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1.
Clin Teach ; : e13488, 2022 Apr 01.
Article in English | MEDLINE | ID: covidwho-1774904

ABSTRACT

BACKGROUND: The COVID-19 pandemic has necessitated the need to develop teaching innovations that provide safe, authentic clinical encounters which facilitate experiential learning. In tandem with the dissemination of teleconsultation and online teaching, this pilot study describes, evaluates and justifies a multi-camera live-streaming teaching session to medical students from the clinical environment. APPROACH: Multiple audio and video inputs capturing an outpatient clinic setting were routed through Open Broadcast Software (OBS) to create a customised feed streamed to remote learners through a videoconferencing platform. Sessions were conducted between September 2020 and March 2021. Twelve students sequentially interacted with a patient who held an iPad. Higher quality Go-Pro cameras captured the scene, allowing students to view the consultation from the patient and doctor's perspective. A consultant then conducted a 'gold standard' patient consultation observed by students. A faculty member remotely facilitated the session, providing pre-clinic teaching and debriefing. The equipment required with costing for a standard and low-cost version is described, as well as a set-up schematic and overview of ideal conditions and barriers encountered during trials. EVALUATION: All students completed a post-participation questionnaire, rating the overall quality of the sessions as 9.7/10. The quality of online facilitation, utility of observing peers' and consultant interaction with the patient, opportunity for peer-to-peer learning and availability of multiple camera angles were particularly valued by students. IMPLICATIONS: This innovation permits an authentic clinical interaction to be experienced by multiple students remotely, promoting equitable access to high-quality teaching, while maintaining the safety of students and patients.

2.
Infectious Medicine ; 2022.
Article in English | ScienceDirect | ID: covidwho-1699253

ABSTRACT

Objective Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019 and has led to a global coronavirus disease 2019 (COVID-19) pandemic. Currently, incomplete understanding of how SARS-CoV-2 arrogates the host cell to establish its life cycle has led to slow progress in the development of effective drugs. Results In this study, we found that SARS-CoV-2 hijacks the host protein EWSR1 (Ewing Sarcoma breakpoint region 1/EWS RNA binding protein 1) to promote the activity of its helicase NSP13 to facilitate viral propagation. NSP13 is highly conserved among coronaviruses and is crucial for virus replication, providing chemical energy to unwind viral RNA replication intermediates. Treatment with different SARS-CoV-2 NSP13 inhibitors in multiple cell lines infected with SARS-CoV-2 effectively suppressed SARS-CoV-2 infection. Using affinity-purification mass spectrometry, the RNA binding protein EWSR1 was then identified as a potent host factor that physically associated with NSP13. Furthermore, silencing EWSR1 dramatically reduced virus replication at both viral RNA and protein levels. Mechanistically, EWSR1 was found to bind to the NTPase domain of NSP13 and potentially enhance its dsRNA unwinding ability. Conclusion In conclusion, our results pinpoint EWSR1 as a novel host factor for NSP13 that could potentially be used for drug repurposing as a therapeutic target for COVID-19.

3.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-308350

ABSTRACT

Background: Coronavirus disease 2019 (COVID-19) has emerged as a major global health threat with a great number of deaths worldwide. Acute kidney injury (AKI) is a common complication in patients admitted to the intensive care unit. We aimed toassess the incidence, risk factors and in-hospital outcomes of AKI in COVID-19 patients admitted to intensive care unit Methods: : we conducted a retrospective observational study in intensive care unit of Tongji hospital, which was assigned responsibility for the treatments of severe COVID-19 patients by Wuhan government. The AKI was defined and staged based onKidney Disease: Improving Global Outcomes (KDIGO) criteria. Mild AKI was defined as stage 1, and severe AKI was defined as stage 2 or stage 3. We used logistic regression analysis to evaluate AKI risk factors and the association between AKI and in-hospital mortality. Results: : A total of 150 patients with COVID-19 were included in our study. The median age of patients was 70 (interquartile range, 60-80) years and 62.7% were male. 70 (46.7%) patients developed AKI during hospitalization, corresponding to the 17.3% in stage 1 and 9.3% in stage 2 and 20.0% in stage 3, respectively. Compared to patients without AKI, patients with AKI had higher proportion of mechanical ventilation mortality and higher in-hospital mortality. 95.5% patients with severe AKI received mechanical ventilation and in-hospital mortality was up to 79.5%. Severe AKI was independently associated with high in-hospital mortality (OR: 4.30;95% CI: 1.83-10.10). Logistic regression analysis demonstrated that high serum interleukin-6 (OR: 2.54;95%CI: 1.00-6.42) and interleukin-10 (OR: 3.02;95%CI: 1.17-7.82) were risk factors for severe AKI development. Conclusions: : severe AKI was associated with high in-hospital mortality and inflammatory response may play a role in AKI development in critically ill patients with COVID-19.

