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1.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-327285

ABSTRACT

The emerging SARS-CoV-2 variants of concern (VOC) harbor mutations associated with increasing transmission and immune escape, hence undermine the effectiveness of current COVID-19 vaccines. In late November of 2021, the Omicron (B.1.1.529) variant was identified in South Africa and rapidly spread across the globe. It was shown to exhibit significant resistance to neutralization by serum not only from convalescent patients, but also from individuals recieving currently used COVID-19 vaccines with multiple booster shots. Therefore, there is an urgent need to develop next generation vaccines against VOCs like Omicron. In this study, we develop a panel of mRNA-LNP-based vaccines using the receptor binding domain (RBD) of Omicron and Delta variants, which are dominant in the current wave of COVID-19. In addition to the Omicron- and Delta-specific vaccines, the panel also includes a Hybrid vaccine that uses the RBD containing all 16 point-mutations shown in Omicron and Delta RBD, as well as a bivalent vaccine composed of both Omicron and Delta RBD-LNP in half dose. Interestingly, both Omicron-specific and Hybrid RBD-LNP elicited extremely high titer of neutralizing antibody against Omicron itself, but few to none neutralizing antibody against other SARS-CoV-2 variants. The bivalent RBD-LNP, on the other hand, generated antibody with broadly neutralizing activity against the wild-type virus and all variants. Surprisingly, similar cross-protection was also shown by the Delta-specifc RBD-LNP. Taken together, our data demonstrated that Omicron-specific mRNA vaccine can induce potent neutralizing antibody response against Omicron, but the inclusion of epitopes from other variants may be required for eliciting cross-protection. This study would lay a foundation for rational development of the next generation vaccines against SARS-CoV-2 VOCs.

2.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325408

ABSTRACT

Background: Since December 2019, 2019-nCoV has emerged in Wuhan, China, the fast pace of transmission is wreaking global public health crisis. Country’s reaction speed is critical for the control of public health emergency (PHE), especially in the early stage of an outbreak. Compared with SARS pandemic, whether has the efficiency of initial public health emergency response to COVID-19 in mainland China been improved? And whether is there still existing vulnerabilities in current PHE system? Studies on this topic are relatively few. We tried to find the answers, evidences and alternatives. Methods: : We conducted a retrospective comparative study. The speed of hospital reporting, pathogen identification and government decision-making between SARS and COVID-19 were compared by selecting 5 critical events from initial public health emergency response timeline. Besides, combining with the two pandemics' progress curves, we discussed the characteristics of their peak time. Results: : (1) SARS completed the entire initial public health emergency response in 127 days, and COVID-19 completed in 44 days. Response speed has been shorted nearly by 3 times. (2) Both the first SARS and COVID-19 cases were reported in 19 days. It doesn't appear that hospital reporting speed becomes faster. (3) The accumulated time completing pathogen identification were 118 days for SARS and 31 days for COVID-19. The speed has been improved by more than 3 times. (4) 9 days after the completion of pathogen identification, national government made emergency policies for SARS while the interval between pathogen identification and national government's decision-making for COVID-19 was 13 days. (5) The peak time of SARS came about 80 days later than that of COVID-19. But both the two pandemics' peak occurred about 20 days after the national government's decision-making, and then the curves went down dramatically. Conclusions: : The speed of initial public health emergency response to pandemic has been improved due to faster identification. However, some deficiencies and challenges in early alert and authorities' decision-making still remain. Therefore, Chinese government should put more stress on improving hospital's sensitivity to new emerging infectious diseases and timeliness of government's decision-making.

3.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-324155

ABSTRACT

The outbreak of the 2019 novel coronavirus disease (COVID-19) infection in China had quickly spread worldwide. Recent reports showed that conjunctivitis symptoms were found in a small number of adult patients diagnosed with COVID-19. But rare children diagnosed with COVID-19 were reported to have eye symptoms. Our case showed a 2 years and 10 months old child confirmed COVID-19 had no symptoms other than conjunctivitis and eyelid dermatitis, suggesting that doctors shouldn’t forget to conduct COVID-19 screening when children come to hospital for ocular surface symptoms during this epidemic period.

