Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 69
Filter
Add filters

Year range
1.
Ann Am Thorac Soc ; 2021 Jul 09.
Article in English | MEDLINE | ID: covidwho-1605425

ABSTRACT

RATIONALE: Both genetic variants and chronic obstructive pulmonary disease (COPD) contribute to the risk of incident severe coronavirus disease 2019 (COVID-19). Whether genetic risk of incident severe COVID-19 is the same regardless of pre-existing COPD is unknown. OBJECTIVES: In this study, we aimed to investigate the potential interaction between genetic risk and COPD in relation to severe COVID-19. METHODS: We constructed a polygenic risk score (PRS) for severe COVID-19 by using 112 single-nucleotide polymorphisms in 430,582 participants from the UK Biobank study. We examined the associations of genetic risk and COPD with severe COVID-19 by using logistic regression models. RESULTS: Of 430,582 participants, 712 participants developed severe COVID-19 as of February 22, 2021, of whom 19.8% had pre-existing COPD. Compared with participants at low genetic risk, those at intermediate genetic risk (OR, 1.34; 95% CI, 1.09-1.66) and high genetic risk (OR, 1.50; 95% CI, 1.18-1.92) had higher risk of severe COVID-19 (P for trend = 0.001), and the association was independent of COPD (P for interaction = 0.76). COPD was associated with a higher risk of incident severe COVID-19 (OR, 1.37; 95% CI, 1.12-1.67; P = 0.002). Participants at high genetic risk and with COPD had a higher risk of severe COVID-19 (OR, 2.05; 95% CI, 1.35-3.04; P < 0.001) than those at low genetic risk and without COPD. CONCLUSIONS: The PRS which combines multiple risk alleles can be effectively used in screening for high-risk populations of severe COVID-19. High genetic risk correlates with a higher risk of severe COVID-19, regardless of pre-existing COPD.

3.
Ren Fail ; 43(1): 1329-1337, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1493366

ABSTRACT

BACKGROUND: This study sought to investigate incidence and risk factors for acute kidney injury (AKI) in hospitalized COVID-19. METHODS: In this retrospective study, we enrolled 823 COVID-19 patients with at least two evaluations of renal function during hospitalization from four hospitals in Wuhan, China between February 2020 and April 2020. Clinical and laboratory parameters at the time of admission and follow-up data were recorded. Systemic renal tubular dysfunction was evaluated via 24-h urine collections in a subgroup of 55 patients. RESULTS: In total, 823 patients were enrolled (50.5% male) with a mean age of 60.9 ± 14.9 years. AKI occurred in 38 (40.9%) ICU cases but only 6 (0.8%) non-ICU cases. Using forward stepwise Cox regression analysis, we found eight independent risk factors for AKI including decreased platelet level, lower albumin level, lower phosphorus level, higher level of lactate dehydrogenase (LDH), procalcitonin, C-reactive protein (CRP), urea, and prothrombin time (PT) on admission. For every 0.1 mmol/L decreases in serum phosphorus level, patients had a 1.34-fold (95% CI 1.14-1.58) increased risk of AKI. Patients with hypophosphatemia were likely to be older and with lower lymphocyte count, lower serum albumin level, lower uric acid, higher LDH, and higher CRP. Furthermore, serum phosphorus level was positively correlated with phosphate tubular maximum per volume of filtrate (TmP/GFR) (Pearson r = 0.66, p < .001) in subgroup analysis, indicating renal phosphate loss via proximal renal tubular dysfunction. CONCLUSION: The AKI incidence was very low in non-ICU patients as compared to ICU patients. Hypophosphatemia is an independent risk factor for AKI in patients hospitalized for COVID-19 infection.


Subject(s)
Acute Kidney Injury/etiology , COVID-19/complications , Hypophosphatemia/complications , Pneumonia, Viral/complications , Acute Kidney Injury/epidemiology , COVID-19/epidemiology , China/epidemiology , Female , Hospitalization , Humans , Hypophosphatemia/epidemiology , Incidence , Intensive Care Units , Kidney Function Tests , Male , Middle Aged , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Retrospective Studies , Risk Factors , SARS-CoV-2
4.
Talanta ; 239: 122974, 2022 Mar 01.
Article in English | MEDLINE | ID: covidwho-1466916

ABSTRACT

Direct RNA detection is critical for providing the RNA insights into gene expression profiling, noncoding RNAs, RNA-associated diseases and pathogens, without reverse transcription. However, classical RNA analysis usually requires RT-PCR, which can cause bias amplification and quantitation errors. To address this challenge, herein we report a microfluidic RNA chip (the microchip prototype) for direct RNA detection, which is primarily based on RNA extension and labeling with DNA polymerase. This detection strategy is of high specificity (discriminating against single-nucleotide differences), rapidity, accuracy, nuclease resistance, and reusability. Further, we have successfully detected disease-associated RNAs in clinical samples, demonstrating its great potentials in biomedical research and clinical diagnosis.


