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1.
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 , Child , Child, Preschool , Coronavirus Infections/virology , Enzyme-Linked Immunosorbent Assay/methods , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/virology , Polymerase Chain Reaction/methods
2.
Clin Infect Dis ; 72(7): 1293, 2021 04 08.
Article in English | MEDLINE | ID: covidwho-1207256

Subject(s)
Humans
3.
The Lancet ; 397(10270):220-232, 2021.
Article | WHO COVID | 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)

4.
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 , /immunology , Adolescent , Adult , Aged , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , /epidemiology , Child , Child, Preschool , China/epidemiology , 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
5.
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 , Coronavirus OC43, Human/immunology , Spike Glycoprotein, Coronavirus/immunology , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Cross Reactions/immunology , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Male , Middle Aged , Severity of Illness Index , Young Adult
6.
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 , 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
7.
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)
/complications , Quality of Life , Aged , /psychology , 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 , Severity of Illness Index , Sleep Wake Disorders/epidemiology , Sleep Wake Disorders/etiology , Surveys and Questionnaires
8.
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

9.
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 , Immunity, Humoral/immunology , /immunology , Adolescent , Adult , Aged , Aged, 80 and over , Animals , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , /virology , China/epidemiology , Chlorocebus aethiops , Female , Humans , Kinetics , Male , Middle Aged , Pandemics , Severity of Illness Index , Spike Glycoprotein, Coronavirus/immunology , Vero Cells , Young Adult
10.
Emerg Microbes Infect ; : 1-26, 2020 Dec 01.
Article in English | MEDLINE | ID: covidwho-953975

ABSTRACT

The pandemic coronavirus disease 2019 (COVID-19) is characterized by systemic infection and multiorgan dysfunction. The association between the kinetics of viral load and clinical outcome in severe COVID-19 patients has not been well established. A retrospective study was performed on clinical specimens from 188 hospitalized severe COVID-19 patients involved in the LOTUS China trial. A total of 578 paired throat swab (TS) and anal swab (AS) samples were collected. Viral load was measured by using quantitative real-time PCR. Viral RNA was detected in 193 (33.4%) TS and 121 (20.9%) AS samples. A higher viral RNA load was found in TS than in AS, with means of 1.0×106 and 2.3×105 copies/ml, respectively. The median number of days from symptom onset to positive virus detection in AS samples was significantly lower in non-survivors than in survivors (14 days vs 19 days, P=0.007). The virus positive rate in AS (P=0.006) and the viral load in AS (P=0.006) were significantly higher in non-survivors than in survivors at week 2 post symptom onset. 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) in COVID-19 patients. A high viral load and early positive virus detection in AS predispose adverse outcomes of COVID-19. Viral replication in extrapulmonary sites should be monitored intensively during antiviral therapy.

12.
Chem Eng J ; : 127742, 2020 Nov 20.
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.

13.
Diabetes Research and Clinical Practice ; 16640, 2020.
Article in English | WHO COVID | ID: covidwho-912147

ABSTRACT

Aims: Diabetes mellitus has been reported to be one of the most prevalent comorbidity in patients with Coronavirus Disease 2019 (COVID-19) We aimed to assess the association of comorbid diabetes with COVID-19 severity or mortality in China

14.
Clin Infect Dis ; 71(15): 713-720, 2020 07 28.
Article in English | MEDLINE | ID: covidwho-909244

ABSTRACT

BACKGROUND: A novel coronavirus (CoV), severe acute respiratory syndrome (SARS)-CoV-2, has infected >75 000 individuals and spread to >20 countries. It is still unclear how fast the virus evolved and how it interacts with other microorganisms in the lung. METHODS: We have conducted metatranscriptome sequencing for bronchoalveolar lavage fluid samples from 8 patients with SARS-CoV-2, and also analyzed data from 25 patients with community-acquired pneumonia (CAP), and 20 healthy controls for comparison. RESULTS: The median number of intrahost variants was 1-4 in SARS-CoV-2-infected patients, ranged from 0 to 51 in different samples. The distribution of variants on genes was similar to those observed in the population data. However, very few intrahost variants were observed in the population as polymorphisms, implying either a bottleneck or purifying selection involved in the transmission of the virus, or a consequence of the limited diversity represented in the current polymorphism data. Although current evidence did not support the transmission of intrahost variants in a possible person-to-person spread, the risk should not be overlooked. Microbiotas in SARS-CoV-2-infected patients were similar to those in CAP, either dominated by the pathogens or with elevated levels of oral and upper respiratory commensal bacteria. CONCLUSION: SARS-CoV-2 evolves in vivo after infection, which may affect its virulence, infectivity, and transmissibility. Although how the intrahost variant spreads in the population is still elusive, it is necessary to strengthen the surveillance of the viral evolution in the population and associated clinical changes.