4.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-324295

ABSTRACT

Objective: To clarify the outcomes of elderly patients with COVID-19. Methods: : All 265 confirmed adult patients with COVID-19 were included in this retrospective study, 43 (16.2%) of whom were 65 years and older. Electronic medical records of the subjects were reviewed to obtain information on clinical characteristics and outcomes. The allocations of medical resource were also recorded. Results: : Only one death case occurred in the elderly. The mortality of elderly patients was no higher than that of young patients (2.3% vs. 0%, P = 0.126). The cure rate was 95.3% in elderly patients and 99.5% in young patients ( P = 0.067), and the duration of hospitalization is 27 days in elderly patients and 18 days in young patients ( P = 0.001). The elderly suffered from more comorbidities (67.4% vs. 24.8%, P < 0.001), most of which is hypertension. Significantly more severe cases occurred in elderly patients compared with young patients (37.2% vs. 16.7%, P = 0.004). The elderly were more likely to present with complications including acute respiratory distress syndrome, acute myocardial injury, septic shock and acute kidney injury (all P < 0.05), respectively. No medical staffs were infected during the treatment of COVID-19. Conclusion: The cure rate and the mortality of the elderly seemed to be no worse than that of the young, though the elderly were with longer hospitalization. Elderly patients with COVID-19 could be treatable if handled properly. More severe cases and complications in elderly patients should prompt for more complex treatment and special considerations.

5.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-324294

ABSTRACT

Objective: To clarify the clinical features of cured patients with coronavirus disease (COVID-19) and the relevance of IgM and IgG testing. Methods: : A total of 187 cured COVID-19 patients with antibody test were followed up every two weeks at Guangzhou Eighth People's hospital. Assessment for general condition, symptoms, epidemiological contact history, polymerase chain reaction (PCR) assay, and antibody tests were performed and recorded. Information from Guangzhou CDC was also screened. Results: : There were 154 (82.4%) patients with positive results for IgG and 35 (18.7%) patients with positive results for IgM. PCR assay was positive in 10 (5.3%) patients. Neither IgG nor IgM results showed a relationship with PCR test results (all P > 0.05). No re-infection was found in the cured patients. Among people who were in close contact with the cured patients, no one was diagnosed with COVID-19 as reported both by the cured patients and the Guangzhou CDC. Factors associated with appearance of IgG comprised hospitalization days (OR: 1.07, 95%CI: 1.02-1.13, P = 0.004) and antibiotics treatment (OR: 2.78, 95%CI: 1.10-7.01, P = 0.031) . Conclusion: In our study, neither re-infection nor human-to-human transmission was found in cured patients with COVID-19. Additionally, neither IgG nor IgM can be used to replace the PCR test in cured patients.

6.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-318916

ABSTRACT

Background: The COVID-19 pandemic caused by the SARS-CoV-2 virus is a major health crisis that is affecting countries across the world. Patients infected with COVID-19 are often associated with mental health disorders, such as anxiety, depression, and sleep disorders. As a non-drug therapy applied in clinics for many years, music intervention is safe, effective, inexpensive, and devoid of side effects. Yet, there is a distinct lack of evidence to support the use of this technique. In this study, we aim to collect and evaluate the clinical evidence, in order to provide a basis for the efficacy and safety of music intervention in the treatment of COVID-19 patients with mental disorders. Methods: : We plan to search a range of electronic databases from inception to the May 2021, including PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang Database, Chinese Biomedical Literature Database, and Chinese Science and Technology Periodical Database (VIP). All randomized controlled trials featuring music intervention to treat mental disorders such as anxiety, depression, or sleep disorders, for patients with COVID-19, will be included. The primary outcomes will be quantitative scores for anxiety, depression, and sleep disorder. The secondary outcomes will be quality of life and the safety profile of music intervention, including adverse events. Two reviewers will carry out the selection of studies, data extraction independently. The Cochrane risk of bias tool will be used to evaluate the risk of bias for the studies. We will use Review Manager V.5.3 software for data analysis. Subgroup analyses and sensitivity analyses are planned to assess the heterogeneity and reliability. Discussion: This is an up-to-date systematic review and meta-analysis of the efficacy and safety of music intervention on mental disorders (anxiety, depression, or sleep disorder) in COVID-19 patients, in order to provide clinicians, researchers, and policy makers, with powerful reference guidelines to facilitate treatment and improve the quality of life in COVID-19 patients with mental disorders. Systematic review registration: OSF 10.17605/OSF.IO/9RCX5

