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1.
Front Public Health ; 9: 741083, 2021.
Article in English | MEDLINE | ID: covidwho-1775896

ABSTRACT

This study aimed to investigate the association between passive smoking and physical and psychological health in Chinese nurses. Participants of this cross-sectional study comprised 2,484 non-smoking nurses. Passive smoking and demographic information were assessed using a self-administered questionnaire. Physical, psychological, and overall health status of nurses were measured using the Cornell Medical Index (CMI) health questionnaire. Multivariate-adjusted odds ratio (OR) and 95% confidence interval (CI) for nurses' health were estimated by exposure to passive smoking using unconditional logistic regression models. A total of 1,219 nurses (49.07%) were exposed to passive smoking. Of these, 609 (24.52%), 160 (6.44%), and 587 (23.63%) nurses had poorer physical, mental, and overall health, respectively. After adjusting for other confounding factors, compared with the non-passive smoking group, passive smoking was associated with poor physical (OR = 1.51, 95% CI: 1.25-1.83), mental (OR = 1.48, 95% CI: 1.07-2.07), and overall (OR = 1.58, 95% CI: 1.30-1.93) health of nurses, respectively. We also carried out subgroup analyses stratified by age, department, and professional title, which showed that most findings supported the main results. This study demonstrated that exposure to passive smoking was a risk factor for overall decreased physical and mental health status among Chinese nurses.


Subject(s)
Health Status , Nurses , Tobacco Smoke Pollution , China/epidemiology , Cross-Sectional Studies , Humans , Surveys and Questionnaires
2.
Signal Transduct Target Ther ; 7(1): 23, 2022 01 25.
Article in English | MEDLINE | ID: covidwho-1655541
3.
Emerg Microbes Infect ; 11(1): 548-551, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-1642258

ABSTRACT

The neutralizing antibody is a potential therapeutic for the ongoing COVID-19 pandemic. As an antiviral agent, numerous mAbs recognize the epitopes that overlap with ACE2-binding sites in the SARS-CoV-2-RBD. Some studies have shown that residual changes on the spike protein can significantly decrease the efficiency of neutralizing antibodies. To address this issue, a therapeutic cocktail could be an effective countermeasure. In the present study, we isolated a fully human neutralizing antibody, JS026, from a convalescent patient. The comparative analysis revealed that JS026 binding to SARS-CoV-2-RBD mainly located between epitopes for class 2 and class 3 mAbs as opposed to that of class 1 (etesevimab) antibodies. A cocktail of etesevimab and JS026 increased neutralizing efficacy against both wild-type SARS-CoV-2 and the recent emergence of Alpha, Beta, Gamma, and Delta variants. JS026 and the cocktail reduced virus titers in the infected lungs of hACE2 transgenic mice and relieved pathological changes. These findings would benefit antibody-based therapeutic countermeasures in the treatment of COVID-19.


Subject(s)
Antibodies, Monoclonal, Humanized/pharmacology , Antibodies, Neutralizing/pharmacology , SARS-CoV-2 , Animals , Antibodies, Viral , COVID-19 , Humans , Mice , Mice, Transgenic , Pandemics , SARS-CoV-2/drug effects
4.
MAbs ; 14(1): 2005507, 2022.
Article in English | MEDLINE | ID: covidwho-1585297

ABSTRACT

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has triggered a serious public health crisis worldwide, and considering the novelty of the disease, preventative and therapeutic measures alike are urgently needed. To accelerate such efforts, the development of JS016, a neutralizing monoclonal antibody directed against the SARS-CoV-2 spike protein, was expedited from a typical 12- to 18-month period to a 4-month period. During this process, transient Chinese hamster ovary cell lines are used to support preclinical, investigational new drug-enabling toxicology research, and early Chemistry, Manufacturing and Controls development; mini-pool materials to supply Phase 1 clinical trials; and a single-clone working cell bank for late-stage and pivotal clinical trials were successively adopted. Moreover, key process performance and product quality investigations using a series of orthogonal and state-of-the-art techniques were conducted to demonstrate the comparability of products manufactured using these three processes, and the results indicated that, despite observed variations in process performance, the primary and high-order structures, purity and impurity profiles, biological and immunological functions, and degradation behaviors under stress conditions were largely comparable. The study suggests that, in particular situations, this strategy can be adopted to accelerate the development of therapeutic biopharmaceuticals and their access to patients.


