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1.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-335275

ABSTRACT

While SARS-CoV-2 pathogenesis has been intensively investigated, the host mechanisms of viral clearance and inflammation resolution are still elusive because of the ethical limitation of human studies based on COVID-19 convalescents. Here we infected Syrian hamsters by authentic SARS-CoV-2 and built an ideal model to simulate the natural recovery process of SARS-CoV-2 infection from severe pneumonia 1,2 . We developed and applied a spatial transcriptomic sequencing technique with subcellular resolution and tissue-scale extensibility, i.e. , Stereo-seq 3 , together with single-cell RNA sequencing (scRNA-seq), to the entire lung lobes of 45 hamsters and obtained an elaborate map of the pulmonary spatiotemporal changes from acute infection, severe pneumonia to the late viral clearance and inflammation resolution. While SARS-CoV-2 infection caused massive damages to the hamster lungs, including naïve T cell infection and deaths related to lymphopenia, we identified a group of monocyte-derived proliferating Slamf9 + Spp1 + macrophages, which were SARS-CoV-2 infection-inducible and cell death-resistant, recruiting neutrophils to clear viruses together. After viral clearance, the Slamf9 + Spp1 + macrophages differentiated into Trem2 + and Fbp1 + macrophages, both responsible for inflammation resolution and replenishment of alveolar macrophages. The existence of this specific macrophage subpopulation and its descendants were validated by RNAscope in hamsters, immunofluorescence in hACE2 mice, and public human autopsy scRNA-seq data of COVID-19 patients. The spatiotemporal landscape of SARS-CoV-2 infection in hamster lungs and the identification of Slamf9 + Spp1 + macrophages that is pivotal to viral clearance and inflammation resolution are important to better understand the critical molecular and cellular players of COVID-19 host defense and also develop potential interventions of COVID-19 immunopathology.

2.
Translational Psychiatry ; 12(1):180-180, 2022.
Article in English | PMC | ID: covidwho-1821577

ABSTRACT

The long-term health consequences of the COVID-19 pandemic on health care workers (HCWs) are largely unclear. The purpose of the present study was to investigate the development of posttraumatic stress disorder (PTSD) in HCWs in a longitudinal manner. Additionally, we further explored the role of risk perception in the evolution of PTSD over time based on a one-year follow-up study. HCWs were recruited from hospitals in Guangdong, China. Demographic information, the PTSD checklist for DSM-5 (PCL-5) and the risk perception questionnaire were obtained online at two different time points: May to June 2020 (T1), with 317 eligible responses, and June 2021 (T2), with 403 eligible responses. Seventy-four HCWs participated in the survey at both T1 and T2. The results revealed that (1) the PTSD prevalence rate in the HCWs (cut-off = 33) increased from 10.73% at T1 to 20.84% at T2, and the HCWs reported significantly higher PTSD scores at T2 than at T1 ( p  < 0.001);(2) risk perception was positively correlated with PTSD ( p  < 0.001);and (3) PTSD at T1 could significantly positively predict PTSD at T2 ( β  = 2.812, p  < 0.01), and this longitudinal effect of PTSD at T1 on PTSD at T2 was mediated by risk perception at T2 (coefficient = 0.154, 95% CI = 0.023 to 0.297). Our data provide a snapshot of the worsening of HCWs’ PTSD along with the repeated pandemic outbreaks and highlight the important role of risk perception in the development of PTSD symptoms in HCWs over time.

