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1.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-329211

ABSTRACT

Numerous mutations in the spike protein of SARS-CoV-2 B.1.1.529 Omicron variant pose a crisis for antibody-based immunotherapies. The efficacy of emergency use authorized (EUA) antibodies that developed in early SARS-CoV-2 pandemic seems to be in flounder. In this work, we examined the Omicron variant neutralization using an early B cell antibody repertoire as well as several EUA antibodies in pseudovirus and authentic virus systems. More than half of the antibodies in the repertoire that showed good activity against WA1/2020 previously had completely lost neutralizing activity against Omicron, while antibody 8G3 from our early B cell repertoire displayed non-regressive activity. EUA antibodies Etesevimab, Casirivimab, Imdevimab and Bamlanivimab neutralized authentic WA1/2020 virus with low half maximal inhibitory concentration (IC50) values, but were entirely desensitized by Omicron. Only Sotrovimab targeting the non-ACE2 overlap epitope showed activity but with a dramatic decrease. Interestingly, antibody 8G3 efficiently neutralized Omicron in pseudovirus and authentic virus systems. 8G3 also showed excellent activity against other variants of concern (VOCs). Collectively, our results suggest that neutralizing antibodies with breadth remains broad neutralizing activity in tackling SARS-CoV-2 infection despite the universal evasion from EUA antibodies by Omicron variant.

2.
Cell Discov ; 8(1): 16, 2022 Feb 15.
Article in English | MEDLINE | ID: covidwho-1692632

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) continue to wreak havoc across the globe. Higher transmissibility and immunologic resistance of VOCs bring unprecedented challenges to epidemic extinguishment. Here we describe a monoclonal antibody, 2G1, that neutralizes all current VOCs and has surprising tolerance to mutations adjacent to or within its interaction epitope. Cryo-electron microscopy structure showed that 2G1 bound to the tip of receptor binding domain (RBD) of spike protein with small contact interface but strong hydrophobic effect, which resulted in nanomolar to sub-nanomolar affinities to spike proteins. The epitope of 2G1 on RBD partially overlaps with angiotensin converting enzyme 2 (ACE2) interface, which enables 2G1 to block interaction between RBD and ACE2. The narrow binding epitope but high affinity bestow outstanding therapeutic efficacy upon 2G1 that neutralized VOCs with sub-nanomolar half maximal inhibitory concentration in vitro. In SARS-CoV-2, Beta or Delta variant-challenged transgenic mice and rhesus macaque models, 2G1 protected animals from clinical illness and eliminated viral burden, without serious impact to animal safety. Mutagenesis experiments suggest that 2G1 is potentially capable of dealing with emerging SARS-CoV-2 variants in the future. This report characterized the therapeutic antibodies specific to the tip of spike against SARS-CoV-2 variants and highlights the potential clinical applications as well as for developing vaccine and cocktail therapy.

3.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325059

ABSTRACT

Background: To explore the effects of short-term low- to moderate- dose glucocorticoids on the immune-inflammatory indicators and 28-d prognoses of patients with regular or severe coronavirus disease 2019 (COVID-19). Methods: : The clinical data and laboratorial examination results of 66 patients with regular or severe type of COVID-19 that treated in Henan Provincial People’s Hospital and Nanyang Central Hospital between January 20 and February 14, 2020 were retrospectively analyzed. Here, 36 patients that had been treated with glucocorticoids were categorized in the glucocorticoids group (GC group), while the other 30 patients that had not been treated with glucocorticoids were categorized in the control group. Results: : The immune-inflammatory indicators and prognoses of the patients in the two groups were compared. The sex, age, clinical types, and complications were not significantly different between the two groups (all P> 0.05). After hospitalization, 33.3% and 6.7% of the patients in the GC group and control group were with chest distress, respectively, and the difference was statistically significant ( P= 0.019). The duration of fever was also significantly different between the two groups (6.91 ± 4.41 vs. 9.21 ± 4.46 days, P= 0.036), but the blood examination results within 24 h after hospitalization were not significantly different between the two groups (all P> 0.05). The C-reactive protein (CRP) and Interleukin-6 (IL-6) levels were lower in the GC group than control group on day 7 ( P= 0.012, P= 0.035) but were not significantly different between the two groups on day 14. The CRP and IL-6 levels were significantly reduced after glucocorticoids treatment on day 3, 5 and 7 (all P< 0.05) in GC group. The median time of hospital stay, and 28-d prognoses were not significantly different between the two groups ( P= 0.080, P> 0.999). Conclusions: Glucocorticoids could decrease the levels of inflammatory indicators, but did not significantly influence other immune-related indicators and 28-d prognoses.

