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1.
Blood ; 138(19):1628-1628, 2021.
Article in English | EuropePMC | ID: covidwho-1601840

ABSTRACT

Background Plasma cell disorders (PCD) are at risk of inadequate immune responses to COVID-19 vaccines due to recognised humoral and cellular immune dysfunction which is multi-factorial and related to host and disease factors. With an estimated risk of 33% mortality from contracting COVID-19 in this population, protection with an anti-SARS-CoV-2 vaccination is critical. Initial extension to vaccination intervals in the United Kingdom to 12 weeks in December 2020 led to concerns that PCD patients would be left vulnerable for an extended period. Methods A clinical audit was performed on measured serological responses in PCD patients after first and second doses of the BNT162b2 and ChAdOx-1 nCoV-19 vaccines. Antibody levels were measured using Elecsys Anti-SARS-CoV-2S assay (Roche) for quantitative detection of IgG Abs, specific for the SARS-CoV-2 spike-protein. Positive cut-off of 0.80 U/mL defined serological response. Testing was performed at (or closest to) 4 and 8-weeks post-dose. Baseline nucleocapsid Ab results were available from previous screening in a subset of patients. All patients on CIT underwent 4-weekly swabs. Clinical information was retrieved from medical records. Results 188 PCD patients (155 multiple myeloma, 18 amyloid, 10 SMM/MGUS, other 5 PCD), median age 64 (range 32-84), had serological assessment after both vaccine doses. Fourteen with previous COVID-19 infection were excluded. Of 174 patients, 112 were tested after first dose. 88% (153) were on chemo-immunotherapy treatment (CIT). Seropositive rate after first dose was 63% (71/112);of those with available negative baseline antibody test, 62% (31/50) seroconverted. After second dose, 89% (154/174) were seropositive;of those with negative baseline antibody, 90% (61/68) seroconverted. Expectedly, paired median titres after second dose were significantly higher than post first dose (n=112, 3.245 U/mL (IQR 0.4-25.55) vs 518 U/mL (IQR 29.40-2187) p<0.0001) (Figure 1A). Of 41 patients seronegative after first dose, 25 (61%) seroconverted after second, though with lower titres than those only requiring one dose (Figure 1B). Active CIT, disease response less than PR, >=4 lines therapy, light-chain disease, male gender and not responding to first dose were significant factors for not responding to two vaccine doses. We explored <400 U/mL as sub-optimal response (in keeping with upcoming booster study eligibility, OCTAVE-DUO(1), also encompassing the lower quartile of reported healthy controls(2)), which included 43% (75/174) patients. Age 70 years, male gender, >=4 lines of treatment were independent predictors of less-than-optimal response (anti-CD38 CIT of borderline significance). Importantly, vaccine dosing intervals classified as =<42 vs >42 days (Figure 1C) or 28 +/- 14 days vs 84 +/- 14 days (excluding n=66 in neither) (Figure 1D) did not show difference in both definitions of response, neither did vaccine type. Fourteen with previous COVID-19 infection responded to one vaccine dose, median titres 2121 U/mL (IQR 23.48-2500)) rising to median 2500 U/mL (IQR 2500-2500) after second dose (Figure 1E), significantly higher than those without previous infection. Conclusion Serological response to COVID-19 vaccine is lower in PCD patients than reported healthy controls at 63% after first dose, rising to 89% after second dose, despite extended dosing intervals. PCD patients should be prioritised for shorter intervals, as we show that patients seronegative after first dose, respond after second dose. Further work in PCD is needed to understand how Ab levels correlate to neutralisation capability, cellular responses, protection from infection and how long seroconversion lasts to better define correlates of protection. A booster vaccination or prophylactic passive antibody strategy may be required for those identified at risk, shown not to have responded to two vaccine doses or to have less-than-optimal response. Results from these trials will be eagerly awaited. References: 1. University of Birmingham. About the OCTAVE Trial 2021 [Available from: https //www.birmingham.ac.uk/research/crctu/trials/octave/patients-and-public/about-octave.aspx. Accessed 1 st August 2021. 2. Avivi I, Balaban R, Shragai T, Sheffer G, Morales M, Aharon A, et al. Humoral response rate and predictors of response to BNT162b2 mRNA COVID19 vaccine in patients with multiple myeloma. Br J Haematol. 2021. Figure 1 Disclosures Wechalekar:  Amgen: Research Funding;Alexion, AstraZeneca Rare Disease: Consultancy;Caelum Biosciences: Other: Clinical Trial Funding;Janssen: Consultancy;Takeda: Honoraria;Celgene: Honoraria. Popat:  AbbVie, BMS, Janssen, Oncopeptides, and Amgen: Honoraria;Takeda: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES;GlaxoSmithKline: Consultancy, Honoraria, Research Funding;Abbvie, Takeda, Janssen, and Celgene: Consultancy;Janssen and BMS: Other: travel expenses. Rabin:  BMS / Celgene: Consultancy, Honoraria, Other: Travel support for meetings;Takeda: Consultancy, Honoraria, Other: Travel support for meetings;Janssen: Consultancy, Honoraria, Other: Travel support for meetings. Yong:  BMS: Research Funding;Amgen: Honoraria;GSK: Honoraria;Takeda: Honoraria;Janssen: Honoraria, Research Funding;Sanofi: Honoraria, Research Funding;Autolus: Research Funding.

