The clinical significance of macrolide resistance in pediatric Mycoplasma pneumoniae infection during COVID-19 pandemic.

Background: Mycoplasma pneumoniae (MP) is a commonly occurring pathogen causing community-acquired pneumonia (CAP) in children. The global prevalence of macrolide-resistant MP (MRMP) infection, especially in Asian regions, is increasing rapidly. However, the prevalence of MRMP and its clinical significance during the COVID-19 pandemic is not clear. Methods: This study enrolled children with molecularly confirmed macrolide-susceptible MP (MSMP) and MRMP CAP from Beijing Children's Hospital Baoding Hospital, Capital Medical University between August 2021 and July 2022. The clinical characteristics, laboratory findings, chest imaging presentations, and strain genotypes were compared between patients with MSMP and MRMP CAP. Results: A total of 520 hospitalized children with MP-CAP were enrolled in the study, with a macrolide resistance rate of 92.7%. Patients with MRMP infection exhibited more severe clinical manifestations (such as dyspnea and pleural effusion) and had a longer hospital stay than the MSMP group. Furthermore, abnormal blood test results (including increased LDH and D-dimer) were more common in the MRMP group (P<0.05). Multilocus variable-number tandem-repeat analysis (MLVA) was performed on 304 samples based on four loci (Mpn13-16), and M3562 and M4572 were the major types, accounting for 74.0% and 16.8% of the strains, respectively. The macrolide resistance rate of M3562 strains was up to 95.1%. Conclusion: The prevalence of MRMP strains in hospitalized CAP patients was extremely high in the Baoding area, and patients infected with MRMP strains exhibited more severe clinical features and increased LDH and D-dimer. M3562 was the predominant resistant clone.

Experts' consensus on severe acute respiratory syndrome coronavirus-2 vaccination of children.

At present, severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)infection is still rampant worldwide.As of September 10, 2021, there were about 222 million confirmed cases of corona virus disease 2019(COVID-19)and more than 4.6 million deaths worldwide.With the development of COVID-19 vaccines and the gradual vaccination worldwide, the increasing number of cases in children and unvaccinated young people has drawn attention.According to World Health Organization surveillance data, the proportion of COVID-19 infection cases in children gradually increased, and the proportion of cases in the age groups of under 5 years and 5-14 years increased from 1.0% and 2.5% in January 2020 to 2.0% and 8.7% in July 2021, respectively.At present, billions of adults have been vaccinated with various COVID-19 vaccines worldwide, and their protective effects including reducing infection and transmission, reducing severe disease and hospitalization, and reducing death, as well as high safety have been confirmed.Canada, the United States, Europe and other countries have approved the emergency COVID-19 vaccination in children and adolescents aged 12 to 17 years, and China has also approved the phased vaccination of COVID-19 vaccination in children and adolescents aged 3 to 17 years. For smooth advancement and implementation of COVID-19 vaccination in children, academic institutions, including National Clinical Research Center for Respiratory Diseases, National Center for Children's Health, and The Society of Pediatrics, Chinese Medical Association organized relevant experts to reach this consensus on COVID-19 vaccination in children.Copyright © 2021 by the Chinese Medical Association.

Twenty key issues on severe acute respiratory syndrome coronavirus-2 vaccination in children.

Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)infection is still worldwide.As a vulnerable group, severe and dead pediatric cases are also reported.Under this severe epidemic situation, children should be well protected.With the widespread vaccination of SARS-CoV-2 vaccine in adults, the infection rate have decreased.Therefore, SARS-CoV-2 vaccine inoculation for children groups step by step is of great significance to the protection of children and the prevention and control of corona virus disease 2019(COVID-19) as a whole.But the safety of children vaccinated with SARS-CoV-2 vaccine is a main concern of parents.Therefore, in order to ensure the safety of vaccination and the implementation of vaccination work, National Clinical Research Center for Respiratory Diseases, National Center for Children's Health and the Society of Pediatrics, Chinese Medical Association organized experts to interpret the main issue of parents about SARS-CoV-2 vaccine for children, in order to answer the doubts of parents.Copyright © 2021 by the Chinese Medical Association.

Global spread of carbapenem-resistant Enterobacteriaceae: Epidemiological features, resistance mechanisms, detection and therapy

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. © 2022 Elsevier GmbH

Lower doses of self-amplifying mRNA drive superior neoantigen-specific CD8 T cell responses in cancer patients versus high doses