3.
Preprint in English | medRxiv | ID: ppmedrxiv-22274797

ABSTRACT

BackgroundAustralia implemented an mRNA-based booster vaccination strategy against the COVID-19 Omicron variant in November 2021. We aimed to evaluate the effectiveness and cost-effectiveness of the booster strategy over 180 days. MethodsWe developed a decision-analytic Markov model of COVID-19 to evaluate the cost-effectiveness of a booster strategy (administered 3 months after 2nd dose) in those aged [≥]16 years in Australia from a healthcare system perspective. The willingness-to-pay threshold was chosen as A$ 50,000. FindingsCompared with 2-doses of COVID-19 vaccines without a booster, Australias booster strategy would incur an additional cost of A$0.88 billion but save A$1.28 billion in direct medical cost and gain 670 quality-adjusted life years (QALYs) in 180 days of its implementation. This suggested the booster strategy is cost-saving, corresponding to a benefit-cost ratio of 1.45 and a net monetary benefit of A$0.43 billion. The strategy would prevent 1.32 million new infections, 65,170 hospitalisations, 6,927 ICU admissions and 1,348 deaths from COVID-19 in 180 days. Further, a universal booster strategy of having all individuals vaccinated with the booster shot immediately once their eligibility is met would have resulted in a gain of 1,599 QALYs, a net monetary benefit of A$1.46 billion and a benefit-cost ratio of 1.95 in 180 days. InterpretationThe COVID-19 booster strategy implemented in Australia is likely to be effective and cost-effective for the Omicron epidemic. Universal booster vaccination would have further improved its effectiveness and cost-effectiveness. FundingNational Natural Science Foundation of China. Bill and Melinda Gates Foundation

4.
Computational Intelligence and Neuroscience : CIN ; 2022, 2022.
Article in English | ProQuest Central | ID: covidwho-1807687

ABSTRACT

According to Dunning’s eclectic theory, the location advantages play a key role in international investment mode choice, in which the country relations are important determinants. In some previous studies, the country relations and another bilateral factor, the country distance, are often confused, which can result in the inconsistency of conclusions. And excepting political factors, the economic dependence and other relations are insufficiently considered in the literature. This article makes a distinction between relation and distance, and puts forward a simplified analytical framework, the indicator system, and some quantitative methods for country relations. The indicators, including political, economic, and social factors, can better satisfy the horizontal analysis of the outbound investment. The economic and social indicators are determined by the magnitude of interaction as well as the share in the home country, and hence, the evaluation results can reflect the differences between the two countries. Finally, by evaluating the relations of other BRICS countries with China, the rationality is illustrated.

6.
Signal Transduct Target Ther ; 6(1): 427, 2021 12 16.
Article in English | MEDLINE | ID: covidwho-1795805

ABSTRACT

Abnormal glucose and lipid metabolism in COVID-19 patients were recently reported with unclear mechanism. In this study, we retrospectively investigated a cohort of COVID-19 patients without pre-existing metabolic-related diseases, and found new-onset insulin resistance, hyperglycemia, and decreased HDL-C in these patients. Mechanistically, SARS-CoV-2 infection increased the expression of RE1-silencing transcription factor (REST), which modulated the expression of secreted metabolic factors including myeloperoxidase, apelin, and myostatin at the transcriptional level, resulting in the perturbation of glucose and lipid metabolism. Furthermore, several lipids, including (±)5-HETE, (±)12-HETE, propionic acid, and isobutyric acid were identified as the potential biomarkers of COVID-19-induced metabolic dysregulation, especially in insulin resistance. Taken together, our study revealed insulin resistance as the direct cause of hyperglycemia upon COVID-19, and further illustrated the underlying mechanisms, providing potential therapeutic targets for COVID-19-induced metabolic complications.


Subject(s)
COVID-19/blood , Hyperglycemia/blood , Insulin Resistance , Lipid Metabolism , Lipids/blood , SARS-CoV-2/metabolism , Adult , Aged , Biomarkers/blood , COVID-19/complications , Female , Humans , Hyperglycemia/etiology , Male , Middle Aged , Retrospective Studies
7.
Risk Manag Healthc Policy ; 13: 1563-1569, 2020.
Article in English | MEDLINE | ID: covidwho-1793247

ABSTRACT

BACKGROUND: Coronavirus disease-2019 (COVID-19) is a new infectious disease. The COVID-19 outbreak has quickly spread globally and now is having remarkable effects on public health and national economies. PURPOSE: Effective measures for prevention and control of nosocomial infection are urgently needed to control COVID-19 infection among medical staff. METHODS: Herein, we described COVID-19 prevention and control strategies that have been implemented in a tertiary hospital in the middle east of China. Hospital layout was adjusted to prevent and control transmission. Other procedures were then implemented to prevent the spread of the virus, including specialized training and evaluation of medical staff, pre-testing and triage, measures to promote early identification of patients, environmental cleaning and disinfection, new medical waste processing procedures, new patient management procedures, timely disinfection of potential sources of nosocomial infection, and strict protective measures. RESULTS: Since the new measures were implemented, to date there have only been three new confirmed cases of COVID-19 infection, no cases of medical staff infection, and no COVID-19-related deaths at the hospital. CONCLUSION: The current report provides a protocol that could be implemented in medical departments in similar cities worldwide.