2.
Innovation (N Y) ; : 100181, 2021 Nov 03.
Article in English | MEDLINE | ID: covidwho-1595417

ABSTRACT

Most COVID-19 convalescents can build effective anti-SARS-CoV-2 humoral immunity, but it remains unclear how long it can maintain and how efficiently it can prevent the reinfection of the emerging SARS-CoV-2 variants. Here, we tested the sera from 248 COVID-19 convalescents around one year post-infection in Wuhan, the earliest known epicenter. SARS-CoV-2 immunoglobulins G (IgG) were well maintained in most patients and potently neutralizes the infection of the original strain and the B.1.1.7 variant. However, varying degrees of immune escape was observed on the other tested variants in a patient-specific manner, with individuals showing remarkably broad neutralization potency. The immune escape can be largely attributed to several critical spike mutations. These results suggest that SARS-CoV-2 can elicit long-lasting immunity but escaped by the emerging variants.

3.
Preprint in English | Other preprints | ID: ppcovidwho-296266

ABSTRACT

5-Methylcytosine (m 5 C) is a widespread post-transcriptional RNA modification and is reported to be involved in manifold cellular responses and biological processes through regulating RNA metabolism. However, its regulatory role in antiviral innate immunity has not yet been elucidated. Here, we report that NSUN2, a typical m 5 C methyltransferase, can negatively regulate type I interferon responses during viral infection. NSUN2 specifically mediates m 5 C methylation of IRF3 mRNA and accelerates its degradation, resulting in low levels of IRF3 and downstream IFN-β production. Knockout or knockdown of NSUN2 could enhance type I interferon responses and downstream ISG expression after viral infection in vitro . And in vivo , the antiviral innate responses is more dramatically enhanced in Nsun2 +/− mice than in Nsun2 +/+ mice. Four highly m 5 C methylated cytosines in IRF3 mRNA were identified, and their mutation could enhance the cellular IRF3 mRNA levels. Moreover, infection with Sendai virus (SeV), vesicular stomatitis virus (VSV), herpes simplex virus 1 (HSV-1), Zika virus (ZIKV), or especially SARS-CoV-2 resulted in a reduction in endogenous levels of NSUN2. Together, our findings reveal that NSUN2 serves as a negative regulator of interferon response by accelerating the fast turnover of IRF3 mRNA, while endogenous NSUN2 levels decrease after viral infection to boost antiviral responses for the effective elimination of viruses. Our results suggest a paradigm of innate antiviral immune responses ingeniously involving NSUN2-mediated m 5 C modification.

5.
Preprint in English | EuropePMC | ID: ppcovidwho-292235

ABSTRACT

Background: SARS-CoV-2 infection and disease severity are influenced by viral entry (VE) gene expression patterns in airway epithelium. The similarities and differences of VE gene expression (ACE2, TMPRSS2, and CTSL) across nasal and bronchial compartments has not been fully characterized using matched samples from large cohorts. Results: Gene expression data from 793 nasal and 1,673 bronchial brushes obtained from individuals participating in lung cancer screening or diagnostic workup revealed that smoking was the only clinical factor significantly and reproducibly associated with VE gene expression. ACE2 and TMPRSS2 expression were higher in smokers in the bronchus but not in the nose. scRNA-seq of nasal brushings indicated that ACE2 co-expressed genes were highly expressed in club and C15orf48 + secretory cells while TMPRSS2 co-expressed genes were highly expressed in keratinizing epithelial cells. In contrast, these ACE2 and TMPRSS2 modules were highly expressed in goblet cells in scRNA-seq from bronchial brushings. Cell-type deconvolution of the RNA-seq confirmed that smoking increased the abundance of several secretory cell populations in the bronchus, but only goblet cells in the nose. Conclusions: The association of ACE2 and TMPRSS2 with smoking in the bronchus is due to their high expression in goblet cells which increase in abundance in current smoker airways. In contrast, in the nose these genes are not predominantly expressed in cell populations modulated by smoking. Smoking-induced VE gene expression changes in the nose likely has minimal impact on SARS-CoV-2 infection, but in the bronchus, smoking may lead to higher viral loads and more severe disease.

