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1.
PLoS Pathog ; 18(3): e1010366, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1793485

ABSTRACT

Tryptophan (Trp) metabolism through the kynurenine pathway (KP) is well known to play a critical function in cancer, autoimmune and neurodegenerative diseases. However, its role in host-pathogen interactions has not been characterized yet. Herein, we identified that kynurenine-3-monooxygenase (KMO), a key rate-limiting enzyme in the KP, and quinolinic acid (QUIN), a key enzymatic product of KMO enzyme, exerted a novel antiviral function against a broad range of viruses. Mechanistically, QUIN induced the production of type I interferon (IFN-I) via activating the N-methyl-d-aspartate receptor (NMDAR) and Ca2+ influx to activate Calcium/calmodulin-dependent protein kinase II (CaMKII)/interferon regulatory factor 3 (IRF3). Importantly, QUIN treatment effectively inhibited viral infections and alleviated disease progression in mice. Furthermore, kmo-/- mice were vulnerable to pathogenic viral challenge with severe clinical symptoms. Collectively, our results demonstrated that KMO and its enzymatic product QUIN were potential therapeutics against emerging pathogenic viruses.

2.
Brain Behav Immun ; 87: 11-17, 2020 07.
Article in English | MEDLINE | ID: covidwho-1719332

ABSTRACT

The severe 2019 outbreak of novel coronavirus disease (COVID-19), which was first reported in Wuhan, would be expected to impact the mental health of local medical and nursing staff and thus lead them to seek help. However, those outcomes have yet to be established using epidemiological data. To explore the mental health status of medical and nursing staff and the efficacy, or lack thereof, of critically connecting psychological needs to receiving psychological care, we conducted a quantitative study. This is the first paper on the mental health of medical and nursing staff in Wuhan. Notably, among 994 medical and nursing staff working in Wuhan, 36.9% had subthreshold mental health disturbances (mean PHQ-9: 2.4), 34.4% had mild disturbances (mean PHQ-9: 5.4), 22.4% had moderate disturbances (mean PHQ-9: 9.0), and 6.2% had severe disturbance (mean PHQ-9: 15.1) in the immediate wake of the viral epidemic. The noted burden fell particularly heavily on young women. Of all participants, 36.3% had accessed psychological materials (such as books on mental health), 50.4% had accessed psychological resources available through media (such as online push messages on mental health self-help coping methods), and 17.5% had participated in counseling or psychotherapy. Trends in levels of psychological distress and factors such as exposure to infected people and psychological assistance were identified. Although staff accessed limited mental healthcare services, distressed staff nonetheless saw these services as important resources to alleviate acute mental health disturbances and improve their physical health perceptions. These findings emphasize the importance of being prepared to support frontline workers through mental health interventions at times of widespread crisis.


Subject(s)
Anxiety Disorders/psychology , Coronavirus Infections/therapy , Depressive Disorder/psychology , Nurses/psychology , Physicians/psychology , Pneumonia, Viral/therapy , Sleep Initiation and Maintenance Disorders/psychology , Adaptation, Psychological , Adolescent , Adult , Anxiety/epidemiology , Anxiety/psychology , Anxiety Disorders/epidemiology , Betacoronavirus , COVID-19 , China/epidemiology , Coronavirus Infections/epidemiology , Cross-Sectional Studies , Depression/epidemiology , Depression/psychology , Depressive Disorder/epidemiology , Disease Outbreaks , Female , Health Services Accessibility , Humans , Male , Mental Health , Mental Health Services , Middle Aged , Nurses/statistics & numerical data , Pandemics , Patient Health Questionnaire , Physicians/statistics & numerical data , Pneumonia, Viral/epidemiology , Psychological Distress , SARS-CoV-2 , Sleep Initiation and Maintenance Disorders/epidemiology , Surveys and Questionnaires , Young Adult
3.
BMC Pulm Med ; 22(1): 52, 2022 Feb 05.
Article in English | MEDLINE | ID: covidwho-1690928

ABSTRACT

COVID-19 has inflicted the world for over two years. The recent mutant virus strains pose greater challenges to disease prevention and treatment. COVID-19 can cause acute respiratory distress syndrome (ARDS) and extrapulmonary injury. Dynamic monitoring of each patient's condition is necessary to timely tailor treatments, improve prognosis and reduce mortality. Point-of-care ultrasound (POCUS) is broadly used in patients with ARDS. POCUS is recommended to be performed regularly in COVID-19 patients for respiratory failure management. In this review, we summarized the ultrasound characteristics of COVID-19 patients, mainly focusing on lung ultrasound and echocardiography. Furthermore, we also provided the experience of using POCUS to manage COVID-19-related ARDS.