4.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315891

ABSTRACT

Objectives: We aimed to explore the association between dynamic antibody responses and the clinical severity of COVID-19. MethodsWe collected complete follow-up data of 777 pathogen-confirmed COVID-19 patients with corresponding IgG/IgM testing results. ResultsWe found the overall positive rates of IgG and IgM in severe patients were slightly higher than those in non-severe patients. In addition, higher IgG levels were detected in severe patients compared with non-severe patients ( P =0.026). Through further analysis, our results showed that the statistical difference in the IgG only significant in serum samples taken ≤14 days from disease onset ( P <0.001). In 74 patients who taken detection more than three times, by analyzing the antibody expression levels at different time points, we found that the difference between IgG was more obvious than that of IgM among severe/non-severe patients. In multivariate logistic regression models, after adjusting for cofactors, the higher anti-SARS-CoV-2 IgG level before 14 days from disease onset was independently associated with severe disease in COVID-19 (OR=1.310, 95%CI= 1.137-1.509).ConclusionWe observed differences in antibody responses among COVID-19 patients with different disease severity. A high IgG level in the first 14 days from disease onset might positively associate with severe disease.

5.
J Affect Disord ; 304: 12-19, 2022 05 01.
Article in English | MEDLINE | ID: covidwho-1683225

ABSTRACT

BACKGROUND: Trauma experience increases the risk of suicidal ideation, but little is known about potentially psychological mechanisms underlying this relationship. This study aims to examine the relationship between coronavirus disease 2019 (COVID-19)-related traumatic event (CTE) exposure and suicidal ideation among hospital workers, and identify mediating roles of sleep disturbances in this relationship. METHODS: Workers in seven designated hospitals in Wuhan, China, were invited to participate in an online survey from May 27, 2020, to July 31, 2020. Participants completed a self-report questionnaire to evaluate demographic characteristics, level of CTE exposures, nightmare frequency, insomnia severity, symptoms of depression and anxiety, and suicidal ideation. A series of correlation analyses were performed, and a mediation model was generated to examine correlations between CTE exposure, sleep disturbances, and suicidal ideation. RESULTS: A total of 16,220 hospital workers were included in the final analysis, 13.3% of them reported suicidal ideation in the past month. CTE exposure was significantly associated with insomnia severity, nightmare frequency, and suicidal ideation. After controlling potential confounders, nightmares but not insomnia, depression, or anxiety were shown to be independent risk factors for suicidal ideation. Pathway analyses showed that the relationship between CTE exposure and suicidal ideation was fully mediated by nightmares (proportion mediated 66.4%) after adjusting for demographic characteristics and psychological confounders. LIMITATIONS: Cross-sectional design precluded the investigation of causal relationships. CONCLUSIONS: CTE exposure increases risk of hospital workers' suicidal ideation that is mediated by nightmares, suggesting nightmares intervention might be considered as a component when developing suicide prevention strategies.


Subject(s)
COVID-19 , Sleep Initiation and Maintenance Disorders , Cross-Sectional Studies , Dreams/psychology , Humans , Sleep Initiation and Maintenance Disorders/epidemiology , Suicidal Ideation
6.
Vaccines (Basel) ; 9(10)2021 Oct 13.
Article in English | MEDLINE | ID: covidwho-1623740

ABSTRACT

The present study assessed the willingness of the general population to receive COVID-19 vaccines and identified factors that influence vaccine hesitancy and resistance. A national online survey was conducted from 29 January 2021 to 26 April 2021 in China. Multinomial logistic regression analyses were conducted to identify factors that influence vaccine hesitancy and resistance. Of the 34,041 participants surveyed, 18,810 (55.3%) were willing to get vaccinated, 13,736 (40.3%) were hesitant, and 1495 (4.4%) were resistant. Rates of vaccine acceptance increased over time, with geographical discrepancies in vaccine hesitancy and resistance between provinces in China. Vaccine safety was the greatest concern expressed by most participants (24,461 [71.9%]), and the major reason for participants' refusing vaccination (974 [65.2%]). Government agencies (23,131 [68.0%]) and social media (20,967 [61.6%]) were the main sources of COVID-19 vaccine information. Compared with vaccination acceptance, female, young and middle-aged, high income, and perceived low-risk of infection were associated with vaccine hesitancy. Histories of allergic reactions to other vaccines and depression symptoms were related to vaccine resistance. Common factors that influenced vaccine hesitancy and resistance were residing in cities and perceiving less protection with vaccines than with other protective measures. The results indicate that the rate of vaccine resistance is relatively low, but vaccine hesitancy is common. Individuals who are female, young and middle-aged, with a high income, and residing in cities are more likely to be hesitant for vaccination and should be the target populations for vaccination campaigns. Specific vaccine messaging from the government and social media could alleviate public concerns about vaccine safety and efficacy.

