Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 82
Filter
Add filters

Year range
1.
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.

2.
Virol J ; 19(1): 2, 2022 01 04.
Article in English | MEDLINE | ID: covidwho-1608023

ABSTRACT

The current COVID-19 pandemic caused by constantly emerging SARS-CoV-2 variants still poses a threat to public health worldwide. Effective next-generation vaccines and optimized booster vaccination strategies are urgently needed. Here, we sequentially immunized mice with a SARS-CoV-2 wild-type inactivated vaccine and a heterologous mutant RBD vaccine, and then evaluated their neutralizing antibody responses against variants including Beta, Delta, Alpha, Iota, Kappa, and A.23.1. These data showed that a third booster dose of heterologous RBD vaccine especially after two doses of inactivated vaccines significantly enhanced the GMTs of nAbs against all SARS-CoV-2 variants we tested. In addition, the WT and variants all displayed good cross-immunogenicity and might be applied in the design of booster vaccines to induce broadly neutralizing antibodies.


Subject(s)
COVID-19 Vaccines , COVID-19 , SARS-CoV-2 , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , COVID-19/prevention & control , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/immunology , Mice , SARS-CoV-2/immunology
3.
Front Immunol ; 12: 766821, 2021.
Article in English | MEDLINE | ID: covidwho-1581335

ABSTRACT

As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants continue to emerge and spread around the world, antibodies and vaccines to confer broad and potent neutralizing activity are urgently needed. Through the isolation and characterization of monoclonal antibodies (mAbs) from individuals infected with SARS-CoV-2, we identified one antibody, P36-5D2, capable of neutralizing the major SARS-CoV-2 variants of concern. Crystal and electron cryo-microscopy (cryo-EM) structure analyses revealed that P36-5D2 targeted to a conserved epitope on the receptor-binding domain of the spike protein, withstanding the three key mutations-K417N, E484K, and N501Y-found in the variants that are responsible for escape from many potent neutralizing mAbs, including some already approved for emergency use authorization (EUA). A single intraperitoneal (IP) injection of P36-5D2 as a prophylactic treatment completely protected animals from challenge of infectious SARS-CoV-2 Alpha and Beta. Treated animals manifested normal body weight and were devoid of infection-associated death up to 14 days. A substantial decrease of the infectious virus in the lungs and brain, as well as reduced lung pathology, was found in these animals compared to the controls. Thus, P36-5D2 represents a new and desirable human antibody against the current and emerging SARS-CoV-2 variants.


Subject(s)
Antibodies, Monoclonal/pharmacology , Antibodies, Neutralizing/pharmacology , Antibodies, Viral/pharmacology , COVID-19/drug therapy , SARS-CoV-2/drug effects , Animals , Antibodies, Monoclonal/chemistry , Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/chemistry , Antibodies, Neutralizing/immunology , Antibodies, Viral/chemistry , Antibodies, Viral/immunology , HEK293 Cells , Humans , Immunization, Passive , Mice
4.
Biology (Basel) ; 11(1)2021 Dec 27.
Article in English | MEDLINE | ID: covidwho-1581041

ABSTRACT

Accurate and timely diagnosis of COVID-19 is indispensable to control its spread. This study proposes a novel explainable COVID-19 diagnosis system called CGENet based on graph embedding and an extreme learning machine for chest CT images. We put forward an optimal backbone selection algorithm to select the best backbone for the CGENet based on transfer learning. Then, we introduced graph theory into the ResNet-18 based on the k-nearest neighbors. Finally, an extreme learning machine was trained as the classifier of the CGENet. The proposed CGENet was evaluated on a large publicly-available COVID-19 dataset and produced an average accuracy of 97.78% based on 5-fold cross-validation. In addition, we utilized the Grad-CAM maps to present a visual explanation of the CGENet based on COVID-19 samples. In all, the proposed CGENet can be an effective and efficient tool to assist COVID-19 diagnosis.

5.
Talanta ; 239: 123086, 2021 Dec 01.
Article in English | MEDLINE | ID: covidwho-1556287

ABSTRACT

Asymptomatic infection of COVID-19 is a global threat for public health. Unfortunately, the study about metabolic dysregulation of asymptomatic infection is barely investigated. Here, we performed carboxylic submetabolome profiling of serum from 62 asymptomatic and 122 control individuals, by a highly sensitive chemical isotope labelling method. Twenty-one discriminative carboxylic features, including 12-hydroxyeicosatetraenoic acid, cholic acid, glycoursodeoxycholic acid and 15,16-dihydroxyoctadeca-9,12-dienoic acid were discovered to be dysregulated in asymptomatic patients. This panel containing 21 carboxylic features could accurately identify asymptomatic patients based on a random forest model, providing an accuracy of 85.7% with only 3.6% false positive rate and 7.1% false negative rate. The dysregulated metabolites found in asymptomatic patients covered several important pathways, such as arachidonic acid metabolism, synthesis of bile acid, ß-oxidation of fatty acids, activation of macrophage and platelet aggregation. This work provided valuable knowledge about serum biomarkers and molecular clues associated with asymptomatic COVID-19 patients.

