COVID-19 vaccine uptake and hesitancy in Chinese patients with asthma.

OBJECTIVE: Both patients and physicians may be hesitant toward vaccination in patients with asthma, which may result in lower vaccine uptake. The aim of this work was to investigate the vaccination rate, the adverse reactions, as well as the factors associated with vaccine acceptance and hesitancy toward COVID-19 vaccination among asthmatic patients in Beijing. METHODS: A multi-center, cross-sectional face-to-face survey was conducted in patients with asthma consecutively recruited from December 2021 to April 2022. The survey included asthma status, COVID-19 vaccine uptake and adverse reactions, and knowledge of and attitude toward COVID-19 vaccination. RESULTS: A total of 261 patients were enrolled. The rate of COVID-19 vaccination during the study period was 73.6%, as compared to 87.64% in the general population in China. Patients who were currently working, had received other vaccines in the past, and had had no adverse reactions to other vaccines, showed a higher rate of COVID-19 vaccination. Patients believing that the vaccination of family members and colleagues had a positive impact on their decision to get vaccinated, were more likely to get the COVID-19 vaccines. The COVID-19 vaccination rate was lower in those with poorly monitored asthma and those using biologic therapies. The adverse effects of COVID-19 vaccines in asthmatic patients were similar to those in the general population. CONCLUSION: The COVID-19 vaccination rate in asthmatic patients was lower than the general population in China. Active measures should be taken to control asthma and increase vaccination rates in these patients.

A comprehensive overview on the transmission, pathogenesis, diagnosis, treatment, and prevention of SARS-CoV-2.

Severe acute respiratory syndrome coronavirus (SARS-CoV) is a single positive-strand RNA virus that is responsible for the current pandemic that the world has been facing since 2019. The primary route of transmission of SARS-CoV-2 is through respiratory tract transmission. However, other transmission routes such as fecal-oral, vertical transmission, and aerosol-eye also exist. In addition, it has been found that the pathogenesis of this virus involves the binding of the virus's S protein to its host cell surface receptor angiotensin-converting enzyme 2, which results in the subsequent membrane fusion that is required for SARS-CoV-2 to replicate and complete its entire life. The clinical symptoms of patients infected with SARS-CoV-2 can range from asymptomatic to severe. The most common symptoms seen include fever, dry cough, and fatigue. Once these symptoms are observed, a nucleic acid test is done using reverse transcription-polymerase chain reaction. This currently serves as the main confirmatory tool for COVID-19. Despite the fact that no cure has been found for SARS-CoV-2, prevention methods such as vaccines, specific facial mask, and social distancing have proven to be quite effective. It is imperative to have a complete understanding of the transmission and pathogenesis of this virus. To effectively develop new drugs as well as diagnostic tools, more knowledge about this virus would be needed.

Pneumonia During the COVID-19 Pandemic in Hubei Province, China: a Case Report of Mucormycosis.

BACKGROUND: Mucor infection cannot be ignored in patients with pulmonary shadowing with cavitation. This paper reports a case of mucormycosis during the COVID-19 pandemic in Hubei Province, China. METHODS: An anesthesiology doctor was initially diagnosed as COVID-19 due to changes in lung imaging. After anti-infective, anti-viral, and symptomatic supportive treatment, some of symptoms were relieved. But some symptoms -'chest pain and discomfort', accompanied by chest sulking and short breath after activities, did not ease. At last, Lichtheimia ramose was detected later by metagenomic next generation sequencing (mNGS) in the bronchoalveolar lavage fluid (BALF). RESULTS: After adjusting amphotericin B for anti-infective treatment, the patient's infection lesions were shrunk and the symptoms were significantly relieved. CONCLUSIONS: The diagnosis of invasive fungal infections is very difficult, and mNGS can make an accurate pathogenic diagnosis of invasive fungal diseases for the clinic and provide a basis for clinical treatment.

Exploring m6A-RNA methylation as a potential therapeutic strategy for acute lung injury and acute respiratory distress syndrome.

