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1.
Emerg Microbes Infect ; 11(1): 1572-1585, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-1873822

ABSTRACT

Cryptococcal meningoencephalitis (CM) is emerging as an infection in HIV/AIDS patients shifted from primarily ART-naive to ART-experienced individuals, as well as patients with COVID-19 and immunocompetent hosts. This fungal infection is mainly caused by the opportunistic human pathogen Cryptococcus neoformans. Brain or central nervous system (CNS) dissemination is the deadliest process for this disease; however, mechanisms underlying this process have yet to be elucidated. Moreover, illustrations of clinically relevant responses in cryptococcosis are currently limited due to the low availability of clinical samples. In this study, to explore the clinically relevant responses during C. neoformans infection, macaque and mouse infection models were employed and miRNA-mRNA transcriptomes were performed and combined, which revealed cytoskeleton, a major feature of HIV/AIDS patients, was a centric pathway regulated in both infection models. Notably, assays of clinical immune cells confirmed an enhanced macrophage "Trojan Horse" in patients with HIV/AIDS, which could be shut down by cytoskeleton inhibitors. Furthermore, myocilin, encoded by MYOC, was found to be a novel enhancer for the macrophage "Trojan Horse," and an enhanced fungal burden was achieved in the brains of MYOC-transgenic mice. Taken together, the findings from this study reveal fundamental roles of the cytoskeleton and MYOC in fungal CNS dissemination, which not only helps to understand the high prevalence of CM in HIV/AIDS but also facilitates the development of novel therapeutics for meningoencephalitis caused by C. neoformans and other pathogenic microorganisms.


Subject(s)
COVID-19 , Cryptococcosis , Cryptococcus neoformans , HIV Infections , Meningoencephalitis , MicroRNAs , Animals , Brain/pathology , Cryptococcosis/microbiology , Cryptococcus neoformans/genetics , Disease Models, Animal , Humans , Macaca , Meningoencephalitis/microbiology , Mice , MicroRNAs/genetics , Transcriptome
2.
Front Med (Lausanne) ; 9: 738541, 2022.
Article in English | MEDLINE | ID: covidwho-1847180

ABSTRACT

Background: The coronavirus disease (COVID-19) pandemic has impacted HIV prevention strategies globally. However, changes in pre-exposure prophylaxis (PrEP) adherence and HIV-related behaviors, and their associations with medication adherence among men who have sex with men (MSM) PrEP users remain unclear since the onset of the COVID-19 pandemic. Methods: A Retrospective Cohort Study of HIV-negative MSM PrEP users was conducted in four Chinese metropolises from December 2018 to March 2020, assessing the changes in PrEP adherence and HIV-related behaviors before and during the COVID-19. The primary outcome was poor PrEP adherence determined from self-reported missing at least one PrEP dose in the previous month. We used multivariable logistic regression to determine factors correlated with poor adherence during COVID-19. Results: We enrolled 791 eligible participants (418 [52.8%] in daily PrEP and 373 [47.2%] in event-driven PrEP). Compared with the data conducted before the COVID-19, the proportion of PrEP users decreased from 97.9 to 64.3%, and the proportion of poor PrEP adherence increased from 23.6 to 50.1% during the COVID-19 [odds ratio (OR) 3.24, 95% confidence interval (CI) 2.62-4.02]. While the percentage of condomless anal intercourse (CAI) with regular partners (11.8 vs. 25.7%) and with casual partners (4.4 vs. 9.0%) both significantly increased. The proportion of those who were tested for HIV decreased from 50.1 to 25.9%. Factors correlated with poor PrEP adherence during the COVID-19 included not being tested for HIV (adjusted odds ratio [aOR] = 1.38 [95% CI: 1.00, 1.91]), using condoms consistently with regular partners (vs. never, aOR = 2.19 [95% CI: 1.16, 4.13]), and being married or cohabitating with a woman (vs. not married, aOR = 3.08 [95% CI: 1.60, 5.95]). Conclusions: Increased poor PrEP adherence and CAI along with the decrease in HIV testing can lead to an increase in HIV acquisition and drug resistance to PrEP. Targeted interventions are needed to improve PrEP adherence and HIV prevention strategies.