8.
Infectious Diseases of Poverty ; 11:1-6, 2022.
Article in English | ProQuest Central | ID: covidwho-1793808

ABSTRACT

Prompt and precise diagnosis of patients is an essential component of malaria control and elimination strategies, it is even more vital for the prevention of malaria re-establishment in the post elimination phase. After eliminating malaria in China, the strategy for prevention of malaria re-establishment was updated in a timely manner from the elimination strategy focusing on each case/focus to the prevention of re-establishment focusing on timely identification of the source of infection. However, there are numerous challenges, such as the persistent large number of imported malaria cases, the long-term threat of border malaria, unknown levels of asymptomatic infections and Plasmodium falciparum HRP2/3 gene deletions, and the continuous spreading of antimalarial drug resistance. Meanwhile, the detection capacity also need to be further improved to meet the timely detection of all sources of infection, otherwise it is bound to occur introduced malaria cases and malaria re-establishment in the presence of malaria vector mosquitoes. Therefore, it is necessary to continuously strengthen the malaria detection competency at all levels, promote the research and development on the malaria parasitological testing technologies, thus improving the timely detection of various sources of infection, and preventing the re-establishment of malaria.

10.
Preprint in English | bioRxiv | ID: ppbiorxiv-487828

ABSTRACT

Increasing evidence supports inter-species transmission of SARS-CoV-2 variants from human to domestic or wild animals during the ongoing COVID-19 pandemic, which is posing great challenges to epidemic control. Clarifying the host range of emerging SARS-CoV-2 variants will provide instructive information for the containment of viral spillover. The spike protein (S) of SARS-CoV-2 is the key determinant of receptor utilization, and therefore amino acid mutations on S will probably alter viral host range. Here, in order to evaluate the impact of S mutations, we constructed 20 Hela cell lines stably expressing ACE2 orthologs from different animals, and prepared 27 pseudotyped SARS-CoV-2 carrying different spike mutants, among which 20 bear single mutation and the other 7 were cloned from emerging SARS-CoV-2 variants, including D614G, Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.135), Lambda (B.1.429) and Mu (B.1.525). Using pseudoviral reporter assay, we identified that the substitutions of T478I and N501Y enabled the pseudovirus to utilize chicken ACE2, indicating potential infectivity to avian species. Furthermore, the S mutants of real SARS-CoV-2 variants comprising N501Y showed significantly acquired abilities to infect cells expressing mouse ACE2, indicating a critical role of N501Y in expanding SARS-CoV-2 host range. In addition, A262S and T478I significantly enhanced the utilization of various mammals ACE2. In summary, our results indicated that T478I and N501Y substitutions were two S mutations important for receptor adaption of SARS-CoV-2, potentially contributing to spillover of the virus to many other animal hosts. Therefore, more attention should be paid to SARS-CoV-2 variants with these two mutations.

