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There are limited data about Omicron infection in children in China. Here, we evaluated the infection fatality rates, clinical features and efficacy of SARS-CoV-2 vaccine in children with Omicron infection in a tertiary hospital during the first wave of SARS-CoV-2 caused by Omicron in China, December 2022-January 2023.We used the week as a statistical unit, and the positive rate of NAT was 0.03% from December 1 to December 7, the week before the Zero-COVID strategy was relaxed. Following the repeal of the Zero-COVID policy, the positive rate of NAT rose to 8.3% in the first week, peaked at 85.2% in the third week, and then steadily fell.The NAT positive rate in children peaked (90.4%) in the third week following the termination of the Zero-COVID policy.43.6% (232/532) of the 532 pediatric patients received vaccinations, with the majority (95.3%, 221/232) receiving two doses and the remainder receiving one.532 of the 641 pediatric patients who tested positive for NAT were seen in the pediatric outpatient clinic. Eventually, 51 pediatric patients were admitted to hospitals. Overall, the symptoms of infection were mild, and the rate of severe disease was low, whereas vaccination had a favorable effect on lowering the risk of severe illness in children.
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It has been more than 2 years since the outbreak of corona virus disease 2019（COVID-19） caused by severe acute respiratory syndrome coronavirus 2（SARS-CoV-2）.SARS-CoV-2 is a member of positive single-stranded RNA viruses and could infect multiple mammals.Palmitoylation is a post-translational lipid modification of protein, which regulates protein localization and trafficking.Spike protein（S）, envelope protein（E） and SARS-CoV-2 receptor ACE2 have been identified of being palmitoylated.This paper reviews the research progress on the palmitoylation of S, E and ACE2, including the sites of palmitoylation of S protein, the enzymes involved in this process, and their functions.Through the integrated review of these contents, which would provide mechanistic insights into the pathogenesis and treatment of COVID-19.
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The global hospitality industry is fast-turning sustainable and environmentally friendly. Behaviour-driven energy conservation is an emerging green hotel operation strategy to support this change. The long-stay accommodation services have gained momentum in the hospitality sector since the COVID-19 pandemic. However, the characteristics of long-stay hotel guests are often overlooked in sustainable interventions. Based on an empirical survey in China, this study aims to explore the factors driving energy-saving behaviours of long-stay hotel guests and to compare their effects on guests for different visiting purposes (leisure, business, and extended-stay resident). The analysis indicates that attitude, personal norm and place attachment present a direct contribution to energy-saving behaviour. Besides, the results support that attitude and personal norm connect environmental values and energy-saving behaviour. Both altruistic and biospheric values have positive effects, while egoistic values seem to play a negative role. Biospheric values have stronger impact on attitude and personal norm of business guests. Place attachment has a stronger influence on extended-stay residents while its contribution to energy-saving behaviours of business guests is smaller than other guests. Besides, leisure guests are more sensitive to moral obligations. This research sheds novel lights on the psychological perspectives of the observed heterogeneity of energy-saving behaviours of hotel guests with different visiting purposes. The findings provide hotel operators with a novel theoretical reference for targeted energy-saving interventions to promote energy-saving actions of long-term hotel guests. The study, therefore, can contribute to sustainable tourism policymaking and behaviour-driven hotel energy management.
