19 pandemic has caused over 220 million infections and 4.5 million deaths worldwide. Current risk factor cannot fully explain the diversity in disease severity. Here, we present a comprehensive analysis of a broad range of patients' laboratory and clinical assessments to investigate the genetic contributions to COVID-19 severity. By performing GWAS analysis, we discovered several concrete associations for laboratory traits and used Mendelian randomization (MR) analysis to further investigate the causality of traits on disease severity. Two causal traits, WBC counts and cholesterol levels, were identified based on MR study, and their functional genes are located at genes MHC complex and ApoE, respectively. Our gene-based analysis and GSEA revealed four interferon pathways, including type I interferon receptor binding and SARS coronavirus and innate immunity. We hope that our work will contribute to studying the genetic mechanisms of disease and serve as a useful reference for COVID-19 diagnosis and treatment.

Trans-ethnic genome-wide association study of severe COVID-19.

COVID-19 has caused numerous infections with diverse clinical symptoms. To identify human genetic variants contributing to the clinical development of COVID-19, we genotyped 1457 (598/859 with severe/mild symptoms) and sequenced 1141 (severe/mild: 474/667) patients of Chinese ancestry. We further incorporated 1401 genotyped and 948 sequenced ancestry-matched population controls, and tested genome-wide association on 1072 severe cases versus 3875 mild or population controls, followed by trans-ethnic meta-analysis with summary statistics of 3199 hospitalized cases and 897,488 population controls from the COVID-19 Host Genetics Initiative. We identified three significant signals outside the well-established 3p21.31 locus: an intronic variant in FOXP4-AS1 (rs1853837, odds ratio OR = 1.28, P = 2.51 × 10-10, allele frequencies in Chinese/European AF = 0.345/0.105), a frameshift insertion in ABO (rs8176719, OR = 1.19, P = 8.98 × 10-9, AF = 0.422/0.395) and a Chinese-specific intronic variant in MEF2B (rs74490654, OR = 8.73, P = 1.22 × 10-8, AF = 0.004/0). These findings highlight an important role of the adaptive immunity and the ABO blood-group system in protection from developing severe COVID-19.

Genome-wide association study of COVID-19 severity among the Chinese population.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes a broad clinical spectrum of coronavirus disease 2019 (COVID-19). The development of COVID-19 may be the result of a complex interaction between the microbial, environmental, and host genetic components. To reveal genetic determinants of susceptibility to COVID-19 severity in the Chinese population, we performed a genome-wide association study on 885 severe or critical COVID-19 patients (cases) and 546 mild or moderate patients (controls) from two hospitals, Huoshenshan and Union hospitals at Wuhan city in China. We identified two loci on chromosome 11q23.3 and 11q14.2, which are significantly associated with the COVID-19 severity in the meta-analyses of the two cohorts (index rs1712779: odds ratio [OR] = 0.49; 95% confidence interval [CI], 0.38-0.63 for T allele; P = 1.38 × 10-8; and index rs10831496: OR = 1.66; 95% CI, 1.38-1.98 for A allele; P = 4.04 × 10-8, respectively). The results for rs1712779 were validated in other two small COVID-19 cohorts in the Asian populations (P = 0.029 and 0.031, respectively). Furthermore, we identified significant eQTL associations for REXO2, C11orf71, NNMT, and CADM1 at 11q23.3, and CTSC at 11q14.2, respectively. In conclusion, our findings highlight two loci at 11q23.3 and 11q14.2 conferring susceptibility to the severity of COVID-19, which might provide novel insights into the pathogenesis and clinical treatment of this disease.

Genomic epidemiology of SARS-CoV-2 in the UAE reveals novel virus mutation, patterns of co-infection and tissue specific host immune response.

To unravel the source of SARS-CoV-2 introduction and the pattern of its spreading and evolution in the United Arab Emirates, we conducted meta-transcriptome sequencing of 1067 nasopharyngeal swab samples collected between May 9th and Jun 29th, 2020 during the first peak of the local COVID-19 epidemic. We identified global clade distribution and eleven novel genetic variants that were almost absent in the rest of the world and that defined five subclades specific to the UAE viral population. Cross-settlement human-to-human transmission was related to the local business activity. Perhaps surprisingly, at least 5% of the population were co-infected by SARS-CoV-2 of multiple clades within the same host. We also discovered an enrichment of cytosine-to-uracil mutation among the viral population collected from the nasopharynx, that is different from the adenosine-to-inosine change previously reported in the bronchoalveolar lavage fluid samples and a previously unidentified upregulation of APOBEC4 expression in nasopharynx among infected patients, indicating the innate immune host response mediated by ADAR and APOBEC gene families could be tissue-specific. The genomic epidemiological and molecular biological knowledge reported here provides new insights for the SARS-CoV-2 evolution and transmission and points out future direction on host-pathogen interaction investigation.

Initial whole-genome sequencing and analysis of the host genetic contribution to COVID-19 severity and susceptibility.

The COVID-19 pandemic has accounted for millions of infections and hundreds of thousand deaths worldwide in a short-time period. The patients demonstrate a great diversity in clinical and laboratory manifestations and disease severity. Nonetheless, little is known about the host genetic contribution to the observed interindividual phenotypic variability. Here, we report the first host genetic study in the Chinese population by deeply sequencing and analyzing 332 COVID-19 patients categorized by varying levels of severity from the Shenzhen Third People's Hospital. Upon a total of 22.2 million genetic variants, we conducted both single-variant and gene-based association tests among five severity groups including asymptomatic, mild, moderate, severe, and critical ill patients after the correction of potential confounding factors. Pedigree analysis suggested a potential monogenic effect of loss of function variants in GOLGA3 and DPP7 for critically ill and asymptomatic disease demonstration. Genome-wide association study suggests the most significant gene locus associated with severity were located in TMEM189-UBE2V1 that involved in the IL-1 signaling pathway. The p.Val197Met missense variant that affects the stability of the TMPRSS2 protein displays a decreasing allele frequency among the severe patients compared to the mild and the general population. We identified that the HLA-A*11:01, B*51:01, and C*14:02 alleles significantly predispose the worst outcome of the patients. This initial genomic study of Chinese patients provides genetic insights into the phenotypic difference among the COVID-19 patient groups and highlighted genes and variants that may help guide targeted efforts in containing the outbreak. Limitations and advantages of the study were also reviewed to guide future international efforts on elucidating the genetic architecture of host-pathogen interaction for COVID-19 and other infectious and complex diseases.

Prevention of and control measures for nosocomial coronavirus disease (COVID-19): 2020 recommendations by authors at Renmin Hospital of Wuhan University

The rapid global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the coronavirus disease 2019 (COVID-19) pandemic. Although COVID-19 is a class B infectious disease, the prevention and control measures used for it in China are commonly used for class A infectious diseases. In the process of the spread of the disease, hospitals will be a key point to influence this pandemic. To prevent and control nosocomial infection of SARS-CoV-2, methods and measures were formulated from the relevant laws and regulations of the National Health Commission of the People's Republic of China, practical experience of the pandemic, and evidence-based medicine in the hospitals fighting this disease. Thus, this report may provide useful recommendations for the prevention and control of COVID-19 in hospitals and clinics.