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1.
Eur J Med Chem ; 228: 114030, 2022 Jan 15.
Article in English | MEDLINE | ID: covidwho-1768048

ABSTRACT

The epidemic coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has now spread worldwide and efficacious therapeutics are urgently needed. 3-Chymotrypsin-like cysteine protease (3CLpro) is an indispensable protein in viral replication and represents an attractive drug target for fighting COVID-19. Herein, we report the discovery of 9,10-dihydrophenanthrene derivatives as non-peptidomimetic and non-covalent inhibitors of the SARS-CoV-2 3CLpro. The structure-activity relationships of 9,10-dihydrophenanthrenes as SARS-CoV-2 3CLpro inhibitors have carefully been investigated and discussed in this study. Among all tested 9,10-dihydrophenanthrene derivatives, C1 and C2 display the most potent SARS-CoV-2 3CLpro inhibition activity, with IC50 values of 1.55 ± 0.21 µM and 1.81 ± 0.17 µM, respectively. Further enzyme kinetics assays show that these two compounds dose-dependently inhibit SARS-CoV-2 3CLprovia a mixed-inhibition manner. Molecular docking simulations reveal the binding modes of C1 in the dimer interface and substrate-binding pocket of the target. In addition, C1 shows outstanding metabolic stability in the gastrointestinal tract, human plasma, and human liver microsome, suggesting that this agent has the potential to be developed as an orally administrated SARS-CoV-2 3CLpro inhibitor.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/drug therapy , Coronavirus 3C Proteases/antagonists & inhibitors , Drug Discovery/methods , Antiviral Agents/chemistry , Antiviral Agents/therapeutic use , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Gastrointestinal Tract/metabolism , Humans , Kinetics , Microsomes, Liver/metabolism , Molecular Docking Simulation , Protein Binding , Structure-Activity Relationship , Viral Nonstructural Proteins/antagonists & inhibitors
2.
PLoS Med ; 19(2): e1003928, 2022 02.
Article in English | MEDLINE | ID: covidwho-1686091

ABSTRACT

BACKGROUND: Digital network-based methods may enhance peer distribution of HIV self-testing (HIVST) kits, but interventions that can optimize this approach are needed. We aimed to assess whether monetary incentives and peer referral could improve a secondary distribution program for HIVST among men who have sex with men (MSM) in China. METHODS AND FINDINGS: Between October 21, 2019 and September 14, 2020, a 3-arm randomized controlled, single-blinded trial was conducted online among 309 individuals (defined as index participants) who were assigned male at birth, aged 18 years or older, ever had male-to-male sex, willing to order HIVST kits online, and consented to take surveys online. We randomly assigned index participants into one of the 3 arms: (1) standard secondary distribution (control) group (n = 102); (2) secondary distribution with monetary incentives (SD-M) group (n = 103); and (3) secondary distribution with monetary incentives plus peer referral (SD-M-PR) group (n = 104). Index participants in 3 groups were encouraged to order HIVST kits online and distribute to members within their social networks. Members who received kits directly from index participants or through peer referral links from index MSM were defined as alters. Index participants in the 2 intervention groups could receive a fixed incentive ($3 USD) online for the verified test result uploaded to the digital platform by each unique alter. Index participants in the SD-M-PR group could additionally have a personalized peer referral link for alters to order kits online. Both index participants and alters needed to pay a refundable deposit ($15 USD) for ordering a kit. All index participants were assigned an online 3-month follow-up survey after ordering kits. The primary outcomes were the mean number of alters motivated by index participants in each arm and the mean number of newly tested alters motivated by index participants in each arm. These were assessed using zero-inflated negative binomial regression to determine the group differences in the mean number of alters and the mean number of newly tested alters motivated by index participants. Analyses were performed on an intention-to-treat basis. We also conducted an economic evaluation using microcosting from a health provider perspective with a 3-month time horizon. The mean number of unique tested alters motivated by index participants was 0.57 ± 0.96 (mean ± standard deviation [SD]) in the control group, compared with 0.98 ± 1.38 in the SD-M group (mean difference [MD] = 0.41),and 1.78 ± 2.05 in the SD-M-PR group (MD = 1.21). The mean number of newly tested alters motivated by index participants was 0.16 ± 0.39 (mean ± SD) in the control group, compared with 0.41 ± 0.73 in the SD-M group (MD = 0.25) and 0.57 ± 0.91 in the SD-M-PR group (MD = 0.41), respectively. Results indicated that index participants in intervention arms were more likely to motivate unique tested alters (control versus SD-M: incidence rate ratio [IRR = 2.98, 95% CI = 1.82 to 4.89, p-value < 0.001; control versus SD-M-PR: IRR = 3.26, 95% CI = 2.29 to 4.63, p-value < 0.001) and newly tested alters (control versus SD-M: IRR = 4.22, 95% CI = 1.93 to 9.23, p-value < 0.001; control versus SD-M-PR: IRR = 3.49, 95% CI = 1.92 to 6.37, p-value < 0.001) to conduct HIVST. The proportion of newly tested testers among alters was 28% in the control group, 42% in the SD-M group, and 32% in the SD-M-PR group. A total of 18 testers (3 index participants and 15 alters) tested as HIV positive, and the HIV reactive rates for alters were similar between the 3 groups. The total costs were $19,485.97 for 794 testers, including 450 index participants and 344 alter testers. Overall, the average cost per tester was $24.54, and the average cost per alter tester was $56.65. Monetary incentives alone (SD-M group) were more cost-effective than monetary incentives with peer referral (SD-M-PR group) on average in terms of alters tested and newly tested alters, despite SD-M-PR having larger effects. Compared to the control group, the cost for one more alter tester in the SD-M group was $14.90 and $16.61 in the SD-M-PR group. For newly tested alters, the cost of one more alter in the SD-M group was $24.65 and $49.07 in the SD-M-PR group. No study-related adverse events were reported during the study. Limitations include the digital network approach might neglect individuals who lack internet access. CONCLUSIONS: Monetary incentives alone and the combined intervention of monetary incentives and peer referral can promote the secondary distribution of HIVST among MSM. Monetary incentives can also expand HIV testing by encouraging first-time testing through secondary distribution by MSM. This social network-based digital approach can be expanded to other public health research, especially in the era of the Coronavirus Disease 2019 (COVID-19). TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR) ChiCTR1900025433.