Subject(s)
COVID-19/diagnostic imaging , Echocardiography , Lung/diagnostic imaging , Point-of-Care Testing , Respiratory Distress Syndrome/diagnostic imaging , Respiratory Therapy/methods , COVID-19/therapy , Humans , Respiratory Distress Syndrome/therapy , Respiratory Distress Syndrome/virology
4.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-319519

ABSTRACT

Multiorgan injuries are a major complication of severe COVID-19;however, its pathogenesis is barely understood. Herein, we profiled the host responses to SARS-CoV-2 infection by performing quantitative proteomics of COVID-19 postmortem samples, and provided a comprehensive proteome map covering the protein alterations in eight different organs/tissues. Our results revealed that lung underwent the most abundant protein alterations mainly enriched in immune-/inflammation-related or morphology-related processes, while surprisingly, other organs/tissues exhibited significant protein alterations mainly enriched in processes related with organ movement, respiration, and metabolism. These results indicate that the major cause of lung injury was excessive inflammatory response, and subsequent intravascular thrombosis and pulmonary architecture/function destruction, while other organs/tissues were mainly injured by hypoxia and functional impairment. Therefore, our findings demonstrate the significant pathophysiological alternations of host proteins/pathways associated with multiorgan injuries of COVID-19, which provides invaluable knowledge about COVID-19-associated host responses and sheds light on the pathogenesis of COVID-19.

5.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-311347

ABSTRACT

Background: Impact of COVID-19 pandemic on Chinese patients with pre-existing headache remains unclear. The present study investigated the impact of COVID-19 pandemic on headache patients in China. Methods: : A survey was conducted through an online survey platform from June 6, 2020. Demographic characteristics, PHQ-9 scores, ISI scores, COVID-19 questionnaires and headache profile section were included in the online questionnaires. Results: : Eventually a total of 15,000 participants from China completed the online questionnaire. Among them, 2806 participants (18.71%) had preexisting headache disorders. Our analysis showed a reality of those participants with remission of headache duration (3.414±6.859 vs 4.033±7.325, P=0.000), headache days per month (1.788±2.989 vs 2.092±3.694, P=0.000), and headache intensity (4.110±1.609 vs 4.290±1.680, P=0.000), during COVID-19. Smoking (OR=1.397, 95% CI 1.090 to 1.790, P=0.008) and getting support from family members during the social isolation (OR=1.656, 95% CI 1.075 to 2.550, P=0.022) were the independent factors of remission in headache duration. Education level (OR=1.478, 95% CI 1.103 to 1.980, P=0.009) and having relative or acquaintance got COVID-19 (OR=0.643, 95% CI 0.458 to 0.902, P=0.011) were the independent factors of remission in headache severity. And participants living in Wuhan area, having COVID-19 symptoms or COVID-19 diagnosis and having relative or acquaintance got COVID-19 are more likely to get headache deteriorated. Conclusions: : Participants presented an overall trend of headache remission during COVID-19. Family supports played an important role in headache remission.

7.
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
11.
Front Psychiatry ; 12: 644899, 2021.
Article in English | MEDLINE | ID: covidwho-1526792

ABSTRACT

The outbreak of coronavirus disease 2019 (COVID-19) has been a global emergency, affecting millions of individuals both physically and psychologically. The present research investigated the associations between social media exposure and depression during the COVID-19 outbreak by examining the mediating role of psychological distress and the moderating role of emotion regulation among members of the general public in China. Participants (N = 485) completed a set of questionnaires online, including demographic information, self-rated physical health, and social media exposure to topics related to COVID-19. The Impact of Event Scale-Revised (IES-R), the Beck Depression Inventory-II (BDI-II), and the Emotion Regulation Questionnaire (ERQ) were utilized to measure psychological distress about COVID-19, depression, and emotion regulation strategies, respectively. Results found that older age and greater levels of social media exposure were associated with more psychological distress about the virus (r = 0.14, p = 0.003; r = 0.22, p < 0.001). Results of the moderated mediation model suggest that psychological distress mediated the relationship between social media exposure and depression (ß = 0.10; Boot 95% CI = 0.07, 0.15). Furthermore, expressive suppression moderated the relationship between psychological distress and depression (ß = 0.10, p = 0.017). The findings are discussed in terms of the need for mental health assistance for individuals at high risk of depression, including the elderly and individuals who reported greater psychological distress and those who showed preference usage of suppression, during the COVID-19 crisis.