6.
IEEE Rev Biomed Eng ; 14: 48-70, 2021.
Article in English | MEDLINE | ID: covidwho-1501336

ABSTRACT

Coronavirus disease 2019 (COVID-19) has emerged as a pandemic with serious clinical manifestations including death. A pandemic at the large-scale like COVID-19 places extraordinary demands on the world's health systems, dramatically devastates vulnerable populations, and critically threatens the global communities in an unprecedented way. While tremendous efforts at the frontline are placed on detecting the virus, providing treatments and developing vaccines, it is also critically important to examine the technologies and systems for tackling disease emergence, arresting its spread and especially the strategy for diseases prevention. The objective of this article is to review enabling technologies and systems with various application scenarios for handling the COVID-19 crisis. The article will focus specifically on 1) wearable devices suitable for monitoring the populations at risk and those in quarantine, both for evaluating the health status of caregivers and management personnel, and for facilitating triage processes for admission to hospitals; 2) unobtrusive sensing systems for detecting the disease and for monitoring patients with relatively mild symptoms whose clinical situation could suddenly worsen in improvised hospitals; and 3) telehealth technologies for the remote monitoring and diagnosis of COVID-19 and related diseases. Finally, further challenges and opportunities for future directions of development are highlighted.


Subject(s)
COVID-19/diagnosis , Pandemics/prevention & control , Technology/methods , Telemedicine/methods , COVID-19/virology , Delivery of Health Care/methods , Humans , SARS-CoV-2/pathogenicity , Wearable Electronic Devices
8.
Signal Transduct Target Ther ; 6(1): 347, 2021 09 25.
Article in English | MEDLINE | ID: covidwho-1437669

ABSTRACT

SARS-CoV-2 mutations contribute to increased viral transmissibility and immune escape, compromising the effectiveness of existing vaccines and neutralizing antibodies. An in-depth investigation on COVID-19 pathogenesis is urgently needed to develop a strategy against SARS-CoV-2 variants. Here, we identified CD147 as a universal receptor for SARS-CoV-2 and its variants. Meanwhile, Meplazeumab, a humanized anti-CD147 antibody, could block cellular entry of SARS-CoV-2 and its variants-alpha, beta, gamma, and delta, with inhibition rates of 68.7, 75.7, 52.1, 52.1, and 62.3% at 60 µg/ml, respectively. Furthermore, humanized CD147 transgenic mice were susceptible to SARS-CoV-2 and its two variants, alpha and beta. When infected, these mice developed exudative alveolar pneumonia, featured by immune responses involving alveoli-infiltrated macrophages, neutrophils, and lymphocytes and activation of IL-17 signaling pathway. Mechanistically, we proposed that severe COVID-19-related cytokine storm is induced by a "spike protein-CD147-CyPA signaling axis": Infection of SARS-CoV-2 through CD147 initiated the JAK-STAT pathway, which further induced expression of cyclophilin A (CyPA); CyPA reciprocally bound to CD147 and triggered MAPK pathway. Consequently, the MAPK pathway regulated the expression of cytokines and chemokines, which promoted the development of cytokine storm. Importantly, Meplazumab could effectively inhibit viral entry and inflammation caused by SARS-CoV-2 and its variants. Therefore, our findings provided a new perspective for severe COVID-19-related pathogenesis. Furthermore, the validated universal receptor for SARS-CoV-2 and its variants can be targeted for COVID-19 treatment.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , Antibodies, Monoclonal, Humanized/pharmacology , Basigin/antagonists & inhibitors , Basigin/metabolism , COVID-19/drug therapy , COVID-19/metabolism , Cytokine Release Syndrome/drug therapy , SARS-CoV-2/metabolism , Angiotensin-Converting Enzyme 2/genetics , Animals , Basigin/genetics , COVID-19/genetics , Chlorocebus aethiops , Cytokine Release Syndrome/genetics , Cytokine Release Syndrome/metabolism , Humans , MAP Kinase Signaling System/drug effects , MAP Kinase Signaling System/genetics , Mice , Mice, Transgenic , SARS-CoV-2/genetics , Vero Cells
9.
Microbiol Spectr ; 9(2): e0059021, 2021 10 31.
Article in English | MEDLINE | ID: covidwho-1434909