N6-methyladenosine (m6A) is the most common methylation modification in mammalian messenger RNA (mRNA) and noncoding RNAs. m6A modification plays a role in the regulation of gene expression and deregulation of m6A methylation has been implicated in many human diseases. Recent publications suggest that exploitation of this methylation process may possess utility against acute lung injury (ALI). ALI and its more severe form, acute respiratory distress syndrome (ARDS) are acute, inflammatory clinical syndromes characterized by poor oxygenation and diffuse pulmonary infiltrates. This syndrome is associated with microvascular endothelial dysfunction, subsequent pulmonary hypertension and may ultimately lead to mortality without rigorous and acute clinical intervention. Over the years, many attempts have been made to detect novel therapeutic avenues for research without much success. The urgency for the discovery of novel therapeutic agents has become more pronounced recently given the current pandemic infection of coronavirus disease 2019 (COVID-2019), still ongoing at the time that this review is being written. We review the current landscape of literature regarding ALI and ARDS etiology, pathophysiology, and therapeutics and present a potential role of m6A methylation. Additionally, we will establish the axiomatic principles of m6A methylation to provide a framework. In conclusion, METTL3, or methyltransferase-like 3, the selective RNA methyltransferase for m6A, is a hub of proinflammatory gene expression regulation in ALI, and using a modern drug discovery strategy will identify new and effective ALI drug candidates targeting METTTL3.

Cryo-EM structure of S-Trimer, a subunit vaccine candidate for COVID-19.

Within a year after its emergence, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over 100 million people worldwide with a death toll over 2 million. Vaccination remains the best hope to ultimately put this pandemic to an end. Here, using Trimer-Tag technology, we produced both wild-type (WT) and furin site mutant (MT) S-Trimers for COVID-19 vaccine studies. Cryo-EM structures of the WT and MT S-Trimers, determined at 3.2 Å and 2.6 Å respectively, revealed that both antigens adopt a tightly closed conformation and their structures are essentially identical to that of the previously solved full-length WT S protein in detergent. The tightly closed conformation is stabilized by fatty acid and polysorbate 80 binding at the receptor binding domains (RBDs) and the N terminal domains (NTDs) respectively. Additionally, we identified an important pH switch in the WT S-Trimer that shows dramatic conformational change and accounts for its increased stability at lower pH. These results validate Trimer-Tag as a platform technology in production of metastable WT S-Trimer as a candidate for COVID-19 subunit vaccine.IMPORTANCEEffective vaccine against SARS-CoV-2 is critical to end the COVID-19 pandemic. Here, using Trimer-Tag technology, we are able to produce stable and large quantities of WT S-Trimer, a subunit vaccine candidate for COVID-19 with high safety and efficacy from animal and Phase 1 clinical trial studies. Cryo-EM structures of the S-Trimer subunit vaccine candidate show that it predominately adopts tightly closed pre-fusion state, and resembles that of the native and full-length spike in detergent, confirming its structural integrity. WT S-Trimer is currently being evaluated in global Phase 2/3 clinical trial. Combining with published structures of the S protein, we also propose a model to dissect the conformation change of the spike protein before receptor binding.

Assessing the impact of COVID-19 on economic recovery: role of potential regulatory responses and corporate liquidity.

We use a variety of organization-level datasets to examine the effectiveness and efficiency of the nations for the coronavirus epidemic. COVID-19 subsidies appear to have saved a significant number of jobs and maintained economic activity during the first wave of the epidemic, according to conclusions drawn from the experiences of EU member countries. General allocation rules may yield near-optimal outcomes in favor of allocation, as firms with high ecological footprints or zombie firms have lower access to government financing than more favorable, commercially owned, and export-inclination firms. Our assumptions show that the pandemic has a considerable negative impact on firm earnings and the percentage of illiquid and non-profitable businesses. Although they are statistically significant, government wage subsidies have a modest impact on corporate losses compared to the magnitude of the economic shock. Larger enterprises, which receive a lesser proportion of the aid, have more room to increase their trade liabilities or liabilities to linked entities. In contrast, according to our estimations, SMEs stand a greater danger of insolvency.

Airborne antibiotic resistome and human health risk in railway stations during COVID-19 pandemic.

