Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 8 de 8
Filter
2.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-318387

ABSTRACT

Potently neutralizing SARS-CoV-2 antibodies often target the receptor binding site (RBS) of spike protein but the variability of RBS epitopes hampers broad neutralization of different clades of coronaviruses and emerging drifted viruses. Here, we identified a human RBS antibody that potently neutralizes SARS-CoV and SARS-CoV-2 variants that belong to clade 1 SARS-related coronavirus. X-ray crystallography revealed coordinated recognition by the heavy chain to conserved sites and the light chain to RBS, allowing for the mimicry of ACE2 binding mode. The minimum footprints in the hypervariable region of RBS contributed to the breadth of neutralization, and the activity was further enhanced by IgG3 switching. Eventually, the coordinated binding resulted in broad neutralization of SARS-CoV and emerging SARS-CoV-2 variants of concern. Furthermore, therapeutic treatment in a hamster model provided protection at low dosage. The structural basis for broadly neutralizing activity informs the design of broad spectrum of therapeutics and vaccines.Funding: This work was supported by Japan Agency for Medical Research and Development grant JP19fk0108111 (TH, YT), JP20fk0108298 (TK, TH, KM, YT), JP20am0101093 (KM), JP20ae0101047 (KM), JP20fk0108251 (HS), and JP20am0101124 (YK), by Ministry of Education, Culture, Sports, Science and Technology grant JPMXS0420100119 (KM) and 20H05773 (TH), by The Naito Foundation (TH), and by Joint Usage/Research Center program of Institute for Frontier Life and Medical Sciences, Kyoto University (KM).Conflict of Interest: AS is an employee of Shionogi & Co., Ltd. MO is a CEO, employee, and shareholder of Trans Chromosomics, Inc. These authors acknowledge a potential conflict of interest and attest that the work contained in this report is free of any bias that might be associated with the commercial goals of the company. TO, YA, MO, TH, KM, and YT declare that an intellectual property application has been filed using the data presented in this paper. The other authors declare that they have no competing interests.Ethical Approval: Animal procedures were approved by the Animal Ethics Committee of the National Institute of Infectious Diseases, Japan, and performed in accordance with the guidelines of the Institutional Animal Care and Use Committee. In vitro escape mutation screening experiments for SARSCoV-2 were performed at the Biosafety Level-3 facility of the Research Center for ZoonosisControl, Hokkaido University, and the National Institute of Infectious Diseases following the institutional guidelines.

3.
Front Psychol ; 12: 730969, 2021.
Article in English | MEDLINE | ID: covidwho-1477867

ABSTRACT

Introduction: Remote work was widely promoted in 2020, as a result of the COVID-19 pandemic. However, the effects of remote work on psychological and physical stress responses and presenteeism of workers remain unclear. This research aims to provide empirical evidence of the implications for people and organizations of this new scenario of working from home. Methods: A two-wave panel survey of before and after the pandemic was performed to investigate the effects of remote work on these aspects among office workers. A total of 3,123 office workers from 23 tertiary industries responded to a questionnaire. Participants were surveyed about their job stress conditions and sleep practices in both 2019 and 2020, who had not done remote work as of 2019 were included in the study. The effects of remote work on psychological and physical stress responses and presenteeism were analyzed by multivariate analysis, with the adjustment of age, gender, overtime, job stressors, social support, and sleep status. Results: The multivariate logistic regression analysis demonstrated that remote work was associated with the reduction of psychological and physical stress responses independently of changes of job stressors, social support, sleep disturbance, and total sleep time on workdays. On the other hand, remote work of 5 days a week (full-remote) was associated with the reduction of work productivity. Conclusion: Promoting remote work can reduce psychological and physical stress responses, however, full-remote work has the risk of worsening presenteeism. From the viewpoint of mental health, the review of working styles is expected to have positive effects, even after the end of the COVID-19 pandemic.

