Identification and validation of basement membrane-associated gene AGRN as prognostic and immune-associated biomarkers in colorectal cancer patients.

Colorectal cancer (COCA) has a poor prognosis, with growing evidence implicating basement membranes (BMs) in cancer progression. Our goal was to investigate the role and predictive significance of BMs in COCA patients. We obtained BMs-related genes from cutting-edge research and used TCGA and GTEx databases for mRNA expression and patient information. Cox regression and LASSO regression were used for prognostic gene selection and risk model construction. We compared prognosis using Kaplan-Meier analysis and examined drug sensitivity differences. The CMAP dataset identified potential small molecule drugs. In vitro tests involved suppressing a crucial gene to observe its impact on tumour metastasis. We developed a 12 BMs-based approach, finding it to be an independent prognostic factor. Functional analysis showed BMs concentrated in cancer-associated pathways, correlating with immune cell infiltration and immune checkpoint activation. High-risk individuals exhibited increased drug sensitivity. AGRN levels were linked to decreased progression-free survival (p < 0.001). AGRN knockdown suppressed tumour growth and metastasis. Our study offers new perspectives on BMs in COCA, concluding that AGRN is a dependable biomarker for patient survival and prognosis.

Avian influenza A virus H7N9 in China, a role reversal from reassortment receptor to the donator.

Reassortment can introduce one or more gene segments of influenza A viruses (IAVs) into another, resulting in novel subtypes. Since 2013, a new outbreak of human highly pathogenic avian influenza has emerged in the Yangtze River Delta (YRD) and South-Central regions of China. In this study, using Anhui province as an example, we discuss the possible impact of H7N9 IAVs on future influenza epidemics through a series of gene reassortment events. Sixty-one human H7N9 isolates were obtained from five outbreaks in Anhui province from 2013 to 2019. Bioinformatics analyses revealed that all of them were characterized by low pathogenicity and high human or mammalian tropism and had introduced novel avian influenza A virus (AIV) subtypes such as H7N2, H7N6, H9N9, H5N6, H6N6, and H10N6 through gene reassortment. In reassortment events, Anhui isolates may donate one or more segments of HA, NA, and the six internal protein-coding genes for the novel subtype AIVs. Our study revealed that H7N9, H9N2, and H5N1 can serve as stable and persistent gene pools for AIVs in the YRD and South-Central regions of China. Novel AIV subtypes might be generated continuously by reassortment. These AIVs may have obtained human-type receptor-binding abilities from their donors and prefer binding to them, which can cause human epidemics through accidental spillover infections. Facing the continual threat of emerging avian influenza, constant monitoring of AIVs should be conducted closely for agricultural and public health.

Epidemiological and clinical characteristics of psittacosis among cases with complicated or atypical pulmonary infection using metagenomic next-generation sequencing: a multi-center observational study in China.

BACKGROUND: Chlamydia psittaci (C. psittaci) causes parrot fever in humans. Development of metagenomic next-generation sequencing (mNGS) enables the identification of C. psittaci. METHODS: This study aimed to determine the epidemiological and clinical characteristics of parrot fever cases in China. A multi-center observational study was conducted in 44 tertiary and secondary hospitals across 14 provinces and municipalities between April 2019 and October 2021. RESULTS: A total of 4545 patients with complicated or atypical pulmonary infection were included in the study, among which the prevalence of C. psittaci was determined to be 2.1% using mNGS. The prevalence of C. psittaci was further determined across demographic groups and types of specimens. It was significantly higher in patients with senior age (2.6% in those > 50 years), winter-spring (3.6%; particularly in December, January, and February), and southwestern (3.4%) and central and southern China (2.7%) (each P < 0.001). Moreover, the prevalence was the highest in bronchoalveolar lavage fluid (BALF) (2.9%), compared with sputum (1.1%) and peripheral blood specimens (0.9%). Additionally, co-infection of principal microorganisms was compared. Certain microorganisms were more likely to co-infect in parrot fever cases, such as Candida albicans in BALF (26.7%) and peripheral blood (6.3%), compared with non-parrot fever cases (19.7% and 1.3%); however, they did not significantly differ (each P > 0.05). CONCLUSION: Parrot fever remains low in patients with complicated or atypical pulmonary infection. It is likely to occur in winter-spring and southwestern region in China. BALF may be the optimal specimen in the application of mNGS. Co-infection of multiple microorganisms should be further considered.