Antimicrobial resistance is recognized as one of the greatest public health concerns. It is becoming an increasingly threat during the COVID-19 pandemic due to increasing usage of antimicrobials, such as antibiotics and disinfectants, in healthcare facilities or public spaces. To explore the characteristics of airborne antibiotic resistome in public transport systems, we assessed distribution and health risks of airborne antibiotic resistome and microbiome in railway stations before and after the pandemic outbreak by culture-independent and culture-dependent metagenomic analysis. Results showed that the diversity of airborne antibiotic resistance genes (ARGs) decreased following the pandemic, while the relative abundance of core ARGs increased. A total of 159 horizontally acquired ARGs, predominantly confering resistance to macrolides and aminoglycosides, were identified in the airborne bacteria and dust samples. Meanwhile, the abundance of horizontally acquired ARGs hosted by pathogens increased during the pandemic. A bloom of clinically important antibiotic (tigecycline and meropenem) resistant bacteria was found following the pandemic outbreak. 251 high-quality metagenome-assembled genomes (MAGs) were recovered from 27 metagenomes, and 86 genera and 125 species were classified. Relative abundance of ARG-carrying MAGs, taxonomically assigned to genus of Bacillus, Pseudomonas, Acinetobacter, and Staphylococcus, was found increased during the pandemic. Bayesian source tracking estimated that human skin and anthropogenic activities were presumptive resistome sources for the public transit air. Moreover, risk assessment based on resistome and microbiome data revealed elevated airborne health risks during the pandemic.

Application of deep learning-based diagnostic systems in screening asymptomatic COVID-19 patients among oversea returnees.

INTRODUCTION: Our study aimed to investigate the performance of deep learning (DL)-based diagnostic systems in alerting against COVID-19, especially among asymptomatic individuals coming from overseas, and to analyze the features of identified asymptomatic patients in detail. METHODOLOGY: DL diagnostic systems were deployed to assist in the screening of COVID-19, including the pneumonia system and pulmonary nodules system. 1,917 overseas returnees who underwent CT examination and rRT-PCR tests were enrolled. DL pneumonia system promptly alerted clinicians to suspected COVID-19 after CT examinations while the performance was evaluated with rRT-PCR results as the reference. The radiological features of asymptomatic COVID-19 cases were described according to the Nomenclature of the Fleischner Society. RESULTS: Fifty-three cases were confirmed as COVID-19 patients by rRT-PCR tests, including 5 asymptomatic cases. DL pneumonia system correctly alerted 50 cases as suspected COVID-19 with a sensitivity of 0.9434 and specificity of 0.9592 (within 2 minutes per case); while the pulmonary nodules system alerted 2 of the 3 missed asymptomatic cases. Additionally, five asymptomatic patients presented different characteristics such as elevated creatine kinase level and prolonged prothrombin time, as well as atypical radiological features. CONCLUSIONS: DL diagnostic systems are promising complementary approaches for prompt screening of imported COVID-19 patients, even the imported asymptomatic cases. Unique clinical and radiological characteristics of asymptomatic cases might be of great value in screening as well. ADVANCES IN KNOWLEDGE: DL-based systems are practical, efficient, and reliable to assist radiologists in screening COVID-19 patients. Differential features of asymptomatic patients might be useful to clinicians in the frontline to differentiate asymptomatic cases.

Successful Treatment of Subacute Thyroiditis After Recombinant COVID-19 Vaccination Using Traditional Chinese Medicine: A Case Report.

Subacute thyroiditis (SAT) is a thyroid inflammatory disease, which can be triggered by viral infection. The severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is considered to be a potent SAT-triggering factor in this COVID-19 pandemic. However, SAT occurring after SARS-CoV-2 vaccination is rarely reported. Despite the high availability of diagnostic tools, the recurrence and steroid dependence as well as delayed diagnosis of SAT remain. This paper reports a rare case where a patient was diagnosed with SAT post receiving a recombinant novel coronavirus vaccine (Anhui Zhifei Longcom Biopharmaceutical Co.Ltd., China), and efficiently treated with traditional Chinese medicine rather than prednisone. We hope that this case report not only contributes to raising awareness of SAT related to the COVID-19 vaccine but also provides an effective remedy in addition to glucocorticoid (GC).

A systematic review of current status and challenges of vaccinating children against SARS-CoV-2.

