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1.
Preprint in English | bioRxiv | ID: ppbiorxiv-225151

ABSTRACT

Cells must detect and respond to molecular events such as the presence or absence of specific small molecules. To accomplish this, cells have evolved methods to measure the presence and concentration of these small molecules in their environment and enact changes in gene expression or behavior. However, cells dont usually change their DNA in response to such outside stimuli. In this work, we have engineered a genetic circuit that can enact specific and controlled genetic changes in response to changing small molecule concentrations. Known DNA sequences can be repeatedly integrated into a genomic array such that their identity and order encodes information about past small molecule concentrations that the cell has experienced. To accomplish this, we use catalytically inactive CRISPR-Cas9 (dCas9) to bind to and block attachment sites for the integrase Bxb1. Therefore, through the co-expression of dCas9 and guide RNA, Bxb1 can be directed to integrate one of two engineered plasmids, which correspond to two orthogonal small molecule inducers that can be recorded with this system. We identified the optimal location of guide RNA binding to the Bxb1 attP integrase attachment site, and characterized the detection limits of the system by measuring the minimal small molecule concentration and shortest induction time necessary to produce measurable differences in array composition as read out by Oxford Nanopore long read sequencing technology.

3.
Am J Respir Crit Care Med ; 2021 Sep 17.
Article in English | MEDLINE | ID: covidwho-1430274

ABSTRACT

RATIONALE: Alteration of human respiratory microbiota had been observed in COVID-19. How the microbiota is associated with the prognosis in COVID-19 is unclear. OBJECTIVES: To characterize the feature and dynamics of the respiratory microbiota and its associations with clinical features in COVID-19 patients. Methods:We conducted metatranscriptome sequencing on 588 longitudinal oropharyngeal swab specimens collected from 192 COVID-19 patients (including 39 deceased patients), and 95 healthy controls from the same geographic area. Meanwhile, the concentration of 27 cytokines and chemokines in plasma was measured for COVID-19 patients. MEASUREMENTS AND MAIN RESULTS: The upper respiratory tract (URT) microbiota in COVID-19 patients differed from that in healthy controls, while deceased patients possessed a more distinct microbiota, both on admission and before discharge/death. The alteration of URT microbiota showed a significant correlation with the concentration of proinflammatory cytokines and mortality. Specifically, Streptococcus-dominated microbiota was enriched in recovered patients, and show high temporal stability and resistance against pathogens. In contrast, the microbiota in deceased patients was more susceptible to secondary infections, and became more deviated from the normality after admission. Moreover, the abundance of S. parasanguinis on admission was significantly correlated with prognosis in non-severe patients (lower vs. higher abundance, odds ratio=7.80, [95% CI 1.70-42.05]). Conclusions:URT microbiota dysbiosis is a remarkable manifestation of COVID-19; its association with mortality suggests it may reflect the interplay between pathogens, symbionts, and the host immune status. Whether URT microbiota could be used as a biomarker for the diagnosis and prognosis of respiratory diseases merits further investigation. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

5.
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
6.
Journal of Physics: D Applied Physics ; 54(40):1-5, 2021.
Article in English | Academic Search Complete | ID: covidwho-1337236

ABSTRACT

This study applied surface discharge plasma treated-air to deactivate the pseudovirus with the SARS-CoV-2S protein in a cold-chain environment. The results of experiments show that the capability of infection of either the dried or the wet COVID-19 pseudovirus are inhibited after exposure to plasma treated-air regardless of whether it is attached to flakes of plastic or a copper sheet. Moreover, various plasma-generated reactive species provide it with an advantage over conventional ozone in deactivating the wet pseudovirus in a cold-chain environment. Our findings provide a potential disinfecting strategy to combat the spread of SARS-CoV-2 through cold-chain systems. [ABSTRACT FROM AUTHOR] Copyright of Journal of Physics: D Applied Physics is the property of IOP Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

7.
Clin Infect Dis ; 72(7): 1293, 2021 04 08.
Article in English | MEDLINE | ID: covidwho-1238184

Subject(s)
COVID-19 , SARS-CoV-2 , Humans
8.
Clin Infect Dis ; 72(10): e545-e551, 2021 05 18.
Article in English | MEDLINE | ID: covidwho-1232187