Subject(s)
Microfluidic Analytical Techniques , RNA , Microfluidics , Nucleotides , Oligonucleotide Array Sequence Analysis , RNA/genetics
5.
Front Med (Lausanne) ; 7: 547, 2020.
Article in English | MEDLINE | ID: covidwho-1389191

ABSTRACT

We report the clinical characteristics, viral shedding duration, and contact tracing for asymptomatic carriers of SARS-CoV-2 in Wuhan, China. The asymptomatic carriers were relatively young (median age: 34.5 years). Chest computed tomography showed no abnormalities. The nasopharyngeal swab was an optimum specimen for RNA testing. The median viral shedding duration was 11.5 days. Notably, 2 months of viral shedding duration were reported in two nurses, which was much longer than previously reported or than usually thought. The transmissibility of SARS-CoV-2 by asymptomatic carriers during the studied period in Wuhan appeared to be weak. Only one patient (1/12) was found to have transmitted the virus to another person. Early asymptomatic carrier detection, isolation, and contact tracing could be useful to mitigate the spread of the disease.

6.
Lancet ; 398(10302): 747-758, 2021 08 28.
Article in English | MEDLINE | ID: covidwho-1376121

ABSTRACT

BACKGROUND: The full range of long-term health consequences of COVID-19 in patients who are discharged from hospital is largely unclear. The aim of our study was to comprehensively compare consequences between 6 months and 12 months after symptom onset among hospital survivors with COVID-19. METHODS: We undertook an ambidirectional cohort study of COVID-19 survivors who had been discharged from Jin Yin-tan Hospital (Wuhan, China) between Jan 7 and May 29, 2020. At 6-month and 12-month follow-up visit, survivors were interviewed with questionnaires on symptoms and health-related quality of life (HRQoL), and received a physical examination, a 6-min walking test, and laboratory tests. They were required to report their health-care use after discharge and work status at the 12-month visit. Survivors who had completed pulmonary function tests or had lung radiographic abnormality at 6 months were given the corresponding tests at 12 months. Non-COVID-19 participants (controls) matched for age, sex, and comorbidities were interviewed and completed questionnaires to assess prevalent symptoms and HRQoL. The primary outcomes were symptoms, modified British Medical Research Council (mMRC) score, HRQoL, and distance walked in 6 min (6MWD). Multivariable adjusted logistic regression models were used to evaluate the risk factors of 12-month outcomes. FINDINGS: 1276 COVID-19 survivors completed both visits. The median age of patients was 59·0 years (IQR 49·0-67·0) and 681 (53%) were men. The median follow-up time was 185·0 days (IQR 175·0-198·0) for the 6-month visit and 349·0 days (337·0-361·0) for the 12-month visit after symptom onset. The proportion of patients with at least one sequelae symptom decreased from 68% (831/1227) at 6 months to 49% (620/1272) at 12 months (p<0·0001). The proportion of patients with dyspnoea, characterised by mMRC score of 1 or more, slightly increased from 26% (313/1185) at 6-month visit to 30% (380/1271) at 12-month visit (p=0·014). Additionally, more patients had anxiety or depression at 12-month visit (26% [331/1271] at 12-month visit vs 23% [274/1187] at 6-month visit; p=0·015). No significant difference on 6MWD was observed between 6 months and 12 months. 88% (422/479) of patients who were employed before COVID-19 had returned to their original work at 12 months. Compared with men, women had an odds ratio of 1·43 (95% CI 1·04-1·96) for fatigue or muscle weakness, 2·00 (1·48-2·69) for anxiety or depression, and 2·97 (1·50-5·88) for diffusion impairment. Matched COVID-19 survivors at 12 months had more problems with mobility, pain or discomfort, and anxiety or depression, and had more prevalent symptoms than did controls. INTERPRETATION: Most COVID-19 survivors had a good physical and functional recovery during 1-year follow-up, and had returned to their original work and life. The health status in our cohort of COVID-19 survivors at 12 months was still lower than that in the control population. FUNDING: Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, the National Natural Science Foundation of China, the National Key Research and Development Program of China, Major Projects of National Science and Technology on New Drug Creation and Development of Pulmonary Tuberculosis, the China Evergrande Group, Jack Ma Foundation, Sino Biopharmaceutical, Ping An Insurance (Group), and New Sunshine Charity Foundation.