Subject(s)
HIV Infections/diagnosis , HIV Testing/instrumentation , Homosexuality, Male , Reimbursement, Incentive , Self-Testing , Sexual and Gender Minorities , Adult , China , Costs and Cost Analysis , HIV Testing/economics , HIV Testing/methods , Humans , Male
3.
Eur J Med Chem ; 228: 114030, 2022 Jan 15.
Article in English | MEDLINE | ID: covidwho-1654355

ABSTRACT

The epidemic coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has now spread worldwide and efficacious therapeutics are urgently needed. 3-Chymotrypsin-like cysteine protease (3CLpro) is an indispensable protein in viral replication and represents an attractive drug target for fighting COVID-19. Herein, we report the discovery of 9,10-dihydrophenanthrene derivatives as non-peptidomimetic and non-covalent inhibitors of the SARS-CoV-2 3CLpro. The structure-activity relationships of 9,10-dihydrophenanthrenes as SARS-CoV-2 3CLpro inhibitors have carefully been investigated and discussed in this study. Among all tested 9,10-dihydrophenanthrene derivatives, C1 and C2 display the most potent SARS-CoV-2 3CLpro inhibition activity, with IC50 values of 1.55 ± 0.21 µM and 1.81 ± 0.17 µM, respectively. Further enzyme kinetics assays show that these two compounds dose-dependently inhibit SARS-CoV-2 3CLprovia a mixed-inhibition manner. Molecular docking simulations reveal the binding modes of C1 in the dimer interface and substrate-binding pocket of the target. In addition, C1 shows outstanding metabolic stability in the gastrointestinal tract, human plasma, and human liver microsome, suggesting that this agent has the potential to be developed as an orally administrated SARS-CoV-2 3CLpro inhibitor.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/drug therapy , Coronavirus 3C Proteases/antagonists & inhibitors , Drug Discovery/methods , Antiviral Agents/chemistry , Antiviral Agents/therapeutic use , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Gastrointestinal Tract/metabolism , Humans , Kinetics , Microsomes, Liver/metabolism , Molecular Docking Simulation , Protein Binding , Structure-Activity Relationship , Viral Nonstructural Proteins/antagonists & inhibitors
4.
Chem Biol Interact ; 351: 109744, 2022 Jan 05.
Article in English | MEDLINE | ID: covidwho-1509623