ABSTRACT

BACKGROUND: The characteristics of neutralizing antibodies (NAbs) and antibody against major antigen proteins related to clinical outcomes in severe coronavirus disease 2019 (COVID-19) patients were still less known. METHODS: NAbs and antibodies targeting nucleocapsid (N), spike protein (S), and the receptor-binding domain (RBD) in longitudinal plasma samples from the LOTUS China trial were measured by microneutralization assay and enzyme-linked immunosorbent assay (ELISA). Viral load was determined by real-time reverse transcription polymerase chain reaction (RT-PCR). A total of 576 plasma and 576 throat swabs were collected from 191 COVID-19 patients. Antibody titers related to adverse outcome and clinical improvement were analyzed. Multivariable adjusted generalized linear mixed model for random effects were developed. RESULTS: After day 28 post symptoms onset, the rate of antibody positivity reached 100% for RBD-immunoglobulin M (IgM), 97.8% for S-IgM, 100% for N-immunoglobulin G (IgG), 100% for RBD-IgG, 91.1% for N-IgM, and 91.1% for NAbs. The NAbs titers increased over time in both survivors and nonsurvivors and correlated to IgG antibodies against N, S, and RBD, whereas its presence showed no statistical correlation with death. N-IgG (slope -2.11, 95% confidence interval [CI] -3.04 to -1.18, P < .0001), S-IgG (slope -2.44, 95% CI -3.35 to -1.54, P < .0001), and RBD-IgG (slope -1.43, 95% CI -1.98 to -.88, P < .0001) were negatively correlated with viral load. S-IgG titers were lower in nonsurvivors than survivors (P = .020) at week 4 after symptoms onset. CONCLUSIONS: IgM and IgG against N, S, and RBD and NAbs developed in most severe COVID-19 patients and do not correlate clearly with clinical outcomes. The levels of IgG antibodies against N, S, and RBD were related to viral clearance.


Subject(s)
COVID-19 , Adult , Antibodies, Viral , Antibody Formation , China/epidemiology , Humans , Immunoglobulin M , SARS-CoV-2
9.
Clin Infect Dis ; 71(15): 778-785, 2020 07 28.
Article in English | MEDLINE | ID: covidwho-1217823

ABSTRACT

BACKGROUND: The emergence of coronavirus disease 2019 (COVID-19) is a major healthcare threat. The current method of detection involves a quantitative polymerase chain reaction (qPCR)-based technique, which identifies the viral nucleic acids when present in sufficient quantity. False-negative results can be achieved and failure to quarantine the infected patient would be a major setback in containing the viral transmission. We aim to describe the time kinetics of various antibodies produced against the 2019 novel coronavirus (SARS-CoV-2) and evaluate the potential of antibody testing to diagnose COVID-19. METHODS: The host humoral response against SARS-CoV-2, including IgA, IgM, and IgG response, was examined by using an ELISA-based assay on the recombinant viral nucleocapsid protein. 208 plasma samples were collected from 82 confirmed and 58 probable cases (qPCR negative but with typical manifestation). The diagnostic value of IgM was evaluated in this cohort. RESULTS: The median duration of IgM and IgA antibody detection was 5 (IQR, 3-6) days, while IgG was detected 14 (IQR, 10-18) days after symptom onset, with a positive rate of 85.4%, 92.7%, and 77.9%, respectively. In confirmed and probable cases, the positive rates of IgM antibodies were 75.6% and 93.1%, respectively. The detection efficiency by IgM ELISA is higher than that of qPCR after 5.5 days of symptom onset. The positive detection rate is significantly increased (98.6%) when combining IgM ELISA assay with PCR for each patient compared with a single qPCR test (51.9%). CONCLUSIONS: The humoral response to SARS-CoV-2 can aid in the diagnosis of COVID-19, including subclinical cases.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections/diagnosis , Coronavirus Infections/immunology , Immunity, Humoral/immunology , Pneumonia, Viral/diagnosis , Pneumonia, Viral/immunology , Adult , Amino Acid Sequence , Antibodies, Viral/immunology , COVID-19 , Child , Child, Preschool , Coronavirus Infections/virology , Enzyme-Linked Immunosorbent Assay/methods , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/virology , Polymerase Chain Reaction/methods , SARS-CoV-2
10.
The Lancet ; 397(10270):220-232, 2021.
Article in English | APA PsycInfo | ID: covidwho-1164655