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BACKGROUNDThe rising breakthrough infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, especially Omicron and its sub-lineages, have raised an urgent need to develop broad-spectrum vaccines against coronavirus disease 2019 (COVID-19). We have developed a mosaic-type recombinant vaccine candidate, named NVSI-06-09, having immune potentials against a broad range of SARS-CoV-2 variants. METHODSAn ongoing randomized, double-blind, controlled phase 2 trial was conducted to evaluate the safety and immunogenicity of NVSI-06-09 as a booster dose in subjects aged 18 years and older from the United Arab Emirates (UAE), who had completed two or three doses of BBIBP-CorV vaccinations at least 6 months prior to the enrollment. The participants were randomly assigned with 1:1 to receive a booster dose of NVSI-06-09 or BBIBP-CorV. The primary outcomes were immunogenicity and safety against SARS-CoV-2 Omicron variant, and the exploratory outcome was cross-immunogenicity against other circulating strains. RESULTSA total of 516 participants received booster vaccination. Interim results showed a similar safety profile between NVSI-06-09 and BBIBP-CorV booster groups, with low incidence of adverse reactions of grade 1 or 2. For immunogenicity, by day 14 after the booster vaccination, the fold rises in neutralizing antibody geometric mean titers (GMTs) from baseline level elicited by NVSI-06-09 were remarkably higher than those by BBIBP-CorV against the prototype strain (19.67 vs 4.47-fold), Omicron BA.1.1 (42.35 vs 3.78-fold), BA.2 (25.09 vs 2.91-fold), BA.4 (22.42 vs 2.69-fold), and BA.5 variants (27.06 vs 4.73-fold). Similarly, the neutralizing GMTs boosted by NVSI-06-09 against Beta and Delta variants were also 6.60-fold and 7.17-fold higher than those boosted by BBIBP-CorV. CONCLUSIONSA booster dose of NVSI-06-09 was well-tolerated and elicited broad-spectrum neutralizing responses against SARS-CoV-2 prototype strain and immune-evasive variants, including Omicron and its sub-lineages. The immunogenicity of NVSI-06-09 as a booster vaccine was superior to that of BBIBP-CorV. (Funded by LIBP and BIBP of Sinopharm; ClinicalTrials.gov number, NCT05293548).
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Coronavirus Infections , Breakthrough Pain , COVID-19ABSTRACT
The receptor-binding domain (RBD) of the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to the human angiotensin-converting enzyme 2 (ACE2) receptor, which is a prerequisite for the virus to enter the cell. C-reactive protein (CRP) is an important marker of inflammation and is a putative soluble pattern recognition receptor. Clinical elevation of CRP levels in patients with COVID-19 is one of the characteristics of the disease;however, whether CRP is involved in COVID-19 pathogenesis is unknown. Here, we report that monomeric CRP (mCRP) can bind to the SARS-CoV-2 spike RBD and competitively inhibit its binding to ACE2. Furthermore, truncated mutant peptide competition assays and surface plasmon resonance binding experiments showed that the cholesterol-binding sequence (CBS, amino acids 35-47) in mCRP was critical for mediating the binding of mCRP to spike RBD. In a cell model of spike RBD and ACE2 interaction, the CBS motif effectively reduced the binding of spike RBD to ACE2 overexpressed on the cell surface. Thus, this study highlights the pattern recognition function of mCRP in innate immunity and provides a preliminary theoretical basis for the development of the CBS motif in mCRP into a functional peptide with both diagnostic significance and potential therapeutic capabilities.
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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is known to present with pulmonary and extra-pulmonary organ complications. In comparison with the 2009 pandemic (pH1N1), SARS-CoV-2 infection is likely to lead to more severe disease, with multi-organ effects, including cardiovascular disease. SARS-CoV-2 has been associated with acute and long-term cardiovascular disease, but the molecular changes govern this remain unknown. In this study, we investigated the landscape of cardiac tissues collected at rapid autopsy from SARS-CoV-2, pH1N1, and control patients using targeted spatial transcriptomics approaches. Although SARS-CoV-2 was not detected in cardiac tissue, host transcriptomics showed upregulation of genes associated with DNA damage and repair, heat shock, and M1-like macrophage infiltration in the cardiac tissues of COVID-19 patients. The DNA damage present in the SARS-CoV-2 patient samples, were further confirmed by gamma-H2Ax immunohistochemistry. In comparison, pH1N1 showed upregulation of Interferon-stimulated genes (ISGs), in particular interferon and complement pathways, when compared with COVID-19 patients. These data demonstrate the emergence of distinct transcriptomic profiles in cardiac tissues of SARS-CoV-2 and pH1N1 influenza infection supporting the need for a greater understanding of the effects on extra-pulmonary organs, including the cardiovascular system of COVID-19 patients, to delineate the immunopathobiology of SARS-CoV-2 infection, and long term impact on health.