ABSTRACT

Remdesivir, an intravenous nucleotide prodrug, has been approved for treating COVID-19 in hospitalized adults and pediatric patients. Upon administration, remdesivir can be readily hydrolyzed to form its active form GS-441524, while the cleavage of the carboxylic ester into GS-704277 is the first step for remdesivir activation. This study aims to assign the key enzymes responsible for remdesivir hydrolysis in humans, as well as to investigate the kinetics of remdesivir hydrolysis in various enzyme sources. The results showed that remdesivir could be hydrolyzed to form GS-704277 in human plasma and the microsomes from human liver (HLMs), lung (HLuMs) and kidney (HKMs), while the hydrolytic rate of remdesivir in HLMs was the fastest. Chemical inhibition and reaction phenotyping assays suggested that human carboxylesterase 1 (hCES1A) played a predominant role in remdesivir hydrolysis, while cathepsin A (CTSA), acetylcholinesterase (AchE) and butyrylcholinesterase (BchE) contributed to a lesser extent. Enzymatic kinetic analyses demonstrated that remdesivir hydrolysis in hCES1A (SHUTCM) and HLMs showed similar kinetic plots and much closed Km values to each other. Meanwhile, GS-704277 formation rates were strongly correlated with the CES1A activities in HLM samples from different individual donors. Further investigation revealed that simvastatin (a therapeutic agent for adjuvant treating COVID-19) strongly inhibited remdesivir hydrolysis in both recombinant hCES1A and HLMs. Collectively, our findings reveal that hCES1A plays a predominant role in remdesivir hydrolysis in humans, which are very helpful for predicting inter-individual variability in response to remdesivir and for guiding the rational use of this anti-COVID-19 agent in clinical settings.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Carboxylesterase/metabolism , Acetylcholinesterase/chemistry , Acetylcholinesterase/metabolism , Adenosine Monophosphate/chemistry , Adenosine Monophosphate/metabolism , Alanine/chemistry , Alanine/metabolism , Butyrylcholinesterase/chemistry , Butyrylcholinesterase/metabolism , Carboxylesterase/chemistry , Cathepsin A/chemistry , Cathepsin A/metabolism , Humans , Hydrolysis/drug effects , Kinetics , Liver/metabolism , Microsomes, Liver/metabolism , Simvastatin/pharmacology
5.
Int J Biol Macromol ; 187: 976-987, 2021 Sep 30.
Article in English | MEDLINE | ID: covidwho-1474606

ABSTRACT

Coronavirus 3C-like protease (3CLpro) is a crucial target for treating coronavirus diseases including COVID-19. Our preliminary screening showed that Ampelopsis grossedentata extract (AGE) displayed potent SARS-CoV-2-3CLpro inhibitory activity, but the key constituents with SARS-CoV-2-3CLpro inhibitory effect and their mechanisms were unrevealed. Herein, a practical strategy via integrating bioactivity-guided fractionation and purification, mass spectrometry-based peptide profiling and time-dependent biochemical assay, was applied to identify the crucial constituents in AGE and to uncover their inhibitory mechanisms. The results demonstrated that the flavonoid-rich fractions (10-17.5 min) displayed strong SARS-CoV-2-3CLpro inhibitory activities, while the constituents in these fractions were isolated and their SARS-CoV-2-3CLpro inhibitory activities were investigated. Among all isolated flavonoids, dihydromyricetin, isodihydromyricetin and myricetin strongly inhibited SARS-CoV-2 3CLpro in a time-dependent manner. Further investigations demonstrated that myricetin could covalently bind on SARS-CoV-2 3CLpro at Cys300 and Cys44, while dihydromyricetin and isodihydromyricetin covalently bound at Cys300. Covalent docking coupling with molecular dynamics simulations showed the detailed interactions between the orthoquinone form of myricetin and two covalent binding sites (surrounding Cys300 and Cys44) of SARS-CoV-2 3CLpro. Collectively, the flavonoids in AGE strongly and time-dependently inhibit SARS-CoV-2 3CLpro, while the newly identified SARS-CoV-2 3CLpro inhibitors in AGE offer promising lead compounds for developing novel antiviral agents.