ABSTRACT

Presents a study which aims to examine consequences of COVID-19 in patients discharged from hospital for 6-months. This ambidirectional cohort study was done at Jin Yin-tan Hospital, the first designated hospital for patients with COVID-19 in Wuhan, Hubei, China. Clinical data for acute phase were retrieved from electronic medical records, including demographic characteristics, clinical characteristics, laboratory test results;and treatment. The disease severity was characterized by the highest seven-category scale during the hospital stay. Data were managed using REDCap electronic data capture tools in order to minimize missing inputs and allow for real-time data validation and quality control. Follow-up consultations were done in the outpatient clinic of Jin Yin-tan Hospital. All participants were interviewed face-to-face by trained physicians and asked to complete a series of questionnaires. For the symptom questionnaire, participants were asked to report newly occurring and persistent symptoms, or any symptoms worse than before COVID-19 development. A total of 2469 patients with COVID-19 were discharged from Jin Yin-tan Hospital between Jan 7, and May 29, 2020, and the follow-up study was done from June 16, 2020, to Sept 3, 2020. This is the largest cohort study with the longest follow-up duration assessing the health consequences of adult patients discharged from hospital recovering from COVID-19. (PsycInfo Database Record (c) 2021 APA, all rights reserved)

11.
Lancet ; 397(10279): 1075-1084, 2021 03 20.
Article in English | MEDLINE | ID: covidwho-1142326

ABSTRACT

BACKGROUND: Wuhan was the epicentre of the COVID-19 outbreak in China. We aimed to determine the seroprevalence and kinetics of anti-SARS-CoV-2 antibodies at population level in Wuhan to inform the development of vaccination strategies. METHODS: In this longitudinal cross-sectional study, we used a multistage, population-stratified, cluster random sampling method to systematically select 100 communities from the 13 districts of Wuhan. Households were systematically selected from each community and all family members were invited to community health-care centres to participate. Eligible individuals were those who had lived in Wuhan for at least 14 days since Dec 1, 2019. All eligible participants who consented to participate completed a standardised electronic questionnaire of demographic and clinical questions and self-reported any symptoms associated with COVID-19 or previous diagnosis of COVID-19. A venous blood sample was taken for immunological testing on April 14-15, 2020. Blood samples were tested for the presence of pan-immunoglobulins, IgM, IgA, and IgG antibodies against SARS-CoV-2 nucleocapsid protein and neutralising antibodies were assessed. We did two successive follow-ups between June 11 and June 13, and between Oct 9 and Dec 5, 2020, at which blood samples were taken. FINDINGS: Of 4600 households randomly selected, 3599 families (78·2%) with 9702 individuals attended the baseline visit. 9542 individuals from 3556 families had sufficient samples for analyses. 532 (5·6%) of 9542 participants were positive for pan-immunoglobulins against SARS-CoV-2, with a baseline adjusted seroprevalence of 6·92% (95% CI 6·41-7·43) in the population. 437 (82·1%) of 532 participants who were positive for pan-immunoglobulins were asymptomatic. 69 (13·0%) of 532 individuals were positive for IgM antibodies, 84 (15·8%) were positive for IgA antibodies, 532 (100%) were positive for IgG antibodies, and 212 (39·8%) were positive for neutralising antibodies at baseline. The proportion of individuals who were positive for pan-immunoglobulins who had neutralising antibodies in April remained stable for the two follow-up visits (162 [44·6%] of 363 in June, 2020, and 187 [41·2%] of 454 in October-December, 2020). On the basis of data from 335 individuals who attended all three follow-up visits and who were positive for pan-immunoglobulins, neutralising antibody levels did not significantly decrease over the study period (median 1/5·6 [IQR 1/2·0 to 1/14·0] at baseline vs 1/5·6 [1/4·0 to 1/11·2] at first follow-up [p=1·0] and 1/6·3 [1/2·0 to 1/12·6] at second follow-up [p=0·29]). However, neutralising antibody titres were lower in asymptomatic individuals than in confirmed cases and symptomatic individuals. Although titres of IgG decreased over time, the proportion of individuals who had IgG antibodies did not decrease substantially (from 30 [100%] of 30 at baseline to 26 [89·7%] of 29 at second follow-up among confirmed cases, 65 [100%] of 65 at baseline to 58 [92·1%] of 63 at second follow-up among symptomatic individuals, and 437 [100%] of 437 at baseline to 329 [90·9%] of 362 at second follow-up among asymptomatic individuals). INTERPRETATION: 6·92% of a cross-sectional sample of the population of Wuhan developed antibodies against SARS-CoV-2, with 39·8% of this population seroconverting to have neutralising antibodies. Our durability data on humoral responses indicate that mass vaccination is needed to effect herd protection to prevent the resurgence of the epidemic. FUNDING: Chinese Academy of Medical Sciences & Peking Union Medical College, National Natural Science Foundation, and Chinese Ministry of Science and Technology. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19/immunology , SARS-CoV-2/immunology , Adolescent , Adult , Aged , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/blood , COVID-19/epidemiology , COVID-19/prevention & control , Child , Child, Preschool , China/epidemiology , Coronavirus Nucleocapsid Proteins/immunology , Cross-Sectional Studies , Female , Follow-Up Studies , Humans , Immunity, Herd/immunology , Immunity, Humoral , Infant , Infant, Newborn , Longitudinal Studies , Male , Mass Vaccination/organization & administration , Middle Aged , Seroepidemiologic Studies , Young Adult
12.
Emerg Microbes Infect ; 10(1): 664-676, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1139855