4.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-310885

ABSTRACT

Background:  The coronavirus disease (COVID-19) pandemic has impacted HIV prevention strategies globally. However, changes in pre-exposure prophylaxis (PrEP) adherence and HIV-related behaviors, and their associations with medication adherence among MSM PrEP users remains unclear since the onset of the COVID-19 pandemic. Methods: A longitudinal observational study of HIV-negative MSM PrEP users was conducted in four Chinese metropolises from February to March 2020, assessing the changes in PrEP adherence and HIV-related behaviours before and during the COVID-19. The primary outcome was poor PrEP adherence determined from self-reported missing at least one PrEP dose in the previous month. We used mulitivariable logistic regression to determine factors correlated with poor adherence during the COVID-19. Findings: We enrolled 791 eligible participants (418 [52·8%] in daily PrEP, 373 [47·2%] in event-driven PrEP). Compared with the data conducted before the COVID-19, the proportion of PrEP users decreased from 97·9% to 64·3%, and the proportion of poor PrEP adherence increased from 23.6% to 50·1% during the COVID-19 (odds ratio [OR] 3·24, 95% confidence interval (CI) 2·61–4·02). While the percentage of condomless anal intercourse (CAI) with regular partners (11·8% vs 25·7%) and with casual partners (4·4% vs 9·0%) both significantly increased. The proportion of those who were tested for HIV decreased from 50·1% to 25·9%. Factors correlated with poor PrEP adherence during the COVID-19 included not being tested for HIV (adjusted odds ratio [aOR]=1·38 [95% CI: 1·00, 1·91]), using condoms consistently with regular partners (vs. never, aOR=2·19 [95% CI: 1·16, 4·13]) and being married or cohabitating with a woman (vs. not married, aOR=3·08 [95% CI: 1·60, 5·95]). Interpretation:  Increased poor PrEP adherence and CAI along with the decrease in HIV testing can lead to increases in HIV acquisition and of drug resistance to PrEP. Targeted interventions are needed to improve PrEP adherence and HIV prevention strategies. Trial Registration: Chinese Clinical Trial Registry (ChiCTR-IIN-17013762). Funding Statement: The Mega-Projects of national science research for the13th Five-Year Plan (2017ZX10201101), the National Natural Science Foundation of China (81872674), and the National Science and Technology Major Project (2018ZX10101001-001-003). Declaration of Interests: We declare no competing interests. Ethics Approval Statement: This study was reviewed and approved by the Medical Science Research Ethics Committee of the First Affiliated Hospital of China Medical University ([2018]2015-139-5).

5.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325065

ABSTRACT

Background: Many Pre-exposure prophylaxis (PrEP) users have difficulty attending the quarterly facility-based HIV testing, which leads to the potential risk of drug resistance in the context of breakthrough infection with low drug compliance. We explored the acceptance of HIV self-testing (HIVST) service among PrEP recipients. Methods: : MSM were recruited for the PrEP demonstration in four major cities in China from December 2018 to September 2019, provided with regimens of both daily and on-demand PrEP. Facility-based HIV testing was provided quarterly at clinic visits. Previous HIV testing history and acceptance of free HIVST kits to use between each quarterly clinic visit was collected. Correlates of levels of acceptance were analysed using multivariable ordinal logistic regression. Results: : We recruited 1,222 MSM. among which 48.5% preferred daily PrEP and 51.5% preferred on-demand PrEP. There was 26.8% (321/1222) had never been to any facility-based HIV testing previously, and the self-reported major reason was that they had already routinely used HIVST. A quarter of the participants (74.5%, 910/1222) had used HIVST previously. There were 1184 MSM (96.9%) accepted to use HIVST between each quarterly clinic visits during PrEP usage, composing 947 ( 77.5%) very willing to, 237(19.4%)willing to, 29 (2.4%) unwilling to, and 9 (0.7%) very unwilling to. Participants preferred daily PrEP (vs. on-demand PrEP, aOR=1.8, 95% CI:1.3-2.4) and had less than 2 times of facility-based HIV testing in the past year (vs. ³2, aOR=1.4,95% CI:1.1-1.9) were more likely to have higher level of acceptance of HIVST. Conclusions: : MSM had high acceptance of HIVST, especially among those preferred daily PrEP and with less facility-based HIV testing in the previous year. Offering HIVST services PrEP recipients is feasible and necessary. Above result is of great significance for promoting HIVST among PrEP users during COVID-19, improving awareness of their HIV infection status and ensuring compliance with medication. Future study should exam the impact of HIVST on HIV testing frequency among PrEP users. Trial registration: ChiCTR1800020374 on 27 th Dec 2018. http://www.chictr.org.cn/searchproj.aspx