Subject(s)
3C Viral Proteases/chemistry , 3C Viral Proteases/metabolism , Ampelopsis/chemistry , Antiviral Agents/pharmacology , Flavonoids/pharmacology , SARS-CoV-2/enzymology , Antiviral Agents/chemistry , Binding Sites/drug effects , Cysteine/metabolism , Flavonoids/chemistry , Flavonols/chemistry , Flavonols/pharmacology , Mass Spectrometry , Models, Molecular , Molecular Docking Simulation , Molecular Dynamics Simulation , Plant Extracts/chemistry , Plant Extracts/pharmacology , Protease Inhibitors/chemistry , Protease Inhibitors/pharmacology , Protein Binding/drug effects , Protein Conformation/drug effects , SARS-CoV-2/drug effects
6.
J Int AIDS Soc ; 24(5): e25737, 2021 05.
Article in English | MEDLINE | ID: covidwho-1242728

ABSTRACT

INTRODUCTION: HIV self-testing (HIVST) is a useful strategy to promote HIV testing among key populations. This study aimed to understand HIV testing behaviours among men who have sex with men (MSM) and specifically how HIVST was used during the coronavirus disease 2019 (COVID-19) measures in China when access to facility-based testing was limited. METHODS: An online cross-sectional study was conducted to recruit men who have sex with men (MSM) in China from May to June of 2020, a period when COVID-19 measures were easing. Data on socio-demographic characteristics, sexual behaviours and HIV testing in the three months before and during COVID-19 measures (23 January 2020) were collected. Chi-square test and logistic regression were used for analyses. RESULTS: Overall, 685 MSM were recruited from 135 cities in 30 provinces of China, whose mean age was 28.8 (SD: 6.9) years old. The majority of participants self-identified as gay (81.9%) and had disclosed their sexual orientation (66.7%). In the last three months, 69.6% ever had sex with men, nearly half of whom had multiple sexual partners (47.2%). Although the overall HIV testing rates before and during COVID-19 measures were comparable, more MSM self-tested for HIV during COVID-19 measures (52.1%) compared to before COVID-19 measures (41.6%, p = 0.038). Fewer MSM used facility-based HIV testing during COVID-19 measures (42.9%) compared to before COVID-19 measures (54.1%, p = 0.038). Among 138 facility-based testers before COVID-19 measures, 59.4% stopped facility-based testing during COVID-19 measures. Among 136 self-testers during COVID-19 measures, 58.1% had no HIV self-testing before COVID-19 measures. Multivariable logistic regression showed that having sex with other men in the last three months (adjusted odds ratio, aOR = 2.04, 95% CI: 1.38 to 3.03), self-identifying as gay (aOR = 2.03, 95% CI: 1.31 to 3.13), ever disclosing their sexual orientation (aOR = 1.72, 95% CI: 1.19 to 2.50) and tested for HIV in three months before COVID-19 measures (aOR = 4.74, 95% CI: 3.35 to 6.70) were associated with HIV testing during COVID-19 measures. CONCLUSIONS: Facility-based HIV testing decreased and HIVST increased among MSM during COVID-19 measures in China. MSM successfully accessed HIVST as substitute for facility-based testing, with no overall decrease in HIV testing rates.


Subject(s)
COVID-19 , HIV Infections/diagnosis , HIV Testing , Homosexuality, Male , Self-Testing , Adult , China , Cross-Sectional Studies , HIV Infections/epidemiology , Humans , Logistic Models , Male , Pandemics , SARS-CoV-2 , Sexual Partners
7.
Fitoterapia ; 152: 104909, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1203052