Subject(s)
Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Animals , Antibodies, Monoclonal/chemistry , Antibodies, Monoclonal/therapeutic use , Antibody Affinity/immunology , Antibody Specificity/immunology , CHO Cells , COVID-19/prevention & control , COVID-19/virology , Chromatography, High Pressure Liquid/methods , Circular Dichroism , Clone Cells , Cricetinae , Cricetulus , Humans , Immunoglobulin G/chemistry , Immunoglobulin G/immunology , Immunoglobulin G/therapeutic use , Isoelectric Point , SARS-CoV-2/metabolism , SARS-CoV-2/physiology , Spike Glycoprotein, Coronavirus/metabolism
5.
Antimicrob Agents Chemother ; 65(8): e0035021, 2021 07 16.
Article in English | MEDLINE | ID: covidwho-1486470

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread rapidly worldwide. This study is the first to report the tolerability, safety, pharmacokinetics (PK), and immunogenicity of a recombinant human anti-SARS-CoV-2 monoclonal antibody, etesevimab (CB6, JS016, LY3832479, or LY-CoV016), in healthy adults. This paper describes a randomized, double-blind, placebo-controlled, phase 1 study. A total of 40 participants were enrolled to receive a single intravenous dose of either etesevimab or placebo in one of four sequential ascending intravenous dose cohorts. All 40 participants completed the study. Seventeen (42.5%) participants experienced 22 treatment emergent adverse events (TEAEs) that were drug-related, and the rates of these TEAEs among different dose cohorts were numerically comparable. No difference was observed between the combined etesevimab group and the placebo group. The exposure after etesevimab infusion increased in an approximately proportional manner as the dose increased from 2.5 to 50 mg/kg. The elimination half-life (t1/2) value did not differ among different dose cohorts and was estimated to be around 4 weeks. Etesevimab was well tolerated after administration of a single dose at a range of 2.5 mg/kg to 50 mg/kg in healthy Chinese adults. The PK profiles of etesevimab in healthy volunteers showed typical monoclonal antibody distribution and elimination characteristics. (This study has been registered at ClinicalTrials.gov under identifier NCT04441918.).


Subject(s)
COVID-19 , SARS-CoV-2 , Adult , Antibodies, Neutralizing , Antibodies, Viral , China , Double-Blind Method , Humans
6.
Nat Commun ; 12(1): 5000, 2021 08 17.
Article in English | MEDLINE | ID: covidwho-1361637

ABSTRACT

The successive emergences and accelerating spread of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineages and evolved resistance to some ongoing clinical therapeutics increase the risks associated with the coronavirus disease 2019 (COVID-19) pandemic. An urgent intervention for broadly effective therapies to limit the morbidity and mortality of COVID-19 and future transmission events from SARS-related coronaviruses (SARSr-CoVs) is needed. Here, we isolate and humanize an angiotensin-converting enzyme-2 (ACE2)-blocking monoclonal antibody (MAb), named h11B11, which exhibits potent inhibitory activity against SARS-CoV and circulating global SARS-CoV-2 lineages. When administered therapeutically or prophylactically in the hACE2 mouse model, h11B11 alleviates and prevents SARS-CoV-2 replication and virus-induced pathological syndromes. No significant changes in blood pressure and hematology chemistry toxicology were observed after injections of multiple high dosages of h11B11 in cynomolgus monkeys. Analysis of the structures of the h11B11/ACE2 and receptor-binding domain (RBD)/ACE2 complexes shows hindrance and epitope competition of the MAb and RBD for the receptor. Together, these results suggest h11B11 as a potential therapeutic countermeasure against SARS-CoV, SARS-CoV-2, and escape variants.


Subject(s)
Angiotensin-Converting Enzyme 2/drug effects , Angiotensin-Converting Enzyme 2/immunology , Antibodies, Neutralizing/administration & dosage , COVID-19/drug therapy , SARS-CoV-2/drug effects , Animals , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/immunology , COVID-19/immunology , COVID-19/mortality , COVID-19/virology , Chlorocebus aethiops , Disease Models, Animal , Epitopes , Female , HEK293 Cells , Haplorhini , Humans , Macaca fascicularis , Male , Mice , Mice, Inbred BALB C , Pandemics , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , Vero Cells , Virus Activation
7.
Geriatr Nurs ; 42(4): 887-893, 2021.
Article in English | MEDLINE | ID: covidwho-1258372

ABSTRACT

BACKGROUND: First-line nursing staff are responsible for protecting residents, the most vulnerable population, from COVID-19 infections. They are at a high risk of being infected with COVID-19 and experience high levels of psychological distress. AIMS: To explore the challenges and coping strategies perceived by nursing staff during the COVID-19 pandemic in China. METHODS: In April,2020, we conducted a qualitative study using in-depth semi-structured interviews with nursing staff. Participants were selected from seven nursing homes in three cities in Hunan Province, China. RESULTS: A total of 21 nursing staff participated in the study, including seven nurse managers, seven registered nurses and seven nursing assistants. Three main themes were identified. Different groups encountered different sources of stress and adopted various coping strategies to fulfil their responsibilities. CONCLUSIONS: Nursing home staff were underprepared for dealing with COVID-19-related challenges. Educational programs to improve the ability to deal with COVID-19 prevention and control are needed.