ABSTRACT

Seasonal human coronaviruses (HCoVs) including HCoV-229E, -OC43, -NL63, and -HKU1 widely spread in global human populations. However, the relevance of humoral response against seasonal HCoVs to COVID-19 pathogenesis is elusive. In this study, we profiled the temporal changes of IgG antibody against spike proteins (S-IgG) of SARS-CoV-2 and seasonal HCoVs in 838 plasma samples collected from 344 COVID-19 patients. We tested the antigenic cross-reactivities of S protein between SARS-CoV-2 and seasonal HCoVs and evaluated the correlations between the levels of HCoV-OC43 S-IgG and the disease severity in COVID-19 patients. We found that SARS-CoV-2 S-IgG titres mounted until days 22-28, whereas HCoV-OC43 antibody titres increased until days 15-21 and then plateaued until day 46. However, IgG titres against HCoV-NL63, -229E, and -HKU1 showed no significant increase. A two-way cross-reactivity was identified between SARS-CoV-2 and HCoV-OC43. Neutralizing antibodies against SARS-CoV-2 were not detectable in healthy controls who were positive for HCoV-OC43 S-IgG. HCoV-OC43 S-IgG titres were significantly higher in patients with severe disease than those in mild patients at days 1-21 post symptom onset (PSO). Higher levels of HCoV-OC43 S-IgG were also observed in patients requiring mechanical ventilation. At days 1-10 PSO, HCoV-OC43 S-IgG titres correlated to disease severity in the age group over 60. Our data indicate that there is a correlation between cross-reactive antibody against HCoV-OC43 spike protein and disease severity in COVID-19 patients.


Subject(s)
Antibodies, Viral/blood , COVID-19/immunology , Coronavirus OC43, Human/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/pathology , Cross Reactions/immunology , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Male , Middle Aged , Severity of Illness Index , Young Adult
13.
Bioorg Med Chem Lett ; 40: 127906, 2021 05 15.
Article in English | MEDLINE | ID: covidwho-1118337

ABSTRACT

Zika virus has emerged as a potential threat to human health globally. A previous drug repurposing screen identified the approved anthelminthic drug niclosamide as a small molecule inhibitor of Zika virus infection. However, as antihelminthic drugs are generally designed to have low absorption when dosed orally, the very limited bioavailability of niclosamide will likely hinder its potential direct repurposing as an antiviral medication. Here, we conducted SAR studies focusing on the anilide and salicylic acid regions of niclosamide to improve physicochemical properties such as microsomal metabolic stability, permeability and solubility. We found that the 5-bromo substitution in the salicylic acid region retains potency while providing better drug-like properties. Other modifications in the anilide region with 2'-OMe and 2'-H substitutions were also advantageous. We found that the 4'-NO2 substituent can be replaced with a 4'-CN or 4'-CF3 substituents. Together, these modifications provide a basis for optimizing the structure of niclosamide to improve systemic exposure for application of niclosamide analogs as drug lead candidates for treating Zika and other viral infections. Indeed, key analogs were also able to rescue cells from the cytopathic effect of SARS-CoV-2 infection, indicating relevance for therapeutic strategies targeting the COVID-19 pandemic.