ABSTRACT

3-Chymotrypsin-like protease (3CLpro) is a virally encoded main proteinase that is pivotal for the viral replication across a broad spectrum of coronaviruses. This study aims to discover the naturally occurring SARS-CoV-2 3CLpro inhibitors from herbal constituents, as well as to investigate the inhibitory mechanism of the newly identified efficacious SARS-CoV-2 3CLpro inhibitors. Following screening of the inhibitory potentials of eighty herbal products against SARS-CoV-2 3CLpro, Ginkgo biloba leaves extract (GBLE) was found with the most potent SARS-CoV-2 3CLpro inhibition activity (IC50 = 6.68 µg/mL). Inhibition assays demonstrated that the ginkgolic acids (GAs) and the bioflavones isolated from GBLE displayed relatively strong SARS-CoV-2 3CLpro inhibition activities (IC50 < 10 µM). Among all tested constituents, GA C15:0, GA C17:1 and sciadopitysin displayed potent 3CLpro inhibition activities, with IC50 values of less than 2 µM. Further inhibition kinetic studies and docking simulations clearly demonstrated that two GAs and sciadopitysin strongly inhibit SARS-CoV-2 3CLprovia a reversible and mixed inhibition manner. Collectively, this study found that both GBLE and the major constituents in this herbal product exhibit strong SARS-CoV-2 3CLpro inhibition activities, which offer several promising leading compounds for developing novel anti-COVID-19 medications via targeting on 3CLpro.


Subject(s)
Antiviral Agents/pharmacology , COVID-19 , Coronavirus Protease Inhibitors/pharmacology , Ginkgo biloba/chemistry , Plant Extracts/pharmacology , SARS-CoV-2/drug effects , Virus Replication/drug effects , Antiviral Agents/therapeutic use , Biflavonoids/pharmacology , Biflavonoids/therapeutic use , COVID-19/drug therapy , Coronavirus Protease Inhibitors/therapeutic use , Flavones/pharmacology , Flavones/therapeutic use , Humans , Molecular Structure , Phytotherapy , Plant Extracts/therapeutic use , Plant Leaves/chemistry , SARS-CoV-2/enzymology , Salicylates/pharmacology , Salicylates/therapeutic use
8.
Int J Biol Sci ; 17(5): 1277-1288, 2021.
Article in English | MEDLINE | ID: covidwho-1191953

ABSTRACT

The angiotensin-converting enzyme 2 (ACE2) receptor has been identified as the cell entry point for SARS-CoV-2. Although ACE2 receptors are present in the bone marrow, the effects of SARS-CoV-2 on the biological activity of bone tissue have not yet been elucidated. In the present study we sought to investigate the impact of SARS-CoV-2 on osteoblastic activity in the context of fracture healing. MicroRNA-4485 (miR-4485), which we found to be upregulated in COVID-19 patients, negatively regulates osteogenic differentiation. We demonstrate this effect both in vitro and in vivo. Moreover, we identified the toll-like receptor 4 (TLR-4) as the potential target gene of miR-4485, and showed that reduction of TLR-4 induced by miR-4485 suppresses osteoblastic differentiation in vitro. Taken together, our findings highlight that up-regulation of miR-4485 is responsible for the suppression of osteogenic differentiation in COVID-19 patients, and TLR-4 is the potential target through which miR-4485 acts, providing a promising target for pro-fracture-healing and anti-osteoporosis therapy in COVID-19 patients.


Subject(s)
COVID-19/pathology , Cell Differentiation , Fracture Healing , MicroRNAs/metabolism , Osteogenesis , SARS-CoV-2/physiology , Adult , Aged , Aged, 80 and over , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/virology , Female , Humans , Male , Middle Aged , SARS-CoV-2/isolation & purification , Toll-Like Receptor 4/metabolism
10.
Br J Clin Pharmacol ; 87(9): 3388-3397, 2021 09.
Article in English | MEDLINE | ID: covidwho-1060954

ABSTRACT

During a pandemic caused by a novel pathogen (NP), drug repurposing offers the potential of a rapid treatment response via a repurposed drug (RD) while more targeted treatments are developed. Five steps of model-informed drug repurposing (MIDR) are discussed: (i) utilize RD product label and in vitro NP data to determine initial proof of potential, (ii) optimize potential posology using clinical pharmacokinetics (PK) considering both efficacy and safety, (iii) link events in the viral life cycle to RD PK, (iv) link RD PK to clinical and virologic outcomes, and optimize clinical trial design, and (v) assess RD treatment effects from trials using model-based meta-analysis. Activities which fall under these five steps are categorized into three stages: what can be accomplished prior to an NP emergence (preparatory stage), during the NP pandemic (responsive stage) and once the crisis has subsided (retrospective stage). MIDR allows for extraction of a greater amount of information from emerging data and integration of disparate data into actionable insight.