4.
J Exp Med ; 218(12)2021 12 06.
Article in English | MEDLINE | ID: covidwho-1467277

ABSTRACT

Adaptive immunity is a fundamental component in controlling COVID-19. In this process, follicular helper T (Tfh) cells are a subset of CD4+ T cells that mediate the production of protective antibodies; however, the SARS-CoV-2 epitopes activating Tfh cells are not well characterized. Here, we identified and crystallized TCRs of public circulating Tfh (cTfh) clonotypes that are expanded in patients who have recovered from mild symptoms. These public clonotypes recognized the SARS-CoV-2 spike (S) epitopes conserved across emerging variants. The epitope of the most prevalent cTfh clonotype, S864-882, was presented by multiple HLAs and activated T cells in most healthy donors, suggesting that this S region is a universal T cell epitope useful for booster antigen. SARS-CoV-2-specific public cTfh clonotypes also cross-reacted with specific commensal bacteria. In this study, we identified conserved SARS-CoV-2 S epitopes that activate public cTfh clonotypes associated with mild symptoms.


Subject(s)
COVID-19/immunology , Epitopes, T-Lymphocyte/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , T-Lymphocytes, Helper-Inducer/immunology , Adult , Antibodies, Viral/immunology , Female , HLA Antigens/immunology , Humans , Lymphocyte Activation , Male
5.
J Exp Med ; 218(12)2021 12 06.
Article in English | MEDLINE | ID: covidwho-1462245

ABSTRACT

Broadly protective vaccines against SARS-related coronaviruses that may cause future outbreaks are urgently needed. The SARS-CoV-2 spike receptor-binding domain (RBD) comprises two regions, the core-RBD and the receptor-binding motif (RBM); the former is structurally conserved between SARS-CoV-2 and SARS-CoV. Here, in order to elicit humoral responses to the more conserved core-RBD, we introduced N-linked glycans onto RBM surfaces of the SARS-CoV-2 RBD and used them as immunogens in a mouse model. We found that glycan addition elicited higher proportions of the core-RBD-specific germinal center (GC) B cells and antibody responses, thereby manifesting significant neutralizing activity for SARS-CoV, SARS-CoV-2, and the bat WIV1-CoV. These results have implications for the design of SARS-like virus vaccines.


Subject(s)
Antibodies, Viral/immunology , Broadly Neutralizing Antibodies/immunology , COVID-19/immunology , Polysaccharides/immunology , SARS Virus/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Amino Acid Motifs , Animals , COVID-19/genetics , COVID-19/prevention & control , COVID-19 Vaccines/genetics , COVID-19 Vaccines/immunology , Female , Humans , Male , Mice , Mice, Inbred BALB C , Polysaccharides/genetics , Protein Domains , SARS Virus/genetics , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics
6.
BMC Infect Dis ; 21(1): 993, 2021 Sep 23.
Article in English | MEDLINE | ID: covidwho-1438260

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) has a broad spectrum from respiratory and nasopharyngeal symptoms, cerebrovascular diseases, impaired consciousness, and skeletal muscle injury. Emerging evidence has indicated the neural spread of this novel coronavirus. Restless legs syndrome (RLS) is a common neurological, sensorimotor disorder, but highly under diagnosis disorder. Restless anal syndrome as restless legs syndrome variant associated with COVID-19 has been previously not published. We report a case presenting with restless anal syndrome following COVID-19. CASE PRESENTATION: Although a 77-year-old male with COVID-19 improved to normal respiratory function 21 days after admission and treatment of favipiravir 200 mg per day for 14 days and dexamethasone 6.6 mg per day for 5 days, the insomnia and anxiety symptoms remained. Several weeks after discharge, he gradually began to experience restless, deep anal discomfort, approximately 10 cm from the perineal region. The following features were observed in the anal region; urge to move is essential, with worsening with rest, improvement with exercise, and worsening at evening. Colonoscopy revealed internal haemorrhoids without other rectal lesions. Neurological findings including deep tendon reflex, perineum loss of sensory and spinal cord injury, revealed no abnormalities. Diabetes militias, kidney dysfunction and iron deficiency status were not confirmed. Family history of RLS and periodic limb movements were not observed. Clonazepam at 1.5 mg per day resulted in the alleviation restless anal discomfort. CONCLUSIONS: We reported a case presenting with restless anal syndrome following affection of COVID-19 as restless legs syndrome variant. This case fulfilled 4 essential features of RLS, urge to move, worsening with rest, improvement with exercise, and worsening at evening. To date, no case of restless anal syndrome associated with COVID-19 has been previously published. This case report may reflect the associative impacts of COVID-19 on the neuropsychiatric state. The long-term outcomes of neuropsychiatric conditions should continue to be monitored.