MLLT11 siRNA Inhibits the Migration and Promotes the Apoptosis of MDA-MB-231 Breast Cancer Cells.

Breast cancer is considered the most prevalent malignancy due to its high incidence rate, recurrence, and metastasis in women that makes it one of the deadliest cancers. The current study aimed to predict the genes associated with the recurrence and metastasis of breast cancer and to validate their effect on MDA-MB-231 cells. Through the bioinformatics analysis, the transcription factor 7 cofactor (MLLT11) as the target gene was obtained. MLLT11-specific siRNA was synthesized and transfected into MDA-MB-231 cells. The results demonstrated that the siRNA significantly reduced the MLLT11 mRNA levels. Moreover, cell migration and invasion, as well as the protein levels of phosphatidylinositol 3-kinase (PI3K), AKT, matrix metalloproteinase (MMP) 2, and MMP9, were significantly lower in the groups treated with siRNA while the apoptosis was augmented. Collectively, MLLT11 siRNA elicited ameliorative properties on breast cancer cells, possibly via the inhibition of the PI3K/AKT signaling pathway.

Seawater intrusion on the west coast of Shenzhen during 1980-2020 due to the influence of anthropogenic activities.

Anthropogenic activities are considered key factors to affect the evolution of seawater intrusion (SWI) status. Understanding the relationships between anthropogenic factors and SWI development is crucial to formulate strategies that are used to mitigate groundwater salinization in coastal areas. In this study, we analyzed changes in land use on the west coast of Shenzhen, Guangdong province, China, over the recent four decades based on remote sensing data, and evaluated the SWI degrees in three historical stages during 1980-2020 based on the hydrochemistry data. Then, combining the timelines of groundwater exploitation, land use, land reclamation, and groundwater salinization, we presented the evolution of SWI affected by anthropogenic activities on the west coast of Shenzhen. It is found that the SWI can be divided into three stages: 1988-1999, a fully developing period; 2000-2009, a partly degrading period; and 2018-2020, a fully degrading period. The interface of saline and fresh groundwater paralleling with the coastline advanced 2 km inland in 20 years and took the next 20 years to retreat about 1 km. The interface advancing and retreating correspond to the excess and the prohibition of groundwater exploitation, respectively. Meanwhile, the construction and demolishment of high-position saltwater aquaculture areas, respectively, corresponded to the increase and decrease of Cl- concentrations in these areas. Besides, the correlation between seawater mixing index (SMI) values and Na+ concentrations became much lower during the desalination of groundwater, which can be considered direct evidence for the SWI retreat.

Codon usage of host-specific P genotypes (VP4) in group A rotavirus.

BACKGROUND: Group A rotavirus (RVA) is a common causative agent of acute gastroenteritis in infants and young children worldwide. RVA P genotypes, determined by VP4 sequences, have been confirmed to infect humans and animals. However, their codon usage patterns that are essential to obtain insights into the viral evolution, host adaptability, and genetic characterization remained unclear, especially across animal hosts. RESULTS: We performed a comprehensive codon usage analysis of eight host-specific RVA P genotypes, including human RVA (P[4] and P[8]), porcine RVA (P[13] and P[23]), and zoonotic RVA (P[1], P[6], P[7] and P[19]), based on 233 VP4 complete coding sequences. Nucleotide composition, relative synonymous codon usage (RSCU), and effective number of codons (ENC) were calculated. Principal component analysis (PCA) based on RSCU values was used to explore the codon usage patterns of different RVA P genotypes. In addition, mutation pressure and natural selection were identified by using ENC-plot, parity rule 2 plot, and neutrality plot analyses. All VP4 sequences preferred using A/U nucleotides (A: 0.354-0.377, U: 0.267-0.314) than G/C nucleotides across genotypes. Similarly, majority of commonly used synonymous codons were likely to end with A/U nucleotides (A: 9/18-12/18, U: 6/18-9/18). In PCA, human, porcine, and zoonotic genotypes clustered separately in terms of RSCU values, indicating the host-specific codon usage patterns; however, porcine and zoonotic genotypes were partly overlapped. Human genotypes, P[4] and P[8], had stronger codon usage bias, as indicated by more over-represented codons and lower ENC, compared to porcine and zoonotic genotypes. Moreover, natural selection was determined to be a predominant driver in shaping the codon usage bias across the eight P genotypes. In addition, mutation pressure contributed to the codon usage bias of human genotypes. CONCLUSIONS: Our study identified a strong codon usage bias of human RVA P genotypes attributable to both natural selection and mutation pressure, whereas similar codon usage bias between porcine and zoonotic genotypes predominantly attributable to natural selection. It further suggests possible cross-species transmission. Therefore, it warrants further surveillance of RVA P genotypes for early identification of zoonotic infection.