7.
J Microbiol Immunol Infect ; 2021 Dec 31.
Article in English | MEDLINE | ID: covidwho-1587209

ABSTRACT

BACKGROUND: Characteristics of children with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Taiwanese households is nascent. We sought to characterize SARS-CoV-2 infection, and estimate the relative risk of infection among children within households during school closures in Taipei and New Taipei City. METHODS: We reviewed consecutive children below 18 years presenting to our emergency department from May 18, 2021 to July 12, 2021 who underwent real-time reverse-transcription polymerase chain reaction (rRT-PCR) for SARS-CoV-2 from respiratory swabs. Demographics, symptoms, and contacts were captured from medical records. Household contact was defined as an individual with confirmed COVID-19 living in the same residence as the child. RESULTS: Among 56 children with SARS-CoV-2, twenty-five (45%) were male with mean age of 7.9 years. Symptoms were nonspecific, with 29% having fever, 32% having cough, and 48% were asymptomatic. The median cycle threshold (Ct) value of SARS-CoV-2 rRT-PCR was 25 (range 11-38). All 56 children reported 94 contacts with a COVID-19 patient, of which 99% were household contacts. The relative risk of infection was 8.5 (95% CI 5.0-14.7) for children whose parent(s) were COVID-19 patients, and 7.3 (95% CI 4.9-11.0) for children whose household grandparent(s) were patients, as compared to children without respective contacts. Children without COVID-19 contacts were all tested negative. CONCLUSIONS: During school closures in Taipei and New Taipei City, children with SARS-CoV-2 infection in our cohort had one or more COVID-19 contacts, mostly within their households. While diagnosing pediatric COVID-19 is challenging as children were often asymptomatic, those without contacts were likely uninfected.

8.
PLoS Pathog ; 17(10): e1009704, 2021 10.
Article in English | MEDLINE | ID: covidwho-1484866

ABSTRACT

Development of effective therapeutics for mitigating the COVID-19 pandemic is a pressing global need. Neutralizing antibodies are known to be effective antivirals, as they can be rapidly deployed to prevent disease progression and can accelerate patient recovery without the need for fully developed host immunity. Here, we report the generation and characterization of a series of chimeric antibodies against the receptor-binding domain (RBD) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. Some of these antibodies exhibit exceptionally potent neutralization activities in vitro and in vivo, and the most potent of our antibodies target three distinct non-overlapping epitopes within the RBD. Cryo-electron microscopy analyses of two highly potent antibodies in complex with the SARS-CoV-2 spike protein suggested they may be particularly useful when combined in a cocktail therapy. The efficacy of this antibody cocktail was confirmed in SARS-CoV-2-infected mouse and hamster models as prophylactic and post-infection treatments. With the emergence of more contagious variants of SARS-CoV-2, cocktail antibody therapies hold great promise to control disease and prevent drug resistance.


Subject(s)
Antibodies, Neutralizing/pharmacology , Antibodies, Viral/pharmacology , COVID-19/immunology , COVID-19/prevention & control , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Cricetinae , Disease Models, Animal , Female , Male , Mice
9.
Risk Manag Healthc Policy ; 14: 4199-4209, 2021.
Article in English | MEDLINE | ID: covidwho-1477680