11.
Front Microbiol ; 12: 803031, 2021.
Article in English | MEDLINE | ID: covidwho-1753384

ABSTRACT

Background: COVID-19 has caused more than 2.6 billion infections and several million deaths since its outbreak 2 years ago. We know very little about the long-term cellular immune responses and the kinetics of neutralizing antibodies (NAbs) to SARS-CoV-2 because it has emerged only recently in the human population. Methods: We collected blood samples from individuals who were from the first wave of the COVID-19 epidemic in Wuhan between December 30, 2019, and February 24, 2020. We analyzed NAbs to SARS-CoV-2 using pseudoviruses and IgG antibodies to SARS-CoV-2 spike (S) and nucleocapsid (N) protein using enzyme-linked immunosorbent assay in patients' sera and determined SARS-CoV-2-specific T-cell responses of patients with ELISpot assays. Results: We found that 91.9% (57/62) and 88.9% (40/45) of COVID-19 patients had NAbs against SARS-CoV-2 in a year (10-11 months) and one and a half years (17-18 months), respectively, after the onset of illness, indicating that NAbs against SARS-CoV-2 waned slowly and possibly persisted over a long period time. Over 80% of patients had IgG antibodies to SARS-CoV-2 S and N protein one and a half years after illness onset. Most patients also had robust memory T-cell responses against SARS-CoV-2 one and a half years after the illness. Among the patients, 95.6% (43/45) had an IFN-γ-secreting T-cell response and 93.8% (15/16) had an IL-2-secreting T-cell response. The T-cell responses to SARS-CoV-2 were positively correlated with antibodies (including neutralizing antibodies and IgG antibodies to S and N protein) in COVID-19 patients. Eighty percent (4/5) of neutralizing antibody-negative patients also had SARS-CoV-2-specific T-cell response. After long-term infection, protective immunity was independent of disease severity, sex, and age. Conclusions: We concluded that SARS-CoV-2 infection elicited a robust and persistent neutralizing antibody and memory T-cell response in COVID-19 patients, indicating that these sustained immune responses, among most SARS-CoV-2-infected people, may play a crucial role in protection against reinfection.

12.
Angewandte Chemie ; 134(12), 2022.
Article in English | ProQuest Central | ID: covidwho-1729095

ABSTRACT

Desirable biosensing assays need to be sensitive, specific, cost‐effective, instrument‐free, and versatile. Herein we report a new strategy termed CLIPON (CRISPR and Large DNA assembly Induced Pregnancy strips for signal‐ON detection) that can deliver these traits. CLIPON integrates a commercial pregnancy test strip (PTS) with four biological elements: the human chorionic gonadotropin (hCG), CRISPR‐Cas12a, crRNA and cauliflower‐like large‐sized DNA assemblies (CLD). CLIPON uses the Cas12a/crRNA complex both to recognize a target of interest and to release CLD‐bound hCG so that target presence can translate into a colorimetric signal on the PTS. We demonstrate the versatility of CLIPON through sensitive and specific detection of HPV genomic DNA, SARS‐CoV‐2 genomic RNA and adenosine. We also engineer a cell phone app and a hand‐held microchip to achieve signal quantification. CLIPON represents an attractive option for biosensing and point‐of‐care diagnostics.

13.
Frontiers in psychology ; 13, 2022.
Article in English | EuropePMC | ID: covidwho-1728393

ABSTRACT

Public welfare fundraising has been used to collect donations for medical supplies and has played an important role in the fight against the COVID-19 pandemic. This paper studies online crowdfunding donations from the Alumni Association of Wuhan University to North American alumni;donation data are used to investigate how individuals' donation behavior is affected by the previous donation amount and information provided by the fundraising platform. First, our results show that one's donation amount is positively affected by the previous donation amount. Second, the donor's positive sentiment in the message that he or she leaves, as measured by either natural language processing or a manual rating, can affect the subsequent anonymity and messages but not the subsequent donation amount. Third, anonymous donations are much smaller than non-anonymous donations.

14.
Infectious Medicine ; 2022.
Article in English | PMC | ID: covidwho-1720101
15.
Frontiers in medicine ; 9, 2022.
Article in English | EuropePMC | ID: covidwho-1696189

ABSTRACT

The coronavirus disease (COVID-19) pandemic has significantly increased the number of patients with acute respiratory distress syndrome (ARDS), necessitating respiratory support. This strain on intensive care unit (ICU) resources forces clinicians to limit the use of mechanical ventilation by seeking novel therapeutic strategies. Awake-prone positioning appears to be a safe and tolerable intervention for non-intubated patients with hypoxemic respiratory failure. Meanwhile, several observational studies and meta-analyses have reported the early use of prone positioning in awake patients with COVID-19-related ARDS (C-ARDS) for improving oxygenation levels and preventing ICU transfers. Indeed, some international guidelines have recommended the early application of awake-prone positioning in patients with hypoxemic respiratory failure attributable to C-ARDS. However, its effectiveness in reducing intubation rate, mortality, applied timing, and optimal duration is unclear. High-quality evidence of awake-prone positioning for hypoxemic patients with COVID-19 is still lacking. Therefore, this article provides an update on the current state of published literature about the physiological rationale, effect, timing, duration, and populations that might benefit from awake proning. Moreover, the risks and adverse effects of awake-prone positioning were also investigated. This work will guide future studies and aid clinicians in deciding on better treatment plans.