Molecular characteristics of a coxsackievirus A12 strain in Zhejiang of China, 2019.

BACKGROUND: Enterovirus A (EV-A), such as enterovirus A71 (EV-A71), generally causes hand, foot, and mouth disease (HFMD). However, limited studies focused on uncommon enterovirus serotypes such as coxsackievirus A12 (CV-A12). This study aimed to provide evidence to determine the molecular characteristics of a CV-A12 strain isolated in Zhejiang province, China. METHODS: In routine surveillance of HFMD, we identified a child case with CV-A12 infection in 2019 in Zhejiang province, China. Enterovirus was examined by using real-time reverse transcription-PCR (qRT-PCR). A partial VP1 sequence was amplified to determine the serotype, and then a full-length CV-A12 genome was sequenced. Nucleotide and amino acid similarity was calculated with those CV-A12 strains available in GenBank. Recombination was detected using RDP 4 and SimPlot. Furthermore, phylogenetic analysis was conducted by using BEAST 1.10, and protein modeling was performed with I-TASSER webserver. RESULTS: A full-length CV-A12 genome PJ201984 was isolated in a Chinese child with HFMD. The similarities with complete coding sequences of the CV-A12 strains in GenBank ranged between 79.3-100% (nucleotide) and 94.4-100% (amino acid), whereas it was 88.7-100.0% (nucleotide) and 97.2-100% (amino acid) when excluding the CV-A12 prototype strain Texas-12. In PJ201984, amino acid variations were more divergent in P2 and P3 regions than those in P1; the majority of those variations in VP1 (13/15) and VP4 (7/8) were similar to those documented in recently isolated CV-A12 strains in China. Furthermore, recombination was identified in P2 region, which involved a CV-A5 strain collected in China. Phylogenetic analysis revealed that PJ201984 clustered together with multiple CV-A12 strains isolated in China and the Netherlands during 2013-2018, as compared to another cluster consisting of CV-A12 strains in China and France during 2009-2015. Additionally, protein models of VP1 and VP4 in PJ201984 were well predicted to be similar to VP1 protein of EV-A71 and VP4 protein of coxsackievirus A21, respectively. CONCLUSIONS: The full-length CV-A12 genome was characterized to have common recombination in P2 region and be phylogenetically related to those CV-A12 strains isolated in recent years, suggesting a continual spread in China. It warrants strengthening the routine surveillance for uncommon enterovirus serotypes, particularly on possible recombination and variation.

Genomic characterization of Rocahepevirus ratti hepatitis E virus genotype C1 in Yunnan province of China.