The immunogenicity and efficacy of RNA-based vaccine platforms has been abundantly shown through their application in prophylactic SARS-CoV2 vaccines. Contrasting to mRNA based vectors, self amplifying mRNA platforms may offer dose-sparing and superior induction of T cell responses, and may also trigger distinct innate immune pathways, which may exert adjuvanting or inhibiting effects on vaccine-induced immunity. Optimal dosing for a novel self-amplifying mRNA (SAM) in a heterologous prime-boost vaccination approach consisting of Chimpanzee Adenovirus (ChAd) prime and SAM boosts was evaluated in two first-in-human phase 1/2 clinical trials assessing personalized neoantigen vaccines in patients with metastatic cancer (NCT03639714, NCT03953235). SAM vaccine dose escalation was performed to assess safety, tolerability, and immunogenicity, including administration of up to 8 SAM doses at 30, 100, or 300μg following a fixed dose of ChAd (1012 vp) over the course of a year. SAM was safe and well tolerated at all 3 dose levels, with no evidence of increasing reactogenicity with sequential doses. However, while immune monitoring via IFNγ ELISpot revealed that the 30μg SAM dose boosted T cell responses induced by the ChAd prime, the 100μg and 300μg SAM doses resulted in maintenance of T cell levels, without a clear T cell boost, suggesting a non-linear and likely bell-shaped dose-response curve to SAM in humans. Follow-up studies in non-human primates (NHPs) using a model antigen revealed dose-dependent increases in serum IFNa levels following administration of increasing SAM doses. Similarly, while multiple inflammatory cytokines were transiently increased following both ChAd and SAM administration in patients, serum IFNa levels were only increased 24h post SAM administration and correlated positively with SAM dose. Increased IFNa levels post SAM dosing suggested activation of mRNA-sensing innate immune pathways that may reduce the amplification of, and/or antigen expression by, the SAM vector and thus blunt T cell boosting at higher SAM doses. In addition, analysis of T cell responses in patients and NHPs showed increased boosting of T cell responses with longer intervals. These data lead to a reduction of the SAM dose to 30μg and adjusting SAM dosing intervals to 8 weeks in the Phase 2 portion of these clinical studies. Multiple patients have been dosed with the adjusted vaccine regimen, and preliminary data suggest robust boosting of ChAd-induced neoantigen-specific T cell responses with the selected SAM dosing regimen and the 30μg dose. We anticipate that this translational approach of adjusting clinical vaccine regimens based on strong translational immune data will increase the potency of our heterologous neoantigen vaccine, and subsequently provide more durable clinical benefit to patients with cancer.

Acute myocarditis following covid-19 mrna vaccination

Introduction: Acute myocarditis after coronavirus disease 2019 (COVID-19) mRNA vaccination is not well described. Recent public reports have signaled that this is an entity that requires ongoing surveillance. The goal of this study is to investigate myocarditis incidence following COVID-19 mRNA vaccination, and to report the clinical course and outcomes. Methods: This is a retrospective population-based cohort study performed at Kaiser Permanente Southern California (KPSC), an integrated health care system in California. Patients who received at least one dose of BNT162b2 (Pfizer) or mRNA-1273 (Moderna) mRNA vaccine were included. Clinically significant cases of acute myocarditis within 10 days of COVID-19 mRNA vaccination were identified between 12/14/2020 and 5/31/2021. Key demographic, clinical, laboratory, diagnostic data, and clinical course were obtained from medical record review. Results: Of 1,776,608 KPSC members who received at least one dose of COVID-19 mRNA vaccines, 12 developed acute myocarditis within 10 days following vaccination, for an estimated incidence of 6.6 cases per 1 million patients. All patients were relatively healthy White or Hispanic men between the ages of 18 and 40 years. Patients reported chest pain two to eight days after vaccine administration (Moderna N=5;Pfizer N=7). Eleven patients developed myocarditis after the second dose, and one after the first dose. Troponin I elevations ranged from 1.53-32.30 ng/mL. All cases were self-limited, with troponin peaking within 24-48 hours of admission and symptom resolution prior to discharge. None of the patients had evidence of decompensated heart failure. Length of stay was 1-4 days, with all patients discharged home and no recurrence, readmission, or major adverse cardiac events. Conclusions: Acute myocarditis after COVID-19 mRNA vaccination is a rare and self-limited event that warrants further description and investigation.

Twenty key issues on severe acute respiratory syndrome coronavirus-2 vaccination in children

Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)infection is still worldwide.As a vulnerable group, severe and dead pediatric cases are also reported.Under this severe epidemic situation, children should be well protected.With the widespread vaccination of SARS-CoV-2 vaccine in adults, the infection rate have decreased.Therefore, SARS-CoV-2 vaccine inoculation for children groups step by step is of great significance to the protection of children and the prevention and control of corona virus disease 2019(COVID-19) as a whole.But the safety of children vaccinated with SARS-CoV-2 vaccine is a main concern of parents.Therefore, in order to ensure the safety of vaccination and the implementation of vaccination work, National Clinical Research Center for Respiratory Diseases, National Center for Children's Health and the Society of Pediatrics, Chinese Medical Association organized experts to interpret the main issue of parents about SARS-CoV-2 vaccine for children, in order to answer the doubts of parents. Copyright © 2021 by the Chinese Medical Association.

Experts' consensus on severe acute respiratory syndrome coronavirus-2 vaccination of children

At present, severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)infection is still rampant worldwide.As of September 10, 2021, there were about 222 million confirmed cases of corona virus disease 2019(COVID-19)and more than 4.6 million deaths worldwide.With the development of COVID-19 vaccines and the gradual vaccination worldwide, the increasing number of cases in children and unvaccinated young people has drawn attention.According to World Health Organization surveillance data, the proportion of COVID-19 infection cases in children gradually increased, and the proportion of cases in the age groups of under 5 years and 5-14 years increased from 1.0% and 2.5% in January 2020 to 2.0% and 8.7% in July 2021, respectively.At present, billions of adults have been vaccinated with various COVID-19 vaccines worldwide, and their protective effects including reducing infection and transmission, reducing severe disease and hospitalization, and reducing death, as well as high safety have been confirmed.Canada, the United States, Europe and other countries have approved the emergency COVID-19 vaccination in children and adolescents aged 12 to 17 years, and China has also approved the phased vaccination of COVID-19 vaccination in children and adolescents aged 3 to 17 years. For smooth advancement and implementation of COVID-19 vaccination in children, academic institutions, including National Clinical Research Center for Respiratory Diseases, National Center for Children's Health, and The Society of Pediatrics, Chinese Medical Association organized relevant experts to reach this consensus on COVID-19 vaccination in children. Copyright © 2021 by the Chinese Medical Association.