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1.
Hum Vaccin Immunother ; : 2094142, 2022 Jul 11.
Article in English | MEDLINE | ID: covidwho-1927246

ABSTRACT

ARCoV is a candidate mRNA vaccine encoding receptor-binding domain of SARS-CoV-2. Its safety, tolerability, and immunogenicity profile have been confirmed in the phase 1 clinical trial in China. A multi-regional phase 3 clinical trial is currently underway to test the efficacy of ARCoV (NCT04847102). Here, we tested the cross-neutralization against SARS-CoV-2 variants of concern (VOCs) of a panel of serum samples from participants in the phase 1 clinical trial of ARCoV by pesudo- and authentic SARS-CoV-2. Our data suggest the immunity induced by the ARCoV vaccine reduced but still has significant neutralization against the Alpha and Delta variants. Moreover, ARCoV maintained activity against the Beta variant, despite of its obvious reduction in neutralizing titers. Our findings further support the solid protective neutralization activity against VOCs induced by ARCoV vaccine.

2.
J Clin Child Adolesc Psychol ; 51(4): 577-592, 2022.
Article in English | MEDLINE | ID: covidwho-1900938

ABSTRACT

Culture plays an important role in the development of mental health, especially during childhood and adolescence. However, less is known about how participation in cultural rituals is related to the wellbeing of youth who are Black, Indigenous, and People of Color (BIPOC), and part of the Global Majority. This is crucial amid the COVID-19 pandemic, a global event that has disproportionally affected BIPOC youth and disrupted participation in rituals. The goal of this paper is to promote advances in clinical child and adolescent psychology focused on rituals. We begin by defining culture and rituals and examining their role on development. We illustrate these issues with the Lunar New Year in China, Maya rituals in México, Ramadan in Turkey, and Black graduations and Latinx funerals in the United States. We discuss how the pandemic has affected participation in these rituals and their potential impact on BIPOC children and adolescents' mental health. We propose future directions and recommendations for research.


Subject(s)
COVID-19 , Pandemics , Adolescent , COVID-19/epidemiology , Ceremonial Behavior , Child , Family , Humans , Mental Health , United States
3.
Nature ; 608(7923): 593-602, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1900499

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages BA.2.12.1, BA.4 and BA.5 exhibit higher transmissibility than the BA.2 lineage1. The receptor binding and immune-evasion capability of these recently emerged variants require immediate investigation. Here, coupled with structural comparisons of the spike proteins, we show that BA.2.12.1, BA.4 and BA.5 (BA.4 and BA.5 are hereafter referred collectively to as BA.4/BA.5) exhibit similar binding affinities to BA.2 for the angiotensin-converting enzyme 2 (ACE2) receptor. Of note, BA.2.12.1 and BA.4/BA.5 display increased evasion of neutralizing antibodies compared with BA.2 against plasma from triple-vaccinated individuals or from individuals who developed a BA.1 infection after vaccination. To delineate the underlying antibody-evasion mechanism, we determined the escape mutation profiles2, epitope distribution3 and Omicron-neutralization efficiency of 1,640 neutralizing antibodies directed against the receptor-binding domain of the viral spike protein, including 614 antibodies isolated from people who had recovered from BA.1 infection. BA.1 infection after vaccination predominantly recalls humoral immune memory directed against ancestral (hereafter referred to as wild-type (WT)) SARS-CoV-2 spike protein. The resulting elicited antibodies could neutralize both WT SARS-CoV-2 and BA.1 and are enriched on epitopes on spike that do not bind ACE2. However, most of these cross-reactive neutralizing antibodies are evaded by spike mutants L452Q, L452R and F486V. BA.1 infection can also induce new clones of BA.1-specific antibodies that potently neutralize BA.1. Nevertheless, these neutralizing antibodies are largely evaded by BA.2 and BA.4/BA.5 owing to D405N and F486V mutations, and react weakly to pre-Omicron variants, exhibiting narrow neutralization breadths. The therapeutic neutralizing antibodies bebtelovimab4 and cilgavimab5 can effectively neutralize BA.2.12.1 and BA.4/BA.5, whereas the S371F, D405N and R408S mutations undermine most broadly sarbecovirus-neutralizing antibodies. Together, our results indicate that Omicron may evolve mutations to evade the humoral immunity elicited by BA.1 infection, suggesting that BA.1-derived vaccine boosters may not achieve broad-spectrum protection against new Omicron variants.