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome (SARS) was reported first in China in 2003. The world is currently coping with coronavirus disease-2019 (COVID-19). We conducted a retrospective study to compare the initial public-health emergency response (PHER) to SARS and COVID-19 in mainland China. METHODS: A qualitative comparative study was conducted to compare the PHER timelines to SARS and COVID-19 by selecting six crucial time points. Besides, we explored the speed of spread, peak time and plateau period of SARS and COVID-19, respectively, by comparing the confirmed cases in the same time interval. RESULTS: The government of the People's Republic of China (PRC) accomplished the entire initial PHER to SARS in 127 days and for COVID-19 in 44 days. The speed of PHER for COVID-19 was 83 days faster. The peak time of SARS arose ~80 days later than that of COVID-19. Though the peak number of confirmed daily cases for COVID-19 was fivefold more than that of SARS, the onset of the stabilization period for COVID-19 was >2 months earlier than that of SARS. CONCLUSION: Overall, the speed of the initial PHER to COVID-19 pandemic was faster than that for SARS. Compared with the speed of hospital reporting and government policymaking, the speed of pathogen identification improved the most. The COVID-19 pandemic curve entered a plateau period earlier than the SARS pandemic curve, which suggests that the pandemic was controlled more effectively because of a timely PHER. The PRC government should emphasize improving the ability of hospitals to restrain infectious diseases by enhancing the direct reporting system and cultivating crisis management to empower relevant individuals to make timely scientific decisions.

10.
Vaccines (Basel) ; 9(10)2021 Oct 13.
Article in English | MEDLINE | ID: covidwho-1471004

ABSTRACT

The present study assessed the willingness of the general population to receive COVID-19 vaccines and identified factors that influence vaccine hesitancy and resistance. A national online survey was conducted from 29 January 2021 to 26 April 2021 in China. Multinomial logistic regression analyses were conducted to identify factors that influence vaccine hesitancy and resistance. Of the 34,041 participants surveyed, 18,810 (55.3%) were willing to get vaccinated, 13,736 (40.3%) were hesitant, and 1495 (4.4%) were resistant. Rates of vaccine acceptance increased over time, with geographical discrepancies in vaccine hesitancy and resistance between provinces in China. Vaccine safety was the greatest concern expressed by most participants (24,461 [71.9%]), and the major reason for participants' refusing vaccination (974 [65.2%]). Government agencies (23,131 [68.0%]) and social media (20,967 [61.6%]) were the main sources of COVID-19 vaccine information. Compared with vaccination acceptance, female, young and middle-aged, high income, and perceived low-risk of infection were associated with vaccine hesitancy. Histories of allergic reactions to other vaccines and depression symptoms were related to vaccine resistance. Common factors that influenced vaccine hesitancy and resistance were residing in cities and perceiving less protection with vaccines than with other protective measures. The results indicate that the rate of vaccine resistance is relatively low, but vaccine hesitancy is common. Individuals who are female, young and middle-aged, with a high income, and residing in cities are more likely to be hesitant for vaccination and should be the target populations for vaccination campaigns. Specific vaccine messaging from the government and social media could alleviate public concerns about vaccine safety and efficacy.