7.
Front Psychiatry ; 12: 782753, 2021.
Article in English | MEDLINE | ID: covidwho-1686549

ABSTRACT

This study aimed to investigate the effects of long-term home quarantine on the mental health of people during the COVID-19 epidemic in Shanghai. We conducted an online questionnaire survey on March 26 2020 and collected data on demographics, level of physical activity (PA), and mental health status of the participants. We assessed the mental health status using the Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder Scale (GAD-7), whereas PA was assessed using International Physical Activity Questionnaire Short Form (IPAQ-SF). Of all 2,409 valid samples, participants reported performing a total of 2015.20 metabolic equivalent of task (MET)-minutes/week of total PA before the outbreak period and 1720.29 MET-minutes/week of total PA during the outbreak period (p < 0.001). Participants who spent a longer time at home reported to have a better performance on the PHQ-9 (p = 0.087) and GAD-7 (p < 0.001). A high level of PA was considered an protective factor against depression (OR = 0.755, 95% CI 0.603-0.944, p < 0.001). Additionally, a high level of PA had a preventative effect on anxiety (OR = 0.741, 95% CI 0.568-0.967, p < 0.001), and a longer working period during the outbreak was shown to be a risk factor for anxiety (11-29 days, OR 1.455, 95% CI 1.110-1.909; 30-60 days OR 1.619, 95% CI 1.227-2.316). Home confinement during the pandemic might not have a negative effect on mental health provided that people engage in more PA indoors. This study encourages interventions for mental health problems through physical exercise.

8.
Front Immunol ; 12: 816745, 2021.
Article in English | MEDLINE | ID: covidwho-1662588

ABSTRACT

COVID-19 patients show heterogeneous and dynamic immune features which determine the clinical outcome. Here, we built a single-cell RNA sequencing (scRNA-seq) dataset for dissecting these complicated immune responses through a longitudinal survey of COVID-19 patients with various categories of outcomes. The data reveals a highly fluctuating peripheral immune landscape in severe COVID-19, whereas the one in asymptomatic/mild COVID-19 is relatively steady. Then, the perturbed immune landscape in peripheral blood returned to normal state in those recovered from severe COVID-19. Importantly, the imbalance of the excessively strong innate immune response and delayed adaptive immunity in the early stage of viral infection accelerates the progression of the disease, indicated by a transient strong IFN response and weak T/B-cell specific response. The proportion of abnormal monocytes appeared early and rose further throughout the severe disease. Our data indicate that a dynamic immune landscape is associated with the progression and recovery of severe COVID-19, and have provided multiple immune biomarkers for early warning of severe COVID-19.


Subject(s)
Adaptive Immunity/immunology , COVID-19/immunology , Interferons/immunology , B-Lymphocytes/immunology , Humans , Immunity, Innate/immunology , SARS-CoV-2/immunology , T-Lymphocytes/immunology
9.
J Immunol ; 208(3): 753-761, 2022 02 01.
Article in English | MEDLINE | ID: covidwho-1614089

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has seriously threatened global public health. Severe COVID-19 has been reported to be associated with an impaired IFN response. However, the mechanisms of how SARS-CoV-2 antagonizes the host IFN response are poorly understood. In this study, we report that SARS-CoV-2 helicase NSP13 inhibits type I IFN production by directly targeting TANK-binding kinase 1 (TBK1) for degradation. Interestingly, inhibition of autophagy by genetic knockout of Beclin1 or pharmacological inhibition can rescue NSP13-mediated TBK1 degradation in HEK-293T cells. Subsequent studies revealed that NSP13 recruits TBK1 to p62, and the absence of p62 can also inhibit TBK1 degradation in HEK-293T and HeLa cells. Finally, TBK1 and p62 degradation and p62 aggregation were observed during SARS-CoV-2 infection in HeLa-ACE2 and Calu3 cells. Overall, our study shows that NSP13 inhibits type I IFN production by recruiting TBK1 to p62 for autophagic degradation, enabling it to evade the host innate immune response, which provides new insights into the transmission and pathogenesis of SARS-CoV-2 infection.