The Rocahepevirus ratti hepatitis E virus genotype C1 (HEV-C1) has been documented to infect humans. However, the understanding of HEV-C1 remains constrained. This study aims to determine the prevalence and genomic characteristics of HEV-C1 in small animals in Yunnan province of southwestern China. A total of 444 liver tissues were collected from animals covering the orders Rodentia, Soricomorpha, Scandentia and Erinaceomorpha in three regions in Yunnan. Then Paslahepevirus balayani and Rocahepevirus were examined using RT-qPCR. The detection rate of Rocahepevirus was 12.95 % (36/278) in animals of order Rodentia, with 14.77 % (35/237) in Rattus tanezumi and 33.33 % (1/3) in Niviventer fulvescens. No Paslahepevirus balayani was detected. Additionally, two full-length Rocahepevirus sequences (MSE-17 and LHK-54) and thirty-three partial ORF1 sequences were amplified and determined to be HEV-C1. MSE-17 and LHK-54 shared moderate nucleotide identity (78.9 %-80.3 %) with HEV-C1 isolated in rats and humans. The HEV-C1 isolated from Niviventer fulvescens demonstrated a 100 % nucleotide identity with that from Rattus tanezumi. The rat HEV-C1 sequences isolated in our study and other Asian HEV-C1 sequences were phylogenetically distant from those isolated in North America and Europe. Furthermore, the two full-length sequences isolated in our study had less amino acid substitutions in the motifs of RNA-dependent RNA polymerase domain (F204L and L238F), compared with other Asian sequences. In summary, HEV-C1 commonly spreads in rats in Yunnan province of China. Our findings suggest a spatially associated phylogeny, and potential cross-species transmission of HEV-C1.

Theory and Engineering Practice of Intermittent Heat Injection-Enhanced Coalbed Methane Extraction.

Because of the strong adsorption characteristics of methane and the low permeability of coal seams, the extraction efficiency of coalbed methane (CBM) is very low. Here, based on the energy conservation equation, we propose the theory of heat injection-enhanced CBM extraction. We developed a device for heat injection-enhanced CBM extraction and performed an on-site heat injection test in the Chengzhuang coal mine. The results showed that when the water injection rate was 0.5 m3/h, the heat injection temperature was 145 °C, with two heat injections, yielding the best CBM extraction effect. This could fully utilize the heat injection equipment and achieve a fast, safe, and efficient extraction. The gas production law of the intermittent heat injection-enhanced CBM extraction method had obvious stages; the CBM concentration and daily gas production were very low during the heat injection stage but were greatly improved during the extraction stage after heat injection. The highest CBM concentration reached 100%, and the maximum daily gas production of CBM increased by 1269 times. The variation law of the cumulative gas production with time was fitted using Wang's empirical formula. Comparative analysis showed that, compared to traditional extraction, intermittent heat injection shortened the extraction time by 6.6 years. Compared with other enhanced CBM extraction methods, the intermittent heat injection method had obvious technical advantages and greater improvements in concentration and CBM extraction speed. Therefore, the results are of great significance for improving the recovery rate of CBM and for reducing greenhouse gas emissions.

Changing serotypes of hand, foot and mouth disease in Shanghai, 2017-2019.

BACKGROUND: Hand, foot, and mouth disease (HFMD) is a common reportable infectious disease that is highly contagious among children in China. This study aimed to characterize the epidemics of HFMD and the serotypes of enterovirus (EV) after the introduction of EV-A71 vaccines in Shanghai, a city in Eastern China. RESULTS: A total of 2271 HFMD cases were recruited in this study from May 2017 through October 2020. Among these cases, a male-to-female ratio of 1.6:1 was observed, and the cases were mainly in 1-4 years old (63.1%). Children of all ages had a relatively similar time span between the onset of HFMD and the initial medical visit (P = 0.5192). The cases were reported year-round with peaks in the summer (2018 and 2019) and fall (2017), which was consistent with previous epidemics of the reported HFMD cases in the Shanghai municipality. Among the specimens that tested positive for EV (n = 1855), CV-A6 was predominantly detected (71.1%), followed by CV-A16 (14.2%) and EV-A71 (7.0%). Notably, the number of HFMD cases infected with EV-A71 increased in 2019. Furthermore, 9.2% of the cases had comorbidities, mostly convulsion, bronchopneumonia, and pneumonia; however, they were not correlated with the EV serotypes. In addition, 31.2% (709/2271) of the cases were vaccinated with EV-A71 vaccines. The time span differed significantly between the time of vaccination and the onset of the disease across the groups based on whether the onset was before or after vaccination (P < 0.001). CONCLUSIONS: CV-A6 is the predominant EV serotype in the epidemic of HFMD in Shanghai; in addition, CV-A16 and EV-A71 may be moderately prevalent. The changing trends in the presence of EV serotypes contributes to the periodicity of the HFMD epidemic. In addition, the minority of HFMD cases may have comorbidities, regardless of the EV serotype. The use of the EV-A71 vaccine has affected the HFMD epidemic. And serotype-specific protection by the EV-A71 vaccine may promote vaccination in children infected with EV-A71 compared to those infected with non-EV-A71 serotypes, which would further change the epidemic scenario of HFMD.