6.
Preprint in English | Other preprints | ID: ppcovidwho-296272

ABSTRACT

New SARS-CoV-2 variants continue to emerge from the current global pandemic, some of which can replicate faster and with greater transmissibility and pathogenicity. In particular, UK501Y.V1 identified in UK, SA501Y.V2 in South Africa, and BR501Y.V3 in Brazil are raising serious concerns as they spread quickly and contain spike protein mutations that may facilitate escape from current antibody therapies and vaccine protection. Here, we constructed a panel of 28 SARS-CoV-2 pseudoviruses bearing single or combined mutations found in the spike protein of these three variants, as well as additional nine mutations that within or close by the major antigenic sites in the spike protein identified in the GISAID database. These pseudoviruses were tested against a panel of monoclonal antibodies (mAbs), including some approved for emergency use to treat SARS-CoV-2 infection, and convalescent patient plasma collected early in the pandemic. SA501Y.V2 pseudovirus was the most resistant, in magnitude and breadth, against mAbs and convalescent plasma, followed by BR501Y.V3, and then UK501Y.V1. This resistance hierarchy corresponds with Y144del and 242-244del mutations in the N-terminal domain as well as K417N/T, E484K and N501Y mutations in the receptor binding domain (RBD). Crystal structural analysis of RBD carrying triple K417N-E484K-N501Y mutations found in SA501Y.V2 bound with mAb P2C-1F11 revealed a molecular basis for antibody neutralization and escape. SA501Y.V2 and BR501Y.V3 also acquired substantial ability to use mouse and mink ACE2 for entry. Taken together, our results clearly demonstrate major antigenic shifts and potentially broadening the host range of SA501Y.V2 and BR501Y.V3, which pose serious challenges to our current antibody therapies and vaccine protection.

7.
Preprint in English | SSRN | ID: ppcovidwho-293491

ABSTRACT

The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) raised a global pandemic and caused over 4.2 million deaths worldwide. However, there is no specific treatment for COVID-19 patients. In this study, we noticed that male COVID-19 patients had a higher severe rate than females, and IL-6 levels act as an independent risk factor for COVID-19 patients. Using single-cell RNA sequencing (scRNA-seq), we identified a macrophage and a fibroblast cell clusters that secreted IL-6 in COVID-19 lungs were specific in COVID-19 lung microenvironment. Gene Set Enrichment Analysis (GSEA), transcriptional factors (TFs) prediction and chromatin immunoprecipitation sequencing (ChIP-seq) revealed that the macrophage and fibroblast inducing the cytokine storm syndrome (CSS) in severe COVID-19 patients, and the trinity of AR, HIF-1α and YY1 regulates the progression of CSS. Our results firstly explained the mechanism of sex disproportion of COVID-19 and provided a novel rationale for combined therapeutic approach for COVID-19 treatment.

8.
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.

11.
Front Chem ; 9: 746134, 2021.
Article in English | MEDLINE | ID: covidwho-1477804

ABSTRACT

Asymptomatic COVID-19 has become one of the biggest challenges for controlling the spread of the SARS-CoV-2. Diagnosis of asymptomatic COVID-19 mainly depends on quantitative reverse transcription PCR (qRT-PCR), which is typically time-consuming and requires expensive reagents. The application is limited in countries that lack sufficient resources to handle large-scale assay during the COVID-19 outbreak. Here, we demonstrated a new approach to detect the asymptomatic SARS-CoV-2 infection using serum metabolic patterns combined with ensemble learning. The direct patterns of metabolites and lipids were extracted by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) within 1 s with simple sample preparation. A new ensemble learning model was developed using stacking strategy with a new voting algorithm. This approach was validated in a large cohort of 274 samples (92 asymptomatic COVID-19 and 182 healthy control), and provided the high accuracy of 93.4%, with only 5% false negative and 7% false positive rates. We also identified a biomarker panel of ten metabolites and lipids, as well as the altered metabolic pathways during asymptomatic SARS-CoV-2 Infection. The proposed rapid and low-cost approach holds promise to apply in the large-scale asymptomatic COVID-19 screening.

12.
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.