6.
Zhongguo Zhong Yao Za Zhi ; 46(19): 5117-5122, 2021 Oct.
Article in Chinese | MEDLINE | ID: covidwho-1485611

ABSTRACT

In order to standardize the clinical diagnosis and treatment decision-making with traditional Chinese medicine for pa-tients of coronavirus disease 2019(COVID-19) and put the latest clinical study evidence into clinical practice, the international trust-worthy traditional Chinese medicine recommendations( TCM Recs) working group started the compilation of Living Evidence-based Guideline for Combination of Traditional Chinese and Western Medicine for Treatment of COVID-19 on the basis of the standards and re-quirements of WHO handbook, GRADE and RIGHT. This proposal mainly introduces the formulation methods and processes of the living guidelines in details, such as the composition of the working group, the collection and identification of clinical issues and out-comes, the production of the living systematic review and the consensus of recommendations. The guidelines will continue to monitor the clinical study evidences of TCM in the prevention and treatment of COVID-19, and conduct regular evidence updating, retrieval and screening. When there is new study evidence, the steering committee will evaluate the possibility of the evidence to change clinical practice or previous recommendations, so as to decide whether the recommendations for the guidelines shall be implemented or upda-ted. The main criteria considered in the guideline updating are as follows:(1) There are new high-quality randomized controlled trial(RCT) evidences for TCM uninvolved in the previous edition of the guidelines;(2) as for the TCM involved in the guidelines, living sys-tematic review shows that new evidence may change the direction or strength of the existing recommendations. The specific implementation of the living evidence-based guidelines will take this proposal as the study basis and framework, in order to ensure the standardization of the formulation process and methods. This will be the first exploration of the methodology for living guidelines in the field of TCM.


Subject(s)
COVID-19/therapy , China , Evidence-Based Medicine , Humans , Medicine, Chinese Traditional , Practice Guidelines as Topic , SARS-CoV-2
8.
Clin Chem ; 67(4): 672-683, 2021 03 31.
Article in English | MEDLINE | ID: covidwho-1165392

ABSTRACT

BACKGROUND: Infectious disease outbreaks such as the COVID-19 (coronavirus disease 2019) pandemic call for rapid response and complete screening of the suspected community population to identify potential carriers of pathogens. Central laboratories rely on time-consuming sample collection methods that are rarely available in resource-limited settings. METHODS: We present a highly automated and fully integrated mobile laboratory for fast deployment in response to infectious disease outbreaks. The mobile laboratory was equipped with a 6-axis robot arm for automated oropharyngeal swab specimen collection; virus in the collected specimen was inactivated rapidly using an infrared heating module. Nucleic acid extraction and nested isothermal amplification were performed by a "sample in, answer out" laboratory-on-a-chip system, and the result was automatically reported by the onboard information platform. Each module was evaluated using pseudovirus or clinical samples. RESULTS: The mobile laboratory was stand-alone and self-sustaining and capable of on-site specimen collection, inactivation, analysis, and reporting. The automated sampling robot arm achieved sampling efficiency comparable to manual collection. The collected samples were inactivated in as short as 12 min with efficiency comparable to a water bath without damage to nucleic acid integrity. The limit of detection of the integrated microfluidic nucleic acid analyzer reached 150 copies/mL within 45 min. Clinical evaluation of the onboard microfluidic nucleic acid analyzer demonstrated good consistency with reverse transcription quantitative PCR with a κ coefficient of 0.979. CONCLUSIONS: The mobile laboratory provides a promising solution for fast deployment of medical diagnostic resources at critical junctions of infectious disease outbreaks and facilitates local containment of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) transmission.