ABSTRACT

To assess the persistence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies produced by natural infection and describe the serological characteristics over 7 months after symptom onset among coronavirus disease 2019 (COVID-19) patients by age and severity group, we followed up COVID-19 convalescent patients confirmed from 1 January to 20 March 2020 in Jiangsu, China and collected serum samples for testing IgM/IgG and neutralizing antibodies against SARS-CoV-2 between 26 August and 28 October 2020. In total, 284 recovered participants with COVID-19 were enrolled in our study. Patients had a mean age of 46.72 years (standard deviation [SD], 17.09), and 138 (48.59%) were male. The median follow-up time after symptom onset was 225.5 (interquartile range [IQR], 219 to 232) days. During the follow-up period (162 to 282 days after symptom onset), the seropositive rate of IgM fluctuated around 25.70% (95% confidence interval [CI], 20.72% to 31.20%) and that of IgG fluctuated around 79.93% (95% CI, 74.79% to 84.43%). Of the 284 patients, 64 participants were tested when discharged from hospital. Compared with that at the acute phase, the IgM/IgG antibody levels and IgM seropositivity have decreased; however, the seropositivity of IgG was not significantly lower at this follow-up (78.13% versus 82.81%). Fifty percent inhibitory dilution (ID50) titers of neutralizing antibody for samples when discharged from hospital (geometric mean titer [GMT], 82; 95% CI, 56 to 121) were significantly higher than those at 6 to 7 months after discharge (GMT, 47; 95% CI, 35 to 63) (P < 0.001). After 7 months from symptom onset, the convalescent COVID-19 patients continued to have high IgG seropositive; however, many plasma samples decreased neutralizing activity. IMPORTANCE The long-term characteristics of anti-SARS-CoV-2 antibodies among COVID-19 patients remain largely unclear. Tracking the longevity of these antibodies can provide a forward-looking reference for monitoring COVID-19. We conducted a comprehensive assessment combining the kinetics of specific and neutralizing antibodies over 7 months with age and disease severity and revealed influencing factors of the protection period of convalescent patients. By observing the long-term antibody levels against SARS-CoV-2 and comparing antibody levels at two time points after symptom onset, we found that the convalescent COVID-19 patients continued to have a high IgG seropositive rate; however, their plasma samples decreased neutralizing activity. These findings provide evidence supporting that the neutralizing activity of SARS-CoV-2-infected persons should be monitored and the administration of vaccine may be needed.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Immunoglobulin G/blood , Immunoglobulin M/blood , SARS-CoV-2/immunology , Adolescent , Adult , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , Child , Female , Humans , Immunoglobulin G/immunology , Immunoglobulin M/immunology , Immunologic Memory/immunology , Male , Middle Aged , Young Adult
10.
BMJ ; 369: m2195, 2020 06 10.
Article in English | MEDLINE | ID: covidwho-1430181

ABSTRACT

OBJECTIVE: To examine the protective effects of appropriate personal protective equipment for frontline healthcare professionals who provided care for patients with coronavirus disease 2019 (covid-19). DESIGN: Cross sectional study. SETTING: Four hospitals in Wuhan, China. PARTICIPANTS: 420 healthcare professionals (116 doctors and 304 nurses) who were deployed to Wuhan by two affiliated hospitals of Sun Yat-sen University and Nanfang Hospital of Southern Medical University for 6-8 weeks from 24 January to 7 April 2020. These study participants were provided with appropriate personal protective equipment to deliver healthcare to patients admitted to hospital with covid-19 and were involved in aerosol generating procedures. 77 healthcare professionals with no exposure history to covid-19 and 80 patients who had recovered from covid-19 were recruited to verify the accuracy of antibody testing. MAIN OUTCOME MEASURES: Covid-19 related symptoms (fever, cough, and dyspnoea) and evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, defined as a positive test for virus specific nucleic acids in nasopharyngeal swabs, or a positive test for IgM or IgG antibodies in the serum samples. RESULTS: The average age of study participants was 35.8 years and 68.1% (286/420) were women. These study participants worked 4-6 hour shifts for an average of 5.4 days a week; they worked an average of 16.2 hours each week in intensive care units. All 420 study participants had direct contact with patients with covid-19 and performed at least one aerosol generating procedure. During the deployment period in Wuhan, none of the study participants reported covid-19 related symptoms. When the participants returned home, they all tested negative for SARS-CoV-2 specific nucleic acids and IgM or IgG antibodies (95% confidence interval 0.0 to 0.7%). CONCLUSION: Before a safe and effective vaccine becomes available, healthcare professionals remain susceptible to covid-19. Despite being at high risk of exposure, study participants were appropriately protected and did not contract infection or develop protective immunity against SARS-CoV-2. Healthcare systems must give priority to the procurement and distribution of personal protective equipment, and provide adequate training to healthcare professionals in its use.