13.
iScience ; 24(9): 102974, 2021 Sep 24.
Article in English | MEDLINE | ID: covidwho-1461109

ABSTRACT

Asymptomatic infection is a big challenge in curbing the spread of COVID-19. However, its identification and pathogenesis elucidation remain issues. Here, by performing comprehensive lipidomic characterization of serum samples from 89 asymptomatic COVID-19 patients and 178 healthy controls, we screened out a panel of 15 key lipids that could accurately identify asymptomatic patients using a new ensemble learning model based on stacking strategy with a voting algorithm. This strategy provided a high accuracy of 96.0% with only 3.6% false positive rate and 4.8% false negative rate. More importantly, the unique lipid metabolic dysregulation was revealed, especially the enhanced synthesis of membrane phospholipids, altered sphingolipids homeostasis, and differential fatty acids metabolic pattern, implicating the specific host immune, inflammatory, and antiviral responses in asymptomatic COVID-19. This study provides a potential prediagnostic method for asymptomatic COVID-19 and molecular clues for the pathogenesis and therapy of this disease.

14.
Journal of analysis and testing ; : 1-13, 2021.
Article in English | EuropePMC | ID: covidwho-1451536

ABSTRACT

The outbreak of severe pneumonia at the end of 2019 was proved to be caused by the SARS-CoV-2 virus spreading out the world. And COVID-19 spread rapidly through a terrible transmission way by human-to-human, which led to many suspected cases waiting to be diagnosed and huge daily samples needed to be tested by an effective and rapid detection method. With an increasing number of COVID-19 infections, medical pressure is severe. Therefore, more efficient and accurate diagnosis methods were keen urgently established. In this review, we summarized several methods that can rapidly and sensitively identify COVID-19;some of them are widely used as the diagnostic techniques for SARS-CoV-2 in various countries, some diagnostic technologies refer to SARS (Severe Acute Respiratory Syndrome) or/and MERS (Middle East Respiratory Syndrome) detection, which may provide potential diagnosis ideas.

15.
JAMA ; 323(16): 1582-1589, 2020 04 28.
Article in English | MEDLINE | ID: covidwho-1453469

ABSTRACT

Importance: Coronavirus disease 2019 (COVID-19) is a pandemic with no specific therapeutic agents and substantial mortality. It is critical to find new treatments. Objective: To determine whether convalescent plasma transfusion may be beneficial in the treatment of critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Design, Setting, and Participants: Case series of 5 critically ill patients with laboratory-confirmed COVID-19 and acute respiratory distress syndrome (ARDS) who met the following criteria: severe pneumonia with rapid progression and continuously high viral load despite antiviral treatment; Pao2/Fio2 <300; and mechanical ventilation. All 5 were treated with convalescent plasma transfusion. The study was conducted at the infectious disease department, Shenzhen Third People's Hospital in Shenzhen, China, from January 20, 2020, to March 25, 2020; final date of follow-up was March 25, 2020. Clinical outcomes were compared before and after convalescent plasma transfusion. Exposures: Patients received transfusion with convalescent plasma with a SARS-CoV-2-specific antibody (IgG) binding titer greater than 1:1000 (end point dilution titer, by enzyme-linked immunosorbent assay [ELISA]) and a neutralization titer greater than 40 (end point dilution titer) that had been obtained from 5 patients who recovered from COVID-19. Convalescent plasma was administered between 10 and 22 days after admission. Main Outcomes and Measures: Changes of body temperature, Sequential Organ Failure Assessment (SOFA) score (range 0-24, with higher scores indicating more severe illness), Pao2/Fio2, viral load, serum antibody titer, routine blood biochemical index, ARDS, and ventilatory and extracorporeal membrane oxygenation (ECMO) supports before and after convalescent plasma transfusion. Results: All 5 patients (age range, 36-65 years; 2 women) were receiving mechanical ventilation at the time of treatment and all had received antiviral agents and methylprednisolone. Following plasma transfusion, body temperature normalized within 3 days in 4 of 5 patients, the SOFA score decreased, and Pao2/Fio2 increased within 12 days (range, 172-276 before and 284-366 after). Viral loads also decreased and became negative within 12 days after the transfusion, and SARS-CoV-2-specific ELISA and neutralizing antibody titers increased following the transfusion (range, 40-60 before and 80-320 on day 7). ARDS resolved in 4 patients at 12 days after transfusion, and 3 patients were weaned from mechanical ventilation within 2 weeks of treatment. Of the 5 patients, 3 have been discharged from the hospital (length of stay: 53, 51, and 55 days), and 2 are in stable condition at 37 days after transfusion. Conclusions and Relevance: In this preliminary uncontrolled case series of 5 critically ill patients with COVID-19 and ARDS, administration of convalescent plasma containing neutralizing antibody was followed by improvement in their clinical status. The limited sample size and study design preclude a definitive statement about the potential effectiveness of this treatment, and these observations require evaluation in clinical trials.