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Coronavirus Infections , COVID-19 , Cardiovascular DiseasesABSTRACT
Large-scale populations in the world have been vaccinated with COVID-19 vaccines, however, breakthrough infections of SARS-CoV-2 are still growing rapidly due to the emergence of immune-evasive variants, especially Omicron. It is urgent to develop effective broad-spectrum vaccines to better control the pandemic of these variants. Here, we present a mosaic-type trimeric form of spike receptor-binding domain (mos-tri-RBD) as a broad-spectrum vaccine candidate, which carries the key mutations from Omicron and other circulating variants. Tests in rats showed that the designed mos-tri-RBD, whether used alone or as a booster shot, elicited potent cross-neutralizing antibodies against not only Omicron but also other immune-evasive variants. Neutralizing antibody titers induced by mos-tri-RBD were substantially higher than those elicited by homo-tri-RBD (containing homologous RBDs from prototype strain) or the inactivated vaccine BBIBP-CorV. Our study indicates that mos-tri-RBD is highly immunogenic, which may serve as a broad-spectrum vaccine candidate in combating SARS-CoV-2 variants including Omicron.
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COVID-19 , Breakthrough PainABSTRACT
BACKGROUND Obesity is associated with a better prognosis in patients with community-acquired pneumonia (the so-called obesity survival paradox), but conflicting results have been found. AIM To investigate the relationship between all-cause mortality and body mass index in patients with community-acquired pneumonia. METHODS This retrospective study included patients with community-acquired pneumonia hospitalized in the First Hospital of Qinhuangdao from June 2013 to November 2018. The patients were grouped as underweight (< 18.5 kg/m2), normal weight (18.5-23.9 kg/m2), and overweight/obesity (≥ 24 kg/m2). The primary outcome was all-cause hospital mortality. RESULTS Among 2327 patients, 297 (12.8%) were underweight, 1013 (43.5%) normal weight, and 1017 (43.7%) overweight/obesity. The all-cause hospital mortality was 4.6% (106/2327). Mortality was lowest in the overweight/obesity group and highest in the underweight group (2.8%, vs 5.0%, vs 9.1%, P < 0.001). All-cause mortality of overweight/obesity patients was lower than normal-weight patients [odds ratio (OR) = 0.535, 95% confidence interval (CI) = 0.334-0.855, P = 0.009], while the all-cause mortality of underweight patients was higher than that of normal-weight patients (OR = 1.886, 95%CI: 1.161-3.066, P = 0.010). Multivariable analysis showed that abnormal neutrophil counts (OR = 2.38, 95%CI: 1.55-3.65, P < 0.001), abnormal albumin levels (OR = 0.20, 95%CI: 0.06-0.72, P = 0.014), high-risk Confusion-Urea-Respiration-Blood pressure-65 score (OR = 2.89, 95%CI: 1.48-5.64, P = 0.002), and intensive care unit admission (OR = 3.11, 95%CI: 1.77-5.49, P < 0.001) were independently associated with mortality. CONCLUSION All-cause mortality of normal-weight patients was higher than overweight/ obesity patients, lower than that of underweight patients. Neutrophil counts, albumin levels, Confusion-Urea-Respiration-Blood pressure-65 score, and intensive care unit admission were independently associated with mortality in patients with community-acquired pneumonia.