Subject(s)
Autophagy , COVID-19/immunology , Interferon Type I/biosynthesis , Methyltransferases/physiology , RNA Helicases/physiology , SARS-CoV-2/physiology , Sequestosome-1 Protein/metabolism , Viral Nonstructural Proteins/physiology , Beclin-1/antagonists & inhibitors , Cell Line , Down-Regulation , Humans , Immune Evasion , Immunity, Innate , Immunoprecipitation , Interferon Type I/genetics , Multiprotein Complexes , Protein Aggregates , Protein Interaction Mapping
10.
BMJ Health Care Inform ; 29(1)2022 Jan.
Article in English | MEDLINE | ID: covidwho-1607921

ABSTRACT

INTRODUCTION: University Hospitals Leicester has codeveloped, with Nervecentre, an Electronic Prescribing and Medicines Administration System that meets specific clinical and interoperability demands of the National Health Service (NHS). METHODS: The system was developed through a frontline-led and agile approach with a project team consisting of clinicians, Information Technology (IT) specialists and the vendor's representatives over an 18-month period. RESULTS: The system was deployed successfully with more than a thousand transcriptions during roll-out. Despite the high caseload and novelty of the system, there was no increase in error rates within the first 3 months of roll-out. Healthcare professionals perceived the new system as efficient with improved clinical workflow, and safe through an integrated medication alert system. DISCUSSION: This case study demonstrates how NHS trusts can successfully co-develop, with vendors, new IT systems which meet interoperability standards such as Fast Healthcare Interoperability Resources, while improving front line clinical experience. CONCLUSION: Alternative methods to the 'big bang' deployment of IT projects, such as 'gradual implementation', must be demonstrated and evaluated for their ability to deliver digital transformation projects in the NHS successfully.


Subject(s)
Electronic Prescribing , State Medicine , Humans
11.
Cell Discov ; 7(1): 60, 2021 Aug 04.
Article in English | MEDLINE | ID: covidwho-1541177

ABSTRACT

Severe coronavirus disease 2019 (COVID-19) is often indicated by lymphopenia and increased myelopoiesis; however, the underlying mechanism is still unclear, especially the alteration of hematopoiesis. It is important to explore to what extent and how hematopoietic stem cells contribute to the impairment of peripheral lymphoid and myeloid compartments in COVID-19 patients. In this study, we used single-cell RNA sequencing to assess bone marrow mononuclear cells from COVID-19 patients with peripheral blood mononuclear cells as control. The results showed that the hematopoietic stem cells in these patients were mainly in the G1 phase and prone to apoptosis, with immune activation and anti-viral responses. Importantly, a significant accumulation of immature myeloid progenitors and a dramatic reduction of lymphoid progenitors in severe cases were identified, along with the up-regulation of transcription factors (such as SPI1, LMO4, ETS2, FLI1, and GATA2) that are important for the hematopoietic stem cell or multipotent progenitor to differentiate into downstream progenitors. Our results indicate a dysregulated hematopoiesis in patients with severe COVID-19.

13.
Sustain Cities Soc ; 76: 103485, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1492614

ABSTRACT

The lack of detailed COVID-19 cases at a fine spatial resolution restricts the investigation of spatial disparities of its attack rate. Here, we collected nearly one thousand self-reported cases from a social media platform during the early stage of COVID-19 epidemic in Wuhan, China. We used kernel density estimation (KDE) to explore spatial disparities of epidemic intensity and adopted geographically weighted regression (GWR) model to quantify influences of population dynamics, transportation, and social interactions on COVID-19 epidemic. Results show that self-reported COVID-19 cases concentrated in commercial centers and populous residential areas. Blocks with higher population density, higher aging rate, more metro stations, more main roads, and more commercial point-of-interests (POIs) have a higher density of COVID-19 cases. These five explanatory variables explain 76% variance of self-reported cases using an OLS model. Commercial POIs have the strongest influence, which increase COVID-19 cases by 28% with one standard deviation increase. The GWR model performs better than OLS model with the adjusted R 2 of 0.96. Spatial heterogeneities of coefficients in the GWR model show that influencing factors play different roles in diverse communities. We further discussed potential implications for the healthy city and urban planning for the sustainable development of cities.