4.
Proc Natl Acad Sci U S A ; 119(23): e2118836119, 2022 06 07.
Article in English | MEDLINE | ID: covidwho-1890407

ABSTRACT

Rapid identification of newly emerging or circulating viruses is an important first step toward managing the public health response to potential outbreaks. A portable virus capture device, coupled with label-free Raman spectroscopy, holds the promise of fast detection by rapidly obtaining the Raman signature of a virus followed by a machine learning (ML) approach applied to recognize the virus based on its Raman spectrum, which is used as a fingerprint. We present such an ML approach for analyzing Raman spectra of human and avian viruses. A convolutional neural network (CNN) classifier specifically designed for spectral data achieves very high accuracy for a variety of virus type or subtype identification tasks. In particular, it achieves 99% accuracy for classifying influenza virus type A versus type B, 96% accuracy for classifying four subtypes of influenza A, 95% accuracy for differentiating enveloped and nonenveloped viruses, and 99% accuracy for differentiating avian coronavirus (infectious bronchitis virus [IBV]) from other avian viruses. Furthermore, interpretation of neural net responses in the trained CNN model using a full-gradient algorithm highlights Raman spectral ranges that are most important to virus identification. By correlating ML-selected salient Raman ranges with the signature ranges of known biomolecules and chemical functional groups­for example, amide, amino acid, and carboxylic acid­we verify that our ML model effectively recognizes the Raman signatures of proteins, lipids, and other vital functional groups present in different viruses and uses a weighted combination of these signatures to identify viruses.


Subject(s)
Machine Learning , Neural Networks, Computer , Viruses , Disease Outbreaks , Pandemics , Serogroup , Viruses/classification
5.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-335494

ABSTRACT

Recent emergence of SARS-CoV-2 Omicron sublineages BA.2.12.1, BA.2.13, BA.4 and BA.5 all contain L452 mutations and show potential higher transmissibility over BA.2. The new variants’ receptor binding and immune evasion capability require immediate investigation, especially on the role of L452 substitutions. Herein, coupled with structural comparisons, we showed that BA.2 sublineages, including BA.2.12.1 and BA.2.13, exhibit increased ACE2-binding affinities compared to BA.1;while BA.4/BA.5 shows the weakest receptor-binding activity due to F486V and R493Q reversion. Importantly, compared to BA.2, BA.2.12.1 and BA.4/BA.5 exhibit stronger neutralization escape from the plasma of 3-dose vaccinees and, most strikingly, from vaccinated BA.1 convalescents. To delineate the underlying evasion mechanism, we determined the escaping mutation profiles, epitope distribution and Omicron sub-lineage neutralization efficacy of 1640 RBD-directed neutralizing antibodies (NAbs), including 614 isolated from BA.1 convalescents. Interestingly, post-vaccination BA.1 infection mainly recalls wildtype-induced humoral memory and elicits antibodies that neutralize both wild-type and BA.1. These cross-reactive NAbs are significantly enriched on non-ACE2-competing epitopes;and surprisingly, the majority are undermined by R346 and L452 substitutions, namely R346K (BA.1.1), L452M (BA.2.13), L452Q (BA.2.12.1) and L452R (BA.4/BA.5), suggesting that R346K and L452 mutations appeared under the immune pressure of Omicron convalescents. Nevertheless, BA.1 infection can also induce new clones of BA.1-specific antibodies that potently neutralize BA.1 but do not respond to wild-type SARS-CoV-2, due to the high susceptibility to N501, N440, K417 and E484. However, these NAbs are largely escaped by BA.2 sublineages and BA.4/BA.5 due to D405N and F486V, exhibiting poor neutralization breadths. As for therapeutic NAbs, LY-CoV1404 (Bamlanivimab) and COV2-2130 (Cilgavimab) can still effectively neutralize BA.2.12.1 and BA.4/BA.5, while the S371F, D405N and R408S mutations carried by BA.2/BA.4/BA.5 sublineages would undermine most broad sarbecovirus NAbs. Together, our results indicate that Omicron can evolve mutations to specifically evade humoral immunity elicited by BA.1 infection. The continuous evolution of Omicron poses great challenges to SARS-CoV-2 herd immunity and suggests that BA.1-derived vaccine boosters may not be ideal for achieving broad-spectrum protection.