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Background: The increased coronavirus disease 2019 (COVID-19) breakthrough cases pose the need of booster vaccinations. In this study, we reported the safety and immunogenicity of a heterologous boost with a recombinant COVID-19 vaccine (CHO cells), named NVSI-06-07, as a third dose in participants who have previously received two doses of the inactivated vaccine (BBIBP-CorV) at pre-specified time intervals. Using homologous boost with BBIBP-CorV as control, the safety and immunogenicity of the heterologous boost with NVSI-06-07 against various SARS-CoV-2 strains, including Omicron, were characterized. Methods: This study is a single-center, randomised, double-blinded, controlled phase 2 trial for heterologous boost of NVSI-06-07 in BBIBP-CorV recipients from the United Arab Emirates (UAE). Healthy adults (aged [≥]18 years) were enrolled and grouped by the specified prior vaccination interval of BBIBP-CorV, i.e., 1-3 months, 4-6 months or [≥]6 months, respectively, with 600 individuals per group. For each group, participants were randomly assigned at 1:1 ratio to receive either a heterologous boost of NVSI-06-07 or a homologous booster dose of BBIBP-CorV. The primary outcome was to comparatively assess the immunogenicity between heterologous and homologous boosts at 14 and 28 days post-boosting immunization, by evaluation of the geometric mean titers (GMTs) of IgG and neutralizing antibodies as well as the corresponding seroconversion rate ([≥]4-fold rise in antibody titers). The secondary outcomes were the safety profile of the boosting strategies within 30 days post vaccination. The exploratory outcome was the immune efficacy against Omicron and other variants of concern (VOCs) of SARS-CoV-2. This trial is registered with ClinicalTrials.gov, NCT05033847. Findings: A total of 1800 individuals who have received two doses of BBIBP-CorV were enrolled, of which 899 participants received a heterologous boost of NVSI-06-07 and 901 received a homologous boost for comparison. No vaccine-related serious adverse event (SAE) and no adverse events of special interest (AESI) were reported. 184 (20.47%) participants in the heterologous boost groups and 177 (19.64%) in the homologous boost groups reported at least one adverse reaction within 30 days. Most of the local and systemic adverse reactions reported were grades 1 (mild) or 2 (moderate), and there was no significant difference in the overall safety between heterologous and homologous boosts. Immunogenicity assays showed that the seroconversion rates in neutralizing antibodies against prototype SARS-CoV-2 elicited by heterologous boost were 89.96% - 97.52% on day 28 post-boosting vaccination, which was much higher than what was induced by homologous boost (36.80% - 81.75%). Similarly, in heterologous NVSI-06-07 booster groups, the neutralizing geometric mean titers (GMTs) against the prototype strain increased by 21.01 - 63.85 folds from baseline to 28 days post-boosting vaccination, whereas only 4.20 - 16.78 folds of increases were observed in homologous BBIBP-CorV booster group. For Omicron variant, the neutralizing antibody GMT elicited by the homologous boost of BBIBP-CorV was 37.91 (95%CI, 30.35-47.35), however, a significantly higher level of neutralizing antibodies with GMT 292.53 (95%CI, 222.81-384.07) was induced by the heterologous boost of NVSI-06-07, suggesting that it may serve as an effective boosting strategy combating the pandemic of Omicron. The similar results were obtained for other VOCs, including Alpha, Beta and Delta, in which the neutralizing response elicited by the heterologous boost was also significantly greater than that of the homologous boost. In the participants primed with BBIBP-CorV over 6 months, the largest increase in the neutralizing GMTs was obtained both in the heterologous and homologous boost groups, and thus the booster vaccination with over 6 months intervals was optimal. Interpretation: Our findings indicated that the heterologous boost with NVSI-06-07 was safe, well-tolerated and immunogenic in adults primed with a full regimen of BBIBP-CorV. Compared to homologous boost with a third dose of BBIBP-CorV, incremental increases in immune responses were achieved by the heterologous boost with NVSI-06-07 against SARS-CoV-2 prototype strain, Omicron variant, and other VOCs. The heterologous BBIBP-CorV/NVSI-06-07 prime-boosting vaccination may be valuable in preventing the pandemic of Omicron. The optimal booster strategy was the heterologous boost with NVSI-06-07 over 6 months after a priming with two doses of BBIBP-CorV.