12.
Front Med (Lausanne) ; 8: 694754, 2021.
Article in English | MEDLINE | ID: covidwho-1485067

ABSTRACT

To investigate the characteristics of SARS-CoV-2 pneumonia and evaluate whether CT scans, especially at a certain CT level, could be used to predict the severity of SARS-CoV-2 pneumonia. In total 118 confirmed patients had been enrolled. All data including epidemiological, clinical characteristics, laboratory results, and images were collected and analyzed when they were administrated for the first time. All patients were divided into two groups. There were 106 severe/critical patients and 12 common ones. A total of 38 of the patients were women. The mean age was 50.5 ± 11.5 years. Overall, 80 patients had a history of exposure. The median time from onset of symptoms to administration was 8.0 days. The main symptoms included fever, cough, anorexia, fatigue, myalgia, headaches, and chills. Lymphocytes and platelets decreased and lactate dehydrogenase increased with increased diseased severity (P < 0.05). Calcium and chloride ions were decreased more significantly in severe/critical patients than in common ones (P < 0.05). The main comorbidities were diabetes, chronic cardiovascular disease, and chronic pulmonary disease, which occurred in 47 patients. In all 69 patients had respiratory failure, which is the most common SARS-CoV-2 complication, and liver dysfunction presented in 37 patients. Nine patients received mechanical ventilation therapy. One patient received continuous blood purification and extracorporeal membrane oxygenation (EMCO) treatments. The average stay was 18.1 ± 10.8 days. Four patients died. The median of the radiographic score was four in common, and five in the severe/critical illness, which was a significant difference between the two groups. The radiographic score was in negative correlation with OI (ρ = -0.467, P < 0.01). The OI in severe/critically ill cases decreased significantly as the disease progressed, which was related to the lesion area in the left lung and right lungs (ρ = 0.688, R = 0.733). OI, the lesion area in the left lung and right lungs, lymphocytes, etc. were associated with different degrees of SARS-CoV-2 pneumonia (P < 0.05). The lesion area in both lungs were possible predictive factors for severe/critical cases. Patients with SARS-CoV-2 pneumonia showed obvious clinical manifestations and laboratory result changes. Combining clinical features and the quantity of the lesion area in the fourth level of CT could effectively predict severe/critical SARS-CoV-2 cases.

13.
Nat Commun ; 12(1): 5654, 2021 09 27.
Article in English | MEDLINE | ID: covidwho-1440471

ABSTRACT

There is an urgent need for animal models to study SARS-CoV-2 pathogenicity. Here, we generate and characterize a novel mouse-adapted SARS-CoV-2 strain, MASCp36, that causes severe respiratory symptoms, and mortality. Our model exhibits age- and gender-related mortality akin to severe COVID-19. Deep sequencing identified three amino acid substitutions, N501Y, Q493H, and K417N, at the receptor binding domain (RBD) of MASCp36, during in vivo passaging. All three RBD mutations significantly enhance binding affinity to its endogenous receptor, ACE2. Cryo-electron microscopy analysis of human ACE2 (hACE2), or mouse ACE2 (mACE2), in complex with the RBD of MASCp36, at 3.1 to 3.7 Å resolution, reveals the molecular basis for the receptor-binding switch. N501Y and Q493H enhance the binding affinity to hACE2, whereas triple mutations at N501Y/Q493H/K417N decrease affinity and reduce infectivity of MASCp36. Our study provides a platform for studying SARS-CoV-2 pathogenesis, and unveils the molecular mechanism for its rapid adaptation and evolution.


Subject(s)
COVID-19/diagnosis , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/metabolism , Amino Acid Substitution , Angiotensin-Converting Enzyme 2/metabolism , Animals , Binding Sites/genetics , COVID-19/mortality , COVID-19/virology , Disease Models, Animal , Female , Humans , Male , Mice , Protein Binding/genetics , Protein Domains/genetics , SARS-CoV-2/genetics , Severity of Illness Index , Spike Glycoprotein, Coronavirus/genetics
15.
Front Med (Lausanne) ; 7: 611460, 2020.
Article in English | MEDLINE | ID: covidwho-1389196