14.
Cell Res ; 31(12): 1230-1243, 2021 12.
Article in English | MEDLINE | ID: covidwho-1475291

ABSTRACT

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the ongoing global pandemic that poses substantial challenges to public health worldwide. A subset of COVID-19 patients experience systemic inflammatory response, known as cytokine storm, which may lead to death. Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) is an important mediator of inflammation and cell death. Here, we examined the interaction of RIPK1-mediated innate immunity with SARS-CoV-2 infection. We found evidence of RIPK1 activation in human COVID-19 lung pathological samples, and cultured human lung organoids and ACE2 transgenic mice infected by SARS-CoV-2. Inhibition of RIPK1 using multiple small-molecule inhibitors reduced the viral load of SARS-CoV-2 in human lung organoids. Furthermore, therapeutic dosing of the RIPK1 inhibitor Nec-1s reduced mortality and lung viral load, and blocked the CNS manifestation of SARS-CoV-2 in ACE2 transgenic mice. Mechanistically, we found that the RNA-dependent RNA polymerase of SARS-CoV-2, NSP12, a highly conserved central component of coronaviral replication and transcription machinery, promoted the activation of RIPK1. Furthermore, NSP12 323L variant, encoded by the SARS-CoV-2 C14408T variant first detected in Lombardy, Italy, that carries a Pro323Leu amino acid substitution in NSP12, showed increased ability to activate RIPK1. Inhibition of RIPK1 downregulated the transcriptional induction of proinflammatory cytokines and host factors including ACE2 and EGFR that promote viral entry into cells. Our results suggest that SARS-CoV-2 may have an unexpected and unusual ability to hijack the RIPK1-mediated host defense response to promote its own propagation and that inhibition of RIPK1 may provide a therapeutic option for the treatment of COVID-19.


Subject(s)
COVID-19/pathology , Receptor-Interacting Protein Serine-Threonine Kinases/metabolism , SARS-CoV-2/physiology , Angiotensin-Converting Enzyme 2/genetics , Animals , COVID-19/drug therapy , COVID-19/mortality , COVID-19/virology , Coronavirus RNA-Dependent RNA Polymerase/genetics , Coronavirus RNA-Dependent RNA Polymerase/metabolism , Cytokines/genetics , Cytokines/metabolism , Down-Regulation/drug effects , ErbB Receptors/metabolism , Humans , Imidazoles/pharmacology , Imidazoles/therapeutic use , Indoles/pharmacology , Indoles/therapeutic use , Lung/pathology , Lung/virology , Mice , Mice, Transgenic , Mutation , Receptor-Interacting Protein Serine-Threonine Kinases/antagonists & inhibitors , SARS-CoV-2/isolation & purification , SARS-CoV-2/metabolism , Survival Rate , Transcriptome/drug effects , Viral Load/drug effects , Virus Internalization
15.
Gigascience ; 10(9)2021 09 28.
Article in English | MEDLINE | ID: covidwho-1443047

ABSTRACT

BACKGROUND: B-cell immunoglobulin repertoires with paired heavy and light chain can be determined by means of 10X single-cell V(D)J sequencing. Precise and quick analysis of 10X single-cell immunoglobulin repertoires remains a challenge owing to the high diversity of immunoglobulin repertoires and a lack of specialized software that can analyze such diverse data. FINDINGS: In this study, specialized software for 10X single-cell immunoglobulin repertoire analysis was developed. SCIGA (Single-Cell Immunoglobulin Repertoire Analysis) is an easy-to-use pipeline that performs read trimming, immunoglobulin sequence assembly and annotation, heavy and light chain pairing, statistical analysis, visualization, and multiple sample integration analysis, which is all achieved by using a 1-line command. Then SCIGA was used to profile the single-cell immunoglobulin repertoires of 9 patients with coronavirus disease 2019 (COVID-19). Four neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were identified from these repertoires. CONCLUSIONS: SCIGA provides a complete and quick analysis for 10X single-cell V(D)J sequencing datasets. It can help researchers to interpret B-cell immunoglobulin repertoires with paired heavy and light chain.