Subject(s)
Adaptation, Psychological , Burnout, Professional/psychology , COVID-19/nursing , COVID-19/psychology , Nursing Homes/organization & administration , Nursing Staff/psychology , Stress, Psychological , COVID-19/epidemiology , China , Female , Humans , Interviews as Topic , Pandemics , Perception , Qualitative Research , SARS-CoV-2
8.
Antimicrob Agents Chemother ; 65(8): e0035021, 2021 07 16.
Article in English | MEDLINE | ID: covidwho-1223556

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread rapidly worldwide. This study is the first to report the tolerability, safety, pharmacokinetics (PK), and immunogenicity of a recombinant human anti-SARS-CoV-2 monoclonal antibody, etesevimab (CB6, JS016, LY3832479, or LY-CoV016), in healthy adults. This paper describes a randomized, double-blind, placebo-controlled, phase 1 study. A total of 40 participants were enrolled to receive a single intravenous dose of either etesevimab or placebo in one of four sequential ascending intravenous dose cohorts. All 40 participants completed the study. Seventeen (42.5%) participants experienced 22 treatment emergent adverse events (TEAEs) that were drug-related, and the rates of these TEAEs among different dose cohorts were numerically comparable. No difference was observed between the combined etesevimab group and the placebo group. The exposure after etesevimab infusion increased in an approximately proportional manner as the dose increased from 2.5 to 50 mg/kg. The elimination half-life (t1/2) value did not differ among different dose cohorts and was estimated to be around 4 weeks. Etesevimab was well tolerated after administration of a single dose at a range of 2.5 mg/kg to 50 mg/kg in healthy Chinese adults. The PK profiles of etesevimab in healthy volunteers showed typical monoclonal antibody distribution and elimination characteristics. (This study has been registered at ClinicalTrials.gov under identifier NCT04441918.).


Subject(s)
COVID-19 , SARS-CoV-2 , Adult , Antibodies, Neutralizing , Antibodies, Viral , China , Double-Blind Method , Humans
9.
PLoS One ; 16(4): e0249656, 2021.
Article in English | MEDLINE | ID: covidwho-1186605

ABSTRACT

BACKGROUND: The pandemic of coronavirus disease 2019 (COVID-19) has global impact, Wuhan in Hubei province is a high-risk area. And the older people in nursing homes are the most susceptible group to COVID-19. The aim of this study was to describe the practice and experience of the first-line medical team, to provide insights of coping with COVID-19 in China. METHOD: This qualitative study used a descriptive phenomenological design to describe the experience of medical staff supported the nursing homes in Wuhan fighting against COVID-19. Unstructured interviews via online video were conducted with seven medical staffs who supported the nursing homes in Wuhan. Data were analyzed using content analysis in five main themes: for nursing homes, we interviewed the difficulties faced at the most difficult time, services for the older people, and prevention and management strategies, for the medical staff, the psychological experience were interviewed, and the implications for public health emergencies were also reported. CONCLUSIONS: It is imperative that effective preventive and response measures be implemented to face the outbreak of COVID-19 and meet the care needs of older people in the context of COVID-19. IMPLICATIONS: Findings will inform managers of some reasonable instructional strategies for implementing effective infection management. Nursing homes need to provide targeted services to help alleviating their bad psychology for residents.


Subject(s)
COVID-19/epidemiology , Health Personnel , Nursing Homes , Adult , Aged , Aged, 80 and over , COVID-19/prevention & control , COVID-19/therapy , China/epidemiology , Communicable Disease Control , Disease Management , Female , Humans , Male , Medical Assistance , Middle Aged , Public Health , Qualitative Research , SARS-CoV-2/isolation & purification
10.
Future Oncol ; 17(10): 1197-1207, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1112570