4.
Front Immunol ; 12: 689866, 2021.
Article in English | MEDLINE | ID: covidwho-1503883

ABSTRACT

Rapid recruitment of neutrophils to an inflamed site is one of the hallmarks of an effective host defense mechanism. The main pathway through which this happens is by the innate immune response. Neutrophils, which play an important part in innate immune defense, migrate into lungs through the modulation actions of chemokines to execute a variety of pro-inflammatory functions. Despite the importance of chemokines in host immunity, little has been discussed on their roles in host immunity. A holistic understanding of neutrophil recruitment, pattern recognition pathways, the roles of chemokines and the pathophysiological roles of neutrophils in host immunity may allow for new approaches in the treatment of infectious and inflammatory disease of the lung. Herein, this review aims at highlighting some of the developments in lung neutrophil-immunity by focusing on the functions and roles of CXC/CC chemokines and pattern recognition receptors in neutrophil immunity during pulmonary inflammations. The pathophysiological roles of neutrophils in COVID-19 and thromboembolism have also been summarized. We finally summarized various neutrophil biomarkers that can be utilized as prognostic molecules in pulmonary inflammations and discussed various neutrophil-targeted therapies for neutrophil-driven pulmonary inflammatory diseases.


Subject(s)
Immunity, Innate/immunology , Neutrophils/immunology , Pneumonia/immunology , Biomarkers/blood , COVID-19/immunology , Cell Degranulation/immunology , Chemokines/immunology , Clinical Trials as Topic , Extracellular Traps/immunology , Humans , Integrins/immunology , Lung/immunology , Lung/pathology , Neutrophils/drug effects , Pneumonia/diagnosis , Pneumonia/drug therapy , Receptors, Pattern Recognition/immunology , Respiratory Burst/immunology , SARS-CoV-2 , Thromboembolism/immunology
5.
J Thorac Dis ; 13(5): 2986-3000, 2021 May.
Article in English | MEDLINE | ID: covidwho-1257381

ABSTRACT

BACKGROUND: Given the high prevalence of coronavirus disease 2019 (COVID-19) globally, and the increased number of patients being discharged, it is necessary to understand the health consequences of COVID-19 to formulate and manage public policy concerning convalescent patients. METHODS: A longitudinal follow-up investigation of 25 patients from a tertiary hospital in Henan provincial was conducted 8 weeks after discharge. Of these patients, 15 attended a second follow-up appointment 8 weeks after that. A throat swab reverse transcription-polymerase chain reaction (RT-PCR) analysis for SARS-CoV-2 and chest computerized tomography (CT) scans were implemented at the first follow-up appointment, and a total of 40 blood samples (25 from the first and 15 from the second follow-up appointment) were collected. Patients' levels of Immunoglobulin G (IgG) antibody against S-Receptor binding domain (S-RBD) and Nucleocapsid Protein (NP) of SARS-CoV-2 and the subpopulation of lymphocytes were evaluated using an enzyme-linked immunoassay (ELISA) test and flow cytometry, respectively. RESULTS: At the first follow-up appointment, 10 of the 25 patients (40.0%) showed complete radiological resolution. Of these patients, 80.0% were classified as moderate, and 80.0% were younger (those whose age was ≤ the median age of all the patients). The predominant patterns of abnormalities included an irregular line (12/25, 48.0%), ground-glass opacity (GGO) (44.0%), and multiple GGOs (28.0%). At the first follow-up appointment, 40.0% (10/25) of patients still had lymphopenia. Of the 15 patients who were followed-up with twice, the ratio of lymphopenia was 80% (12/15), 60.0% (9/15), and 46.7% (7/15) at 0, 8, and 16 weeks after discharge, respectively. This was mainly due to a decrease in the cluster of differentiation (CD) 4+ T lymphocyte, which was observed in 60% (9/15), 60% (9/15), and 46.7% (7/15) of total patients at 0, 8, and 16 weeks after discharge, respectively. All of the patients were S-RBD and NP IgG antibody positive at the first follow-up appointment. 40.0% (6/15) and 66.7% (10/15) of patients showed a decrease over 50.0% in the level of NP and S-RBD IgG antibodies, respectively, at the second follow-up appointment. The NP and S-RBD IgG antibodies' levels declined to 44.6% (P=0.044) and 28.1% (P=0.18), respectively. 0 and 26.7% (4/15) of patients turned from NP and S-RBD IgG antibody positive to negative, respectively. CONCLUSIONS: About half of the patients still showed at least 1 abnormality in chest CT scans 8 weeks after discharge and lymphopenia 16 weeks after discharge. The level of the IgG antibody had declined by the follow-up appointment. Notably, the S-RBD IgG antibody declined more dramatically than that of NP. These results may have implications in the making of policies related to disease prevention, the long-term management of discharged patients, and vaccines' development.