6.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-335258

ABSTRACT

The recently emerged SARS-CoV-2 Omicron sublineages BA.2.12.1, BA.2.13, BA.4 and BA.5 all contain L452 mutations and show potential higher transmissibility over BA.2 1 . The new variants’ receptor binding and immune evasion capability require immediate investigation, especially on the role of L452 substitutions. Herein, coupled with structural comparisons, we show that BA.2 sublineages, including BA.2.12.1 and BA.2.13, exhibit increased ACE2-binding affinities compared to BA.1;while BA.4/BA.5 displays the weakest receptor-binding activity due to F486V and R493Q reversion. Importantly, compared to BA.2, BA.2.12.1 and BA.4/BA.5 exhibit stronger neutralization evasion against the plasma of 3-dose vaccinees and, most strikingly, of vaccinated BA.1 convalescents. To delineate the underlying evasion mechanism, we determined the escaping mutation profiles 2 , epitope distribution 3 and Omicron sublineage neutralization efficacy of 1640 RBD-directed neutralizing antibodies (NAbs), including 614 isolated from BA.1 convalescents. Interestingly, post-vaccination BA.1 infection mainly recalls wildtype (WT) induced humoral memory and elicits antibodies that neutralize both WT and BA.1. These cross-reactive NAbs are significantly enriched on non-ACE2-competing epitopes;and surprisingly, the majority are undermined by R346 and L452 substitutions, namely R346K (BA.1.1), L452M (BA.2.13), L452Q (BA.2.12.1) and L452R (BA.4/BA.5), suggesting that R346K and L452 mutations appeared under the immune pressure induced by Omicron convalescents. Nevertheless, BA.1 infection can also induce new clones of BA.1-specific antibodies that potently neutralize BA.1 but do not respond to WT SARS-CoV-2 due to the high susceptibility to N501, N440, K417 and E484. However, these NAbs are largely escaped by BA.2 sublineages and BA.4/BA.5 due to D405N and F486V, exhibiting poor neutralization breadths. As for therapeutic NAbs, LY-CoV1404 (Bebtelovimab 4 ) and COV2-2130 (Cilgavimab 5 ) can still effectively neutralize BA.2.12.1 and BA.4/BA.5, while the S371F, D405N and R408S mutations carried by BA.2/BA.4/BA.5 sublineages would undermine most broad sarbecovirus NAbs. Together, our results indicate that Omicron can evolve mutations to specifically evade humoral immunity elicited by BA.1 infection. The continuous evolution of Omicron poses great challenges to SARS-CoV-2 herd immunity and suggests that BA.1-derived vaccine boosters may not be ideal for achieving broad-spectrum protection.

7.
Journal of Social and Personal Relationships ; : 02654075221098419, 2022.
Article in English | Sage | ID: covidwho-1820030

ABSTRACT

The COVID-19 pandemic has introduced unprecedented challenges and demands for parents or caregivers of children who experienced disruptions in social support and feelings of isolation. Mindful emotion regulation may be a resilient factor for parents? psychosocial outcomes. Mindful emotion regulation refers to individuals? inherent capacities to regulate emotions mindfully, i.e., through paying attention to one?s experiences in the present moment nonjudgmentally. Based on the theoretical and empirical literature associating mindful emotion regulation with loneliness and perceived social support, the current study tested the effects of mindful emotion regulation on later changes in perceived social support and loneliness in U.S. parents during the pandemic. Participants were 147 parents/caregivers who were living with at least one child or adolescent in their household during the pandemic in the USA. Data were collected from a national online sample at four time points: baseline (April 7?21, 2020), 30-, 60-, and 90-days later. Results of longitudinal mediational structural equation modeling showed that mindful emotion regulation was directly associated with increased perceived social support and decreased loneliness. Moreover, mindful emotion regulation was also associated with perceived social support indirectly through its effects on loneliness. Focusing on the needs of parents is important for promoting family and child wellbeing to ameliorate negative health consequences. More research is needed to elucidate whether and how mindful emotion regulation may be beneficial for parents in the social relationship domain.