Subject(s)
Antibodies, Neutralizing/therapeutic use , Antibodies, Viral/therapeutic use , Betacoronavirus/immunology , Coronavirus Infections/therapy , Pneumonia, Viral/therapy , Respiratory Distress Syndrome/therapy , Adult , Aged , Antibodies, Viral/blood , Antiviral Agents/therapeutic use , Blood Donors , COVID-19 , Coronavirus Infections/drug therapy , Coronavirus Infections/physiopathology , Critical Illness , Female , Glucocorticoids/therapeutic use , Humans , Immunization, Passive , Immunoglobulin G/blood , Immunoglobulin M/blood , Male , Methylprednisolone/therapeutic use , Middle Aged , Organ Dysfunction Scores , Pandemics , Pneumonia, Viral/drug therapy , Pneumonia, Viral/physiopathology , SARS-CoV-2
16.
J Virol ; : JVI0125321, 2021 Sep 29.
Article in English | MEDLINE | ID: covidwho-1443353

ABSTRACT

Over the past 20 years, Severe acute respiratory syndrome CoV (SARS-CoV), Middle East respiratory syndrome CoV (MERS-CoV) and severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), have all emerged, causing severe epidemic human respiratory diseases throughout the globe. Developing broad spectrum drugs would be invaluable in responding to new emerging coronaviruses of the future and could address unmet urgent clinical needs. Main protease (Mpro, also known as 3CLpro) has a major role in the replication of a coronavirus life cycle and is one of the most important drug targets for anticoronavirus agents. We show that a natural product, noncovalent inhibitor shikonin, can pan-main protease inhibitor of SARS-CoV-2, SARS-CoV, MERS-CoV, HCoV-HKU1, HCoV-NL63 and HCoV-229E with micromolar IC50 values. Structures of the main protease of different coronavirus genus, SARS-CoV from betacoronaviruses and HCoV-NL63 from alphacoronaviruses, were determined by X-ray crystallography and reveals that the inhibitor interacts with key active-site residues in a unique mode. The structure of the main protease inhibitor complex presents an opportunity to discover a novel series of broad-spectrum inhibitors. These data provide substantial evidence that shikonin and its derivatives may be effective against most coronaviruses, as well as emerging coronaviruses in the future. Given the importance of main protease for the coronavirus therapeutic indication, insights from these studies should accelerate the development and design of safer and more effective antiviral agents. Importance The current pandemic has created an urgent need for broad spectrum inhibitors of SARS-CoV-2. Main protease is relatively conservative compared with the spike protein and thus is one of the most promising drug targets for developing anticoronavirus agents. We have solved crystal structures of main protease of SARS-CoV and HCoV-NL63 bound to shikonin. The structures provide important insights that have broad implications for understanding the structural basis underlying enzyme activity, and can facilitate rational design of broad spectrum anticoronavirus ligands as new therapeutic agents.

17.
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
18.
Nat Commun ; 12(1): 5652, 2021 09 27.
Article in English | MEDLINE | ID: covidwho-1440473

ABSTRACT

The emergence of numerous variants of SARS-CoV-2, the causative agent of COVID-19, has presented new challenges to the global efforts to control the COVID-19 pandemic. Here, we obtain two cross-neutralizing antibodies (7D6 and 6D6) that target Sarbecoviruses' receptor-binding domain (RBD) with sub-picomolar affinities and potently neutralize authentic SARS-CoV-2. Crystal structures show that both antibodies bind a cryptic site different from that recognized by existing antibodies and highly conserved across Sarbecovirus isolates. Binding of these two antibodies to the RBD clashes with the adjacent N-terminal domain and disrupts the viral spike. Both antibodies confer good resistance to mutations in the currently circulating SARS-CoV-2 variants. Thus, our results have direct relevance to public health as options for passive antibody therapeutics and even active prophylactics. They can also inform the design of pan-sarbecovirus vaccines.


Subject(s)
Antibodies, Viral/immunology , Broadly Neutralizing Antibodies/immunology , COVID-19/therapy , Immunization, Passive/methods , SARS-CoV-2/immunology , Animals , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/immunology , Antibodies, Monoclonal/isolation & purification , Antibodies, Monoclonal/metabolism , Antibodies, Viral/administration & dosage , Antibodies, Viral/isolation & purification , Antibodies, Viral/metabolism , Binding Sites/genetics , Binding Sites/immunology , Broadly Neutralizing Antibodies/administration & dosage , Broadly Neutralizing Antibodies/isolation & purification , Broadly Neutralizing Antibodies/metabolism , CHO Cells , COVID-19/epidemiology , COVID-19/immunology , COVID-19/virology , Chlorocebus aethiops , Cricetulus , Epitopes/immunology , HEK293 Cells , Humans , Mice , Middle East Respiratory Syndrome Coronavirus/genetics , Middle East Respiratory Syndrome Coronavirus/immunology , Neutralization Tests , Pandemics/prevention & control , Protein Multimerization , Receptors, Virus/metabolism , SARS-CoV-2/genetics , Sf9 Cells , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/metabolism , Vero Cells
19.
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.

SELECTION OF CITATIONS
SEARCH DETAIL
...