16.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-325501

ABSTRACT

Background: Many COVID-19 patients have been discharged, but lung injury, including pulmonary fibrosis, might lead to long-term impairment. This study aimed to evaluate predictors and monitors of pulmonary fibrosis in patients with COVID-19. Methods Thirty-five convalescent patients with severe COVID-19, after appropriate medical treatments, were recruited. According to evidence of fibrosis on initial computed tomography (CT), the patients were divided into mild-to-moderate and severe groups. Levels of transforming growth factor beta (TGF-β), chemokine ligand 18 (CCL18), type III procollagen peptide (PⅢP), hyaluronic acid (HA), laminin (LN), and type IV collagen (CⅣ) were determined. Laboratory tests, clinical data, and CT features at different stages were collected and analyzed, and the prognostic performance of these parameters was evaluated. Results Severe fibrosis was found in 76.29% (26/35) of patients. However, most baseline laboratory characteristics were normal. Fibrosis indicators (TGF-β: 66.67 ± 158.57 vs 55.84 ± 126.43 pg/mL, P = 0.006;CCL18: 364.27 ± 167.70 vs 84.47 ± 60.67 ng/mL, P = 0.000;PⅢP: 54.12 ± 55.34 vs 17.15 ± 2.48 ng/mL, P = 0.000;HA: 122.47 ± 78.84 vs 59.74 ± 18.01 ng/mL, p = 0.000;LN: 55.43 ± 46.44 vs 24.25 ± 7.79 ng/mL, P = 0.000;CⅣ: 24.77 ± 14.97 vs 15.32 ± 1.15 ng/mL, P = 0.001) were elevated in patients compared with controls. Over 90 days’ follow-up, HRCT scores gradually decreased from 22.48 ± 16.13 to 10.33 ± 11.11 (P < 0.001), and mMRC scores decreased from 3.27 ± 0.32 to 1.48 ± 0.33, and all fibrosis indicators, except for PⅢP, gradually declined with the improvement of pulmonary fibrosis. Moreover, TGF-β and CCL18 levels were lower in the mild-to-moderate than severe fibrosis group (88.16 ± 97.45 vs 205.93 ± 170.57 pg/mL, P = 0.024;241.84 ± 125.37 vs 366.64 ± 161.06 ng/mL, P = 0.038), and patients with elevated baseline levels of serum TGF-β and CCL18 had longer rehabilitation times. Conclusions TGF-β and CCL18 may be promising biomarkers for predicting and monitoring the development of pulmonary fibrosis in patients with COVID-19.

17.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325010

ABSTRACT

Background: Since December 2019, COVID-19 has rapidly swept the world. It is particularly important to understand the dynamic changes of the whole disease course of non-severe patients from the onset to the follow-up after discharge. Methods: : On February 1, 2020, 18 cases of non-severe COVID-19 appeared in a hospital in Beijing. All patients were SARS-CoV-2 RNA positive by RT-PCR for pharyngeal swabs. We recorded the clinical information and viral dynamics of these patients from the onset of the disease to 2 months after discharge. According to the severity of lung consolidation, 18 patients were divided into two groups (mild pulmonary consolidation group [imaging score ≤10];severe pulmonary consolidation group [imaging score >10]). Results: : Eighteen patients (median age 43) were included, including 14 females. Fever (11/18) and cough (8/18) were the most common symptoms. The duration of SARS-CoV-2 RNA positive in mild pulmonary consolidation group was significantly longer than severe pulmonary consolidation group (the median time was 30 days and 13 days, respectively, P= 0.0031). Two months after discharge, almost all patients were followed up for IgM antibody disappearance and IgG antibody production. Conclusion: In non-severe COVID-19 patients, the positive duration of the SARS-CoV-2 RNA in patients with mild pulmonary consolidation was longer than the severe pulmonary consolidation. However, it is necessary for a large sample to verify our conclusions.