ABSTRACT

Background: The data on long-term outcomes of patients infected by SARS-CoV-2 and treated with extracorporeal membrane oxygenation (ECMO) in China are merely available. Methods: A retrospective study included 73 patients infected by SARS-CoV-2 and treated with ECMO in 21 intensive care units in Hubei, China. Data on demographic information, clinical features, laboratory tests, ECMO durations, complications, and living status were collected. Results: The 73 ECMO-treated patients had a median age of 62 (range 33-78) years and 42 (63.6%) were males. Before ECMO initiation, patients had severe respiratory failure on mechanical ventilation with a median PO2/FiO2 of 71.9 [interquartile range (IQR), 58.6-87.0] mmHg and a median PCO2 of 62 [IQR, 43-84] mmHg on arterial blood analyses. The median duration from symptom onset to invasive mechanical ventilation, and to ECMO initiation was19 [IQR, 15-25] days, and 23 [IQR, 19-31] days. Before and after ECMO initiation, the proportions of patients receiving prone position ventilation were 58.9 and 69.9%, respectively. The median duration of ECMO support was 18.5 [IQR 12-30] days. During the treatments with ECMO, major hemorrhages occurred in 31 (42.5%) patients, and oxygenators were replaced in 21 (28.8%) patients. Since ECMO initiation, the 30-day mortality and 60-day mortality were 63.0 and 80.8%, respectively. Conclusions: In Hubei, China, the ECMO-treated patients infected by SARS-CoV-2 were of a broad age range and with severe hypoxemia. The durations of ECMO support, accompanied with increased complications, were relatively long. The long-term mortality in these patients was considerably high.

16.
Biosaf Health ; 3(6): 312-318, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1372900

ABSTRACT

Since the outbreak at the end of 2019, SARS-CoV-2 has been spreading around the world for more than one year. Scientists have been intensely conducting research on this newly emerged coronavirus and the disease caused by it. Angiotensin-converting enzyme 2 (ACE2), as a receptor mediating the cellular entry of SARS-CoV-2, has become a hot spot for researchers. Here, we summarized the recent progresses on the function, expression and distribution characteristics of ACE2 in human body and among populations. We further discussed the interaction mechanism of ACE2 and SARS-CoV-2 S protein, focusing on key residues that effect interaction and binding ability of SARS-CoV-2 variants. This will facilitate researchers to better understand SARS-CoV-2 infection and transmission route, adaptation mechanism, and designing treatment strategies.

17.
Int J Mol Sci ; 22(9)2021 Apr 28.
Article in English | MEDLINE | ID: covidwho-1359279

ABSTRACT

Deeply understanding the virus-host interaction is a prerequisite for developing effective anti-viral strategies. Traditionally, the transporter associated with antigen processing type 1 (TAP1) is critical for antigen presentation to regulate adaptive immunity. However, its role in controlling viral infections through modulating innate immune signaling is not yet fully understood. In the present study, we reported that TAP1, as a product of interferon-stimulated genes (ISGs), had broadly antiviral activity against various viruses such as herpes simplex virus 1 (HSV-1), adenoviruses (AdV), vesicular stomatitis virus (VSV), dengue virus (DENV), Zika virus (ZIKV), and influenza virus (PR8) etc. This antiviral activity by TAP1 was further confirmed by series of loss-of-function and gain-of-function experiments. Our further investigation revealed that TAP1 significantly promoted the interferon (IFN)-ß production through activating the TANK binding kinase-1 (TBK1) and the interferon regulatory factor 3 (IRF3) signaling transduction. Our work highlighted the broadly anti-viral function of TAP1 by modulating innate immunity, which is independent of its well-known function of antigen presentation. This study will provide insights into developing novel vaccination and immunotherapy strategies against emerging infectious diseases.


Subject(s)
ATP Binding Cassette Transporter, Subfamily B, Member 2/immunology , Antiviral Agents/immunology , Host Microbial Interactions/immunology , Interferon Type I/biosynthesis , ATP Binding Cassette Transporter, Subfamily B, Member 2/antagonists & inhibitors , ATP Binding Cassette Transporter, Subfamily B, Member 2/deficiency , ATP Binding Cassette Transporter, Subfamily B, Member 2/genetics , Animals , Gene Knockout Techniques , HEK293 Cells , Humans , Immunity, Innate , Interferon Regulatory Factor-3/immunology , Mice , Models, Immunological , RAW 264.7 Cells , Toll-Like Receptors/agonists , Virus Diseases/immunology
18.
Front Psychiatry ; 12: 690295, 2021.
Article in English | MEDLINE | ID: covidwho-1305691