11.
EClinicalMedicine ; 40: 101111, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1401436

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) has evolved into a worldwide pandemic, and has been found to be closely associated with mental and neurological disorders. We aimed to comprehensively quantify the association between mental and neurological disorders, both pre-existing and subsequent, and the risk of susceptibility, severity and mortality of COVID-19. METHODS: In this systematic review and meta-analysis, we searched PubMed, Web of Science, Embase, PsycINFO, and Cochrane library databases for studies published from the inception up to January 16, 2021 and updated at July 7, 2021. Observational studies including cohort and case-control, cross-sectional studies and case series that reported risk estimates of the association between mental or neurological disorders and COVID-19 susceptibility, illness severity and mortality were included. Two researchers independently extracted data and conducted the quality assessment. Based on I2 heterogeneity, we used a random effects model to calculate pooled odds ratios (OR) and 95% confidence intervals (95% CI). Subgroup analyses and meta-regression analysis were also performed. This study was registered on PROSPERO (registration number: CRD 42021230832). FINDING: A total of 149 studies (227,351,954 participants, 89,235,737 COVID-19 patients) were included in this analysis, in which 27 reported morbidity (132,727,798), 56 reported illness severity (83,097,968) and 115 reported mortality (88,878,662). Overall, mental and neurological disorders were associated with a significant high risk of infection (pre-existing mental: OR 1·67, 95% CI 1·12-2·49; and pre-existing neurological: 2·05, 1·58-2·67), illness severity (mental: pre-existing, 1·40, 1·25-1·57; sequelae, 4·85, 2·53-9·32; neurological: pre-existing, 1·43, 1·09-1·88; sequelae, 2·17, 1·45-3·24), and mortality (mental: pre-existing, 1·47, 1·26-1·72; neurological: pre-existing, 2·08, 1·61-2·69; sequelae, 2·03, 1·66-2·49) from COVID-19. Subgroup analysis revealed that association with illness severity was stronger among younger COVID-19 patients, and those with subsequent mental disorders, living in low- and middle-income regions. Younger patients with mental and neurological disorders were associated with higher mortality than elders. For type-specific mental disorders, susceptibility to contracting COVID-19 was associated with pre-existing mood disorders, anxiety, and attention-deficit hyperactivity disorder (ADHD); illness severity was associated with both pre-existing and subsequent mood disorders as well as sleep disturbance; and mortality was associated with pre-existing schizophrenia. For neurological disorders, susceptibility was associated with pre-existing dementia; both severity and mortality were associated with subsequent delirium and altered mental status; besides, mortality was associated with pre-existing and subsequent dementia and multiple specific neurological diseases. Heterogeneities were substantial across studies in most analysis. INTERPRETATION: The findings show an important role of mental and neurological disorders in the context of COVID-19 and provide clues and directions for identifying and protecting vulnerable populations in the pandemic. Early detection and intervention for neurological and mental disorders are urgently needed to control morbidity and mortality induced by the COVID-19 pandemic. However, there was substantial heterogeneity among the included studies, and the results should be interpreted with caution. More studies are needed to explore long-term mental and neurological sequela, as well as the underlying brain mechanisms for the sake of elucidating the causal pathways for these associations. FUNDING: This study is supported by grants from the National Key Research and Development Program of China, the National Natural Science Foundation of China, Special Research Fund of PKUHSC for Prevention and Control of COVID-19, and the Fundamental Research Funds for the Central Universities.

12.
Signal Transduct Target Ther ; 6(1): 331, 2021 09 01.
Article in English | MEDLINE | ID: covidwho-1392811

ABSTRACT

The recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the causative agent of ongoing global pandemic of COVID-19, may trigger immunosuppression in the early stage and overactive immune response in the late stage of infection; However, the underlying mechanisms are not well understood. Here we demonstrated that the SARS-CoV-2 nucleocapsid (N) protein dually regulated innate immune responses, i.e., the low-dose N protein suppressed type I interferon (IFN-I) signaling and inflammatory cytokines, whereas high-dose N protein promoted IFN-I signaling and inflammatory cytokines. Mechanistically, the SARS-CoV-2 N protein dually regulated the phosphorylation and nuclear translocation of IRF3, STAT1, and STAT2. Additionally, low-dose N protein combined with TRIM25 could suppress the ubiquitination and activation of retinoic acid-inducible gene I (RIG-I). Our findings revealed a regulatory mechanism of innate immune responses by the SARS-CoV-2 N protein, which would contribute to understanding the pathogenesis of SARS-CoV-2 and other SARS-like coronaviruses, and development of more effective strategies for controlling COVID-19.


Subject(s)
COVID-19/immunology , Coronavirus Nucleocapsid Proteins/immunology , Immunity, Innate , SARS-CoV-2/immunology , Signal Transduction/immunology , A549 Cells , COVID-19/pathology , Caco-2 Cells , HEK293 Cells , Hep G2 Cells , Humans , Interferon Type I/immunology , Phosphoproteins/immunology
13.
Commun Biol ; 4(1): 1034, 2021 08 31.
Article in English | MEDLINE | ID: covidwho-1380915