8.
J Nurs Manag ; 30(4): 901-912, 2022 May.
Article in English | MEDLINE | ID: covidwho-1779260

ABSTRACT

AIMS: We aim to study the effect of role overload, work engagement and perceived organisational support on nurses' job performance, including task performance, interpersonal facilitation and job dedication. BACKGROUND: Many nurses have suffered from role overload at work during the COVID-19 pandemic. However, the investigations of the influence mechanisms and boundary conditions through and under which role overload is associated with job performance have shown inconsistent results. METHODS: A total of 595 Chinese nurses were studied from November 2020 to February 2021. Confirmatory factor analysis, maximum likelihood estimation and bootstrapping analysis were used to test the mediating process and the moderating effect. RESULTS: Work engagement partly mediated the relationships of role overload with task performance (ß = -.253, p < .001, 95% CI: [-.315, -.204]) and interpersonal facilitation (ß = -.202, p < .001, 95% CI: [-.261, -.145]); work engagement also fully mediated the relationship between role overload and job dedication (ß = -.239, p < .001, 95% CI: [-.302, -.186]). Perceived organisational support moderated the relationships of role overload with task performance, interpersonal facilitation and work dedication (ß = -.171, p < .001, ß = -.154, p < .001 and ß = -.175, p < .001, respectively). CONCLUSIONS: Work engagement is the linchpin linking role overload to distal outcomes of job performance. Perceived organisational support mitigates the ways in which role overload undermines job performance. IMPLICATIONS FOR NURSING MANAGEMENT: Hospital administrators can minimize the effects of role overload and create a more supportive organisational environment to promote the job performance of nurses.


Subject(s)
COVID-19 , Nurses , Work Performance , COVID-19/epidemiology , Cross-Sectional Studies , Humans , Job Satisfaction , Pandemics , Surveys and Questionnaires , Work Engagement
9.
Lancet Microbe ; 3(3): e193-e202, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1721237

ABSTRACT

BACKGROUND: Safe and effective vaccines are urgently needed to end the COVID-19 pandemic caused by SARS-CoV-2 infection. We aimed to assess the preliminary safety, tolerability, and immunogenicity of an mRNA vaccine ARCoV, which encodes the SARS-CoV-2 spike protein receptor-binding domain (RBD). METHODS: This single centre, double-blind, randomised, placebo-controlled, dose-escalation, phase 1 trial of ARCoV was conducted at Shulan (Hangzhou) hospital in Hangzhou, Zhejiang province, China. Healthy adults aged 18-59 years negative for SARS-CoV-2 infection were enrolled and randomly assigned using block randomisation to receive an intramuscular injection of vaccine or placebo. Vaccine doses were 5 µg, 10 µg, 15 µg, 20 µg, and 25 µg. The first six participants in each block were sentinels and along with the remaining 18 participants, were randomly assigned to groups (5:1). In block 1 sentinels were given the lowest vaccine dose and after a 4-day observation with confirmed safety analyses, the remaining 18 participants in the same dose group proceeded and sentinels in block 2 were given their first administration on a two-dose schedule, 28 days apart. All participants, investigators, and staff doing laboratory analyses were masked to treatment allocation. Humoral responses were assessed by measuring anti-SARS-CoV-2 RBD IgG using a standardised ELISA and neutralising antibodies using pseudovirus-based and live SARS-CoV-2 neutralisation assays. SARS-CoV-2 RBD-specific T-cell responses, including IFN-γ and IL-2 production, were assessed using an enzyme-linked immunospot (ELISpot) assay. The primary outcome for safety was incidence of adverse events or adverse reactions within 60 min, and at days 7, 14, and 28 after each vaccine dose. The secondary safety outcome was abnormal changes detected by laboratory tests at days 1, 4, 7, and 28 after each vaccine dose. For immunogenicity, the secondary outcome was humoral immune responses: titres of neutralising antibodies to live SARS-CoV-2, neutralising antibodies to pseudovirus, and RBD-specific IgG at baseline and 28 days after first vaccination and at days 7, 15, and 28 after second vaccination. The exploratory outcome was SARS-CoV-2-specific T-cell responses at 7 days after the first vaccination and at days 7 and 15 after the second vaccination. This trial is registered with www.chictr.org.cn (ChiCTR2000039212). FINDINGS: Between Oct 30 and Dec 2, 2020, 230 individuals were screened and 120 eligible participants were randomly assigned to receive five-dose levels of ARCoV or a placebo (20 per group). All participants received the first vaccination and 118 received the second dose. No serious adverse events were reported within 56 days after vaccination and the majority of adverse events were mild or moderate. Fever was the most common systemic adverse reaction (one [5%] of 20 in the 5 µg group, 13 [65%] of 20 in the 10 µg group, 17 [85%] of 20 in the 15 µg group, 19 [95%] of 20 in the 20 µg group, 16 [100%] of 16 in the 25 µg group; p<0·0001). The incidence of grade 3 systemic adverse events were none (0%) of 20 in the 5 µg group, three (15%) of 20 in the 10 µg group, six (30%) of 20 in the 15 µg group, seven (35%) of 20 in the 20 µg group, five (31%) of 16 in the 25 µg group, and none (0%) of 20 in the placebo group (p=0·0013). As expected, the majority of fever resolved in the first 2 days after vaccination for all groups. The incidence of solicited systemic adverse events was similar after administration of ARCoV as a first or second vaccination. Humoral immune responses including anti-RBD IgG and neutralising antibodies increased significantly 7 days after the second dose and peaked between 14 and 28 days thereafter. Specific T-cell response peaked between 7 and 14 days after full vaccination. 15 µg induced the highest titre of neutralising antibodies, which was about twofold more than the antibody titre of convalescent patients with COVID-19. INTERPRETATION: ARCoV was safe and well tolerated at all five doses. The acceptable safety profile, together with the induction of strong humoral and cellular immune responses, support further clinical testing of ARCoV at a large scale. FUNDING: National Key Research and Development Project of China, Academy of Medical Sciences China, National Natural Science Foundation China, and Chinese Academy of Medical Sciences.