Subject(s)
COVID-19 , Restless Legs Syndrome , Spinal Cord Injuries , Aged , Anxiety , Humans , Male , Restless Legs Syndrome/complications , Restless Legs Syndrome/drug therapy , SARS-CoV-2
7.
Immunity ; 54(10): 2385-2398.e10, 2021 10 12.
Article in English | MEDLINE | ID: covidwho-1370548

ABSTRACT

Potent neutralizing SARS-CoV-2 antibodies often target the spike protein receptor-binding site (RBS), but the variability of RBS epitopes hampers broad neutralization of multiple sarbecoviruses and drifted viruses. Here, using humanized mice, we identified an RBS antibody with a germline VH gene that potently neutralized SARS-related coronaviruses, including SARS-CoV and SARS-CoV-2 variants. X-ray crystallography revealed coordinated recognition by the heavy chain of non-RBS conserved sites and the light chain of RBS with a binding angle mimicking the angiotensin-converting enzyme 2 (ACE2) receptor. The minimum footprints in the hypervariable region of RBS contributed to the breadth of neutralization, which was enhanced by immunoglobulin G3 (IgG3) class switching. The coordinated binding resulted in broad neutralization of SARS-CoV and emerging SARS-CoV-2 variants of concern. Low-dose therapeutic antibody treatment in hamsters reduced the virus titers and morbidity during SARS-CoV-2 challenge. The structural basis for broad neutralizing activity may inform the design of a broad spectrum of therapeutics and vaccines.


Subject(s)
Broadly Neutralizing Antibodies/immunology , Cross Reactions/immunology , SARS-CoV-2/immunology , Animals , Betacoronavirus/immunology , Binding Sites, Antibody , Broadly Neutralizing Antibodies/chemistry , Broadly Neutralizing Antibodies/therapeutic use , COVID-19/prevention & control , COVID-19/therapy , COVID-19/virology , Cricetinae , Humans , Immunoglobulin Class Switching , Immunoglobulin Fab Fragments/chemistry , Immunoglobulin Fab Fragments/metabolism , Immunoglobulin G/chemistry , Immunoglobulin G/immunology , Mice , Protein Domains , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/metabolism
8.
Int J Environ Res Public Health ; 18(9)2021 04 24.
Article in English | MEDLINE | ID: covidwho-1231457

ABSTRACT

Complaints of cognitive functions (CCFs), defined as subjective cognitive dysfunction, affect social function; additionally, for workers, this condition is an important factor in presenteeism and mediates the effect of depressive symptoms on presenteeism. This study aimed to investigate whether CCFs mediate the relationships among insomnia, state anxiety (SA), and presenteeism. Participants were 471 Japanese adult workers evaluated using the Athens Insomnia Scale, State-Trait Anxiety Inventory (Form Y), Cognitive Complaints in Bipolar Disorder Rating Assessment, and Work Limitations Questionnaire 8 to assess insomnia, SA, CCFs, and presenteeism, respectively. Path analysis was used to evaluate the correlations between variables. CCFs significantly mediated the associations among insomnia, SA, and presenteeism. To address the presenteeism associated with insomnia and SA, it may be useful to assess the mediating roles of CCFs.


Subject(s)
Presenteeism , Sleep Initiation and Maintenance Disorders , Adult , Anxiety/epidemiology , Cognition , Humans , Japan/epidemiology , Sleep Initiation and Maintenance Disorders/epidemiology
SELECTION OF CITATIONS
SEARCH DETAIL