ABSTRACT

COVID-19 has caused numerous infections with diverse clinical symptoms. To identify human genetic variants contributing to the clinical development of COVID-19, we genotyped 1457 (598/859 with severe/mild symptoms) and sequenced 1141 (severe/mild: 474/667) patients of Chinese ancestry. We further incorporated 1401 genotyped and 948 sequenced ancestry-matched population controls, and tested genome-wide association on 1072 severe cases versus 3875 mild or population controls, followed by trans-ethnic meta-analysis with summary statistics of 3199 hospitalized cases and 897,488 population controls from the COVID-19 Host Genetics Initiative. We identified three significant signals outside the well-established 3p21.31 locus: an intronic variant in FOXP4-AS1 (rs1853837, odds ratio OR = 1.28, P = 2.51 × 10-10, allele frequencies in Chinese/European AF = 0.345/0.105), a frameshift insertion in ABO (rs8176719, OR = 1.19, P = 8.98 × 10-9, AF = 0.422/0.395) and a Chinese-specific intronic variant in MEF2B (rs74490654, OR = 8.73, P = 1.22 × 10-8, AF = 0.004/0). These findings highlight an important role of the adaptive immunity and the ABO blood-group system in protection from developing severe COVID-19.


Subject(s)
COVID-19/ethnology , COVID-19/genetics , Genome-Wide Association Study , Genetic Predisposition to Disease/genetics , Humans , Introns/genetics , Polymorphism, Single Nucleotide
14.
J Clin Med ; 10(16)2021 Aug 11.
Article in English | MEDLINE | ID: covidwho-1376852

ABSTRACT

With the decreasing incidence of peptic ulcer bleeding (PUB) over the past two decades, the clinician experience of managing patients with PUB has also declined, especially for young endoscopists. A patient with PUB management requires collaborative care involving the emergency department, gastroenterologist, radiologist, and surgeon, from initial assessment to hospital discharge. The application of artificial intelligence (AI) methods has remarkably improved people's lives. In particular, AI systems have shown great potential in many areas of gastroenterology to increase human performance. Colonoscopy polyp detection or diagnosis by an AI system was recently introduced for commercial use to improve endoscopist performance. Although PUB is a longstanding health problem, these newly introduced AI technologies may soon impact endoscopists' clinical practice by improving the quality of care for these patients. To update the current status of AI application in PUB, we reviewed recent relevant literature and provided future perspectives that are required to integrate such AI tools into real-world practice.

15.
PLoS Pathog ; 17(8): e1009758, 2021 08.
Article in English | MEDLINE | ID: covidwho-1352713

ABSTRACT

Since the pandemic of COVID-19 has intensely struck human society, small animal model for this infectious disease is in urgent need for basic and pharmaceutical research. Although several COVID-19 animal models have been identified, many of them show either minimal or inadequate pathophysiology after SARS-CoV-2 challenge. Here, we describe a new and versatile strategy to rapidly establish a mouse model for emerging infectious diseases in one month by multi-route, multi-serotype transduction with recombinant adeno-associated virus (AAV) vectors expressing viral receptor. In this study, the proposed approach enables profound and enduring systemic expression of SARS-CoV-2-receptor hACE2 in wild-type mice and renders them vulnerable to SARS-CoV-2 infection. Upon virus challenge, generated AAV/hACE2 mice showed pathophysiology closely mimicking the patients with severe COVID-19. The efficacy of a novel therapeutic antibody cocktail RBD-chAbs for COVID-19 was tested and confirmed by using this AAV/hACE2 mouse model, further demonstrating its successful application in drug development.


Subject(s)
COVID-19 , Communicable Diseases, Emerging , Disease Models, Animal , 3T3 Cells , Angiotensin-Converting Enzyme 2/genetics , Animals , Antibodies, Viral/immunology , Antibodies, Viral/therapeutic use , COVID-19/immunology , COVID-19/pathology , COVID-19/physiopathology , Chlorocebus aethiops , Dependovirus/genetics , Humans , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Transduction, Genetic , Vero Cells
16.
Front Psychiatry ; 12: 695017, 2021.
Article in English | MEDLINE | ID: covidwho-1334956