Subject(s)
Drug Repositioning , Pandemics , Research Design , Retrospective Studies
11.
SSRN; 2020.
Preprint | SSRN | ID: ppcovidwho-916

ABSTRACT

Background: The clinical characteristics and outcomes of surgical treatment of patients with COVID-19 remain unclear. This study aimed to determine whether surg

12.
SSRN; 2020.
Preprint | SSRN | ID: ppcovidwho-816

ABSTRACT

Background: The aim of this study was to explore the impact that COVID-19 has had on the mental health of the healthcare personnel in the Hubeprovince, China.

13.
Acta Orthop ; 91(6): 639-643, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-748293

ABSTRACT

Background and purpose - Following the outbreak of COVID-19 in December 2019, in China, many hip fracture patients were unable to gain timely admission and surgery. We assessed whether delayed surgery improves hip joint function and reduces major complications better than nonoperative therapy. Patients and methods - In this retrospective observational study, we collected data from 24 different hospitals from January 1, 2020, to July 20, 2020. 145 patients with hip fractures aged 65 years or older were eligible. Clinical data was extracted from electronic medical records. The primary outcomes were visual analogue scale (VAS) score and Harris Hip Score. Major complications, including deep venous thrombosis (DVT) and pneumonia within 1 month and 3 months, were collected for further analysis. Results - Of the 145 hip fracture patients 108 (median age 72; 70 females) received delayed surgery and 37 (median age 74; 20 females) received nonoperative therapy. The median time from hip fracture injury to surgery was 33 days (IQR 24-48) in the delayed surgery group. Hypertension, in about half of the patients in both groups, and cerebral infarction, in around a quarter of patients in both groups, were the most common comorbidities. Both VAS score and Harris Hip Score were superior in the delayed surgery group. At the 3-month follow-up, the median VAS score was 1 in the delayed surgery group and 2.5 in the nonoperative group (p < 0.001). Also, the percentage of complications was higher in the nonoperative group (p = 0.004 for DVT, p < 0.001 for pulmonary infection). Interpretation - In hip fracture patients, delayed surgery compared with nonoperative therapy significantly improved hip function and reduced various major complications.


Subject(s)
Cerebral Infarction , Conservative Treatment , Fracture Fixation , Hip Fractures , Hypertension , Postoperative Complications , Time-to-Treatment/statistics & numerical data , Aged , COVID-19/epidemiology , COVID-19/prevention & control , Cerebral Infarction/epidemiology , Cerebral Infarction/etiology , Cerebral Infarction/prevention & control , China/epidemiology , Conservative Treatment/adverse effects , Conservative Treatment/methods , Conservative Treatment/statistics & numerical data , Electronic Health Records/statistics & numerical data , Female , Fracture Fixation/adverse effects , Fracture Fixation/methods , Fracture Fixation/statistics & numerical data , Hip Fractures/epidemiology , Hip Fractures/therapy , Humans , Hypertension/epidemiology , Hypertension/etiology , Hypertension/prevention & control , Male , Outcome and Process Assessment, Health Care , Postoperative Complications/epidemiology , Postoperative Complications/prevention & control , SARS-CoV-2
15.
Aging (Albany, NY Online) ; 12, 2020.
Article in English | MEDLINE | ID: covidwho-614563

ABSTRACT

As the outbreak of coronavirus disease 2019 (COVID-19) progresses, prognostic markers for early identification of high-risk individuals are an urgent medical need. Italy has one of the highest numbers of SARS-CoV-2-related deaths and one of the highest mortality rates. Worldwide, a more severe course of COVID-19 is associated with older age, comorbidities, and male sex. Hence, we searched for possible genetic components of COVID-19 severity among Italians by looking at expression levels and variants in ACE2 and TMPRSS2 genes, crucial for viral infection.Exome and SNP-array data from a large Italian cohort were used to compare the rare-variants burden and polymorphisms frequency with Europeans and East Asians. Moreover, we looked into gene expression databases to check for sex-unbalanced expression.While we found no significant evidence that ACE2 is associated with disease severity/sex bias, TMPRSS2 levels and genetic variants proved to be possible candidate disease modulators, prompting for rapid experimental validations on large patient cohorts. Currently, the coronavirus disease 2019 (COVID-19) crisis has rapidly spread worldwide. As the earliest outbreak area of the pandemic, Wuhan, People's Republic of China, is gradually recovering to its normal state under the effective control of government authorities. Outpatient services in major hospitals are now being restored. An accumulation of asymptomatic infections is a potential risk for medical personnel, especially when there is crowding in hospitals. As the biggest center for orthopaedic patients in Wuhan, our orthopaedic outpatient department admits >300 patients per day. Optimal guidelines on how to handle this huge number of patients during the post-outbreak stage of the COVID-19 pandemic, particularly with regard to potential asymptomatic infection, are urgently needed for orthopaedic surgeons. We have developed and proposed applicable guidelines to fill this knowledge gap, including the necessary protective strategies for medical personnel in orthopaedic outpatient and inpatient wards as well as during surgery. We also have provided mental health recommendations for health-care workers. To the best of our knowledge, these guidelines are the first of their kind for orthopaedic surgeons who are slowly reestablishing medical activity following the pandemic.