Subject(s)
Coronavirus Infections/prevention & control , Health Personnel , Infection Control/instrumentation , Pandemics/prevention & control , Personal Protective Equipment/supply & distribution , Pneumonia, Viral/prevention & control , Adult , Betacoronavirus , COVID-19 , China , Coronavirus Infections/diagnosis , Cross-Sectional Studies , Female , Humans , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Intensive Care Units , Male , Middle Aged , Occupational Exposure/prevention & control , Pneumonia, Viral/diagnosis , SARS-CoV-2
11.
Atmospheric Pollution Research ; : 101209, 2021.
Article in English | ScienceDirect | ID: covidwho-1415195

ABSTRACT

Knowing the contribution rates and sharing rate of local source emissions to the atmospheric environmental capacity (AEC) is of great significance to the formulation of regional air pollution source control measures. Based on WRF-CALPUFF coupling models and the second pollution source survey data, Wuhan was taken as the research area, and the contribution rates of point and area source emissions to the SO2, NO2 and PM2.5 concentration in national pollutant control points (abbreviated as "national control points"), the AEC and its source emission sharing rate of each region were calculated. The results showed that WRF-CALPUFF had better reproducibility, the contribution rates of different pollution source emissions to the SO2, NO2 and PM2.5 concentration in national control points had obvious spatial distribution characteristics, and the contribution rates of key point sources to the SO2 concentration of each national control point exceeded 40%, while the contribution rates of the main urban area source to the NO2 and PM2.5 concentrations exceed 60%;the AEC of SO2, NO2 and PM2.5 in different regions had obvious seasonal and spatial changes, and the source emissions of NO2 and PM2.5 in the main urban area were 8.7 times and 3 times of its AEC, respectively. The calculation results from source sharing rate of regional AEC showed that the AEC of SO2 was mainly shared by point sources, and the AEC of NO2 and PM2.5 was mainly shared by area sources, but the sharing rate of SO2, NO2 and PM2.5 AEC from different regional source emissions showed different characteristics. The analysis of air quality improvement during the 7th Military World Games in 2019 and the COVID-19 pandemic in 2020 shows that the calculation formula about regional source sharing rate of AEC proposed in this paper is reasonable and the implementation of refined control to regional source emissions with the source sharing rate of regional AEC plays an important role on the continued improvement of Wuhan air quality.

12.
Contemp Clin Trials ; 109: 106540, 2021 10.
Article in English | MEDLINE | ID: covidwho-1363910

ABSTRACT

There are currently no validated pharmacotherapies for posttraumatic stress disorder (PTSD)-related insomnia. The purpose of the National Adaptive Trial for PTSD-Related Insomnia (NAP Study) is to efficiently compare to placebo the effects of three insomnia medications with different mechanisms of action that are already prescribed widely to veterans diagnosed with PTSD within U.S. Department of Veterans Affairs (VA) Medical Centers. This study plans to enroll 1224 patients from 34 VA Medical Centers into a 12- week prospective, randomized placebo-controlled clinical trial comparing trazodone, eszopiclone, and gabapentin. The primary outcome measure is insomnia, assessed with the Insomnia Severity Index. A novel aspect of this study is its adaptive design. At the recruitment midpoint, an interim analysis will be conducted to inform a decision to close recruitment to any "futile" arms (i.e. arms where further recruitment is very unlikely to yield a significant result) while maintaining the overall study recruitment target. This step could result in the enrichment of the remaining study arms, enhancing statistical power for the remaining comparisons to placebo. This study will also explore clinical, actigraphic, and biochemical predictors of treatment response that may guide future biomarker development. Lastly, due to the COVID-19 pandemic, this study will allow the consenting process and follow-up visits to be conducted via video or phone contact if in-person meetings are not possible. Overall, this study aims to identify at least one effective pharmacotherapy for PTSD-related insomnia, and, perhaps, to generate definitive negative data to reduce the use of ineffective insomnia medications. NATIONAL CLINICAL TRIAL (NCT) IDENTIFIED NUMBER: NCT03668041.