Subject(s)
COVID-19/complications , Survivors , Aged , Anxiety/etiology , COVID-19/physiopathology , COVID-19/psychology , Depression/etiology , Exercise Tolerance , Fatigue/etiology , Female , Follow-Up Studies , Humans , Longitudinal Studies , Lung/physiopathology , Male , Middle Aged , Muscle Weakness/etiology , Quality of Life , SARS-CoV-2 , Walk Test
7.
Front Med (Lausanne) ; 8: 684101, 2021.
Article in English | MEDLINE | ID: covidwho-1332124

ABSTRACT

Some patients retested positive for SARS-CoV-2 following negative testing results and discharge. However, the potential risk factors associated with redetectable positive testing results in a large sample of patients who recovered from COVID-19 have not been well-estimated. A total of 745 discharged patients were enrolled between January 30, 2020, and September 9, 2020, in Guangzhou, China. Data on the clinical characteristics, comorbidities, drug therapy, RT-PCR testing, and contact modes to close contacts were collected. Patients who tested positive for SARS-CoV-2 after discharge were confirmed by guidelines issued by China. The repositive rate in different settings was calculated. Among 745 discharged patients, 157 (21.1%; 95% CI, 18.2-24.0%) tested repositive and the repositive rate was 16.8% (95% CI, 14.1-24.0%) for nasopharyngeal swabs and 9.7% (95% CI, 7.0-12.5%) for anal swabs. Among them, 55 (35.0%) were asymptomatic, 15 (9.6%) had mild symptoms, 83 (52.9%) had moderate symptoms, and 4 (2.6%) had severe symptoms at the first admission. The days from discharge to repositivity was 8.0 (IQR, 8.0-14.0). Most repositive patients were without clinical symptoms, and lymphocyte cell counts were higher than before being discharged. The likelihood of repositive testing for SARS-CoV-2 RNA was significantly higher among patients who were of younger age (OR, 3.88; 95% CI, 1.74-8.66, 0-17 years old), had asymptomatic severity (OR, 4.36; 95% CI, 1.47-12.95), and did not have clinical symptoms (OR, 1.89; 95% CI, 1.32-2.70, without fever). No other positive patients emerged within the families or close contacts of repositive patients. Our findings support prolonged but intermittent viral shedding as the probable cause for this phenomenon; we need to familiarize with the possibility that the virus will remain endemic.

8.
Journal for Immunotherapy of Cancer ; 8(Suppl 3):A485-A486, 2020.
Article in English | ProQuest Central | ID: covidwho-1318081

ABSTRACT

BackgroundHER2 potently inhibits innate immunity through cGAS–STING signaling,1 Meanwhile HER2 antibody induced ADCP will also lead to macrophage mediated immune suppression. Both preclinical and clinical studies have suggested a coordination of engagement of innate and adaptive immunity with the combination of an anti-HER2 antibody and an immune checkpoint blockade. KN026 is a novel bispecific antibody that simultaneously binds to two distinct HER2 epitopes. KN046 is a novel bispecific antibody that blocks both PD-L1 interaction with PD-1/CD80 and CTLA-4 interaction with CD80/CD86. Here we reported the interim results from an ongoing phase Ib dose escalation and expansion study assessing the safety, tolerability and preliminary efficacy for KN026 in combination with KN046 in Patients with HER2 aberrated solid tumors.MethodsThis study enrolled pts with solid tumors who failed available standard of care, HER2 aberration status confirmed locally (HER2 mutation, HER2 amplification and/or HER2 overexpression). Eligible pts received combination of KN026 and KN046 at three dose levels until disease progression, unacceptable toxicity or withdrawal of informed consent (DL1: KN026 20 mg/kg Q2W + KN046 3 mg/kg Q2W;DL2: KN026 20 mg/kg Q2W with loading on Days 1, 8 of Cycle 1 + KN046 5 mg/kg Q3W;DL3: KN026 30 mg/kg Q3W with loading on Days 1, 8 of Cycle 1 + KN046 5 mg/kg Q3W). Tumor response was evaluated Q8W per RECIST 1.1. Primary endpoint was DLT and key secondary endpoints were efficacy parameters (ORR, DOR, PFS).ResultsAs of the Sep. 08, 2020, 25 pts were enrolled into DL1 (n = 20, 3 for dose escalation), DL2 (n = 3) and DL3 (n = 2) (mGC/GEJ 15 pts;mCRC 8 pts;other solid tumors 2 pts). 15 pts remained on the study treatment and 10 pts discontinued treatment due to disease progression (n=5), death (n=2) and other reasons (n=3). 18 pts had HER2-positive status (12 of 18 failed previous trastuzumab therapy), 2 pts had HER2 mutation and 5 pts had HER2 low expression (without FISH amplification). No DLTs were observed. No pts experienced LVEF decreased or other clinically meaningful cardiac AEs. Treatment-related TEAEs occurred in 23 (92%) pts, of which 6 (24%) pts experienced grade 3 or above treatment-related TEAEs. 11 (44%) pts experienced irAEs, majority were of grade 1 or 2 except that 1 patient experienced grade 3 immune-mediated endocrinopathy. The most common (frequency ≥ 15%) KN026 or KN046 related TEAEs were infusion related reaction (n=11, 44.0%), anaemia (n=9, 36.0%), white blood cell count decreased (n=6, 24.0%), diarrhea (n=5, 20.0%), AST increased (n=5, 20.0%), platelet count decreased (n=5, 20.0%), rash (n=5, 20.0%) and ALT increased (n=4, 16.0%). The objective response rate in pts with HER2-positive tumors (n = 14 efficacy evaluable pts) was 9/14 (64.3%, 95% CI 35.1~87.2%) and disease control rate 13/14 (92.9%, 95% CI 66.1~99.8%). 4 out of 5 pts with HER2 mutation or low expression achieved SD including one patient with SD for more than 24 weeks. 2 death cases due to disease progression were reported, both only received one cycle of KN026 plus KN046 due to COVID-19 restriction.ConclusionsKN026 combined with KN046 is well tolerated and has demonstrated preliminary albeit profound anti-tumor activity in HER2-positive solid tumors.Trial RegistrationClinical trial information: NCT04040699ReferenceShiying Wu, Qian Zhang, Fei Zhang, et al. HER2 recruits AKT1 to disrupt STING signalling and suppress antiviral defence and antitumour immunity. Nature Cell Biology 2019;21:1027–1040.