Subject(s)
Antiviral Agents/pharmacology , Niclosamide/analogs & derivatives , Niclosamide/pharmacology , SARS-CoV-2/drug effects , Zika Virus/drug effects , Animals , Antiviral Agents/chemical synthesis , Antiviral Agents/metabolism , Binding Sites , Chlorocebus aethiops , Drug Stability , Humans , Microbial Sensitivity Tests , Microsomes, Liver/metabolism , Molecular Docking Simulation , Molecular Structure , Niclosamide/metabolism , Protein Binding , Rats , Serine Endopeptidases/chemistry , Serine Endopeptidases/metabolism , Structure-Activity Relationship , Vero Cells , Viral Nonstructural Proteins/chemistry , Viral Nonstructural Proteins/metabolism , Viral Proteins/chemistry , Viral Proteins/metabolism
14.
Lancet ; 397(10270): 220-232, 2021 01 16.
Article in English | MEDLINE | ID: covidwho-1065678

ABSTRACT

BACKGROUND: The long-term health consequences of COVID-19 remain largely unclear. The aim of this study was to describe the long-term health consequences of patients with COVID-19 who have been discharged from hospital and investigate the associated risk factors, in particular disease severity. METHODS: We did an ambidirectional cohort study of patients with confirmed COVID-19 who had been discharged from Jin Yin-tan Hospital (Wuhan, China) between Jan 7, 2020, and May 29, 2020. Patients who died before follow-up, patients for whom follow-up would be difficult because of psychotic disorders, dementia, or re-admission to hospital, those who were unable to move freely due to concomitant osteoarthropathy or immobile before or after discharge due to diseases such as stroke or pulmonary embolism, those who declined to participate, those who could not be contacted, and those living outside of Wuhan or in nursing or welfare homes were all excluded. All patients were interviewed with a series of questionnaires for evaluation of symptoms and health-related quality of life, underwent physical examinations and a 6-min walking test, and received blood tests. A stratified sampling procedure was used to sample patients according to their highest seven-category scale during their hospital stay as 3, 4, and 5-6, to receive pulmonary function test, high resolution CT of the chest, and ultrasonography. Enrolled patients who had participated in the Lopinavir Trial for Suppression of SARS-CoV-2 in China received severe acute respiratory syndrome coronavirus 2 antibody tests. Multivariable adjusted linear or logistic regression models were used to evaluate the association between disease severity and long-term health consequences. FINDINGS: In total, 1733 of 2469 discharged patients with COVID-19 were enrolled after 736 were excluded. Patients had a median age of 57·0 (IQR 47·0-65·0) years and 897 (52%) were men. The follow-up study was done from June 16, to Sept 3, 2020, and the median follow-up time after symptom onset was 186·0 (175·0-199·0) days. Fatigue or muscle weakness (63%, 1038 of 1655) and sleep difficulties (26%, 437 of 1655) were the most common symptoms. Anxiety or depression was reported among 23% (367 of 1617) of patients. The proportions of median 6-min walking distance less than the lower limit of the normal range were 24% for those at severity scale 3, 22% for severity scale 4, and 29% for severity scale 5-6. The corresponding proportions of patients with diffusion impairment were 22% for severity scale 3, 29% for scale 4, and 56% for scale 5-6, and median CT scores were 3·0 (IQR 2·0-5·0) for severity scale 3, 4·0 (3·0-5·0) for scale 4, and 5·0 (4·0-6·0) for scale 5-6. After multivariable adjustment, patients showed an odds ratio (OR) 1·61 (95% CI 0·80-3·25) for scale 4 versus scale 3 and 4·60 (1·85-11·48) for scale 5-6 versus scale 3 for diffusion impairment; OR 0·88 (0·66-1·17) for scale 4 versus scale 3 and OR 1·77 (1·05-2·97) for scale 5-6 versus scale 3 for anxiety or depression, and OR 0·74 (0·58-0·96) for scale 4 versus scale 3 and 2·69 (1·46-4·96) for scale 5-6 versus scale 3 for fatigue or muscle weakness. Of 94 patients with blood antibodies tested at follow-up, the seropositivity (96·2% vs 58·5%) and median titres (19·0 vs 10·0) of the neutralising antibodies were significantly lower compared with at the acute phase. 107 of 822 participants without acute kidney injury and with estimated glomerular filtration rate (eGFR) 90 mL/min per 1·73 m2 or more at acute phase had eGFR less than 90 mL/min per 1·73 m2 at follow-up. INTERPRETATION: At 6 months after acute infection, COVID-19 survivors were mainly troubled with fatigue or muscle weakness, sleep difficulties, and anxiety or depression. Patients who were more severely ill during their hospital stay had more severe impaired pulmonary diffusion capacities and abnormal chest imaging manifestations, and are the main target population for intervention of long-term recovery. FUNDING: National Natural Science Foundation of China, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, National Key Research and Development Program of China, Major Projects of National Science and Technology on New Drug Creation and Development of Pulmonary Tuberculosis, and Peking Union Medical College Foundation.