6.
Hum Cell ; 34(2): 419-435, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1084737

ABSTRACT

Since December 2019, the novel coronavirus SARS-CoV-2 pandemic (COVID-19) outbroke in Wuhan and spread in China. Here we aimed to investigate the clinical and radiological characteristics of COVID-19 cases. We collected and analyzed the clinical data of 172 hospitalized cases of COVID-19 who were diagnosed via qRT-PCR of nasopharyngeal swabs during January 2020 and February 2020. The chest images were reviewed by radiologists and respirologists. The older patients with COVID-19 in Henan Province had more severe disease and worse prognosis. The male sex, smoking history and Wuhan exposure of patients are not related to the severity or prognosis of COVID-19. Family gatherings were showed among 26.7% of patients. A greater proportion of patients in the severe group suffer from combined chronic diseases. CT results showed that most patients had bilateral lung lesions and multiple lung lobes. The lungs of severe patients are more damaged. Both the infection range and inflammatory factor levels are related to the poor prognosis. Antiviral drugs, immunoglobulin and traditional Chinese medicine are mainly used for the treatment of COVID-19 patients. The discharge rate of COVID-19 patients was 93.0%, and the mortality rate was 2.3%. Case type, lymphocyte ratio grade, and respiratory failure at admission are risk factors for poor prognosis, except for the number of infiltrating lung lobes. The results showed that severe disease process, lymphopenia and respiratory failure are risk factors for the COVID-19.


Subject(s)
COVID-19/diagnosis , Adult , Aged , Antiviral Agents/therapeutic use , COVID-19/epidemiology , COVID-19/mortality , COVID-19/therapy , China/epidemiology , Comorbidity , Diagnosis, Differential , Female , Glycosides , Humans , Immunoglobulins/therapeutic use , Lung/diagnostic imaging , Lymphocyte Count , Lymphopenia , Male , Medicine, Chinese Traditional , Middle Aged , Pregnanes , Prognosis , Risk Factors , Severity of Illness Index , Sex Factors , Smoking/adverse effects , Tomography, X-Ray Computed
7.
Sci Rep ; 11(1): 3187, 2021 02 04.
Article in English | MEDLINE | ID: covidwho-1065963

ABSTRACT

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is a novel coronavirus causing the COVID-19 pandemic in 2020. High adaptive plasticity on the spike protein of SASR-CoV-2 enables it to transmit across different host species. In the present study, we collected 2092 high-quality genome sequences of SARS-CoV-2 from 160 regions in over 50 countries and reconstructed their phylogeny. We also analyzed the polymorphic interaction between spike protein and human ACE2 (hACE2). Phylogenetic analysis of SARS-CoV-2 suggests that SARS-CoV-2 is probably originated from a recombination event on the spike protein between a bat coronavirus and a pangolin coronavirus that endows it humans infectivity. Compared with other regions in the S gene of SARS-CoV-2, the direct-binding sites of the receptor-binding domain (RBD) is more conserved. We focused on 3,860 amino acid mutations in spike protein RBD (T333-C525) of SARS-CoV-2 and simulated their differential stability and binding affinity to hACE2 (S19-D615). The results indicate no preference for SARS-CoV-2 infectivity on people of different ethnic groups. The variants in the spike protein of SARS-CoV-2 may also be a good indicator demonstrating the transmission route of SARS-CoV-2 from its natural reservoir to human hosts.