Vaccine Uptake to Prevent Meningitis and Encephalitis in Shanghai, China.

Multiple vaccines may prevent meningitis and encephalitis (M/E). In China, the meningococcal vaccine and Japanese encephalitis vaccine (JEV) have been included in the expanded program of immunization (EPI). The pneumococcal vaccine, Haemophilus influenzae type b (Hib) vaccine, rotavirus vaccine, and enterovirus 71 (EV-71) vaccine are non-EPI vaccines and are self-paid. We aim to investigate the uptake of these M/E vaccines in children and the related knowledge and health beliefs among family caregivers. A total of 1011 family caregivers with children aged 1-6 years in Shanghai, China were included in the study. The uptake of the pneumococcal vaccine, Hib-containing vaccine, rotavirus vaccine, and EV-71 vaccine remained at 44.0-48.1% in children, compared with the higher uptake of the meningococcal vaccine (88.8%) and JEV (87.1%). Moreover, family caregivers had limited knowledge on the M/E pathogens and possible vaccines. Their health beliefs were moderate to high. Then, a health belief model (HBM) and a structural equation model were established. The uptake of four non-EPI vaccines was significantly influenced by family income (ß = 0.159), knowledge (ß = 0.354), self-efficacy (ß = 0.584), and perceived susceptibility (ß = 0.212) within an HBM. Therefore, it warrants further improving the uptake rate for these non-EPI vaccines to prevent potential M/E in children. A specific health promotion may empower the caregivers' decision-making on childhood vaccination.

Codon Usage of Hepatitis E Viruses: A Comprehensive Analysis.

Hepatitis E virus (HEV) is an emerging zoonotic pathogen with multiple species and genotypes, which may be classified into human, animal, and zoonotic HEV. Codon usage bias of HEV remained unclear. This study aims to characterize the codon usage of HEV and elucidate the main drivers influencing the codon usage bias. A total of seven HEV genotypes, HEV-1 (human HEV), HEV-3 and HEV-4 (zoonotic HEV), HEV-8, HEV-B, HEV-C1, and HEV-C2 (emerging animal HEV), were included in the study. Complete coding sequences, ORF1, ORF2, and ORF3, were accordingly obtained in the GenBank. Except for HEV-8, the other six genotypes tended to use codons ending in G/C. Based on the analysis of relatively synonymous codon usage (RSCU) and principal component analysis (PCA), codon usage bias was determined for HEV genotypes. Codon usage bias differed widely across human, zoonotic, and animal HEV genotypes; furthermore, it varied within certain genotypes such as HEV-4, HEV-8, and HEV-C1. In addition, dinucleotide abundance revealed that HEV was affected by translation selection to form a unique dinucleotide usage pattern. Moreover, parity rule 2 analysis (PR2), effective codon number (ENC)-plot, and neutrality analysis were jointly performed. Natural selection played a leading role in forming HEV codon usage bias, which was predominant in HEV-1, HEV-3, HEV-B and HEV-C1, while affected HEV-4, HEV-8, and HEV-C2 in combination with mutation pressure. Our findings may provide insights into HEV evolution and codon usage bias.

Potential utility of miRNAs for liquid biopsy in breast cancer.