Subject(s)
COVID-19/complications , Quality of Life , Aged , COVID-19/epidemiology , COVID-19/psychology , COVID-19 Serological Testing/statistics & numerical data , China/epidemiology , Cohort Studies , Comorbidity , Fatigue/epidemiology , Fatigue/etiology , Female , Humans , Length of Stay/statistics & numerical data , Male , Middle Aged , Muscle Weakness/epidemiology , Muscle Weakness/etiology , Pandemics , SARS-CoV-2 , Severity of Illness Index , Sleep Wake Disorders/epidemiology , Sleep Wake Disorders/etiology , Surveys and Questionnaires
15.
Preprint | SciFinder | ID: ppcovidwho-4030

ABSTRACT

A review. As of 30 March, 2020, there are now more than 700 000 cases of the COVID-19 in global, and 35 020 people have lost their lives. WHO has declared that COVID-19 caused by SARS-CoV-2 virus has global pandemic characteristics on 12 March 2020. There is currently no vaccine or specific medicine against the virus. The most effective measures to SARS-CoV-2 are still early detection and quarantine of new sources of infection, and early diagnosis and supportive treatments for confirmed patients. Therefore, it is critical to understand the nature of the virus and its clin. characteristics, in order to respond to the COVID-19 outbreak. This review is focused on recent and current trends on SARS-CoV-2 genome, structure, clin. disease, epidemiol., laboratory diagnosis and treatment.

16.
Commun Biol ; 3(1): 780, 2020 12 11.
Article in English | MEDLINE | ID: covidwho-975030

ABSTRACT

Coronavirus Disease 2019 (COVID-19) has caused a global pandemic. Here we profiled the humoral response against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) by measuring immunoglobulin (Ig) A, IgM, and IgG against nucleocapsid and spike proteins, along with IgM and IgG antibodies against receptor-binding domain (RBD) of the spike protein and total neutralizing antibodies (NAbs). We tested 279 plasma samples collected from 176 COVID-19 patients who presented and enrolled at different stages of their disease. Plasma dilutions were optimized and based on the data, a single dilution of plasma was used. The mean absorbance at 450 nm was measured for Ig levels and NAbs were measured using geometric mean titers. We demonstrate that more severe cases have a late-onset in the humoral response compared to mild/moderate infections. All the antibody titers continue to rise in patients with COVID-19 over the disease course. However, these levels are mostly unrelated to disease severity. The appearance time and titers of NAbs showed a significant positive correlation to the antibodies against spike protein. Our results suggest the late onset of antibody response as a risk factor for disease severity, however, there is a limited role of antibody titers in predicting disease severity of COVID-19.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , Immunity, Humoral/immunology , SARS-CoV-2/immunology , Adolescent , Adult , Aged , Aged, 80 and over , Animals , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19/epidemiology , COVID-19/virology , China/epidemiology , Chlorocebus aethiops , Female , Humans , Kinetics , Male , Middle Aged , Pandemics , SARS-CoV-2/physiology , Severity of Illness Index , Spike Glycoprotein, Coronavirus/immunology , Vero Cells , Young Adult
17.
Front Pediatr ; 8: 585629, 2020.
Article in English | MEDLINE | ID: covidwho-961648