Subject(s)
Coronavirus Infections/epidemiology , Coronavirus , Pandemics , Pneumonia, Viral/epidemiology , Severe Acute Respiratory Syndrome , Betacoronavirus , Genetic Variation , Genomics , Humans
16.
Preprint | SSRN | ID: ppcovidwho-721

ABSTRACT

Background: Starting in December 2019, the SARS-CoV-2 virus caused severe pneumonia in Wuhan and spread nationwide and globally Here, we report the clinical fe

18.
Preprint | SSRN | ID: ppcovidwho-577

ABSTRACT

Background: Various forms of model have been applied to predict the trend of the epidemic since the outbreak of COVID-19 at the hardest-hit city of Wuhan br b

19.
Cell Stem Cell ; 27(6): 937-950.e9, 2020 12 03.
Article in English | MEDLINE | ID: covidwho-779663

ABSTRACT

Neurological complications are common in patients with COVID-19. Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal pathogen of COVID-19, has been detected in some patient brains, its ability to infect brain cells and impact their function is not well understood. Here, we investigated the susceptibility of human induced pluripotent stem cell (hiPSC)-derived monolayer brain cells and region-specific brain organoids to SARS-CoV-2 infection. We found that neurons and astrocytes were sparsely infected, but choroid plexus epithelial cells underwent robust infection. We optimized a protocol to generate choroid plexus organoids from hiPSCs and showed that productive SARS-CoV-2 infection of these organoids is associated with increased cell death and transcriptional dysregulation indicative of an inflammatory response and cellular function deficits. Together, our findings provide evidence for selective SARS-CoV-2 neurotropism and support the use of hiPSC-derived brain organoids as a platform to investigate SARS-CoV-2 infection susceptibility of brain cells, mechanisms of virus-induced brain dysfunction, and treatment strategies.

20.
Biomed Res Int ; 2020: 1594726, 2020.
Article in English | MEDLINE | ID: covidwho-633800

ABSTRACT

Acute kidney injury (AKI) is a common complication of sepsis and has also been observed in some patients suffering from the new coronavirus pneumonia COVID-19, which is currently a major global concern. Thymoquinone (TQ) is one of the most active ingredients in Nigella sativa seeds. It has a variety of beneficial properties including anti-inflammatory and antioxidative activities. Here, we investigated the possible protective effects of TQ against kidney damage in septic BALB/c mice. Eight-week-old male BALB/c mice were divided into four groups: control, TQ, cecal ligation and puncture (CLP), and TQ+CLP. CLP was performed after 2 weeks of TQ gavage. After 48 h, we measured the histopathological alterations in the kidney tissue and the serum levels of creatinine (CRE) and blood urea nitrogen (BUN). We also evaluated pyroptosis (NLRP3, caspase-1), apoptosis (caspase-3, caspase-8), proinflammatory (TNF-α, IL-1ß, and IL-6)-related protein and gene expression levels. Our results demonstrated that TQ inhibited CLP-induced increased serum CRE and BUN levels. It also significantly inhibited the high levels of NLRP3, caspase-1, caspase-3, caspase-8, TNF-α, IL-1ß, and IL-6 induced by CLP. Furthermore, NF-κB protein level was significantly decreased in the TQ+CLP group than in the CLP group. Together, our results indicate that TQ may be a potential therapeutic agent for sepsis-induced AKI.


Subject(s)
Acute Kidney Injury/drug therapy , Acute Kidney Injury/etiology , Benzoquinones/therapeutic use , Sepsis/complications , Sepsis/drug therapy , Acute Kidney Injury/pathology , Animals , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Antioxidants/therapeutic use , Apoptosis/drug effects , Betacoronavirus , Blood Urea Nitrogen , Coronavirus Infections/complications , Coronavirus Infections/drug therapy , Creatinine/blood , Cytokines/metabolism , Disease Models, Animal , Humans , Inflammation Mediators/metabolism , Kidney/drug effects , Kidney/metabolism , Kidney/pathology , Male , Mice , Mice, Inbred BALB C , NF-kappa B/metabolism , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/drug therapy
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