The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has inflicted immense damage to countries, economies and societies worldwide. Authorized COVID-19 vaccines based on different platforms have been widely inoculated in adults, showing up to 100% immunogenicity with significant efficacy in preventing SARS-CoV-2 infections and the occurrence of severe COVID-19. It has also greatly slowed the evolution of SARS-CoV-2 variants, as shown in clinical trials and real-world evidence. However, the total dosage of COVID-19 vaccines for children is much smaller than that for adults due to limitations from parental concern of vaccine safety, presenting a potential obstacle in ending the COVID-19 pandemic. SARS-CoV-2 not only increases the risk of severe multisystem inflammatory syndrome (MIS-C) in children, but also negatively affects children's psychology and academics, indirectly hindering the maintenance and progress of normal social order. Therefore, this article examines the clinical manifestations of children infected with SARS-CoV-2, the status of vaccination against COVID-19 in children, vaccination-related adverse events, and the unique immune mechanisms of children. In particular, the necessity and challenges of vaccinating children against SARS-CoV-2 were highlighted from the perspectives of society and family. In summary, parental hesitancy is unnecessary as adverse events after COVID-19 vaccination have been proven to be infrequent, comprise of mild symptoms, and have a good prognosis.

Identifying factors contributing to increased susceptibility to COVID-19 risk: a systematic review of Mendelian randomization studies.

BACKGROUND: To summarize modifiable factors for coronavirus disease 2019 (COVID-19) suggested by Mendelian randomization studies. METHODS: In this systematic review, we searched PubMed, EMBASE and MEDLINE, from inception to 15 November 2021, for Mendelian randomization studies in English. We selected studies that assessed associations of genetically predicted exposures with COVID-19-related outcomes (severity, hospitalization and susceptibility). Risk of bias of the included studies was evaluated based on the consideration of the three main assumptions for instrumental variable analyses. RESULTS: We identified 700 studies through systematic search, of which 50 Mendelian randomization studies were included. Included studies have explored a wide range of socio-demographic factors, lifestyle attributes, anthropometrics and biomarkers, predisposition to diseases and druggable targets in COVID-19 risk. Mendelian randomization studies suggested that increases in smoking, obesity and inflammatory factors were associated with higher risk of COVID-19. Predisposition to ischaemic stroke, combined bipolar disorder and schizophrenia, attention-deficit and hyperactivity disorder, chronic kidney disease and idiopathic pulmonary fibrosis was potentially associated with higher COVID-19 risk. Druggable targets, such as higher protein expression of histo-blood group ABO system transferase (ABO), interleukin (IL)-6 and lower protein expression of 2'-5' oligoadenylate synthetase 1 (OAS1) were associated with higher risk of COVID-19. There was no strong genetic evidence supporting the role of vitamin D, glycaemic traits and predisposition to cardiometabolic diseases in COVID-19 risk. CONCLUSION: This review summarizes modifiable factors for intervention (e.g. smoking, obesity and inflammatory factors) and proteomic signatures (e.g. OAS1 and IL-6) that could help identify drugs for treating COVID-19.

SARS-CoV-2 RNA elements share human sequence identity and upregulate hyaluronan via NamiRNA-enhancer network.

BACKGROUND: Since late 2019, SARS-CoV-2 infection has resulted in COVID-19 accompanied by diverse clinical manifestations. However, the underlying mechanism of how SARS-CoV-2 interacts with host and develops multiple symptoms is largely unexplored. METHODS: Bioinformatics analysis determined the sequence similarity between SARS-CoV-2 and human genomes. Diverse fragments of SARS-CoV-2 genome containing Human Identical Sequences (HIS) were cloned into the lentiviral vector. HEK293T, MRC5 and HUVEC were infected with laboratory-packaged lentivirus or transfected with plasmids or antagomirs for HIS. Quantitative RT-PCR and chromatin immunoprecipitation assay detected gene expression and H3K27ac enrichment, respectively. UV-Vis spectroscopy assessed the interaction between HIS and their target locus. Enzyme-linked immunosorbent assay evaluated the hyaluronan (HA) levels of culture supernatant and plasma of COVID-19 patients. FINDINGS: Five short sequences (24-27 nt length) sharing identity between SARS-CoV-2 and human genome were identified. These RNA elements were highly conserved in primates. The genomic fragments containing HIS were predicted to form hairpin structures in silico similar to miRNA precursors. HIS may function through direct genomic interaction leading to activation of host enhancers, and upregulation of adjacent and distant genes, including cytokine genes and hyaluronan synthase 2 (HAS2). HIS antagomirs and Cas13d-mediated HIS degradation reduced HAS2 expression. Severe COVID-19 patients displayed decreased lymphocytes and elevated D-dimer, and C-reactive proteins, as well as increased plasma hyaluronan. Hymecromone inhibited hyaluronan production in vitro, and thus could be further investigated as a therapeutic option for preventing severe outcome in COVID-19 patients. INTERPRETATION: HIS of SARS-CoV-2 could promote COVID-19 progression by upregulating hyaluronan, providing novel targets for treatment. FUNDING: The National Key R&D Program of China (2018YFC1005004), Major Special Projects of Basic Research of Shanghai Science and Technology Commission (18JC1411101), and the National Natural Science Foundation of China (31872814, 32000505).