ABSTRACT

Introduction: The COVID-19 pandemic has affected all aspects of life worldwide. The aim of the present study was to review and describe and acknowledge the impact of COVID-19 on the pediatric health care system at a pediatric tertiary hospital in Wenzhou. Methods: A retrospective study was conducted at Yuying Children's Hospital of Wenzhou Medical University, a public pediatric tertiary hospital in Southern Zhejiang Province that specializes in pediatrics. The data regarding the primary diagnosis of patients were extracted from the electronic medical records system of the hospital. Data for outpatients and inpatients treated at the pediatric department were analyzed in the time frame of 22 weeks since the beginning of the pandemic (from December 30, 2019 to June 2, 2020) and compared with data from the same period in 2019. Results: The total number of outpatient cases in the previous 22 weeks of the year declined from 560,620 in 2019 to 247,030 in 2020, and inpatient cases decreased from 14,177 to 7,555. This negative trend settled by week 6 and 7 and subsequently approached the 2019 numbers. The most noticeable decrease in the number of cases was observed in children of preschool age. Moreover, the number of weekly visits decreased at the beginning of the epidemic, reached the lowest value during the lockdown period, and recovered after the lockdown. Conclusion: Based on the results of this study, clinical practice in a pediatric department in Wenzhou was substantially affected by the epidemic and measures such as physical distancing and increased personal hygiene, particularly in preschool-age children. An understanding of the trends and impacts of the pandemic on pediatric patients and health systems will facilitate better preparation of pediatricians in the future.

18.
Emerg Microbes Infect ; 9(1): 2707-2714, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-953975

ABSTRACT

To identify the association between the kinetics of viral load and clinical outcome in severe coronavirus disease 2019 (COVID-19) patients, a retrospective study was performed by involved 188 hospitalized severe COVID-19 patients in the LOTUS China trial. Among the collected 578 paired throat swab (TS) and anal swab (AS) samples, viral RNA was detected in 193 (33.4%) TS and 121 (20.9%) AS. A higher viral RNA load was found in TS than that of AS, with means of 1.0 × 106 and 2.3 × 105 copies/ml, respectively. In non-survivors, the viral RNA in AS was detected earlier than that in survivors (median of 14 days vs 19 days, P = 0.007). The positivity and viral load in AS were higher in non-survivors than that of survivors at week 2 post symptom onset (P = 0.006). A high initial viral load in AS was associated with death (OR 1.368, 95% CI 1.076-1.741, P = 0.011), admission to the intensive care unit (OR 1.237, 95% CI 1.001-1.528, P = 0.049) and need for invasive mechanical ventilation (OR 1.340, 95% CI 1.076-1.669, P = 0.009). Our findings indicated viral replication in extrapulmonary sites should be monitored intensively during antiviral therapy.


Subject(s)
Anal Canal/virology , COVID-19/virology , SARS-CoV-2/isolation & purification , Viral Load , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/mortality , Female , Humans , Male , Middle Aged , Pharynx/virology , RNA, Viral/analysis , Retrospective Studies , Time Factors , Virus Replication , Young Adult
20.
Chem Eng J ; 421: 127742, 2021 Oct 01.
Article in English | MEDLINE | ID: covidwho-938805

ABSTRACT

SARS-CoV-2 is a highly contagious virus and is causing a global pandemic. SARS-CoV-2 infection depends on the recognition of and binding to the cellular receptor human angiotensin-converting enzyme 2 (hACE2) through the receptor-binding domain (RBD) of the spike protein, and disruption of this process can effectively inhibit SARS-CoV-2 invasion. Plasma-activated water efficiently inactivates bacteria and bacteriophages by causing damage to biological macromolecules, but its effect on coronavirus has not been reported. In this study, pseudoviruses with the SARS-CoV-2 S protein were used as a model, and plasma-activated water (PAW) effectively inhibited pseudovirus infection through S protein inactivation. The RBD was used to study the molecular details, and the RBD binding activity was inactivated by plasma-activated water through the RBD modification. The short-lived reactive species in the PAW, such as ONOO-, played crucial roles in this inactivation. Plasma-activated water after room-temperature storage of 30 days remained capable of significantly reducing the RBD binding with hACE2. Together, our findings provide evidence of a potent disinfection strategy to combat the epidemic caused by SARS-CoV-2.

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