18.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-324821

ABSTRACT

Coronavirus Disease 2019 (COVID-19) has become a world-wide pandemic. Hospitalized patients of COVID-19 suffer from a high mortality rate, motivating the development of convenient and practical methods for clinicians to promptly identify high-risk patients. Here we developed a risk score using clinical data from 1,479 inpatients admitted to Tongji Hospital, Wuhan, China (development cohort) and externally validated with data from two other centers: 141 inpatients from Jinyintan Hospital in Wuhan (validation cohort 1) and 432 inpatients from the Third People’s Hospital Shenzhen (validation cohort 2). The risk score is based on three biomarkers readily available in routine blood samples and can be easily translated into a probability of death. The risk score can predict the mortality of individual patients more than 12 days in advance with more than 90% accuracy across all cohorts. Moreover, the Kaplan-Meier score shows that patients upon admission can clearly be differenciated into low, medium or high risk, with an AUC score of 0.9551. In summary, a simple risk score was validated to predict death in patients infected with COVID-19 and was validated in independent cohorts.

19.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-324552

ABSTRACT

Background: With the widespread outbreak of novel coronavirus diseases 2019(COVID-19), more and more death cases were reported, however, limited data are available for the patients who died. We aimed to explore the clinial characteristics of deaths with COVID-19 pneumonia Methods: : We abstracted and analyzed epidemiological, demographic, clinical, and laboratory data from 83 death cases with COVID-19 pneumonia in East hospital of Wuhan university Renmin hospital,between January 26, 2020, and February 28, 2020. Results: : Of the 83 deaths, none was the medical staff. The mean age was 71.8 years (SD 13.2;range, 34-97 years) and 53(63.9%) were male. The median from onset to admission was 10 days (IQR 7-14: range, 2-43 days), to death was 17days (IQR 14-21: range, 6-54 days). Most deaths (66[80%]) had underlying comorbid diseases, the most of which was hypertension [47(57%)]. The main initial symptoms of these 83 deaths were shortness of breath(98.8%), fever(94%) and myalgia or fatigue(90.4%). Laboratory analyses showed the lymphocytopenia in 69(83%) deaths, hypoalbuminemia in 77(93%) deaths, the elevation of lactate dehydrogenase in 79(95%) deaths, procalcitonin in 69(83%) deaths and C-reactive protein in 79(95%) deaths. All 83 patients received antiviral treatment, 81(97.6%) deaths received antibiotic therapy, and 54(65.1%) deaths received glucocorticoid therapy and 20(24.1%) patients received invasive mechanical ventilation. Conclusion: Most of the deaths with COVID-19 pneumonia were elderly patients with underlying comorbid diseases, especially those over 70 years of age. The time of death was mostly 15-21 days after the onset of the disease. More care should be given to the elderly in the further prevention and control strategies of COVID-19.

20.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-324281

ABSTRACT

Background: Coronavirus disease 2019 (COVID-19) was identified as a serious public health emergency. The Chinese government required people to stay at home. The purpose of this study was to analyse the effect of home exercise prescription solutions on the physical and mental health of youth during the COVID-19 period. Methods: A home exercise prescription was formulated after investigating and categorizing the home exercise status of 4000 undergraduates during the period of COVID-19. In this prospective cohort study, 200 young people were recruited for a home exercise prescription intervention, and 200 individuals did not undergo any intervention for 4 weeks in February 2020. Physical and mental health indexes including anxiety factors, obsessive-compulsive symptoms factors, depression factors, somatization subscale factors, and sleep and diet factors were evaluated. Results: Of 4,000 undergraduates living at home, 64.8% were dissatisfied with their physical and mental condition. Ninety-three percent wanted to adopt an exercise practice at home during the period of COVID-19. In the prospective cohort study, the average anxiety scores and sleep and diet scores before the intervention were 2.14 ± 0.43 and 2.24 ± 0.54, respectively, in the intervention group. After 4 weeks, participants reported that negative emotions were reduced. The scores for all factors were less than 2 points, and there were significant differences between the pre-intervention and post-intervention time points ( P  < 0.05). Differences between the two groups were statistically significant at 2 and 4 weeks (P < 0.05). Conclusion: There was an urgent need for home exercise programmes for youth during the period of COVID-19. Formulating appropriate home exercise prescriptions could help maintain physical and mental health, enhance immunity, and prevent disease. Trial registration ChiCTR, ChiCTR2000030090, Registered February 24th, 2020. http://www.chictr.org.cn/edit.aspx

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