Subject(s)
Immunoglobulins/metabolism , Single-Cell Analysis/methods , Software , Antibodies, Monoclonal/chemistry , Antibodies, Monoclonal/genetics , Antibodies, Monoclonal/metabolism , COVID-19/pathology , COVID-19/virology , Humans , Immunoglobulins/chemistry , Immunoglobulins/genetics , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification
16.
Cell Discov ; 7(1): 89, 2021 Sep 28.
Article in English | MEDLINE | ID: covidwho-1440469

ABSTRACT

SARS-CoV-2 outbreak has been declared by World Health Organization as a worldwide pandemic. However, there are many unknowns about the antigen-specific T-cell-mediated immune responses to SARS-CoV-2 infection. Here, we present both single-cell TCR-seq and RNA-seq to analyze the dynamics of TCR repertoire and immune metabolic functions of blood T cells collected from recently discharged COVID-19 patients. We found that while the diversity of TCR repertoire was increased in discharged patients, it returned to basal level ~1 week after becoming virus-free. The dynamics of T cell repertoire correlated with a profound shift of gene signatures from antiviral response to metabolism adaptation. We also demonstrated that the top expanded T cell clones (~10% of total T cells) display the key anti-viral features in CD8+ T cells, confirming a critical role of antigen-specific T cells in fighting against SARS-CoV-2. Our work provides a basis for further analysis of adaptive immunity in COVID-19 patients, and also has implications in developing a T-cell-based vaccine for SARS-CoV-2.

18.
Cell Mol Immunol ; 18(10): 2313-2324, 2021 10.
Article in English | MEDLINE | ID: covidwho-1392820

ABSTRACT

In response to emerging infectious diseases, such as the recent pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it is critical to quickly identify and understand responsible pathogens, risk factors, host immune responses, and pathogenic mechanisms at both the molecular and cellular levels. The recent development of multiomic technologies, including genomics, proteomics, metabolomics, and single-cell transcriptomics, has enabled a fast and panoramic grasp of the pathogen and the disease. Here, we systematically reviewed the major advances in the virology, immunology, and pathogenic mechanisms of SARS-CoV-2 infection that have been achieved via multiomic technologies. Based on well-established cohorts, omics-based methods can greatly enhance the mechanistic understanding of diseases, contributing to the development of new diagnostics, drugs, and vaccines for emerging infectious diseases, such as COVID-19.


Subject(s)
COVID-19/genetics , COVID-19/metabolism , Genomics , Metabolomics , COVID-19/immunology , COVID-19/pathology , Host-Pathogen Interactions , Humans , Pandemics , SARS-CoV-2/physiology , Single-Cell Analysis , Transcriptome
19.
J Immunol ; 207(7): 1848-1856, 2021 10 01.
Article in English | MEDLINE | ID: covidwho-1377034

ABSTRACT

Immune cell responses are strikingly altered in patients with severe coronavirus disease 2019 (COVID-19), but the immunoregulatory process in these individuals is not fully understood. In this study, 23 patients with mild and 22 patients with severe COVID-19 and 6 asymptomatic carriers of COVID-19 were enrolled, along with 44 healthy controls (HC). Peripheral immune cells in HC and patients with COVID-19 were comprehensively profiled using mass cytometry. We found that in patients with severe COVID-19, the number of HLA-DRlow/- monocytes was significantly increased, but that of mucosal-associated invariant T (MAIT) cells was greatly reduced. MAIT cells were highly activated but functionally impaired in response to Escherichia coli and IL-12/IL-18 stimulation in patients with severe COVID-19, especially those with microbial coinfection. Single-cell transcriptome analysis revealed that IFN-stimulated genes were significantly upregulated in peripheral MAIT cells and monocytes from patients with severe COVID-19. IFN-α pretreatment suppressed MAIT cells' response to E. coli by triggering high levels of IL-10 production by HLA-DRlow/--suppressive monocytes. Blocking IFN-α or IL-10 receptors rescued MAIT cell function in patients with severe COVID-19. Moreover, plasma from patients with severe COVID-19 inhibited HLA-DR expression by monocytes through IL-10. These data indicate a unique pattern of immune dysregulation in severe COVID-19, which is characterized by enrichment of suppressive HLA-DRlow/- monocytes associated with functional impairment of MAIT cells through the IFN/IL-10 pathway.


Subject(s)
COVID-19/immunology , Escherichia coli Infections/immunology , Escherichia coli/physiology , Interleukin-10/metabolism , Monocytes/immunology , Mucosal-Associated Invariant T Cells/immunology , SARS-CoV-2/physiology , Adolescent , Adult , Asymptomatic Diseases , Cells, Cultured , Child , Coinfection , Disease Progression , Female , Humans , Immune Tolerance , Lymphocyte Activation , Male , Middle Aged , Severity of Illness Index , Young Adult
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