Subject(s)
COVID-19 , Sleep Initiation and Maintenance Disorders , Stress Disorders, Post-Traumatic , Veterans , Humans , Pandemics , Prospective Studies , SARS-CoV-2 , Sleep Initiation and Maintenance Disorders/drug therapy , Sleep Initiation and Maintenance Disorders/etiology , Stress Disorders, Post-Traumatic/drug therapy , Stress Disorders, Post-Traumatic/epidemiology
13.
Emerg Microbes Infect ; 10(1): 1626-1637, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1348038

ABSTRACT

Coronaviruses (CoVs) can infect a variety of hosts, including humans, livestock and companion animals, and pose a serious threat to human health and the economy. The current COVID-19 pandemic, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has killed millions of people. Unfortunately, effective treatments for CoVs infection are still lacking, suggesting the importance of coronavirus vaccines. Our previous work showed that CoV nonstuctural protein 14 (nsp14) functions as (guanine-N7)-methyltransferase (N7-MTase), which is involved in RNA cap formation. Moreover, we found that N7-MTase is well conserved among different CoVs and is a universal target for developing antivirals against CoVs. Here, we show that N7-MTase of CoVs can be an ideal target for designing live attenuated vaccines. Using murine hepatitis virus strain A59 (MHV-A59), a representative and well-studied model of coronaviruses, we constructed N7-MTase-deficient recombinant MHV D330A and Y414A. These two mutants are highly attenuated in mice and exhibit similar replication efficiency to the wild-type (WT) virus in the cell culture. Furthermore, a single dose immunization of D330A or Y414A can induce long-term humoral immune responses and robust CD4+ and CD8+ T cell responses, which can provide full protection against the challenge of a lethal-dose of MHV-A59. Collectively, this study provides an ideal strategy to design live attenuated vaccines for coronavirus by abolishing viral RNA N7-MTase activity. This approach may apply to other RNA viruses that encode their own conservative viral N7-methyltransferase.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/prevention & control , SARS-CoV-2/immunology , Vaccines, Attenuated/immunology , Animals , COVID-19 Vaccines/administration & dosage , Cytokines/biosynthesis , Humans , Immunity, Cellular , Immunity, Humoral , Immunogenicity, Vaccine , Interferon Type I/biosynthesis , Male , Mice , Mutation , Vaccines, Attenuated/administration & dosage , Viral Nonstructural Proteins/genetics , Viral Nonstructural Proteins/immunology
15.
NPJ Climate and Atmospheric Science ; 4(1), 2021.
Article in English | ProQuest Central | ID: covidwho-1317819

ABSTRACT

The less improvement of ambient visibility suspects the government’s efforts on alleviating PM2.5 pollution. The COVID-19 lockdown reduced PM2.5 and increased visibility in Wuhan. Compared to pre-lockdown period, the PM2.5 concentration decreased by 39.0 μg m−3, dominated by NH4NO3 mass reduction (24.8 μg m−3) during lockdown period. The PM2.5 threshold corresponding to visibility of 10 km (PTV10) varied in 54–175 μg m−3 and an hourly PM2.5 of 54 μg m−3 was recommended to prevent haze occurrence. The lockdown measures elevated PTV10 by 9–58 μg m−3 as the decreases in PM2.5 mass scattering efficiency and optical hygroscopicity. The visibility increased by 107%, resulted from NH4NO3 extinction reduction. The NH4NO3 mass reduction weakened its mutual promotion with aerosol water and increased PM2.5 deliquescence humidity. Controlling TNO3 (HNO3 + NO3−) was more effective to reduce PM2.5 and improve visibility than NHx (NH3 + NH4+) unless the NHx reduction exceeded 11.7–17.5 μg m−3.