ABSTRACT

Background: University students who are exposed to coronavirus disease 2019 (COVID-19) could be mentally distressed. We aimed to evaluate the pattern and risk factors of mental health and suicidal behavior among students who experienced long-term school closure due to the COVID-19 pandemic. Methods: This large-sample, cross-sectional, online survey was conducted from June 29, 2020, to July 18, 2020. Eleven thousand two hundred fifty four participants were recruited from 30 universities located in Wuhan, Hubei Province, China. The prevalence of symptoms of depression, anxiety, insomnia, and posttraumatic stress disorder (PTSD) and suicidal behavior was evaluated using the Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, Insomnia Severity Index, Posttraumatic Stress Disorder Checklist for DSM-5, and questions about suicidal ideation and attempts, respectively. Logistic regression was used to explore risk factors for mental health problems and suicidal behavior. Results: The prevalence of mental health problems was 41.5% for depressive symptoms, 32.6% for anxiety symptoms, 35.0% for insomnia symptoms, 8.5% for PTSD symptoms, and 2.0% for suicidal behavior. Participants with high stress during the pandemic were at higher risk of symptoms of depression [adjusted odds ratio (OR) = 1.67, 95% confidence interval (CI) = 1.43-1.95, p < 0.01), anxiety (adjusted OR = 1.90, 95% CI = 1.63-2.23, p < 0.01), insomnia (adjusted OR = 1.64, 95% CI = 1.44-1.87, p < 0.01), PTSD (adjusted OR = 1.71, 95% CI = 1.38-2.11, p < 0.01) and suicidal behavior (adjusted OR = 3.51, 95% CI = 2.28-5.40, p < 0.01). Distant relationship with parents, changes in lifestyle and alcohol use during the pandemic were associated with higher risk of mental health symptoms and suicidal behavior, whereas regular physical exercise reduced the risk of mental health problems. Conclusions: The psychological symptoms and suicidal behavior were relatively high among students who attended university in Wuhan, China after 6 months of the COVID-19 outbreak in China. Comprehensive mental health services and suicide prevention strategies are essential for university students during the COVID-19 pandemic.

17.
Nat Commun ; 12(1): 4543, 2021 07 27.
Article in English | MEDLINE | ID: covidwho-1328844

ABSTRACT

The outbreak of coronavirus disease 2019 (COVID-19) is a global health emergency. Various omics results have been reported for COVID-19, but the molecular hallmarks of COVID-19, especially in those patients without comorbidities, have not been fully investigated. Here we collect blood samples from 231 COVID-19 patients, prefiltered to exclude those with selected comorbidities, yet with symptoms ranging from asymptomatic to critically ill. Using integrative analysis of genomic, transcriptomic, proteomic, metabolomic and lipidomic profiles, we report a trans-omics landscape for COVID-19. Our analyses find neutrophils heterogeneity between asymptomatic and critically ill patients. Meanwhile, neutrophils over-activation, arginine depletion and tryptophan metabolites accumulation correlate with T cell dysfunction in critical patients. Our multi-omics data and characterization of peripheral blood from COVID-19 patients may thus help provide clues regarding pathophysiology of and potential therapeutic strategies for COVID-19.


Subject(s)
COVID-19/genetics , COVID-19/metabolism , Critical Illness , Genomics/methods , Humans , Lipidomics/methods , Metabolomics/methods , Neutrophils/metabolism , Transcriptome/genetics
18.
J Microbiol Immunol Infect ; 54(5): 801-807, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1275504

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) manifests symptoms as common etiologies of respiratory tract infections (RTIs). During the pandemic of COVID-19, identifying the etiologies correctly from patients with RTI symptoms was crucial in not only disease control but preventing healthcare system from collapsing. By applying sensitive PCR-based molecular assays, we detected the etiologic agents and delineated the epidemiologic picture of RTIs in the early phase of COVID-19 pandemic. METHODS: From December 2019 to February 2020, we screened patients presented with RTIs using multiplex PCR-based diagnostic assays. Data from pediatric and adult patients were compared with different months and units in the hospital. RESULTS: Of all 1631 patients including 1445 adult and 186 pediatric patients screened, 8 viruses and 4 bacteria were identified. Positive rates were 25% in December, 37% in January, and 20% in February, with pediatric patients having higher positive rates than adults (Ps < 0.001). In pediatric patients, RhV/EnV was the most commonly detected, followed by parainfluenza viruses. Most Mycoplasma pneumoniae infection occurred in pediatric patients. RhV/EnV was the most commonly detected agent in pediatric patients admitted to intensive care units (ICUs), while influenza accounted for the majority of adult cases with critical illness. Noticeably, seasonal coronavirus ranked second in both adult and pediatric patients with ICU admission. CONCLUSION: While we focused on the pandemic of COVID-19, common etiologies still accounted for the majority of RTIs and lead to severe diseases, including other seasonal coronaviruses.