Subject(s)
COVID-19 , SARS-CoV-2 , Adult , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , China , Humans , Immunogenicity, Vaccine , Immunoglobulin G , Pandemics/prevention & control , Spike Glycoprotein, Coronavirus , Vaccines, Synthetic , mRNA Vaccines
10.
Innovation (Camb) ; 3(2): 100221, 2022 Mar 29.
Article in English | MEDLINE | ID: covidwho-1713028

ABSTRACT

The highly pathogenic and readily transmissible SARS-CoV-2 has caused a global coronavirus pandemic, urgently requiring effective countermeasures against its rapid expansion. All available vaccine platforms are being used to generate safe and effective COVID-19 vaccines. Here, we generated a live-attenuated candidate vaccine strain by serial passaging of a SARS-CoV-2 clinical isolate in Vero cells. Deep sequencing revealed the dynamic adaptation of SARS-CoV-2 in Vero cells, resulting in a stable clone with a deletion of seven amino acids (N679SPRRAR685) at the S1/S2 junction of the S protein (named VAS5). VAS5 showed significant attenuation of replication in multiple human cell lines, human airway epithelium organoids, and hACE2 mice. Viral fitness competition assays demonstrated that VAS5 showed specific tropism to Vero cells but decreased fitness in human cells compared with the parental virus. More importantly, a single intranasal injection of VAS5 elicited a high level of neutralizing antibodies and prevented SARS-CoV-2 infection in mice as well as close-contact transmission in golden Syrian hamsters. Structural and biochemical analysis revealed a stable and locked prefusion conformation of the S trimer of VAS5, which most resembles SARS-CoV-2-3Q-2P, an advanced vaccine immunogen (NVAX-CoV2373). Further systematic antigenic profiling and immunogenicity validation confirmed that the VAS5 S trimer presents an enhanced antigenic mimic of the wild-type S trimer. Our results not only provide a potent live-attenuated vaccine candidate against COVID-19 but also clarify the molecular and structural basis for the highly attenuated and super immunogenic phenotype of VAS5.