16.
J Agric Food Chem ; 68(41): 11434-11448, 2020 Oct 14.
Article in English | MEDLINE | ID: covidwho-1301138

ABSTRACT

The dried fruits of Amomum tsao-ko were first revealed to have hypoglycemic effects on db/db mice at a concentration of 200 mg/kg. In order to clarify the antidiabetic constituents, 19 new flavanol-fatty alcohol hybrids, tsaokoflavanols A-S (1-19), were isolated and determined by extensive spectroscopic data and ECD calculations. Most of the compounds showed α-glucosidase and PTP1B dual inhibition, among which 1, 2, 6, 11, and 18 exhibited obvious activity against α-glucosidase with IC50 values of 5.2-9.0 µM, 20-35 times stronger than that of acarbose (IC50, 180.0 µM); meanwhile, 6, 10-12, and 19 were PTP1B/TCPTP-selective inhibitors with IC50 values of 56.4-80.4 µM, 2-4 times stronger than that of suramin sodium (IC50, 200.5 µM). Enzyme kinetics study indicated that compounds 1, 2, 6, and 11 were α-glucosidase and PTP1B mixed-type inhibitors with Ki values of 13.0, 11.7, 2.9, and 5.3 µM and 142.3, 88.9, 39.2, and 40.8 µM, respectively. Docking simulations proved the importance of hemiacetal hydroxy, the orientation of 3,4-dihydroxyphenyl, and the length of alkyl in binding with α-glucosidase and PTP1B.


Subject(s)
Amomum/chemistry , Fatty Alcohols/chemistry , Flavanones/chemistry , Glycoside Hydrolase Inhibitors/chemistry , Hypoglycemic Agents/chemistry , Plant Extracts/chemistry , Protein Tyrosine Phosphatase, Non-Receptor Type 1/antagonists & inhibitors , Fatty Alcohols/isolation & purification , Flavanones/isolation & purification , Fruit/chemistry , Glycoside Hydrolase Inhibitors/isolation & purification , Humans , Hypoglycemic Agents/isolation & purification , Plant Extracts/isolation & purification , Protein Tyrosine Phosphatase, Non-Receptor Type 1/chemistry , alpha-Glucosidases/chemistry
17.
Psychiatry Res ; 301: 113977, 2021 07.
Article in English | MEDLINE | ID: covidwho-1213479

ABSTRACT

Coronavirus disease 2019 (COVID-19) has become a pandemic. As the first city struck by the COVID-19 outbreak, Wuhan had implemented unprecedented public health interventions. The mental health of pregnant women during these anti-epidemic controls remains unknown. A total of 274 pregnant women living in Wuhan during the COVID-19 outbreak took part in our investigation online. The data on mental health conditions were evaluated using Edinburgh Postnatal Depression Scale (EPDS), Self-Rating Anxiety Scale (SAS), Chinese Perceived Stress Scale (CPSS), and Pittsburgh Sleep Quality Index (PSQI). We also collected the information on physical health status and precautionary measures against COVID-19. The prevalence of depression, anxiety, stress, and poor sleep quality was 16.1%, 13.9%, 42.7%, 37.6%, respectively. Comparing to SAS, PSQI score in pregnant women who participated in the survey after April 8 (date of Wuhan reopening), those data collected before April 8 were significantly higher. High levels of stress, severe health concerns over the fetus, and poor hygienic practices were negatively associated with mental health conditions. In conclusion, a large proportion of pregnant women reported psychological symptoms during the epidemic, which negatively related to the severe health concerns over fetus and poor hygienic practices. More psychological support during the epidemic would promote maternal mental well-being.


Subject(s)
COVID-19/psychology , Depression/epidemiology , Mental Health/statistics & numerical data , Pregnant Women/psychology , Stress, Psychological/epidemiology , Adult , Anxiety/epidemiology , Anxiety/psychology , Anxiety Disorders/epidemiology , COVID-19/epidemiology , China/epidemiology , Cross-Sectional Studies , Depression/psychology , Female , Health Status , Humans , Pandemics , Pregnancy , Psychiatric Status Rating Scales , Public Health , SARS-CoV-2 , Sleep , Surveys and Questionnaires
18.
Med Sci Monit ; 27: e929986, 2021 Apr 17.
Article in English | MEDLINE | ID: covidwho-1148369

ABSTRACT

BACKGROUND This retrospective study aimed to investigate the factors associated with disease severity and patient outcomes in 631 patients with COVID-19 who were reported to the Jiangsu Commission of Health between January 1 and March 20, 2020. MATERIAL AND METHODS We conducted an epidemiological investigation enrolling 631 patients with laboratory-confirmed COVID-19 from our clinic from January to March 2020. Patients' information was collected through a standard questionnaire. Then, we described the patients' epidemiological characteristics, analyzed risk factors associated with disease severity, and assessed causes of zero mortality. Additionally, some key technologies for epidemic prevention and control were identified. RESULTS Of the 631 patients, 8.46% (n=53) were severe cases, and no deaths were recorded (n=0). The epidemic of COVID-19 has gone through 4 stages: a sporadic phase, an exponential growth phase, a peak plateau phase, and a declining phase. The proportion of severe cases was significantly different among the 4 stages and 13 municipal prefectures (P<0.001). Factors including age >65 years old, underlying medical conditions, highest fever >39.0°C, dyspnea, and lymphocytopenia (<1.0×109/L) were early warning signs of disease severity (P<0.05). In contrast, earlier clinic visits were associated with better patient outcomes (P=0.029). Further, the viral load was a potentially useful marker associated with COVID-19 infection severity. CONCLUSIONS The study findings from the beginning of the COVID-19 epidemic in Jiangsu Province, China showed that patients who were more than 65 years of age and with comorbidities and presented with a fever of more than 39.0°C developed more severe disease. However, mortality was prevented in this initial patient population by early supportive clinical management.