Breast cancer (BC) remains the most prevalent malignancy due to its incidence rate, recurrence, and metastasis in women. Conventional strategies of cancer detection- mammography and tissue biopsy lack the capacity to detect the complete cancer genomic landscape. Besides, they often give false- positive or negative results. The presence of this and other disadvantages such as invasiveness, high-cost, and side effects necessitates developing new strategies to overcome the BC burden. Liquid biopsy (LB) has been brought to the fore owing to its early detection, screening, prognosis, simplicity of the technique, and efficient monitoring. Remarkably, microRNAs (miRNAs)- gene expression regulators seem to play a major role as biomarkers detected in the samples of LB. Particularly, miR-21 and miR-155 among other possible candidates seem to serve as favorable biomarkers in the diagnosis and prognosis of BC. Hence, this review will assess the potential utility of miRNAs as biomarkers and will highlight certain promising candidates for the LB approach in the diagnosis and management of BC that may optimize the patient outcome.

WSP from "Nostoc commune" Vauch. suppresses gastric cancer migration via EGFRVIII signaling.

Introduction: A number of evidences have proved that "Nostoc commune" Vauch can improve human immunity and prevent diseases, however, the specific mechanism remains unclear. The biological activity of the main protein component of "Nostoc commune" Vauch extracellular matrix- a water-stress protein (WSP) still needs to be elucidated. Methods: In our study, we validated the role of WSP in gastric cancer metastasis at the cellular level, the organoid level and in mouse models, and also studied the role of EGFRVIII and downstream signaling molecules after WSP treatment. Results: We found that WSP can significantly inhibit the metastasis of gastric cancer cells. Interestingly, we found that the anti-metastasis ability of WSP on gastric cancer was related to membrane protein receptor EGFRVIII, which was realized by inhibiting the downstream EGFRVIII signaling pathway. In terms of mechanism, WSP can inhibit the downstream EGFRVIII signaling pathway Akt-PI3K and further inhibit the secretion of cancer-related metastasis proteins such as MMP2 and MMP9, thus, significantly affecting the metastasis of gastric cancer cells. Discussion: Given the anticancer properties of WSP, drug developers and manufacturers can further develop protein drugs for cancer patients using protein engineering techniques based on the properties of WSP.

Accuracy of the intermittently scanned continuous glucose monitoring system in critically ill patients: a prospective, multicenter, observational study.

OBJECTIVE: Continuous glucose monitoring (CGM) has the potential to improve glucose control in the intensive care unit (ICU) setting. We sought to evaluate the accuracy of the intermittently scanned CGM (isCGM) system in critically ill patients. RESEARCH DESIGN AND METHODS: Adult patients were consecutively enrolled from three ICUs from August 2020 to January 2021. The performance of FreeStyle Libre Pro was evaluated against the venous blood glucose samples as a reference. Numerical accuracy was examined by the mean absolute relative difference (MARD), the Bland-Altman analysis, and the International Organization for Standardization criteria. Clinical accuracy was assessed by performing the Clarke and consensus error grid analysis. RESULTS: A total of 122 patients were included and 3416 matched glucose pairs were analyzed. The overall MARD was 18.0%, and the highest MARD (33.1%) was observed in the hypoglycemic range (<70 mg/dL). The Bland-Altman analysis revealed a mean bias of -11.7 mg/dL, with the 95% limits of agreement of -73.0 to 49.5 mg/dL. The percentages of isCGM glucose values within ±15%/15, ±20%/20, and ±30%/30 mg/dL were 49.8%, 64.7%, and 84.5%, respectively. The Clarke and consensus error grid analysis showed acceptable clinical accuracy with 98.5% and 98.8% of glucose values falling into zones A and B. CONCLUSIONS: Our study demonstrated suboptimal overall accuracy of isCGM for critically ill patients. Whether the adjunctive use of isCGM could improve glucose management and health outcomes in the critically ill needs further investigation. CLINICAL TRIAL REGISTRATION: ChiCTR2100042036, Chinese Clinical Trial Registry.

Association between Adult Vaccine Hesitancy and Parental Acceptance of Childhood COVID-19 Vaccines: A Web-Based Survey in a Northwestern Region in China.