ABSTRACT

Aims: To evaluate the efficacy of TruScreen (TS01) for high-risk human papillomavirus (HR-HPV) women compared with other methods in reducing colposcopy referral rates in hospitals. Methods: A single-center, prospective, case-control study was conducted from December 2019 to June 2020. Results: Among 139 (46.2%) HR-HPV-positive patients, 58 were CIN1, 52 were CIN2-3 and 29 had cervical cancer (n = 29). The sensitivity and specificity of detecting CIN2+ by TS01, colposcopy and HPV16/18 testing were 96.3% and 46.4%, 85.2% and 40.5% and 59.3% and 74.1%, respectively. The highest sensitivity was 96.3% at HPV16/18 and TS01 (each positive results), and the highest specificity was 83.6% at HPV16/18 and TS01 (both positive) for CIN2+ compared with the other methods. Conclusion: TS01 is a noninvasive screening method and can be used to diagnose cervical lesions quickly. It is especially suitable as triage tool for HR-HPV-positive women facing SARS-CoV-2 exposure and infection risks in hospital.


Subject(s)
COVID-19/epidemiology , Cervical Intraepithelial Neoplasia/diagnosis , Early Detection of Cancer/methods , Papillomavirus Infections/complications , SARS-CoV-2 , Uterine Cervical Neoplasms/diagnosis , Adolescent , Adult , Aged , Aged, 80 and over , Colposcopy , Female , Humans , Middle Aged , Prospective Studies , Sensitivity and Specificity , Triage/methods , Young Adult
11.
PLoS Pathog ; 17(1): e1009220, 2021 01.
Article in English | MEDLINE | ID: covidwho-1088772

ABSTRACT

The eponymous member of the interferon regulatory factor (IRF) family, IRF1, was originally identified as a nuclear factor that binds and activates the promoters of type I interferon genes. However, subsequent studies using genetic knockouts or RNAi-mediated depletion of IRF1 provide a much broader view, linking IRF1 to a wide range of functions in protection against invading pathogens. Conserved throughout vertebrate evolution, IRF1 has been shown in recent years to mediate constitutive as well as inducible host defenses against a variety of viruses. Fine-tuning of these ancient IRF1-mediated host defenses, and countering strategies by pathogens to disarm IRF1, play crucial roles in pathogenesis and determining the outcome of infection.


Subject(s)
Communicable Diseases/immunology , Communicable Diseases/therapy , Host-Pathogen Interactions/immunology , Immunity, Innate/immunology , Interferon Regulatory Factor-1/metabolism , Animals , Communicable Diseases/metabolism , Humans , Interferon Regulatory Factor-1/immunology
13.
Front Med (Lausanne) ; 7: 567296, 2020.
Article in English | MEDLINE | ID: covidwho-993366

ABSTRACT

Background: Around the globe, moderate cases account for the largest proportion of all coronavirus disease 2019 (COVID-19) patients, and deteriorated moderate patients contribute the most in mortality. However, published articles failed to address the deterioration details of moderate cases, especially on when and how they deteriorated. Methods: All moderate COVID-19 patients hospitalized in Guangdong Province from January 14 to March 16, 2020, were included in this multicenter retrospective cohort study and were divided into deteriorated and non-deteriorated groups according to clinical status. Symptoms and demographic, therapeutic, and laboratory test result characteristics were collected to explore the features of disease deterioration. Results: Of 1,168 moderate patients included, 148 (13%) deteriorated to severe (130 cases) or critical (18 cases) status. Over 20% of the older subgroup (>50 years old) showed deterioration. The median time for deterioration was 11 days after onset [interquartile range (IQR) 9-14 days]. In addition, 12.2% severe cases could further develop to critical status after 3 days (IQR 2-6.5 days) of having a severe condition. Respiratory dysfunction and hypoxia were the major manifestations as disease deterioration, while 76 cases (52.1%) showed respiratory rate >30 breaths/min, 119 cases (80.4%) showed SaO2 <93%, 100 cases (67.5%) had 201 < PaO2/FiO2 < 300, and 27 cases (18.9%) had blood lactic acid >2.0 mmol/L. In view of multiple organ dysfunction, 87.8% of acute respiratory distress syndrome (ARDS), 20.2% of acute kidney injury (AKI), 6.8% of coagulopathy, 4% of acute heart failure (AHF), 3.4% of acute hepatic injury (AHI), and 5.4% of shock occurred in deteriorated patients, while organ injury occurred in the following sequence: ARDS, AKI, AHF, coagulopathy, AHI, and shock. Conclusions: The deteriorated pattern of moderate COVID-19 patients is characterized as the 11th day from onset (IQR 9-14 days) being an important time point of disease deterioration with further exacerbation to critical condition in 3 days (IQR 2-6.5 days), A RDS followed by AKI being the typical modes of sequential organ damage.