9.
Journal for Immunotherapy of Cancer ; 8(Suppl 3):A207, 2020.
Article in English | ProQuest Central | ID: covidwho-1318067

ABSTRACT

BackgroundHER2 potently inhibits innate immunity through cGAS–STING signalling,1 meanwhile HER2 antibody induced ADCP will also lead to macrophage mediated immune suppression. Preclinical and clinical studies suggested a coordination of engagement of innate and adaptive immunity with the combination of an anti-HER2 antibody and an immune checkpoint blockade. KN026 is a novel bispecific antibody that simultaneously binds to two distinct HER2 epitopes. KN046 is a novel bispecific antibody that blocks both PD-L1 interaction with PD-1 and CTLA-4 interaction with CD80/CD86. Here we reported the interim results from an ongoing phase Ib dose escalation and expansion study assessing the safety, tolerability and preliminary efficacy for KN026 in combination with KN046.MethodsThis study enrolled pts with solid tumors who failed available standard of care, HER2 aberration status confirmed locally (HER2 mutation, HER2 amplification and/or HER2 overexpression). Eligible pts received combination of KN026 and KN046 at two dose levels until disease progression, unacceptable toxicity or withdrawal of informed consent (DL1: KN026 20 mg/kg Q2W + KN046 3 mg/kg Q2W;DL2: KN026 20 mg/kg Q2W with loading on Days 1, 8 of Cycle 1 + KN046 5 mg/kg Q3W). Tumor response was evaluated Q8W per RECIST 1.1. Primary endpoint was DLT and key secondary endpoints were efficacy parameters (ORR, DOR, PFS).ResultsAs of the Jul. 13, 2020, 21 pts were enrolled into DL1 (n = 18, 3 for dose escalation) and DL2 (n = 3) (mGC/GEJ 12 pts;mCRC 7 pts;other solid tumors 2 pts). 11 pts remained on the study treatment and 10 pts discontinued treatment due to disease progression (n=5), death (n=2) and other reasons (n=3). 15 pts had HER2-positive status (11 of 15 failed previous trastuzumab therapy), 1 pts had HER2 mutation and 5 pts had HER2 low expression (without FISH amplification). No DLTs were observed. No pts experienced LVEF decreased or other clinically meaningful cardiac AEs. Treatment-related TEAEs occurred in 13 pts, of which 1 pts experienced grade 3 or above treatment-related TEAEs. 7 pts experienced irAEs, all of which were grade 1 or 2. The most common (≥ 10%) KN026 or KN046 related TEAEs were anaemia (n=5, 23.8%), AST increased (n=4, 19.0%), rash (n=4, 19.0%), diarrhea (n=4, 19.0%), blood bilirubin increased (n=3, 14.3%) and infusion related reaction (n=3, 14.3%). The objective response rate in pts with HER2-positive tumors (n = 7 efficacy evaluable pts) was 4/7 (57.1%, 95% CI 18.4~90.1%) and disease control rate 6/7 (85.7%, 95% CI 42.1~99.6%). 3 pts with HER2 mutation or low expression achieved SD including one patient with SD for more than 24 weeks. 2 death cases only received one cycle of KN026 plus KN046 due to COVID-19 restriction before died from clinical deterioration from underlying tumors.ConclusionsKN026 combined with KN046 is well tolerated and has demonstrated profound anti-tumor activity in HER2-positive solid tumors.Trial RegistrationNCT04040699Ethics ApprovalThe study was approved by Beijing Cancer Hospital Institution’s Ethics Board, approval number 2019YJZ37.ConsentWritten informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.ReferenceShiying Wu, Qian Zhang, Fei Zhang, et al. HER2 recruits AKT1 to disrupt STING signalling and suppress antiviral defence and antitumour immunity. Nature Cell Biology 2019;21: 1027–1040.