Subject(s)
COVID-19/epidemiology , Disease Outbreaks , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/etiology , Adult , COVID-19/diagnosis , Child , Humans , Influenza, Human/diagnosis , Influenza, Human/epidemiology , Multiplex Polymerase Chain Reaction , Pandemics , Parainfluenza Virus 1, Human , Parainfluenza Virus 2, Human , Pneumonia, Mycoplasma/diagnosis , Pneumonia, Mycoplasma/epidemiology , Retrospective Studies , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Seasons , Taiwan/epidemiology
19.
Sci Rep ; 11(1): 12425, 2021 06 14.
Article in English | MEDLINE | ID: covidwho-1268002

ABSTRACT

Saliva has significant advantages as a test medium for detection of SARS-CoV-2 infection in patients, such as ease of collection, minimal requirement of supplies and trained personnel, and safety. Comprehensive validation in a large cohort of prospectively collected specimens with unknown SARS-CoV-2 status should be performed to evaluate the potential and limitations of saliva-based testing. We developed a saliva-based testing pipeline for detection of SARS-CoV-2 nucleic acids using real-time reverse transcription PCR (RT-PCR) and droplet digital PCR (ddPCR) readouts, and measured samples from 137 outpatients tested at a curbside testing facility and 29 inpatients hospitalized for COVID-19. These measurements were compared to the nasal swab results for each patient performed by a certified microbiology laboratory. We found that our saliva testing positively detects 100% (RT-PCR) and 93.75% (ddPCR) of curbside patients that were identified as SARS-CoV-2 positive by the Emergency Use Authorization (EUA) certified nasal swab testing assay. Quantification of viral loads by ddPCR revealed an extremely wide range, with 1 million-fold difference between individual patients. Our results demonstrate for both community screening and hospital settings that saliva testing reliability is on par with that of the nasal swabs in detecting infected cases, and has potential for higher sensitivity when combined with ddPCR in detecting low-abundance viral loads that evade traditional testing methods.


Subject(s)
COVID-19/diagnosis , SARS-CoV-2/genetics , Saliva/virology , Adult , COVID-19/virology , Female , Humans , Male , Middle Aged , RNA, Viral/analysis , RNA, Viral/genetics , RNA, Viral/metabolism , Reagent Kits, Diagnostic , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2/isolation & purification , Viral Load
20.
Front Immunol ; 12: 662989, 2021.
Article in English | MEDLINE | ID: covidwho-1256380

ABSTRACT

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative pathogen of current COVID-19 pandemic, and insufficient production of type I interferon (IFN-I) is associated with the severe forms of the disease. Membrane (M) protein of SARS-CoV-2 has been reported to suppress host IFN-I production, but the underlying mechanism is not completely understood. In this study, SARS-CoV-2 M protein was confirmed to suppress the expression of IFNß and interferon-stimulated genes induced by RIG-I, MDA5, IKKϵ, and TBK1, and to inhibit IRF3 phosphorylation and dimerization caused by TBK1. SARS-CoV-2 M could interact with MDA5, TRAF3, IKKϵ, and TBK1, and induce TBK1 degradation via K48-linked ubiquitination. The reduced TBK1 further impaired the formation of TRAF3-TANK-TBK1-IKKε complex that leads to inhibition of IFN-I production. Our study revealed a novel mechanism of SARS-CoV-2 M for negative regulation of IFN-I production, which would provide deeper insight into the innate immunosuppression and pathogenicity of SARS-CoV-2.


Subject(s)
Interferon Type I/biosynthesis , SARS-CoV-2/immunology , Ubiquitin/metabolism , Viral Matrix Proteins/immunology , DEAD Box Protein 58/metabolism , HEK293 Cells , Humans , I-kappa B Kinase/metabolism , Interferon Regulatory Factor-3/metabolism , Interferon-Induced Helicase, IFIH1/metabolism , Proteolysis , Receptors, Immunologic/metabolism , Signal Transduction , TNF Receptor-Associated Factor 3/metabolism
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