11.
Cell Res ; 32(4): 375-382, 2022 04.
Article in English | MEDLINE | ID: covidwho-1707327

ABSTRACT

Monoclonal antibodies represent important weapons in our arsenal to against the COVID-19 pandemic. However, this potential is severely limited by the time-consuming process of developing effective antibodies and the relative high cost of manufacturing. Herein, we present a rapid and cost-effective lipid nanoparticle (LNP) encapsulated-mRNA platform for in vivo delivery of SARS-CoV-2 neutralization antibodies. Two mRNAs encoding the light and heavy chains of a potent SARS-CoV-2 neutralizing antibody HB27, which is currently being evaluated in clinical trials, were encapsulated into clinical grade LNP formulations (named as mRNA-HB27-LNP). In vivo characterization demonstrated that intravenous administration of mRNA-HB27-LNP in mice resulted in a longer circulating half-life compared with the original HB27 antibody in protein format. More importantly, a single prophylactic administration of mRNA-HB27-LNP provided protection against SARS-CoV-2 challenge in mice at 1, 7 and even 63 days post administration. In a close contact transmission model, prophylactic administration of mRNA-HB27-LNP prevented SARS-CoV-2 infection between hamsters in a dose-dependent manner. Overall, our results demonstrate a superior long-term protection against SARS-CoV-2 conferred by a single administration of this unique mRNA antibody, highlighting the potential of this universal platform for antibody-based disease prevention and therapy against COVID-19 as well as a variety of other infectious diseases.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Antibodies, Neutralizing/therapeutic use , Antibodies, Viral/therapeutic use , COVID-19/prevention & control , Cricetinae , Humans , Liposomes , Mice , Nanoparticles , Pandemics/prevention & control , RNA, Messenger/genetics , Spike Glycoprotein, Coronavirus
12.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-327486

ABSTRACT

Constantly emerging SARS-CoV-2 variants, such as Omicron BA.1, BA.1.1 and BA.2, pose a severe challenge to COVID-19 control 1–10 . Broad-spectrum antibody therapeutics and vaccines are needed for defending against future SARS-CoV-2 variants and sarbecovirus pandemics 11–14 ;however, we have yet to gain a comprehensive understanding of the epitopes capable of inducing broad sarbecovirus neutralization. Here, we report the identification of 241 anti-RBD broad sarbecovirus neutralizing antibodies isolated from 44 SARS-CoV-2 vaccinated SARS convalescents. Neutralizing efficacy of these antibodies against D614G, SARS-CoV-1, Omicron variants (BA.1, BA.1.1, BA.2), RATG13 and Pangolin-GD is tested, and their binding capability to 21 sarbecovirus RBDs is measured. High-throughput yeast-display mutational screening was further applied to determine each antibody’s RBD escaping mutation profile, and unsupervised epitope clustering based on escaping mutation hotspots was performed 7,15–18 . A total of 6 clusters of broad sarbecovirus neutralizing antibodies with diverse breadth and epitopes were identified, namely Group E1 (S309 19 , BD55-3152 site), E3 (S2H97 20 site), F1 (CR3022 21 , S304 22 site), F2 (DH1047 23 , BD55-3500 site), F3 (ADG-2 24 , BD55-3372 site) and B’ (S2K146 25 site). Members of E1, F2 and F3 demonstrate the highest neutralization potency;yet, Omicron, especially BA.2, has evolved multiple mutations (G339D, N440K, T376A, D405N, R408S) to escape antibodies of these groups. Nevertheless, broad sarbecovirus neutralizing antibodies that survived Omicron would serve as favorable therapeutic candidates. Furthermore, structural analyses of selected drug candidates propose two non-competing antibody pairing strategies, E1-F2 and E1-F3, as broad-spectrum antibody cocktails. Together, our work provides a comprehensive epitope map of broad sarbecovirus neutralizing antibodies and offers critical instructions for designing broad-spectrum vaccines.

13.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-325098

ABSTRACT

Parents have been vulnerable to psychological distress during the COVID-19 pandemic due to the disruptions in social support including restricted connections to support networks and loss of access to healthcare, schools and day care centers, and community services. Based on the literature associating mindful emotion regulation with loneliness and perceived social support, the current study tested a mediation model in which mindful emotion regulation was associated with perceived social support through its mediated effect on loneliness in parents. Participants were 147 parents or those in near-parent roles caring for at least one child in their household during the pandemic in the USA. Data were collected from a national online sample at four time points: baseline (April 7-21, 2020), 30-, 60-, and 90-days later. Results of longitudinal mediational structural equation modeling supported the hypothesis that mindful emotion regulation predicted perceived social support through its mediated effect on reduced loneliness. Focusing on the needs of parents is important for promoting family and child wellbeing to ameliorate negative health consequences. Our findings indicate that mindful emotion regulation may be a promising strategy to promote perceived social support in parents by reducing feelings of loneliness during stressful times.