Subject(s)
Angiotensin-Converting Enzyme 2/genetics , COVID-19/virology , Spike Glycoprotein, Coronavirus/genetics , Animals , Binding Sites , Humans , Mutation , Polymorphism, Genetic , Protein Binding , SARS-CoV-2/genetics
8.
Clinical eHealth ; 3:7-15, 2020.
Article in English | PMC | ID: covidwho-822402

ABSTRACT

The aim is to diagnose COVID-19 earlier and to improve its treatment by applying medical technology, the “COVID-19 Intelligent Diagnosis and Treatment Assistant Program (nCapp)” based on the Internet of Things. Terminal eight functions can be implemented in real-time online communication with the “cloud” through the page selection key. According to existing data, questionnaires, and check results, the diagnosis is automatically generated as confirmed, suspected, or suspicious of 2019 novel coronavirus (2019-nCoV) infection. It classifies patients into mild, moderate, severe or critical pneumonia. nCapp can also establish an online COVID-19 real-time update database, and it updates the model of diagnosis in real time based on the latest real-world case data to improve diagnostic accuracy. Additionally, nCapp can guide treatment. Front-line physicians, experts, and managers are linked to perform consultation and prevention. nCapp also contributes to the long-term follow-up of patients with COVID-19. The ultimate goal is to enable different levels of COVID-19 diagnosis and treatment among different doctors from different hospitals to upgrade to the national and international through the intelligent assistance of the nCapp system. In this way, we can block disease transmission, avoid physician infection, and epidemic prevention and control as soon as possible.

9.
SSRN; 2020.
Preprint | SSRN | ID: ppcovidwho-745

ABSTRACT

Background: SARS-CoV-2 is causing a worldwide health crisis. We aimed to present clinical and CT features for a cohort of patients in Henan, China with more foc

10.
Mil Med Res ; 7(1): 41, 2020 09 04.
Article in English | MEDLINE | ID: covidwho-745023

ABSTRACT

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, coronavirus disease 2019 (COVID-19), affecting more than seventeen million people around the world. Diagnosis and treatment guidelines for clinicians caring for patients are needed. In the early stage, we have issued "A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)"; now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline. We formed a working group of clinical experts and methodologists. The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas: chemoprophylaxis, diagnosis, treatments, and discharge management. We searched the literature for direct evidence on the management of COVID-19, and assessed its certainty generated recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. Finally, we issued 34 statements. Among them, 6 were strong recommendations for, 14 were weak recommendations for, 3 were weak recommendations against and 11 were ungraded consensus-based statement. They covered topics of chemoprophylaxis (including agents and Traditional Chinese Medicine (TCM) agents), diagnosis (including clinical manifestations, reverse transcription-polymerase chain reaction (RT-PCR), respiratory tract specimens, IgM and IgG antibody tests, chest computed tomography, chest x-ray, and CT features of asymptomatic infections), treatments (including lopinavir-ritonavir, umifenovir, favipiravir, interferon, remdesivir, combination of antiviral drugs, hydroxychloroquine/chloroquine, interleukin-6 inhibitors, interleukin-1 inhibitors, glucocorticoid, qingfei paidu decoction, lianhua qingwen granules/capsules, convalescent plasma, lung transplantation, invasive or noninvasive ventilation, and extracorporeal membrane oxygenation (ECMO)), and discharge management (including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge). We also created two figures of these recommendations for the implementation purpose. We hope these recommendations can help support healthcare workers caring for COVID-19 patients.


Subject(s)
Chemoprevention/methods , Clinical Laboratory Techniques/methods , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Adult , Betacoronavirus , COVID-19 , COVID-19 Testing , Coronavirus Infections/diagnosis , Coronavirus Infections/prevention & control , Evidence-Based Medicine , Female , Humans , Male , Middle Aged , Pandemics/prevention & control , Patient Discharge/standards , Pneumonia, Viral/diagnosis , Pneumonia, Viral/prevention & control , Practice Guidelines as Topic , SARS-CoV-2
11.
Endosc Ultrasound ; 9(4): 211-219, 2020.
Article in English | MEDLINE | ID: covidwho-707630

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus with higher transmissibility compared with SARS coronavirus (SARS-CoV) and Middle East respiratory distress syndrome coronavirus. Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 is an unprecedented global crisis that has not been experienced, which is still disrupting health systems, economies, and societies around the world by the rapid spread. Bronchoscopy plays an important role in diagnosis and therapy of pulmonary diseases, especially in patients with severe pulmonary infection, however, application of bronchoscopy in patients suspected or confirmed SARS-CoV-2 infection is extremely limited for the potential airborne transmission from aerosol generated during the procedure. This consensus statement was completed by expert panel of Interventional & Minimally Invasive Respiratory Committee of China Medical Education Association, and the issues were summarized as seven key topics to define the indications of bronchoscopy and matters needing attentions on the bronchoscopy procedures in patients with COVID-19, as well as the protective precaution strategies to avoid nosocomial SARS-CoV-2 infection.

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