ABSTRACT

Objectives: The coronavirus disease 2019 (COVID-19) pandemic may have an impact on the psychological distress of organ transplant recipients. We aimed to assess the status of psychological distress and its association with quality of life (QoL) in organ transplant recipients during the COVID-19 pandemic. Materials and Methods: A cross-sectional survey was carried out with 305 organ transplant recipients during March 30 and April 2, 2020, in Wuhan. Psychological distress comprised depression, anxiety, insomnia, and post-traumatic stress disorder (PTSD), which were assessed using the Patient Health Questionnaire-9, the seven-item Generalized Anxiety Disorder questionnaire, the Insomnia Severity Index, and Impact of event scale-revised. QoL was assessed using the Chinese version of the short Form 36-item health survey. Results: The prevalence of depression, anxiety, insomnia, and PTSD in organ transplant recipients was 13.4, 6.9, 11.8, and 30.5%, respectively. Organ transplant recipients with depression had significantly lower scores in all eight dimensions of QoL compared with participants without depression (all p < 0.05). Lower scores on the QoL dimensions of role physical, bodily pain, general health, vitality, role emotional, and mental health were found in organ transplant recipients with anxiety, insomnia, or PTSD compared with their counterparts without the respective disorder (all p < 0.05). Limitation: The cross-sectional study design limited us to make causal conclusion and the influence of potential confounders cannot be ruled out. Conclusions: Psychological distress was prevalent in organ transplant recipients during the COVID-19 pandemic, and those with depression, anxiety, insomnia, and PTSD had poorer QoL. Therefore, timely psychological counseling, COVID-19 related health education, and essential community medical services should be provided to organ transplant recipients to relieve their psychological distress, and to improve their QoL.

19.
Cell Discov ; 7(1): 49, 2021 Jul 06.
Article in English | MEDLINE | ID: covidwho-1298837

ABSTRACT

SARS-CoV-2 infection causes a wide spectrum of clinical manifestations in humans, and olfactory dysfunction is one of the most predictive and common symptoms in COVID-19 patients. However, the underlying mechanism by which SARS-CoV-2 infection leads to olfactory disorders remains elusive. Herein, we demonstrate that intranasal inoculation with SARS-CoV-2 induces robust viral replication in the olfactory epithelium (OE), not the olfactory bulb (OB), resulting in transient olfactory dysfunction in humanized ACE2 (hACE2) mice. The sustentacular cells and Bowman's gland cells in the OE were identified as the major target cells of SARS-CoV-2 before invasion into olfactory sensory neurons (OSNs). Remarkably, SARS-CoV-2 infection triggers massive cell death and immune cell infiltration and directly impairs the uniformity of the OE structure. Combined transcriptomic and quantitative proteomic analyses revealed the induction of antiviral and inflammatory responses, as well as the downregulation of olfactory receptor (OR) genes in the OE from the infected animals. Overall, our mouse model recapitulates olfactory dysfunction in COVID-19 patients and provides critical clues for understanding the physiological basis for extrapulmonary manifestations of COVID-19.

20.
BMC Neurol ; 21(1): 224, 2021 Jun 15.
Article in English | MEDLINE | ID: covidwho-1270926

ABSTRACT

BACKGROUND: The global status of the COVID-19 pandemic is not optimistic. This is a particularly vulnerable time for patients with pre-existing headache disorders. The present study aimed to investigate the impact of the COVID-19 pandemic on headache patients in China. METHODS: A survey was conducted through an online survey platform on June 6, 2020. Demographic characteristics, the PHQ-9, the ISI, a COVID-19 questionnaire and a headache profile survey were included in the online questionnaire. RESULTS: Eventually, a total of 15,000 participants from China completed the online questionnaire. Among them, 2806 participants had pre-existing headache disorders. Our analysis showed reductions in the duration of headaches (3.414 ± 6.859 vs 4.033 ± 7.325 h, P<0.001), number of headache days per month (1.788 ± 2.989 vs 2.092 ± 3.694, P<0.001), and headache intensity (4.110 ± 1.609 vs 4.290 ± 1.680, P<0.001) during the COVID-19 pandemic. Smoking (OR = 1.397, 95% CI 1.090 to 1.790, P = 0.008) and getting support from family members during social isolation (OR = 1.656, 95% CI 1.075 to 2.550, P = 0.022) were independent factors affecting the reduction in the duration of headaches. Education level (OR = 1.478, 95% CI 1.103 to 1.980, P = 0.009) and having a relative or acquaintance who contracted COVID-19 (OR = 0.643, 95% CI 0.458 to 0.902, P = 0.011) were the independent factors affecting the reduction in headache severity. Living in the Wuhan area, having symptoms or a diagnosis of COVID-19 and having relatives or acquaintances who had contracted COVID-19 were associated with the worsening of headaches. CONCLUSIONS: Participants experienced an overall trend towards the improvement of headaches during the COVID-19 pandemic. Family support might play an important role in the improvement of headaches.


Subject(s)
COVID-19 , Headache/epidemiology , China/epidemiology , Humans , Pandemics , Patient Health Questionnaire , SARS-CoV-2
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