Evaluation of Clinical and Immune Responses in Recovered Children with Mild COVID-19.

The coronavirus disease 2019 (COVID-19) has spread globally and variants continue to emerge, with children are accounting for a growing share of COVID-19 cases. However, the establishment of immune memory and the long-term health consequences in asymptomatic or mildly symptomatic children after severe acute respiratory syndrome coronavirus 2 infection are not fully understood. We collected clinical data and whole blood samples from discharged children for 6-8 months after symptom onset among 0-to-14-year-old children. Representative inflammation signs returned to normal in all age ranges. The infants and young children (0-4 years old) had lung lesions that persisted for 6-8 months and were less responsive for antigen-specific IgG secretion. In the 5-to-14-year-old group, lung imaging abnormalities gradually recovered, and the IgG-specific antibody response was strongest. In addition, we found a robust IgM+ memory B cell response in all age. Memory T cells specific for the spike or nucleocapsid protein were generated, with no significant difference in IFN-γ response among all ages. Our study highlights that although lung lesions caused by COVID-19 can last for at least 6-8 months in infants and young children, most children have detectable residual neutralizing antibodies and specific cellular immune responses at this stage.

The SARS-CoV-2 Nucleocapsid Protein and Its Role in Viral Structure, Biological Functions, and a Potential Target for Drug or Vaccine Mitigation.

The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the world is still expanding. Thus, there is an urgent need to better understand this novel virus and find a way to control its spread. Like other coronaviruses, the nucleocapsid (N) protein is one of the most crucial structural components of SARS-CoV-2. This protein shares 90% homology with the severe acute respiratory syndrome coronavirus N protein, implying functional significance. Based on the evolutionary conservation of the N protein in coronavirus, we reviewed the currently available knowledge regarding the SARS-CoV-2 N protein in terms of structure, biological functions, and clinical application as a drug target or vaccine candidate.

The self-assembled nanoparticle-based trimeric RBD mRNA vaccine elicits robust and durable protective immunity against SARS-CoV-2 in mice.

As COVID-19 continues to spread rapidly worldwide and variants continue to emerge, the development and deployment of safe and effective vaccines are urgently needed. Here, we developed an mRNA vaccine based on the trimeric receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein fused to ferritin-formed nanoparticles (TF-RBD). Compared to the trimeric form of the RBD mRNA vaccine (T-RBD), TF-RBD delivered intramuscularly elicited robust and durable humoral immunity as well as a Th1-biased cellular response. After further challenge with live SARS-CoV-2, immunization with a two-shot low-dose regimen of TF-RBD provided adequate protection in hACE2-transduced mice. In addition, the mRNA template of TF-RBD was easily and quickly engineered into a variant vaccine to address SARS-CoV-2 mutations. The TF-RBD multivalent vaccine produced broad-spectrum neutralizing antibodies against Alpha (B.1.1.7) and Beta (B.1.351) variants. This mRNA vaccine based on the encoded self-assembled nanoparticle-based trimer RBD provides a reference for the design of mRNA vaccines targeting SARS-CoV-2.

The Rapid Assessment and Early Warning Models for COVID-19.

Human beings have experienced a serious public health event as the new pneumonia (COVID-19), caused by the severe acute respiratory syndrome coronavirus has killed more than 3000 people in China, most of them elderly or people with underlying chronic diseases or immunosuppressed states. Rapid assessment and early warning are essential for outbreak analysis in response to serious public health events. This paper reviews the current model analysis methods and conclusions from both micro and macro perspectives. The establishment of a comprehensive assessment model, and the use of model analysis prediction, is very efficient for the early warning of infectious diseases. This would significantly improve global surveillance capacity, particularly in developing regions, and improve basic training in infectious diseases and molecular epidemiology.

Analysis of ACE2 Gene-Encoded Proteins Across Mammalian Species.

Human beings are currently experiencing a serious public health event. Novel coronavirus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus (SARS-CoV-2), has infected about 3 million people worldwide and killed more than 200,000, most being the elderly or people with potential chronic diseases or in immunosuppressive states. According to big data analysis, there are many proteins homologous to or interacting with the angiotensin-converting enzyme 2 (ACE2), which, therefore, may not be the only receptor for the novel coronavirus; other receptors may also exist in host cells of different species. These potential receptors may also play an important role in the infection process of the novel coronavirus. The current study aimed to discover such key proteins or receptors and analyze the susceptibility of different animals to the novel coronavirus, in order to reveal the transmission process of the virus in cross-species infection. We analyzed the proteins coded by the ACE2 gene in different mammalian species and predicted their correlation and homology with the human ACE2 receptor. The major finding of our predictive analysis suggested ACE2 gene-encoded proteins to be highly homologous across mammals. Based on their high homology, their possibility of binding the spike-protein of SARS-CoV-2 is quite high and species such as Felis catus, Bos taurus, Rattus norvegicus etc. may be potential susceptible hosts; special monitoring is particularly required for livestock that are in close contact with humans. Our results might provide ideas for the prevention and control of the novel coronavirus pneumonia.