Suicidal Ideation and Mental Health Help-Seeking Behaviors Among Older Chinese Adults During the COVID-19 Pandemic.

OBJECTIVE: To examine prevalence and correlates of suicidal ideation in older Chinese adults (OCAs) during the COVID-19 pandemic, as well as mental health help-seeking behaviors of suicidal OCAs. BACKGROUND: Few data on suicidal behaviors of older adults during the pandemic are available. METHODS: In this cross-sectional survey, 1159 OCAs completed an online self-administered questionnaire between 23 February and 25 March 2020. A standardized single question and the 12-item General Health Questionnaire were used to assess the presence of suicidal ideation and common mental health problems (CMHPs), respectively. Suicidal ideators were further asked about their perceived need for mental health care and help-seeking from mental health workers. RESULTS: 4.1% of the OCAs experienced suicidal ideation during the past 2 weeks. Among the suicidal OCAs, 31.9% perceived a need for mental health care but only 10.6% had sought help from mental health workers. Factors significantly associated with suicidal ideation were a marital status of "others" (OR=2.39, P = .021), disagreement regarding the successful containment of the pandemic (OR=2.43, P = .022), physical health problems (OR=2.23, P = .012), and CMHPs (OR=4.99, P < .001). CONCLUSIONS: During the COVID-19 pandemic, OCAs constitute a subpopulation that needs mental health services for suicidal problems but tends not to seek mental health help. Mental health services for OCAs may include mental health education, periodic evaluation of risk of suicide, expanded psychosocial support, and, when necessary, psychological crisis intervention and psychiatric treatment.

A systematic review of Vaccine Breakthrough Infections by SARS-CoV-2 Delta Variant.

Vaccines are proving to be highly effective in controlling hospitalization and deaths associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, as shown by clinical trials and real-world evidence. However, a deadly second wave of coronavirus disease 2019 (COVID-19), infected by SARS-CoV-2 variants, especially the Delta (B.1.617.2) variant, with an increased number of post-vaccination breakthrough infections were reported in the world recently. Actually, Delta variant not only resulted in a severe surge of vaccine breakthrough infections which was accompanied with high viral load and transmissibility, but also challenged the development of effective vaccines. Therefore, the biological characteristics and epidemiological profile of Delta variant, the current status of Delta variant vaccine breakthrough infections and the mechanism of vaccine breakthrough infections were discussed in this article. In addition, the significant role of the Delta variant spike (S) protein in the mechanism of immune escape of SARS-CoV-2 was highlighted in this article. In particular, we further discussed key points on the future SARS-CoV-2 vaccine research and development, hoping to make a contribution to the early, accurate and rapid control of the COVID-19 epidemic.

A systematic review of Vaccine Breakthrough Infections by SARS-CoV-2 Delta Variant

Vaccines are proving to be highly effective in controlling hospitalization and deaths associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, as shown by clinical trials and real-world evidence. However, a deadly second wave of coronavirus disease 2019 (COVID-19), infected by SARS-CoV-2 variants, especially the Delta (B.1.617.2) variant, with an increased number of post-vaccination breakthrough infections were reported in the world recently. Actually, Delta variant not only resulted in a severe surge of vaccine breakthrough infections which was accompanied with high viral load and transmissibility, but also challenged the development of effective vaccines. Therefore, the biological characteristics and epidemiological profile of Delta variant, the current status of Delta variant vaccine breakthrough infections and the mechanism of vaccine breakthrough infections were discussed in this article. In addition, the significant role of the Delta variant spike (S) protein in the mechanism of immune escape of SARS-CoV-2 was highlighted in this article. In particular, we further discussed key points on the future SARS-CoV-2 vaccine research and development, hoping to make a contribution to the early, accurate and rapid control of the COVID-19 epidemic.