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1.
Nat Commun ; 14(1): 1058, 2023 Feb 24.
Article in English | MEDLINE | ID: covidwho-2288034

ABSTRACT

SARS-CoV-2 Omicron variants feature highly mutated spike proteins with extraordinary abilities in evading antibodies isolated earlier in the pandemic. Investigation of memory B cells from patients primarily with breakthrough infections with the Delta variant enables isolation of a number of neutralizing antibodies cross-reactive to heterologous variants of concern (VOCs) including Omicron variants (BA.1-BA.4). Structural studies identify altered complementarity determining region (CDR) amino acids and highly unusual heavy chain CDR2 insertions respectively in two representative cross-neutralizing antibodies-YB9-258 and YB13-292. These features are putatively introduced by somatic hypermutation and they are heavily involved in epitope recognition to broaden neutralization breadth. Previously, insertions/deletions were rarely reported for antiviral antibodies except for those induced by HIV-1 chronic infections. These data provide molecular mechanisms for cross-neutralization of heterologous SARS-CoV-2 variants by antibodies isolated from Delta variant infected patients with implications for future vaccination strategy.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Antibodies, Neutralizing , Antibodies, Viral , Spike Glycoprotein, Coronavirus
2.
J Clin Med ; 12(6)2023 Mar 20.
Article in English | MEDLINE | ID: covidwho-2263331

ABSTRACT

Door-to-balloon (DTB) time significantly affects the prognosis of patients with ST-segment elevation myocardial infarction (STEMI). The effects of temporal differences in emergency department (ED) arrival time on DTB time and on different segments of DTB time remain inconclusive. Therefore, we performed a retrospective study in a tertiary hospital between January 2013 and December 2021 and investigated the relationship between a patient's arrival time and both their DTB time and different segments of their DTB time. Of 732 STEMI patients, 327 arrived during the daytime (08:01-16:00), 268 during the evening (16:01-24:00), and 137 at night (00:01-08:00). Significantly higher odds of delay in DTB time were observed during the nighttime (adjusted odds ratio (aOR): 2.87; 95% confidence interval (CI): 1.50-5.51, p = 0.002) than during the daytime. This delay was mainly attributed to a delay in cardiac catheterization laboratory (cath lab) activation-to-arrival time (aOR: 6.25; 95% CI: 3.75-10.40, p < 0.001), particularly during the 00:00-04:00 time range. Age, sex, triage level, and whether patients arrived during the COVID-19 pandemic also had independent effects on different segments of DTB time. Further studies are required to investigate the root causes of delay in DTB time and to develop specific strategies for improvement.

3.
Nature ; 604(7907): 723-731, 2022 04.
Article in English | MEDLINE | ID: covidwho-1799583

ABSTRACT

Studying tissue composition and function in non-human primates (NHPs) is crucial to understand the nature of our own species. Here we present a large-scale cell transcriptomic atlas that encompasses over 1 million cells from 45 tissues of the adult NHP Macaca fascicularis. This dataset provides a vast annotated resource to study a species phylogenetically close to humans. To demonstrate the utility of the atlas, we have reconstructed the cell-cell interaction networks that drive Wnt signalling across the body, mapped the distribution of receptors and co-receptors for viruses causing human infectious diseases, and intersected our data with human genetic disease orthologues to establish potential clinical associations. Our M. fascicularis cell atlas constitutes an essential reference for future studies in humans and NHPs.


Subject(s)
Macaca fascicularis , Transcriptome , Animals , Cell Communication , Macaca fascicularis/genetics , Receptors, Virus/genetics , Transcriptome/genetics , Wnt Signaling Pathway
4.
One Health ; 13: 100343, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1510164

ABSTRACT

INTRODUCTION: The negative impact of the coronavirus disease 2019 (COVID-19) pandemic on mental health and physical activity is well reported. While prior studies showed a positive influence of pet ownership on physical activity and mental health, the interactions between the pandemic and pet ownership are not well studied. OBJECTIVE: To determine the association between pet ownership, physical activity levels and mental health during the COVID-19 pandemic. MATERIALS AND METHODS: A cross-sectional study was conducted from May 19 to July 13, 2020 among Singapore residents aged 21 to 64 years through a previously published questionnaire. Inverse probability treatment weighting was used to develop mixed-effects models for outcome comparisons. We recorded participant data on pet ownership, duration and intensity of physical activity, and RAND 36-item Health Survey mental health domains during the COVID-19 pandemic. RESULTS: The questionnaire was completed by 431 pet owners and 103 non-pet owners. A greater proportion of pet owners were female, non-married, employed and owned pets in the past. Pet owners reported 31.8 (95% CI 13.6 to 50; p = .001) more minutes per week of mild-intensity physical activity compared to non-pet owners. No statistically significant differences were found for moderate- and vigorous-intensity physical activity. Pet owners had better emotional well-being (ꞵ = 9.66, 95% CI 4.97 to 14.4; p < .001), energy (ꞵ = 8.29, 95% CI 3.46 to 13.1; p = .001) and social functioning (ꞵ = 11.2, 95% CI 5.03 to 17.4; p < .001) scores than non-pet owners. However, no statistically significant difference was observed for general health scores. Pet owner physical activity levels, general health, emotional well-being and energy scores correlated positively with pet attachment scores. CONCLUSION: Pet ownership was associated with greater physical activity levels and better mental health, particularly in main caregivers with higher pet attachment scores. These findings suggest that pet ownership is beneficial to physical and mental well-being during periods of social isolation amidst a global pandemic.

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