Could Environment Affect the Mutation of H1N1 Influenza Virus?

H1N1 subtype influenza A viruses are the most common type of influenza A virus to infect humans. The two major outbreaks of the virus in 1918 and 2009 had a great impact both on human health and social development. Though data on their complete genome sequences have recently been obtained, the evolution and mutation of A/H1N1 viruses remain unknown to this day. Among many drivers, the impact of environmental factors on mutation is a novel hypothesis worth studying. Here, a geographically disaggregated method was used to explore the relationship between environmental factors and mutation of A/H1N1 viruses from 2000-2019. All of the 11,721 geo-located cases were examined and the data was analysed of six environmental elements according to the time and location (latitude and longitude) of those cases. The main mutation value was obtained by comparing the sequence of the influenza virus strain with the earliest reported sequence. It was found that environmental factors systematically affect the mutation of A/H1N1 viruses. Minimum temperature displayed a nonlinear, rising association with mutation, with a maximum ~15 °C. The effects of precipitation and social development index (nighttime light) were more complex, while population density was linearly and positively correlated with mutation of A/H1N1 viruses. Our results provide novel insight into understanding the complex relationships between mutation of A/H1N1 viruses and environmental factors.

Efficacy, acceptability and tolerability of 8 atypical antipsychotics in Chinese patients with acute schizophrenia: A network meta-analysis.

OBJECTIVE: We aimed to create hierarchies of the efficacy, acceptability and tolerability of eight atypical antipsychotics in the treatment of Chinese patients with acute schizophrenia. METHOD: We systematically searched for RCT articles published between January 1st 2005 and December 31st 2014 in electronic databases (Medline, Pubmed, Embase, the Cochrane Library and ClinicalTrial.gov for studies in English and the China National Knowledge Infrastructure, Wan Fang, and VIP Information/Chinese Scientific Journals Database for studies in Chinese). The primary outcome was efficacy, as measured by the change of PANSS total score. Pairwise comparisons were performed using random-effects model by the Dersimonian-Laird method and network meta-analyses were performed in a Bayesian set. RESULTS: Sixty high-quality RCTs with 6418 participants were included. A pattern of superiority from olanzapine, paliperidone and amisulpride was seen in the primary outcome. Only paliperidone was found better than aripiprazole (odds ratio, 0.49 [95% credible intervals, 0.25 to 0.99]), ziprasidone (0.42 [0.21 to 0.85]) and quetiapine (0.36 [0.13 to 0.93]) in terms of all-cause discontinuation. The best and worst drugs in terms of weight gain, EPS and somnolence were aripiprazole and olanzapine, clozapine and amisulpride, aripiprazole and clozapine, respectively. The rank of efficacy did not change substantially in sensitivity analyses or in meta-regressions. CONCLUSION: Our findings provided the hierarchies of eight antipsychotics in efficacy, acceptability and tolerability. These findings are expected to help Chinese clinicians to select the appropriate antipsychotic drug for their patients.

[Mechanism of oral absorption of panaxnotoginseng saponins].