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COVID-19 , Drug-Related Side Effects and Adverse ReactionsABSTRACT
The spike (S) protein receptor-binding domain (RBD) of SARS-CoV-2 is an attractive target for COVID-19 vaccine developments, which naturally exists in a trimeric form. Here, guided by structural and computational analyses, we present a mutation-integrated trimeric form of RBD (mutI tri-RBD) as a broadly protective vaccine candidate, in which three RBDs were individually grafted from three different circulating SARS-CoV-2 strains including the prototype, Beta (B.1.351) and Kappa (B.1.617). The three RBDs were then connected end-to-end and co-assembled to possibly mimic the native trimeric arrangements in the natural S protein trimer. The recombinant expression of the mutI tri-RBD, as well as the homo-tri-RBD where the three RBDs were all truncated from the prototype strain, by mammalian cell exhibited correct folding, strong bio-activities, and high stability. The immunization of both the mutI tri-RBD and homo-tri-RBD plus aluminum adjuvant induced high levels of specific IgG and neutralizing antibodies against the SARS-CoV-2 prototype strain in mice. Notably, regarding to the immune-escape Beta (B.1.351) variant, mutI tri-RBD elicited significantly higher neutralizing antibody titers than homo-tri-RBD. Furthermore, due to harboring the immune-resistant mutations as well as the evolutionarily convergent hotspots, the designed mutI tri-RBD also induced strong broadly neutralizing activities against various SARS-CoV-2 variants, especially the variants partially resistant to homo-tri-RBD. Homo-tri-RBD has been approved by the China National Medical Products Administration to enter clinical trial (No. NCT04869592), and the superior broad neutralization performances against SARS-CoV-2 support the mutI tri-RBD as a more promising vaccine candidate for further clinical developments.
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COVID-19ABSTRACT
PurposeThis paper empirically investigates how cultural variations in individualism and tightness affected the containment of COVID-19 using data from 54 nations during a 30-day period of government intervention.Design/methodology/approachThe authors utilized the hierarchical regression approach to check the effects of three cultural variables – the individualism measure, taken from Hofstede’s six-dimension national culture index, and the measure of cultural tightness, based on the three tightness–looseness indexes calculated by Irem Uz (2015) and their interaction – on the changes in the prevalence rate (ΔPR) and crude mortality rate (ΔCMR) and case fatality rate (CFR) while controlling for the stringency of government responses to COVID-19, median age and population density.FindingsSignificant relationships were found between cultural variables and national performance in slowing the spread of the coronavirus, measured by ΔPR, ΔCMR and CFR. After controlling for the stringency of government responses, median age and population density, the authors found that cultural tightness and individualism as well as their interactions remain to be pivotal. Loose and individualistic cultures led to faster increases in PR and CMR and higher CFR. A four-quadrant conceptual framework is developed to categorize and discuss the national differences.Originality/valueThe paper integrated two constructs – cultural tightness–looseness and individualism–collectivism – to form a theoretical lens to guide the authors’ analyses while using the real-time COVID-19 data as a natural experiment for theorizing and testing. This study’s findings have significant policy implications in government responses, strategic planning, cultural adaptability and policy implementations for the world’s continuous battle against the pandemic.
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Previous studies revealed that the susceptibility, contacting preference, and recovery probability markedly alter the epidemic outbreak size and threshold. The recovery probability of an infected node is closely related to its obtained resources. How to allocate limited resources to infected neighbors is extremely important for containing the epidemic spreading on complex networks. In this paper, we proposed an epidemic spreading model on complex networks, in which we assume that the node has heterogeneous susceptibility and contacting preference, and susceptible nodes are willing to share their resources to neighbors. Through a developed heterogeneous mean-field theory and a large number of numerical simulations, we find that the recovered nodes provide resources uniformly to their infected neighbor nodes, and the epidemic spreading can be suppressed optimally on homogeneous and heterogeneous networks. Besides, altering the susceptibility and contacting preference does not qualitatively change the results. The susceptibility of the node decreases, which makes the outbreak threshold of epidemic spreading increase, and the outbreak size decreases. Our theory agrees well with the numerical simulations.