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1.
JAMA Netw Open ; 6(4): e2310887, 2023 04 03.
Artigo em Inglês | MEDLINE | ID: covidwho-2299273

RESUMO

Importance: Older patients living in nursing homes are at very high risk of mortality after getting COVID-19. Objective: To evaluate outcomes following oral antiviral treatment for COVID-19 among nonhospitalized older patients living in nursing homes. Design, Setting, and Participants: This is a territory-wide, retrospective cohort study conducted between February 16 and March 31, 2022, with the last follow-up date on April 25, 2022. Participants were patients with COVID-19 living in nursing homes in Hong Kong. Data analysis was performed from May to June 2022. Exposures: Molnupiravir, nirmatrelvir/ritonavir, or no oral antiviral treatment. Main Outcomes and Measures: The primary outcome was hospitalization for COVID-19, and the secondary outcome was risk of inpatient disease progression (ie, admission to intensive care unit, use of invasive mechanical ventilation, and/or death). Results: Of 14 617 patients (mean [SD] age, 84.8 [10.2] years; 8222 women [56.2%]), 8939 (61.2%) did not use oral antivirals, 5195 (35.5%) used molnupiravir, and 483 (3.3%) used nirmatrelvir/ritonavir. Compared with patients who did not use oral antivirals, those who used molnupiravir and nirmatrelvir/ritonavir were more likely to be female and less likely to have comorbid illnesses and hospitalization in the past year. At a median (IQR) follow-up of 30 (30-30) days, 6223 patients (42.6%) were hospitalized and 2307 patients (15.8%) experienced inpatient disease progression. After propensity score weighting, both molnupiravir and nirmatrelvir/ritonavir were associated with a reduced risk of hospitalization (molnupiravir, weighted hazard ratio [wHR], 0.46; 95% CI, 0.37-0.57; P < .001; nirmatrelvir/ritonavir, wHR, 0.46; 95% CI, 0.32-0.65; P < .001) and inpatient disease progression (molnupiravir, wHR, 0.35; 95% CI, 0.23-0.51; P < .001; nirmatrelvir/ritonavir, wHR, 0.17; 95% CI, 0.06-0.44; P < .001). Nirmatrelvir/ritonavir was comparable to molnupiravir in achieving better clinical outcomes (hospitalization, wHR, 1.00; 95% CI, 0.75-1.33; P = .99; inpatient disease progression, wHR, 0.49; 95% CI, 0.20-1.20; P = .12). Conclusions and Relevance: In this retrospective cohort study, the use of oral antivirals to treat COVID-19 was associated with a reduced risk of hospitalization and inpatient disease progression among patients living in nursing homes. The findings of this study of nursing home residents could be reasonably extrapolated to other frail older patients living in the community.


Assuntos
COVID-19 , Ritonavir , Humanos , Feminino , Idoso de 80 Anos ou mais , Masculino , Estudos Retrospectivos , Ritonavir/uso terapêutico , COVID-19/epidemiologia , Tratamento Farmacológico da COVID-19 , Pacientes Internados , Antivirais/uso terapêutico , Progressão da Doença
2.
Intern Med J ; 2023 Apr 24.
Artigo em Inglês | MEDLINE | ID: covidwho-2304665

RESUMO

Infection remains a significant contributor to morbidity and mortality in patients with myeloma. This guideline was developed by a multidisciplinary group of clinicians who specialise in the management of patients with myeloma and infection from the medical and scientific advisory group from Myeloma Australia and the National Centre for Infections in Cancer. In addition to summarising the current epidemiology and risk factors for infection in patients with myeloma, this guideline provides recommendations that address three key areas in the prevention of infection: screening for latent infection, use of antimicrobial prophylaxis and immunoglobulin replacement and vaccination against leading respiratory infections (severe acute respiratory syndrome coronavirus 2, influenza and Streptococcus pneumoniae) and other preventable infections. This guideline provides a practical approach to the prevention of infection in patients with myeloma and harmonises the clinical approach to screening for infection, use of prophylaxis and vaccination to prevent infectious complications.

3.
Clin Infect Dis ; 2022 Aug 29.
Artigo em Inglês | MEDLINE | ID: covidwho-2237330

RESUMO

BACKGROUND: We examined the effectiveness of molnupiravir and nirmatrelvir/ritonavir in reducing hospitalization and deaths in a real-world cohort of non-hospitalized COVID-19 patients. METHODS: This was a territory-wide retrospective cohort study in Hong Kong. Non-hospitalized COVID-19 patients who attended designated outpatient clinics between 16 February and 31 March 2022 were identified. Patients hospitalized on the day of the first clinic appointment or used both oral antivirals were excluded. The primary endpoint was hospitalization. The secondary endpoint was a composite of intensive care unit admission, invasive mechanical ventilation use, and/or death. RESULTS: Of 93,883 patients, 83,154 (88.6%), 5,808 (6.2%), and 4,921 (5.2%) were oral antiviral non-users, molnupiravir users, and nirmatrelvir/ritonavir users respectively. Compared to non-users, oral antiviral users were older and had more comorbidities, lower complete vaccination rate, and more hospitalizations in the previous year. Molnupiravir users were older, and had more comorbidities, lower complete vaccination rate, and more hospitalizations in the previous year than nirmatrelvir/ritonavir users. At a median follow-up of 30 days, 1,931 (2.1%) patients were hospitalized and 225 (0.2%) patients developed the secondary endpoint. After propensity score weighting, nirmatrelvir/ritonavir use (weighted hazard ratio 0.79, 95%CI 0.65-0.95, P = 0.011) but not molnupiravir use (weighted hazard ratio 1.17, 95%CI 0.99-1.39, P = 0.062) was associated with a reduced risk of hospitalization than non-users. The use of molnupiravir or nirmatrelvir/ritonavir was not associated with a lower risk of the secondary endpoint as compared to non-users. CONCLUSION: Use of nirmatrelvir/ritonavir but not molnupiravir was associated with a reduced risk of hospitalization in real-world non-hospitalized COVID-19 patients.