16.
JMIR Mhealth Uhealth ; 8(9): e20156, 2020 09 18.
Article in English | MEDLINE | ID: covidwho-596139

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 outbreak has had a significant impact on global health, the economy, and society as a whole. Various measures are being taken to respond to the pandemic, with digital media playing a pivotal role, especially in the use of visual data to disseminate information, mobile health to coordinate medical resources, social media to promote public health campaigns, and digital tools to assist population management and disease tracing. However, digital media also faces some challenges like misinformation, lack of guidance, and information leakage. We encourage the increased use of digital media with a focus on improving trust, building social solidarity, reducing chaos, educating the public on prevention measures, and reducing the medical burden in facility-based sites.


Subject(s)
Coronavirus Infections/prevention & control , Internet , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , COVID-19 , Coronavirus Infections/epidemiology , Humans , Information Dissemination/methods , Pneumonia, Viral/epidemiology , Social Media , Telemedicine/organization & administration
17.
J Bone Joint Surg Am ; 102(13): 1116-1122, 2020 Jul 01.
Article in English | MEDLINE | ID: covidwho-594091

ABSTRACT

The SARS-CoV-2 (severe acute respiratory syndrome-coronavirus 2) was reported in Wuhan, Hubei Province, People's Republic of China, and, subsequently, in other provinces and regions across the People's Republic of China and >212 countries. COVID-19, the disease caused by this coronavirus, was declared a worldwide pandemic by the World Health Organization (WHO). The incidence of patients with fracture who are also positive for COVID-19 is on the rise. The diagnosis and management of such patients can be complicated as their clinical characteristics are heterogeneous. Furthermore, a surgical procedure can be particularly challenging given that the use of high-speed devices results in aerosol generation. In this study, we develop and propose globally applicable guidelines to fill this knowledge gap and we identify and propose the necessary protective strategies for medical personnel in an orthopaedic emergency department and in the inpatient wards. We also introduce diagnostic criteria, surgical complication management, and follow-up strategies for infected patients. These guidelines may be helpful to decrease the infection rate of orthopaedic trauma personnel and to provide diagnosis and treatment therapy for patients with fracture and COVID-19.


Subject(s)
Coronavirus Infections/diagnosis , Fracture Fixation/standards , Fractures, Bone/diagnosis , Fractures, Bone/surgery , Pandemics , Pneumonia, Viral/diagnosis , Betacoronavirus , COVID-19 , Coronavirus Infections/complications , Emergencies , Fractures, Bone/complications , Humans , Perioperative Care , Pneumonia, Viral/complications , Practice Guidelines as Topic , SARS-CoV-2
18.
J Bone Joint Surg Am ; 102(15): e87, 2020 08 05.
Article in English | MEDLINE | ID: covidwho-541758

ABSTRACT

Currently, the coronavirus disease 2019 (COVID-19) crisis has rapidly spread worldwide. As the earliest outbreak area of the pandemic, Wuhan, People's Republic of China, is gradually recovering to its normal state under the effective control of government authorities. Outpatient services in major hospitals are now being restored. An accumulation of asymptomatic infections is a potential risk for medical personnel, especially when there is crowding in hospitals. As the biggest center for orthopaedic patients in Wuhan, our orthopaedic outpatient department admits >300 patients per day. Optimal guidelines on how to handle this huge number of patients during the post-outbreak stage of the COVID-19 pandemic, particularly with regard to potential asymptomatic infection, are urgently needed for orthopaedic surgeons. We have developed and proposed applicable guidelines to fill this knowledge gap, including the necessary protective strategies for medical personnel in orthopaedic outpatient and inpatient wards as well as during surgery. We also have provided mental health recommendations for health-care workers. To the best of our knowledge, these guidelines are the first of their kind for orthopaedic surgeons who are slowly reestablishing medical activity following the pandemic.


