Global Spread of Carbapenem-Resistant Enterobacteriaceae: Epidemiological Features, Resistance Mechanisms, Detection and Therapy

Summary Bacterial drug resistance has become a global public health threat, among which the infection of carbapenem-resistant Enterobacterales (CRE) is one of the top noticeable issues in the global anti-infection area due to limited therapy options. In recent years, the prevalence of CRE transmission around the world has increased, and the transmission of COVID-19 has intensified the situation to a certain extent. CRE resistance can be induced by carbapenemase, porin, efflux pump, penicillin-binding protein alteration, and biofilm production. Deletion, mutation, insertion, and post-transcriptional modification of corresponding coding genes may affect the sensitivity of Enterobacterales bacteria to carbapenems. Clinical and laboratory methods to detect CRE and explore its resistance mechanisms are being developed. Due to the limited options of antibiotics, the clinical treatment of CRE infection also faces severe challenges. The clinical therapies of CRE include single or combined use of antibiotics, and some new antibiotics and treatment methods are also being developed. Hence, this review summarizes the epidemiology, resistance mechanisms, screening and clinical treatments of CRE infection, to provide references for clinical prevention, control and treatment of CRE infection.

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.

Research and clinical translation progress of SARS-CoV-2 detection approaches based on CRISPR technology

Since the Corona Virus Disease 2019 (COVID-19) caused by the infection of SARS-CoV-2 was first reported in 2019, COVID-19 has spread rapidly around the world, causing serious negative impacts on the daily life and work of people around the world. Recently, several studies on SARS-CoV-2 detection approaches based on Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technology have been reported, showing that CRISPR technology can be used to detect SARS-CoV-2 rapidly, sensitively, specifically, visually and on-site. There are already detection kits based on CRISPR technology in clinical application at home and abroad, and good clinical feedback has been obtained. Therefore, the SARS-CoV-2 detection method based on CRISPR technology is expected to overcome the shortcomings of the existing RT-PCR approach in clinical practice, and replace RT-PCR as the gold standard for the next generation of SARS-CoV-2 nucleic acid detection. In this article, the research and progress of SARS-CoV-2 nucleic acid detection methods based on CRISPR technology are introduced, the principle and clinical application of CRISPR technology are reviewed, and the future development of the technology is prospected in order to promote its clinical transformation speed.

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.

Recent advance of ACE2 and microbiota dysfunction in COVID-19 pathogenesis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the coronavirus disease 2019 (COVID-19) and has become the world's most pressing public health threat. Although not as common as respiratory symptoms, a substantial proportion of patients with COVID-19 presented the gastrointestinal symptoms. ACE2, as the receptor of SARS-CoV and SARS-CoV-2, is highly expressed in the epithelia of the epithelium cells in lung and intestine. In addition, ACE2 is essential for the innate immunity, amino acid transportation and the homeostasis of intestinal microecology. The composition of gut microbiota in COVID-19 patients was altered and concordant with inflammatory, which may explain the gastrointestinal symptoms in patients. Here we reviewed and discussed the evolving role for ACE2 and gut microbiota in SARS-CoV-2 infection which might provide innovative approaches to targeting ACE2 and gut microbiota for the COVID-19 therapy.

CRISPR-Based Approaches for Efficient and Accurate Detection of SARS-CoV-2.

An outbreak of COVID-19, caused by infection with SARS-CoV-2 in Wuhan, China in December 2019, spread throughout the country and around the world, quickly. The primary detection technique for SARS-CoV-2, the reverse-transcription polymerase chain reaction (RT-PCR)-based approach, requires expensive reagents and equipment and skilled personnel. In addition, for SARS-CoV-2 detection, specimens are usually shipped to a designated laboratory for testing, which may extend the diagnosis and treatment time of patients with COVID-19. The latest research shows that clustered regularly interspaced short palindromic repeats (CRISPR)-based approaches can quickly provide visual, rapid, ultrasensitive, and specific detection of SARS-CoV-2 at isothermal conditions. Therefore, CRISPR-based approaches are expected to be developed as attractive alternatives to conventional RT-PCR methods for the efficient and accurate detection of SARS-CoV-2. Recent advances in the field of CRISPR-based biosensing technologies for SARS-CoV-2 detection and insights into their potential use in many applications are reviewed in this article.

SARS-CoV-2 vaccine candidates in rapid development.

The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still spreading globally. The scientific community is attempting to procure an effective treatment and prevention strategy for COVID-19. A rising number of vaccines for COVID-19 are being developed at an unprecedented speed. Development platforms include traditional inactivated or live attenuated virus vaccines, DNA or RNA vaccines, recombinant viral vector vaccines, and protein or peptide subunit vaccines. There are 23 vaccines in the clinical evaluation stage and at least 140 candidate vaccines in preclinical evaluation. In this review, we describe research regarding basic knowledge on the virus, updates on the animal models, current landscape of vaccines in clinical evaluation and updated research results on vaccine development. Safe and effective COVID-19 vaccines require further investigation.

Prokaryotic expression of affinity peptides to spike protein of transmissible gastroenteritis virus

Objective: Prokaryotic expression of affinity peptides to spike protein of transmissible gastroenteritis virus (TGEV) and analysis of viral affinity activity were conducted to provide basis for establishment of TGEV diagnostic methods. Method: In this study, a tandem gene containing the TGEV spike protein affinity peptide was synthesized. After sub-cloning, the gene was inserted into prokaryotic expression vectors of pET-32a and pGEX-6p-1 to obtain recombinant plasmids pET-32a-SQHT and pGEX-6p-SQHT. The recombinant plasmids were identified by single enzyme digestion of BamH I, double enzyme digestion of BamH I/Xho I and sequencing. Then, the recombinant plasmids were transformed into E. coli Rosetta (DE3) and induced by IPTG to obtain the expression of recombinant protein. Finally, the biological activity of expression products was measured. Result: A gene about 150 bp of TGEV spike protein affinity peptide was obtained by sub-cloning. Two recombinant plasmids, pET-32a-SQHT and pGEX-6p-SQHT, were constructed and expressed by induction successfully. The molecular weights of the two recombinant proteins were 25 and 31 ku, respectively. Western blot analysis showed that the two recombinant proteins had good affinity with TGEV virions. Dot-ELISA analysis showed that the minimum binding titer of the two recombinant proteins binding to the TGEV virions was TCID sub 50 /sub 5x10 sup 2 /sup mL sup -1 /sup . Specificity experiments showed that the recombinant proteins TRX-SQHT and GST SQHT did not bind to PEDV or PoRV.