China has initiated the COVID-19 vaccination for children aged 15-17 years since late July 2020. This study aimed to determine the association between adult vaccine hesitancy and parental acceptance of childhood COVID-19 vaccines in a multi-ethnicity area of northwestern China. A web-based investigation was performed with a convenience sampling strategy to recruit the parents aged 20-49 years. In a total of 13,451 valid respondents, 66.1% had received the COVID-19 vaccination, 26.6% were intent to receive, while 7.3% were not intent, with an increasing vaccine hesitancy (p < 0.001). Moreover, vaccination uptake of four common vaccines in their children remained low (29.0% for influenza vaccine, 17.9% for pneumonia vaccine, 10.9% for rotavirus vaccine, 8.0% for Enterovirus-71 vaccine), while overall parental acceptance of childhood COVID-19 vaccines was 50.0% (32.7% for those aged 0-5, 46.6% for 6-10, 73.3% for 11-18; p < 0.001). Vaccination uptake of these four vaccines and parental acceptance of childhood COVID-19 vaccine were negatively associated with adult vaccine hesitancy. In addition, respondents mostly preferred childhood COVID-19 vaccines with weak mild common adverse events (ß = 1.993) and no severe adverse events (ß = 1.731), demonstrating a positive association with adult vaccine hesitancy. Thus, it warrants specific countermeasures to reduce adult vaccine hesitancy and improve strategies for childhood vaccination.

Epidemiological and co-infection characteristics of common human coronaviruses in Shanghai, 2015-2020: a retrospective observational study.

The coronavirus disease (COVID-19) pandemic is a major challenge worldwide. However, the epidemic potential of common human coronaviruses (HCoVs) remains unclear. This study aimed to determine the epidemiological and co-infection characteristics of common HCoVs in individuals with influenza-like illness (ILI) and severe acute respiratory infection (SARI). This retrospective, observational, multicentre study used data collected from patients admitted to nine sentinel hospitals with ILI and SARI from January 2015 through December 2020 in Shanghai, China. We prospectively tested patients for a total of 22 respiratory pathogens using multi-real-time polymerase chain reaction. Of the 4541 patients tested, 40.37% (1833/4541) tested positive for respiratory pathogens and 3.59% (163/4541) tested positive for common HCoVs. HCoV infection was more common in the non-endemic season for respiratory pathogens (odds ratio: 2.33, 95% confidence interval: 1.64-3.31). HCoV-OC43 (41.72%, 68/163) was the most common type of HCoV detected. The co-infection rate was 31.29% (51/163) among 163 HCoV-positive cases, with HCoV-229E (53.13%, 17/32), the HCoV type that was most frequently associated with co-infection. Respiratory pathogens responsible for co-infections with HCoVs included parainfluenza virus, rhinovirus/enterovirus, influenza A virus, and adenovirus. Furthermore, we identified one patient co-infected with HCoV-OC43 and HCoV-NL63/HKU1. The prevalence of common HCoVs remains low in ILI/SARI cases, in Shanghai. However, the seasonal pattern of HCoVs may be opposite to that of other respiratory pathogens. Moreover, HCoVs are likely to co-exist with specific respiratory pathogens. The potential role of co-infections with HCoVs and other pathogenic microorganisms in infection and pathogenesis of ILI and SARI warrants further study.

COVID-19 vaccine coverage, concerns, and preferences among Chinese ICU clinicians: a nationwide online survey.