10.
Nano Today ; 40: 101243, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1300951

ABSTRACT

The outbreak of SARS-coronavirus 2 (SARS-CoV2) has become a global health emergency. Although enormous efforts have been made, there is still no effective treatment against the new virus. Herein, a TiO2 supported single-atom nanozyme containing atomically dispersed Ag atoms (Ag-TiO2 SAN) is designed to serve as a highly efficient antiviral nanomaterial. Compared with traditional nano-TiO2 and Ag, Ag-TiO2 SAN exhibits higher adsorption (99.65%) of SARS-CoV2 pseudovirus. This adsorption ability is due to the interaction between SAN and receptor binding domain (RBD) of spike 1 protein of SARS-CoV2. Theoretical calculation and experimental evidences indicate that the Ag atoms of SAN strongly bind to cysteine and asparagine, which are the most abundant amino acids on the surface of spike 1 RBD. After binding to the virus, the SAN/virus complex is typically phagocytosed by macrophages and colocalized with lysosomes. Interestingly, Ag-TiO2 SAN possesses high peroxidase-like activity responsible for reactive oxygen species production under acid conditions. The highly acidic microenvironment of lysosomes could favor oxygen reduction reaction process to eliminate the virus. With hACE2 transgenic mice, Ag-TiO2 SAN showed efficient anti-SARS-CoV2 pseudovirus activity. In conclusion, Ag-TiO2 SAN is a promising nanomaterial to achieve effective antiviral effects for SARS-CoV2.

11.
Drug Des Devel Ther ; 15: 2059-2089, 2021.
Article in English | MEDLINE | ID: covidwho-1231276

ABSTRACT

Purpose: One of the most common types of male infertility is recognized as oligoasthenozoospermia (OA), characterized by low sperm count and quality in males. As a traditional Chinese medicine (TCM), Cuscutae Semen-Mori Fructus coupled-herbs (CSMFCH) has been known to act a curative effect on OA for thousands of years. Nevertheless, the substantial basis and molecular mechanism of CSMFCH in treating OA remain elusive. Methods: Herein, an integrated approach, including network pharmacology, molecular docking, and experiment validation, was utilized to reveal the new candidate active component and mechanism of CSMFCH in treating OA. Results: The results show that kaempferol is the most significant bioactive component of CSMFCH on OA. The mechanism and targets of CSMFCH against OA are relevant to hormone regulation, oxidant stress, and reproductive promotion. In order to validate network pharmacology results, molecular docking and experiment validation were conducted. In detail, molecular docking was employed to verify the strong binding interactions between kaempferol and the core targets. UHPLC-Q-Orbitrap-MS was used to identify kaempferol in the CSMFCH extract. In vitro and in vivo experiments further proved CSMFCH and kaempferol could enhance the mouse Leydig (TM3) and mouse Sertoli (TM4) cell viability, improve the male reproductive organ weights, sperm quality, and decrease testis tissue damage in the OA mouse model induced by CP. Conclusion: Our results not only identify the new candidate active component of CSMFCH in treating OA but also provide new insights into the mechanisms of CSMFCH against OA.


Subject(s)
Asthenozoospermia/drug therapy , Drugs, Chinese Herbal/therapeutic use , Molecular Docking Simulation , Plant Extracts/therapeutic use , Animals , Cell Proliferation/drug effects , Cells, Cultured , Chromatography, High Pressure Liquid , Disease Models, Animal , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/isolation & purification , Fruit/chemistry , Male , Mass Spectrometry , Medicine, Chinese Traditional , Mice , Mice, Inbred Strains , Plant Extracts/chemistry , Plant Extracts/isolation & purification
12.
Lab Chip ; 21(10): 2019-2026, 2021 05 18.
Article in English | MEDLINE | ID: covidwho-1211288

ABSTRACT

The COVID-19 pandemic, caused by SARS-CoV-2, currently poses an urgent global medical crisis for which there remains a lack of affordable point-of-care testing (POCT). In particular, resource-limited areas need simple and easily disseminated testing solutions to manage the outbreak. In this work, a microfluidic-integrated lateral flow recombinase polymerase amplification (MI-IF-RPA) assay was developed for rapid and sensitive detection of SARS-CoV-2, which integrates the reverse transcription recombinase polymerase amplification (RT-RPA) and a universal lateral flow (LF) dipstick detection system into a single microfluidic chip. The single-chamber RT-RPA reaction components are mixed with running buffer, and then delivered to the LF detection strips for biotin- and FAM-labelled amplified analyte sequences, which can provide easily interpreted positive or negative results. Testing requires only a simple nucleic acid extraction and loading, then incubation to obtain results, approximately 30 minutes in total. SARS-CoV-2 armored RNA particles were used to validate the MI-IF-RPA system, which showed a limit of detection of 1 copy per µL, or 30 copies per sample. Chip performance was further evaluated using clinically diagnosed cases of COVID-19 and revealed a sensitivity of 97% and specificity of 100%, highly comparable to current reverse transcription-polymerase chain reaction (RT-PCR)-based diagnostic assays. This MI-IF-RPA assay is portable and comprises affordable materials, enabling mass production and decreased risk of contamination. Without the need for specialized instrumentation and training, MI-IF-RPA assay can be used as a complement to RT-PCR for low-cost COVID-19 screening in resource-limited areas.