14.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-324297

ABSTRACT

Background: Coronavirus Disease 2019 (COVID-19) outbreak in Wuhan, China spreading rapidly worldwide. Over 100 countries have reported surpassing 100,000 laboratory-confirmed cases of COVID- 19, and in which 2.1% were under aged 19 years. However, little is known about the imaging features about pediatric COVID-19 patients. Herein, we report two cases about COVID-19 involving the clinical data as well as chest images. Case presentation: Two pediatric patients admitted to hospital because of high fever or dry cough. Both children had been recent exposure to the COVID-19 confirmed patients of their family members. Real-time polymerase chain reaction(RT-PCR) test of these two patients’ sputum were positive for SARS-CoV-2 nucleic acid, and diagnosed as COVID-19 infection. Laboratory tests indicate normal white cell count (5.02 x10

16.
Environ Res ; 207: 112161, 2022 05 01.
Article in English | MEDLINE | ID: covidwho-1670475

ABSTRACT

BACKGROUND: Congenital anomalies (CAs) are the leading causes for children's disabilities and mortalities worldwide. The associations between air pollution and CAs are not fully characterized in fetuses born by in vitro fertilization (IVF) who are at high risk of congenital anomalies. METHODS: We conducted a cross-sectional study including 16,971 IVF cycles from three hospitals in Hebei Province, China, 2014-2019. Air quality data was obtained from 149 air monitoring stations. Individual average daily concentrations of PM2.5, PM10, NO2, SO2, CO, and O3 were estimated by spatiotemporal kriging method. Exposure windows were divided into 5: preantral follicle period, antral follicle period, germinal period, embryonic period and early fetal period. Logistic generalized estimating equations were used to estimate the associations between air pollutants and overall or organ-system specific congenital anomalies. Negative control exposure method was used to detect and reduce bias of estimation. RESULTS: We found increasing levels of PM2.5 and PM10 were associated with higher risk of overall congenital anomalies during early fetal period, equating gestation 10-12 weeks (OR: 1.05, 95% CI: 1.02-1.09, p = 0.013 for a 10 µg/m3 increase of PM2.5; OR: 1.03, 95% CI: 1.01-1.06, p = 0.021 for a 10 µg/m3 increase of PM10). Cleft lip and cleft palate were associated with PM10 in germinal period and early fetal period. The CAs of eye, ear, face and neck were related to CO in preantral follicle stage. We did not find an association between chromosome abnormalities and air pollution exposure. CONCLUSIONS: We concluded that ambient air pollution was a risk factor for congenital anomalies in the fetuses conceived through IVF, especially exposure in early fetal period.


Subject(s)
Air Pollutants , Air Pollution , Air Pollutants/analysis , Air Pollutants/toxicity , Air Pollution/analysis , Air Pollution/statistics & numerical data , Child , China/epidemiology , Cross-Sectional Studies , Female , Fertilization in Vitro , Humans , Particulate Matter/analysis , Particulate Matter/toxicity , Parturition , Pregnancy
17.
Signal Transduct Target Ther ; 6(1): 438, 2021 12 24.
Article in English | MEDLINE | ID: covidwho-1585880

ABSTRACT

Messenger RNA (mRNA) vaccine technology has shown its power in preventing the ongoing COVID-19 pandemic. Two mRNA vaccines targeting the full-length S protein of SARS-CoV-2 have been authorized for emergency use. Recently, we have developed a lipid nanoparticle-encapsulated mRNA (mRNA-LNP) encoding the receptor-binding domain (RBD) of SARS-CoV-2 (termed ARCoV), which confers complete protection in mouse model. Herein, we further characterized the protection efficacy of ARCoV in nonhuman primates and the long-term stability under normal refrigerator temperature. Intramuscular immunization of two doses of ARCoV elicited robust neutralizing antibodies as well as cellular response against SARS-CoV-2 in cynomolgus macaques. More importantly, ARCoV vaccination in macaques significantly protected animals from acute lung lesions caused by SARS-CoV-2, and viral replication in lungs and secretion in nasal swabs were completely cleared in all animals immunized with low or high doses of ARCoV. No evidence of antibody-dependent enhancement of infection was observed throughout the study. Finally, extensive stability assays showed that ARCoV can be stored at 2-8 °C for at least 6 months without decrease of immunogenicity. All these promising results strongly support the ongoing clinical trial.