Subject(s)
COVID-19/epidemiology , SARS-CoV-2 , Adult , Aged , COVID-19/diagnosis , COVID-19/history , COVID-19/virology , China/epidemiology , Comorbidity , Female , Geography, Medical , History, 21st Century , Humans , Male , Middle Aged , Mortality , Open Reading Frames , Population Surveillance , RNA, Viral , Real-Time Polymerase Chain Reaction , Risk Factors , SARS-CoV-2/classification , SARS-CoV-2/genetics , Seasons , Severity of Illness Index , Viral Load
19.
Epidemiol Infect ; 149: e48, 2021 02 10.
Article in English | MEDLINE | ID: covidwho-1129262

ABSTRACT

To understand the characteristics and influencing factors related to cluster infections in Jiangsu Province, China, we investigated case reports to explore transmission dynamics and influencing factors of scales of cluster infection. The effectiveness of interventions was assessed by changes in the time-dependent reproductive number (Rt). From 25th January to 29th February, Jiangsu Province reported a total of 134 clusters involving 617 cases. Household clusters accounted for 79.85% of the total. The time interval from onset to report of index cases was 8 days, which was longer than that of secondary cases (4 days) (χ2 = 22.763, P < 0.001) and had a relationship with the number of secondary cases (the correlation coefficient (r) = 0.193, P = 0.040). The average interval from onset to report was different between family cluster cases (4 days) and community cluster cases (7 days) (χ2 = 28.072, P < 0.001). The average time interval from onset to isolation of patients with secondary infection (5 days) was longer than that of patients without secondary infection (3 days) (F = 9.761, P = 0.002). Asymptomatic patients and non-familial clusters had impacts on the size of the clusters. The average reduction in the Rt value in family clusters (26.00%, 0.26 ± 0.22) was lower than that in other clusters (37.00%, 0.37 ± 0.26) (F = 4.400, P = 0.039). Early detection of asymptomatic patients and early reports of non-family clusters can effectively weaken cluster infections.


Subject(s)
COVID-19/epidemiology , Coinfection/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/virology , Child , Child, Preschool , China/epidemiology , Cluster Analysis , Female , Humans , Infant , Male , Middle Aged , Young Adult
20.
Cell Res ; 31(4): 395-403, 2021 04.
Article in English | MEDLINE | ID: covidwho-1091494

ABSTRACT

The upcoming flu season in the Northern Hemisphere merging with the current COVID-19 pandemic raises a potentially severe threat to public health. Through experimental coinfection with influenza A virus (IAV) and either pseudotyped or live SARS-CoV-2 virus, we found that IAV preinfection significantly promoted the infectivity of SARS-CoV-2 in a broad range of cell types. Remarkably, in vivo, increased SARS-CoV-2 viral load and more severe lung damage were observed in mice coinfected with IAV. Moreover, such enhancement of SARS-CoV-2 infectivity was not observed with several other respiratory viruses, likely due to a unique feature of IAV to elevate ACE2 expression. This study illustrates that IAV has a unique ability to aggravate SARS-CoV-2 infection, and thus, prevention of IAV infection is of great significance during the COVID-19 pandemic.


Subject(s)
COVID-19/pathology , Coinfection/pathology , Influenza A virus/physiology , Orthomyxoviridae Infections/pathology , SARS-CoV-2/physiology , Angiotensin-Converting Enzyme 2/deficiency , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , Animals , COVID-19/virology , Cathepsin L/genetics , Cathepsin L/metabolism , Cell Line , Coinfection/virology , Humans , Influenza A virus/isolation & purification , Lung/pathology , Mice , Mice, Transgenic , Orthomyxoviridae Infections/virology , RNA, Guide/metabolism , SARS-CoV-2/isolation & purification , Serine Endopeptidases/genetics , Serine Endopeptidases/metabolism , Severity of Illness Index , Viral Load , Virus Internalization
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