Subject(s)
COVID-19 , Recombinases , Humans , Microfluidics , Nucleic Acid Amplification Techniques , Pandemics , Recombinases/genetics , SARS-CoV-2 , Sensitivity and Specificity
13.
BMC Public Health ; 21(1): 796, 2021 04 26.
Article in English | MEDLINE | ID: covidwho-1204057

ABSTRACT

BACKGROUND: We investigated college students' attitude and compliance towards a prevention strategy involving use of non-pharmaceutical interventions (NPIs) against coronavirus disease 2019 (COVID-19). METHODS: We conducted a cross-sectional online survey in four universities in Guangdong Province (China) based on purposive sampling. A self-administered questionnaire was given to College students (CSs) to measure the supportive attitude towards an outbreak control strategy and adoption of NPIs in respondents. RESULTS: A total of 44,446 CSs participated between 31 January and 10 February 2020; 92.7% of respondents supported the outbreak control strategy. The proportion of respondents who avoided public places, wore a facemask, avoid gatherings, and washed hands more frequently than usual was 94.8, 92.8, 91.2 and 86.9%. respectively. A total of 76.5% respondents adopted all four measures. A supportive attitude was associated with NPI adoption. Students who were female, postgraduate, anxious, and not depressed tended to have a higher supportive attitude and higher chance of NPI adoption. CONCLUSIONS: Higher supportiveness towards the disease control strategy for the Chinese public may lead to higher adoption rate of NPIs. Psychosocial factors were related to a supportive attitude and adoption of the NPI. We believe that our findings could aid policymakers to create NPIs to prevent and control emerging infectious diseases such as COVID-19.


Subject(s)
COVID-19 , China , Cross-Sectional Studies , Female , Humans , Male , SARS-CoV-2 , Students , Surveys and Questionnaires
14.
Neurology ; 95(11): e1479-e1487, 2020 09 15.
Article in English | MEDLINE | ID: covidwho-1197357

ABSTRACT

OBJECTIVE: To investigate new-onset neurologic impairments associated with coronavirus disease 2019 (COVID-19). METHODS: A retrospective multicenter cohort study was conducted between January 18 and March 20, 2020, including people with confirmed COVID-19 from 56 hospitals officially designated in 3 Chinese regions; data were extracted from medical records. New-onset neurologic events as assessed by neurology consultants based on manifestations, clinical examination, and investigations were noted, in which critical events included disorders of consciousness, stroke, CNS infection, seizures, and status epilepticus. RESULTS: We enrolled 917 people with average age 48.7 years and 55% were male. The frequency of new-onset critical neurologic events was 3.5% (32/917) overall and 9.4% (30/319) among those with severe or critical COVID-19. These were impaired consciousness (n = 25) or stroke (n = 10). The risk of critical neurologic events was highly associated with age above 60 years and previous history of neurologic conditions. Noncritical events were seen in fewer than 1% (7/917), including muscle cramp, unexplained headache, occipital neuralgia, tic, and tremor. Brain CT in 28 people led to new findings in 9. Findings from lumbar puncture in 3 with suspected CNS infection, unexplained headache, or severe occipital neuralgia were unremarkable. CONCLUSIONS: People with COVID-19 aged over 60 and with neurologic comorbidities were at higher risk of developing critical neurologic impairment, mainly impaired consciousness and cerebrovascular accidents. Brain CT should be considered when new-onset brain injury is suspected, especially in people under sedation or showing an unexplained decline in consciousness. Evidence of direct acute insult of severe acute respiratory syndrome coronavirus 2 to the CNS is lacking.


Subject(s)
Central Nervous System Diseases/virology , Coronavirus Infections/complications , Pneumonia, Viral/complications , Adolescent , Adult , Aged , Aged, 80 and over , Betacoronavirus , COVID-19 , Central Nervous System Diseases/epidemiology , Child , Child, Preschool , China/epidemiology , Cohort Studies , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Pandemics , Retrospective Studies , Risk Factors , SARS-CoV-2 , Young Adult
15.
Eur J Hum Genet ; 29(8): 1312-1315, 2021 08.
Article in English | MEDLINE | ID: covidwho-1191639