BACKGROUND: Clinicians in intensive care units (ICUs) have been prioritized for COVID-19 vaccination. We aim to understand the reasons behind vaccination refusal, and assess preferences for COVID-19 vaccines among Chinese ICU clinicians. RESEARCH DESIGN AND METHODS: ICU clinicians throughout China's mainland were contacted to participate in an online survey. We compared concerns with vaccination status, and through a discrete choice experiment (DCE) assessed preferences for vaccines in terms of effectiveness, risk of adverse reactions, duration of immunity, and whether coworkers have been vaccinated. RESULTS: Among 11,951 ICU respondents from 252 prefecture-level regions, vaccination coverage was 75.4%, with an additional 9.2% not vaccinated but intending to, and 16.1% not vaccinated and not intending to. ICU clinicians not intending to be vaccinated significantly expressed more concerns about the speed of vaccine development (30.1%) and adverse reactions (65.9%). In the DCE, the only significant difference in preferences of a COVID-19 vaccine was for safety, with those not intending to have a stronger preference for a vaccine with fewer adverse reactions (OR = 4.49), compared to those already vaccinated (OR = 2.90) or those intending to vaccinate (OR = 3.46). CONCLUSION: Increasing vaccination coverage among Chinese ICU clinicians will require strong norms surrounding vaccination and transparency about safety information.

Association of coagulation dysfunction with cardiac injury among hospitalized patients with COVID-19.

Cardiac injury is a common complication of the coronavirus disease 2019 (COVID-19), and is associated with adverse clinical outcomes. In this study, we aimed to reveal the association of cardiac injury with coagulation dysfunction. We enrolled 181 consecutive patients who were hospitalized with COVID-19, and studied the clinical characteristics and outcome of these patients. Cardiac biomarkers high-sensitivity troponin I (hs-cTnI), myohemoglobin and creatine kinase-myocardial band (CK-MB) were assessed in all patients. The clinical outcomes were defined as hospital discharge or death. The median age of the study cohort was 55 (IQR, 46-65) years, and 102 (56.4%) were males. Forty-two of the 181 patients (23.2%) had cardiac injury. Old age, high leukocyte count, and high levels of aspartate transaminase (AST), D-dimer and serum ferritin were significantly associated with cardiac injury. Multivariate regression analysis revealed old age and elevated D-dimer levels as being strong risk predictors of in-hospital mortality. Interleukin 6 (IL6) levels were comparable in patients with or without cardiac injury. Serial observations of coagulation parameters demonstrated highly synchronous alterations of D-dimer along with progression to cardiac injury. Cardiac injury is a common complication of COVID-19 and is an independent risk factor for in-hospital mortality. Old age, high leukocyte count, and high levels of AST, D-dimer and serum ferritin are significantly associated with cardiac injury, whereas IL6 are not. Therefore, the pathogenesis of cardiac injury in COVID-19 may be primarily due to coagulation dysfunction along with microvascular injury.

Surface electrocardiographic characteristics in coronavirus disease 2019: repolarization abnormalities associated with cardiac involvement.

AIMS: The coronavirus disease 2019 (COVID-19) has spread rapidly around the globe, causing significant morbidity and mortality. This study aims to describe electrocardiographic (ECG) characteristics of COVID-19 patients and to identify ECG parameters that are associated with cardiac involvement. METHODS AND RESULTS: The study included patients who were hospitalized with COVID-19 diagnosis and had cardiac biomarker assessments and simultaneous 12-lead surface ECGs. Sixty-three hospitalized patients (median 53 [inter-quartile range, 43-65] years, 76.2% male) were enrolled, including patients with (n = 23) and without (n = 40) cardiac injury. Patients with cardiac injury were older, had more pre-existing co-morbidities, and had higher mortality than those without cardiac injury. They also had prolonged QTc intervals and more T wave changes. Logistic regression model identified that the number of abnormal T waves (odds ratio (OR), 2.36 [95% confidence interval (CI), 1.38-4.04], P = 0.002) and QTc interval (OR, 1.31 [95% CI, 1.03-1.66], P = 0.027) were independent indicators for cardiac injury. The combination model of these two parameters along with age could well discriminate cardiac injury (area the under curve 0.881, P < 0.001) by receiver operating characteristic analysis. Cox regression model identified that the presence of T wave changes was an independent predictor of mortality (hazard ratio, 3.57 [1.40, 9.11], P = 0.008) after adjustment for age. CONCLUSIONS: In COVID-19 patients, presence of cardiac injury at admission is associated with poor clinical outcomes. Repolarization abnormalities on surface ECG such as abnormal T waves and prolonged QTc intervals are more common in patients with cardiac involvement and can help in further risk stratification.