14.
Open Forum Infect Dis ; 7(10): ofaa432, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-894631

ABSTRACT

BACKGROUND: Short-term recurrence of positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ribonucleic acid (RNA) polymerase chain reaction (PCR) in discharged coronavirus disease 2019 (COVID-19) patients attracts the public's concern. This study aimed to determine the clinical and epidemiological results of such patients. METHODS: This retrospective study was conducted on 32 designated hospitals for COVID-19 patients discharged from January 14 to March 10, 2020. After 28-day followed-up, patients who tested positive again for SARS-CoV-2 RNA and confirmed by reverse-transcriptase polymerase chain reaction were re-admitted to hospital for further treatments. All of the close contacts of patients who tested positive again were asked to self-segregate for 14 days. Data of epidemiology, symptoms, laboratory tests, and treatments were analyzed in those patients, and their close contacts were investigated. RESULTS: Of 1282 discharged patients, 189 (14.74%) tested positive again for SARS-CoV-2 RNA during 28-day follow-up. The median time from discharge to the next positive test was 8 days (interquartile range [IQR], 5-13). Patients in the group that tested positive again were younger (34 vs 45 years, P < .001) with a higher proportion of moderate symptoms (95.77% vs 84.35%, P < .001) in the first hospitalization than in the negative group. During the second hospitalization, all patients who tested positive again showed normal peripheral white blood cells and lymphocytes and no new symptoms of COVID-19; 78.31% further improved on chest computed tomography scan compared with the first discharge, yet 25.93% accepted antiviral therapy. The median time of re-positive to negative test was 8 days (IQR, 4-15). None of the close contacts developed COVID-19. CONCLUSIONS: Our data suggest that the short-term recurrence of positive SARS-CoV-2 RNA in discharged patients is not a relapse of COVID-19, and the risk of onward transmission is very low. This provides important information for managing COVID-19 patients.

15.
SSRN; 2020.
Preprint | SSRN | ID: ppcovidwho-1679

ABSTRACT

Background: Around the globe, moderate cases account for the largest proportion of all COVID-19 patients, and deteriorated moderate patients contribute the most

16.
SSRN; 2020.
Preprint | SSRN | ID: ppcovidwho-1432

ABSTRACT

Background: Recurrence of positive SARS-CoV-2 RNA in discharged COVID-19 patients attracts the public’s concern. It remained unknown whether this phenomenon mea

17.
SSRN; 2020.
Preprint | SSRN | ID: ppcovidwho-909

ABSTRACT

Background: COVID-19 has already become a global pandemic. There are few detailed descriptions of moderate cases and their clinical progression. Our aim was to

18.
Nature ; 584(7819): 120-124, 2020 08.
Article in English | MEDLINE | ID: covidwho-381744

ABSTRACT

An outbreak of coronavirus disease 2019 (COVID-19)1-3, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)4, has spread globally. Countermeasures are needed to treat and prevent further dissemination of the virus. Here we report the isolation of two specific human monoclonal antibodies (termed CA1 and CB6) from a patient convalescing from COVID-19. CA1 and CB6 demonstrated potent SARS-CoV-2-specific neutralization activity in vitro. In addition, CB6 inhibited infection with SARS-CoV-2 in rhesus monkeys in both prophylactic and treatment settings. We also performed structural studies, which revealed that CB6 recognizes an epitope that overlaps with angiotensin-converting enzyme 2 (ACE2)-binding sites in the SARS-CoV-2 receptor-binding domain, and thereby interferes with virus-receptor interactions by both steric hindrance and direct competition for interface residues. Our results suggest that CB6 deserves further study as a candidate for translation to the clinic.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Betacoronavirus/immunology , Coronavirus Infections/immunology , Coronavirus Infections/virology , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/immunology , Angiotensin-Converting Enzyme 2 , Animals , Antibodies, Neutralizing/chemistry , Antibodies, Neutralizing/pharmacology , Antibodies, Viral/chemistry , Antibodies, Viral/pharmacology , Betacoronavirus/chemistry , Binding, Competitive , COVID-19 , Cell Line , Chlorocebus aethiops , Crystallization , Crystallography, X-Ray , Female , Humans , In Vitro Techniques , Macaca mulatta/immunology , Macaca mulatta/virology , Male , Models, Molecular , Neutralization Tests , Pandemics , Peptidyl-Dipeptidase A/chemistry , Peptidyl-Dipeptidase A/metabolism , Protein Binding/drug effects , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/antagonists & inhibitors , Spike Glycoprotein, Coronavirus/metabolism , Vero Cells , Viral Load/immunology
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