ABSTRACT

Critically ill coronavirus disease 2019 (COVID-19) is characterized by severe cytokine storms, a hyperinflammatory condition intimately related to the development of fatal outcomes. Why some individuals seem particularly vulnerable to severe cytokine storms is still unknown. Primary immunodeficiency (PID)-related genes are inherited factors that dysregulate host inflammatory responses to infection, especially hemophagocytic lymphohistiocytosis (HLH)-related genes, established as contributors to the development of excessive cytokine storms. We analyzed the association between PID gene variants with severe cytokine storms in COVID-19. We conducted whole-exome sequencing in 233 hospitalized COVID-19 patients and identified four PID gene (UNC13D, AP3B1, RNF168, DHX58) variants were significantly enriched in COVID-19 patients experiencing severe cytokine storms. The total percentage of COVID-19 patients with variants in UNC13D or AP3B1, two typical HLH genes, was dramatically higher in high-level cytokine group than in low-level group (33.3 vs. 5.7%, P < 0.001). Germline variants in UNC13D and AP3B1 were associated with the development of severe cytokine storms, fatal outcomes in COVID-19. These findings advance the understanding of individual susceptibility to severe cytokine storms and help optimize the current management of COVID-19.


Subject(s)
Adaptor Protein Complex 3/genetics , Adaptor Protein Complex beta Subunits/genetics , COVID-19/genetics , COVID-19/pathology , Membrane Proteins/genetics , Adaptor Protein Complex 3/metabolism , Adaptor Protein Complex beta Subunits/metabolism , Aged , COVID-19/immunology , COVID-19/metabolism , Cytokine Release Syndrome/genetics , Humans , Lymphohistiocytosis, Hemophagocytic/genetics , Membrane Proteins/metabolism , Middle Aged
16.
Pharmaceutics ; 13(4)2021 Apr 14.
Article in English | MEDLINE | ID: covidwho-1187021

ABSTRACT

Since coronavirus disease 2019 (COVID-19) is a serious new worldwide public health crisis with significant morbidity and mortality, effective therapeutic treatments are urgently needed. Drug repurposing is an efficient and cost-effective strategy with minimum risk for identifying novel potential treatment options by repositioning therapies that were previously approved for other clinical outcomes. Here, we used an integrated network-based pharmacologic and transcriptomic approach to screen drug candidates novel for COVID-19 treatment. Network-based proximity scores were calculated to identify the drug-disease pharmacological effect between drug-target relationship modules and COVID-19 related genes. Gene set enrichment analysis (GSEA) was then performed to determine whether drug candidates influence the expression of COVID-19 related genes and examine the sensitivity of the repurposing drug treatment to peripheral immune cell types. Moreover, we used the complementary exposure model to recommend potential synergistic drug combinations. We identified 18 individual drug candidates including nicardipine, orantinib, tipifarnib and promethazine which have not previously been proposed as possible treatments for COVID-19. Additionally, 30 synergistic drug pairs were ultimately recommended including fostamatinib plus tretinoin and orantinib plus valproic acid. Differential expression genes of most repurposing drugs were enriched significantly in B cells. The findings may potentially accelerate the discovery and establishment of an effective therapeutic treatment plan for COVID-19 patients.

17.
Asian J Psychiatr ; 60: 102656, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1184783

ABSTRACT

BACKGROUND AND AIM: Recently, the availability and usefulness of mobile self-help mental health applications have increased, but few applications deal with COVID-19-related psychological problems. This study explored the intervention efficacy of a mobile application on addressing psychological problems related to COVID-19. METHODS: A longitudinal control trial involving 129 Chinese participants with depression symptoms was conducted through the mobile application "Care for Your Mental Health and Sleep during COVID-19" (CMSC) based on WeChat. Participants were divided into two groups: mobile internet cognitive behavioral therapy (MiCBT) and wait-list. The primary outcome was improvement in depression symptoms. Secondary outcomes included improvement in anxiety and insomnia. The MiCBT group received three self-help CBT intervention sessions in one week via CMSC. RESULTS: The MiCBT group showed significant improvement in depression and insomnia (allP < 0.05) compared with the wait-list group. Although both groups showed significant improvement in anxiety at the intervention's end, compared with the wait-list group, the MiCBT group had no significant advantage. Correlation analysis showed that improvement in depression and anxiety had a significant positive association with education level. Changes in insomnia were significantly negatively correlated with anxiety of COVID-19 at the baseline. CMSC was considered helpful (n=68, 81.9 %) and enjoyable (n=54, 65.9 %) in relieving depression and insomnia during the COVID-19 outbreak. CONCLUSIONS: CMSC is verified to be effective and convenient for improving COVID-19-related depression and insomnia symptoms. A large study with sufficient evidence is required to determine its continuous effect on reducing mental health problems during the pandemic.