Subject(s)
COVID-19 Nucleic Acid Testing/methods , COVID-19/diagnosis , Laboratories , Mobile Health Units , Pathology, Molecular/methods , RNA, Viral/analysis , Adult , Automobiles , COVID-19/epidemiology , COVID-19 Nucleic Acid Testing/instrumentation , Female , Humans , Lab-On-A-Chip Devices , Male , Microfluidic Analytical Techniques/instrumentation , Microfluidic Analytical Techniques/methods , Middle East Respiratory Syndrome Coronavirus/chemistry , Molecular Diagnostic Techniques/instrumentation , Molecular Diagnostic Techniques/methods , Pandemics , Pathology, Molecular/instrumentation , Robotics , SARS-CoV-2/chemistry
9.
J Integr Med ; 19(4): 317-326, 2021 07.
Article in English | MEDLINE | ID: covidwho-1142063

ABSTRACT

BACKGROUND: The therapeutic evidence collected from well-designed studies is needed to help manage the global pandemic of the coronavirus disease 2019 (COVID-19). Evaluating the quality of therapeutic data collected during this most recent pandemic is important for improving future clinical research under similar circumstances. OBJECTIVE: To assess the methodological quality and variability in implementation of randomized controlled trials (RCTs) for treating COVID-19, and to analyze the support that should be provided to improve data collected during an urgent pandemic situation. SEARCH STRATEGY: PubMed, Excerpta Medica Database, China National Knowledge Infrastructure, Wanfang, and Chongqing VIP, and the preprint repositories including Social Science Research Network and MedRxiv were systematically searched, up to September 30, 2020, using the keywords "coronavirus disease 2019 (COVID-19)," "2019 novel coronavirus (2019-nCoV)," "severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2)," "novel coronavirus pneumonia (NCP)," "randomized controlled trial (RCT)" and "random." INCLUSION CRITERIA: RCTs studying the treatment of COVID-19 were eligible for inclusion. DATA EXTRACTION AND ANALYSIS: Screening of published RCTs for inclusion and data extraction were each conducted by two researchers. Analysis of general information on COVID-19 RCTs was done using descriptive statistics. Methodological quality was assessed using the risk-of-bias tools in the Cochrane Handbook for Systematic Reviews of Interventions (Version 5.1.0). Variability in implementation was assessed by comparing consistency between RCT reports and registration information. RESULTS: A total of 5886 COVID-19 RCTs were identified. Eighty-one RCTs were finally included, of which, 45 had registration information. Methodological quality of the RTCs was not optimal due to deficiencies in five main domains: allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, and selective reporting. Comparisons of consistency between published protocols and registration information showed that the 45 RCTs with registration information had common deviations in seven items: inclusion and exclusion criteria, sample size, outcomes, research sites of recruitment, interventions, and blinding. CONCLUSION: The methodological quality of COVID-19 RCTs conducted in early to mid 2020 was consistently low and variability in implementation was common. More support for implementing high-quality methodology is needed to obtain the quality of therapeutic evidence needed to provide positive guidance for clinical care. We make an urgent appeal for accelerating the construction of a collaborative sharing platform and preparing multidisciplinary talent and professional teams to conduct excellent clinical research when faced with epidemic diseases of the future. Further, variability in RCT implementation should be clearly reported and interpreted to improve the utility of data resulting from those trials.


Subject(s)
COVID-19/epidemiology , COVID-19/therapy , Randomized Controlled Trials as Topic/methods , Randomized Controlled Trials as Topic/standards , COVID-19/virology , Humans , Pandemics , SARS-CoV-2/drug effects
10.
World J. Tradit. Chin. Med. ; 2(6): 124-131, 20200401.
Article in English | WHO COVID, ELSEVIER | ID: covidwho-742909

ABSTRACT

Since December 2019 the Coronavirus Disease 2019 (COVID-19) has erupted in many places around the world, which is strong infectious and highly epidemic. After the outbreak of COVID-19 in China, traditional Chinese medicine (TCM) has been in the front line of the fight against the epidemic. It has shown characteristics and advantages in the prevention and treatment of COVID-19. TCM also played an important role in the winter of 2002 and in the spring of 2003 during the outbreak of severe acute respiratory syndrome (SARS). This article compares the strategies, programs, measures, resource investments, and effects of TCM for the prevention and treatment of COVID-19 with those for SARS. At present, the involvement of TCM has been earlier, faster, and more comprehensive in the fight against the epidemic and has shown good clinical efficacy and treatment prospects.

11.
Chinese J. Lab. Med. ; 7(43): 683-686, 20200711.
Article in Chinese | WHO COVID, ELSEVIER | ID: covidwho-706586

ABSTRACT

The medical laboratories have played the important role in fighting against the pandemic of COVID-19. It's critical to improve response strategy and better prepare to create robust and sustainable medical laboratories for future outbreaks of public health events. The general framework to guide the construction of the qualified medical laboratories is discussed.

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