Subject(s)
Betacoronavirus , Coronavirus Infections/prevention & control , Delivery of Health Care/organization & administration , Infection Control/organization & administration , Orthopedics , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , COVID-19 , China , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Humans , Pneumonia, Viral/epidemiology , Pneumonia, Viral/transmission , Practice Guidelines as Topic , SARS-CoV-2
19.
Aging (Albany NY) ; 12(9): 7619-7625, 2020 05 07.
Article in English | MEDLINE | ID: covidwho-197510

ABSTRACT

Hip fractures in the elderly account for more than half of osteoporotic fractures and represent a substantial economic and social burden. Novel coronavirus pneumonia (COVID-19), which began to spread in December 2019, has created challenges in the management of elderly hip fracture patients, not only by influencing the choice of operation and postoperative rehabilitation methods, but also by generating new risks for the medical staff. During this period, our infection and orthopedic treatment unit in the center of the epidemic area effectively treated 82 elderly patients with hip fracture, and no cross-infection occurred. Therefore, our experience in prevention and treatment is worth recommending to frontline anti-epidemic personnel.


Subject(s)
Coronavirus Infections/prevention & control , Cross Infection/prevention & control , Hip Fractures/therapy , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Aged , Aged, 80 and over , Betacoronavirus/isolation & purification , COVID-19 , China/epidemiology , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Cross Infection/virology , Hip Fractures/prevention & control , Humans , Pneumonia, Viral/epidemiology , Pneumonia, Viral/transmission , SARS-CoV-2
20.
J Bone Joint Surg Am ; 102(9): 750-758, 2020 05 06.
Article in English | MEDLINE | ID: covidwho-153966

ABSTRACT

BACKGROUND: Studies of the novel coronavirus-induced disease COVID-19 in Wuhan, China, have elucidated the epidemiological and clinical characteristics of this disease in the general population. The present investigation summarizes the clinical characteristics and early prognosis of COVID-19 infection in a cohort of patients with fractures. METHODS: Data on 10 patients with a fracture and COVID-19 were collected from 8 different hospitals located in the Hubei province from January 1, 2020, to February 27, 2020. Analyses of early prognosis were based on clinical outcomes and trends in laboratory results during treatment. RESULTS: All 10 patients presented with limited activity related to the fracture. The most common signs were fever, cough, and fatigue at the time of presentation (7 patients each). Other, less common signs included sore throat (4 patients), dyspnea (5 patients), chest pain (1 patient), nasal congestion (1 patient), headache (1 patient), dizziness (3 patients), abdominal pain (1 patient), and vomiting (1 patient). Lymphopenia (<1.0 × 10 cells/L) was identified in 6 of 10 patients, 9 of 9 patients had a high serum level of D-dimer, and 9 of 9 patients had a high level of C-reactive protein. Three patients underwent surgery, whereas the others were managed nonoperatively because of their compromised status. Four patients died on day 8 (3 patients) or day 14 (1 patient) after admission. The clinical outcomes for the surviving patients are not yet determined. CONCLUSIONS: The clinical characteristics and early prognosis of COVID-19 in patients with fracture tended to be more severe than those reported for adult patients with COVID-19 without fracture. This finding may be related to the duration between the development of symptoms and presentation. Surgical treatment should be carried out cautiously or nonoperative care should be chosen for patients with fracture in COVID-19-affected areas, especially older individuals with intertrochanteric fractures. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.


Subject(s)
Coronavirus Infections/diagnosis , Fractures, Bone/therapy , Pneumonia, Viral/diagnosis , Adult , Aged , Aged, 80 and over , COVID-19 , China , Coronavirus Infections/complications , Coronavirus Infections/mortality , Female , Fractures, Bone/complications , Fractures, Bone/mortality , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/mortality , Prognosis , Retrospective Studies , Time Factors
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