Subject(s)
COVID-19 Vaccines/pharmacology , COVID-19/immunology , Immunogenicity, Vaccine , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , /pharmacology , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/prevention & control , COVID-19 Vaccines/immunology , Chlorocebus aethiops , Humans , Macaca fascicularis , Vero Cells , /immunology
19.
Cell Res ; 31(1): 25-36, 2021 01.
Article in English | MEDLINE | ID: covidwho-1387275

ABSTRACT

Structural principles underlying the composition and synergistic mechanisms of protective monoclonal antibody cocktails are poorly defined. Here, we exploited antibody cooperativity to develop a therapeutic antibody cocktail against SARS-CoV-2. On the basis of our previously identified humanized cross-neutralizing antibody H014, we systematically analyzed a fully human naive antibody library and rationally identified a potent neutralizing antibody partner, P17, which confers effective protection in animal model. Cryo-EM studies dissected the nature of the P17 epitope, which is SARS-CoV-2 specific and distinctly different from that of H014. High-resolution structure of the SARS-CoV-2 spike in complex with H014 and P17, together with functional investigations revealed that in a two-antibody cocktail, synergistic neutralization was achieved by S1 shielding and conformational locking, thereby blocking receptor attachment and viral membrane fusion, conferring high potency as well as robustness against viral mutation escape. Furthermore, cluster analysis identified a hypothetical 3rd antibody partner for further reinforcing the cocktail as pan-SARS-CoVs therapeutics.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19 , Epitopes/immunology , SARS-CoV-2/immunology , Single-Chain Antibodies/immunology , Animals , Antibodies, Neutralizing/pharmacology , Antibodies, Viral/pharmacology , COVID-19/immunology , COVID-19/prevention & control , Chlorocebus aethiops , Disease Models, Animal , Humans , Single-Chain Antibodies/pharmacology , Vero Cells
20.
Bioorg Chem ; 115: 105196, 2021 10.
Article in English | MEDLINE | ID: covidwho-1322004

ABSTRACT

So far, there is still no specific drug against COVID-19. Taking compound 1 with anti-EBOV activity as the lead, fifty-four 12N-substituted aloperine derivatives were synthesized and evaluated for the anti-SARS-CoV-2 activities using pseudotyped virus model. Among them, 8a exhibited the most potential effects against both pseudotyped and authentic SARS-CoV-2, as well as SARS-CoV and MERS-CoV, indicating a broad-spectrum anti-coronavirus profile. The mechanism study disclosed that 8a might block a late stage of viral entry, mainly via inhibiting host cathepsin B activity rather than directly targeting cathepsin B protein. Also, 8a could significantly reduce the release of multiple inflammatory cytokines in a time- and dose-dependent manner, such as IL-6, IL-1ß, IL-8 and MCP-1, the major contributors to cytokine storm. Therefore, 8a is a promising agent with the advantages of broad-spectrum anti-coronavirus and anti-cytokine effects, thus worthy of further investigation.


Subject(s)
Antiviral Agents/pharmacology , Piperidines/pharmacology , Quinolizidines/pharmacology , SARS-CoV-2/drug effects , Virus Internalization/drug effects , Animals , Antiviral Agents/chemical synthesis , Antiviral Agents/pharmacokinetics , Antiviral Agents/toxicity , Cathepsin B/antagonists & inhibitors , Chlorocebus aethiops , Cytokines/metabolism , HEK293 Cells , Humans , Male , Mice , Microbial Sensitivity Tests , Molecular Structure , Piperidines/chemical synthesis , Piperidines/pharmacokinetics , Piperidines/toxicity , Quinolizidines/chemical synthesis , Quinolizidines/pharmacokinetics , Quinolizidines/toxicity , Rats, Sprague-Dawley , Structure-Activity Relationship , Vero Cells
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