Subject(s)
Anxiety/therapy , COVID-19/psychology , Cognitive Behavioral Therapy/methods , Depression/therapy , Sleep Initiation and Maintenance Disorders/psychology , Sleep Initiation and Maintenance Disorders/therapy , Anxiety/psychology , COVID-19/epidemiology , Depression/psychology , Female , Humans , Male , Mental Health , Pandemics , SARS-CoV-2 , Sleep Initiation and Maintenance Disorders/diagnosis , Treatment Outcome
18.
Comput Struct Biotechnol J ; 19: 1661-1671, 2021.
Article in English | MEDLINE | ID: covidwho-1144574

ABSTRACT

Neutralizing antibody targeting to the SARS-CoV-2 could provide powerful therapies. A neutralizing antibody CC12.1 which was found in SARS-CoV-2 patient samples provides potential protection from disease. The aim of molecular dynamics simulations is to identify key epitopes that are crucial to the antibody binding of SARS-CoV-2 spike glycoprotein receptor binding domain (RBD) to promote the development of superior antibodies. Binding modes of the antibody were investigated and compared with RBD bound receptor ACE2. Key epitopes were revealed and a distal motif of RBD (residue numbers 473-488) was demonstrated by analyzing dynamic trajectories. Compared to the receptor ACE2, conformation of RBD could be better stabilized through additional interaction of antibody with the distal motif of RBD, which was further found driven by electrostatic complementarity. By further analysis of the extensive hydrogen-bonding networks, residues D405, K417, Y421, Y453, L455, R457, Y473, A475, N487, G502, Y505 of RBD, which mainly interacted with CDR H3/L3 and two conserved motifs SNY, SGGS, were identified as key epitopes. Higher binding free energy calculated after point mutations on key residues confirms the crucial role for the specific binding. Subsequently, mutations of VH V98E and VL G68D in CC12.1, which could significantly enhance the binding affinity of the antibody, were also proposed. The results indicate the key epitopes for antibody binding and give explanations for failure of neutralization antibody caused by specific residues mutations on structural basis. Simulations of two point mutations on antibody provide feasible information for advanced antibody design.

19.
World J Clin Cases ; 9(7): 1499-1512, 2021 Mar 06.
Article in English | MEDLINE | ID: covidwho-1134503

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, which has lasted for nearly a year, has made people deeply aware of the strong transmissibility and pathogenicity of SARS-CoV-2 since its outbreak in December 2019. By December 2020, SARS-CoV-2 had infected over 65 million people globally, resulting in more than 1 million deaths. At present, the exact animal origin of SARS-CoV-2 remains unclear and antiviral vaccines are now undergoing clinical trials. Although the social order of human life is gradually returning to normal, new confirmed cases continue to appear worldwide, and the majority of cases are sporadic due to environmental factors and lax self-protective consciousness. This article provides the latest understanding of the epidemiology and risk factors of nosocomial and community transmission of SARS-CoV-2, as well as strategies to diminish the risk of transmission. We believe that our review will help the public correctly understand and cope with SARS-CoV-2.

20.
BMC Infect Dis ; 21(1): 206, 2021 Feb 24.
Article in English | MEDLINE | ID: covidwho-1102331

ABSTRACT

BACKGROUND: There is limited information on the difference in epidemiology, clinical characteristics and outcomes of the initial outbreak of the coronavirus disease (COVID-19) in Wuhan (the epicenter) and Sichuan (the peripheral area) in the early phase of the COVID-19 pandemic. This study was conducted to investigate the differences in the epidemiological and clinical characteristics of patients with COVID-19 between the epicenter and peripheral areas of pandemic and thereby generate information that would be potentially helpful in formulating clinical practice recommendations to tackle the COVID-19 pandemic. METHODS: The Sichuan & Wuhan Collaboration Research Group for COVID-19 established two retrospective cohorts that separately reflect the epicenter and peripheral area during the early pandemic. The epidemiology, clinical characteristics and outcomes of patients in the two groups were compared. Multivariate regression analyses were used to estimate the adjusted odds ratios (aOR) with regard to the outcomes. RESULTS: The Wuhan (epicenter) cohort included 710 randomly selected patients, and the peripheral (Sichuan) cohort included 474 consecutive patients. A higher proportion of patients from the periphery had upper airway symptoms, whereas a lower proportion of patients in the epicenter had lower airway symptoms and comorbidities. Patients in the epicenter had a higher risk of death (aOR=7.64), intensive care unit (ICU) admission (aOR=1.66), delayed time from illness onset to hospital and ICU admission (aOR=6.29 and aOR=8.03, respectively), and prolonged duration of viral shedding (aOR=1.64). CONCLUSIONS: The worse outcomes in the epicenter could be explained by the prolonged time from illness onset to hospital and ICU admission. This could potentially have been associated with elevated systemic inflammation secondary to organ dysfunction and prolonged duration of virus shedding independent of age and comorbidities. Thus, early supportive care could achieve better clinical outcomes.


Subject(s)
COVID-19/complications , SARS-CoV-2 , Adult , Aged , COVID-19/virology , China/epidemiology , Comorbidity , Female , Humans , Intensive Care Units , Male , Middle Aged , Retrospective Studies , Virus Shedding
SELECTION OF CITATIONS
SEARCH DETAIL
...