AIM: To study the mechanism of absorption after oral administration of panaxnotoginseng saponins (PNS). METHODS: Caco-2 cells and rat models were applied to evaluate the degradation of both ginsenoside Rb1 (Rb1) and ginsenoside Rg1 (Rg1) in PNS in gastrointestinal lumen, and the transport mechanism of PNS across the intestinal mucosa, and the barrier function of stomach, intestine and liver involved in absorption process. RESULTS: Rb1 and Rg1 proved to be readily eliminated in stomach, but stable in relatively neutral circumstance. Both Rb1 and Rg1 in PNS, especially for Rb1, degraded significantly in the contents of large intestine. However, both of them kept mainly intact in the contents of small intestine. Uptake of both Rb1 and Rg1 by Caco-2 cell monolayer was inhibited at low temperature, but not by cyclosporine A, and the change in the apical pH showed no pronounced effect. Uptake and transport were non-saturable and increased linearly with increasing of concentrations of Rb1 and Rg1 over the range of concentration tested, which indicated a passive transport. There was no significant difference of absorption characteristic between monomer (Rb1 and Rg1) and mixture (PNS). Uptake amount of Rg1 [(1.07 +/- 0.16) microg x mg(-1) (protein)] (C0 = 1 mg x mL(-1)) in Caco-2 cells was a little higher than that of Rb1 [(0.77 +/- 0.03) microg x mg(-1) (protein)] (C0 = 1 mg x mL(-1)). Meanwhile, apparent permeability coefficient of (5.9 +/- 1.0) x 10(-8) cm x s(-1) (C0 = 1 mg x mL(-1)) for Rb1 and (2.59 +/- 0.17) x 10(-7) cm x s(-1) (C0 = 1 mg x mL(-1)) for Rg1 from apical compartment to basolateral compartment predicted an incompletely absorption. Transports of both Rb1 and Rg1 were not influenced by cyclosporine A. The investigation on the pharmacokinetic behavior of Rb1 and Rg1 after different routes of administration to rats showed that the absolute bioavailability after peroral (po), intraduodenal (id), and portal venous (pv) administration is 0.71% , 2.75% and 65.77% respectively for Rb1, and 3.29%, 6.60% and 50.56% respectively for Rg1. CONCLUSION: Transport across Caco-2 cell monolayer for PNS (include Rb1 and Rg1) is a simple passive diffusion process. No efflux transporters in Caco-2 cells and other components in PNS showed effects on it. The elimination in stomach, large intestine and liver contributed to the low bioavailability of PNS, but the low membrane permeability might be a more important factor dominating the extent of absorption.

Paliperidone extended-release tablets in Chinese patients with schizophrenia: meta-analysis of randomized controlled trials.

BACKGROUND: Previous meta-analyses have compared paliperidone extended-release (ER) tablets with other antipsychotics, but none have involved Chinese patients or studies from People's Republic of China. Further, the results of these meta-analyses may not be applicable to Chinese patients. In the present study, we evaluated the efficacy, safety, and acceptability of paliperidone ER compared with other second-generation antipsychotics (SGAs) for Chinese patients with schizophrenia. METHODS: Randomized controlled studies of paliperidone ER and other SGAs as oral monotherapy in the acute phase treatment of schizophrenia were retrieved from Medline, Embase, and the Cochrane Library (CENTRAL), as well as from Chinese databases including the China National Knowledge Infrastructure, Wanfang, and VIP Information/Chinese Scientific Journals Database. We pooled data on response rates, chance of withdrawal due to adverse events, probability of adverse events, and odds of withdrawal for any reason. RESULTS: Fifty randomized controlled trials were identified. The response rate for paliperidone ER was significantly higher than that of other pooled SGAs (risk ratio [RR] 0.83, 95% confidence interval [CI] 0.72-0.96) and ziprasidone (RR 0.57, 95% CI 0.39-0.82). Paliperidone ER significantly reduced the chance of withdrawal due to adverse events and the chance of any adverse events compared with other pooled SGAs (RR 0.32, 95% CI 0.17-0.58 and RR 0.88, 95% CI 0.79-0.97) and risperidone (RR 0.31, 95% CI 0.14-0.67 and RR 0.70, 95% CI 0.57-0.86). The incidence of extrapyramidal symptoms on paliperidone ER was comparable with other pooled SGAs (RR 0.94, 95% CI 0.66-1.35) and significantly lower than that of risperidone (RR 0.56, 0.41-0.77) but higher than that of olanzapine (RR 1.88, 95% CI 1.05-3.36). Paliperidone ER was superior to other pooled SGAs (RR 0.32, 95% CI 0.21-0.49 and RR 0.50, 95% CI 0.35-0.72) and olanzapine (RR 0.23, 95% CI 0.15-0.33 and RR 0.33, 95% CI 0.23-0.47) as far as weight gain and somnolence were concerned. Further, prolactin-related adverse events caused by paliperidone ER were comparable with other pooled SGAs (RR 1.30, 95% CI 0.73-2.33), but outnumbered those caused by olanzapine (RR 7.53, 95% CI 2.05-27.71). CONCLUSION: Paliperidone ER is efficacious, safe, and well accepted when compared with other pooled SGAs for the treatment of Chinese patients with schizophrenia.