4.
Lancet Oncol ; 23(8): 1031-1043, 2022 08.
Artigo em Inglês | MEDLINE | ID: covidwho-1926992

RESUMO

BACKGROUND: Zanubrutinib is a next-generation, selective Bruton tyrosine kinase inhibitor with efficacy in relapsed chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). We compared zanubrutinib with bendamustine-rituximab to determine its effectiveness as frontline therapy in patients with CLL or SLL. METHODS: We conducted an open-label, multicentre, phase 3 study at 153 academic or community hospitals in 14 countries and regions. Eligible patients had untreated CLL or SLL requiring treatment as per International Workshop on CLL criteria; were aged 65 years or older, or 18 years or older and had comorbidities; and had an Eastern Cooperative Oncology Group performance status score of 0-2. A central interactive web response system randomly assigned patients without del(17)(p13·1) to zanubrutinib (group A) or bendamustine-rituximab (group B) by sequential block method (permutated blocks with a random block size of four). Patients with del(17)(p13·1) were enrolled in group C and received zanubrutinib. Zanubrutinib was administered orally at 160 mg twice per day (28-day cycles); bendamustine at 90 mg/m2 of body surface area on days 1 and 2 for six cycles plus rituximab at 375 mg/m2 of body surface area the day before or on day 1 of cycle 1, and 500 mg/m2 of body surface area on day 1 of cycles 2-6, were administered intravenously. The primary endpoint was progression-free survival per independent review committee in the intention-to-treat population in groups A and B, with minimum two-sided α of 0·05 for superiority. Safety was analysed in all patients who received at least one dose of study treatment. The study is registered with ClinicalTrials.gov, NCT03336333, and is closed to recruitment. FINDINGS: Between Oct 31, 2017, and July 22, 2019, 590 patients were enrolled; patients without del(17)(p13·1) were randomly assigned to zanubrutinib (group A; n=241) or bendamustine-rituximab (group B; n=238). At median follow-up of 26·2 months (IQR 23·7-29·6), median progression-free survival per independent review committee was not reached in either group (group A 95% CI not estimable [NE] to NE; group B 28·1 months to NE). Progression-free survival was significantly improved in group A versus group B (HR 0·42 [95% CI 0·28 to 0·63]; two-sided p<0·0001). The most common grade 3 or worse adverse event was neutropenia (27 [11%] of 240 patients in group A, 116 [51%] of 227 in group B, and 17 [15%] of 111 patients in group C). Serious adverse events occurred in 88 (37%) of 240 patients in group A, 113 (50%) of 227 patients in group B, and 45 (41%) of 111 patients in group C. Adverse events leading to death occurred in 11 (5%) of 240 patients in group A, 12 (5%) of 227 patients in group B, and three (3%) of 111 patients in group C, most commonly due to COVID-19 (four [2%] of 240 patients in group A), diarrhoea, and aspiration pneumonia (two each [1%] of 227 patients in group B). INTERPRETATION: Zanubrutinib significantly improved progression-free survival versus bendamustine-rituximab, with an acceptable safety profile consistent with previous studies. These data support zanubrutinib as a potential new treatment option for untreated CLL and SLL. FUNDING: BeiGene.


Assuntos
COVID-19 , Leucemia Linfocítica Crônica de Células B , Sequoia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cloridrato de Bendamustina , Humanos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/patologia , Piperidinas , Pirazóis , Pirimidinas , Rituximab
5.
Sustainability ; 14(5):2580, 2022.
Artigo em Inglês | MDPI | ID: covidwho-1708740

RESUMO

This research outlines the fluctuation in confirmed active cases of coronavirus disease 2019 (COVID-19), as related to the changes in the Victoria state government’s rules and restrictions. Further, this study examines the impact of government restrictions on the performance of construction in Victoria, Australia. The data analyses in this paper identify the specific effects on industrial production, during the different lockdown stages, in three local construction companies. Companies were selected from different points along the supply chain. Company A is a supplier involved in the manufacturing of structural steel. Company B conducts logistics and procurement. Company C is a construction engineering business specializing in foundations. After reviewing relevant case studies and theories, data analyses were developed in collaboration with these companies. The results revealed that the impact of restrictions on the workers on individual construction projects was not significant. Stage 4 restrictions (Victoria’s highest lockdown level) significantly impacted overall income by limiting construction to only servicing essential infrastructure or essential businesses. The novel contribution of this study is the data analysis outcome for Victoria, where a high level of restrictions were experienced, such as curfew and enforced isolation at home, relative to other countries. In 2021 and 2022 (omicron variant dominated), Victoria was again at the brink of an infection wave, which showed a similar pattern to July 2020, and endured the world’s longest COVID-19 lockdown. The research findings contribute to the body of knowledge by providing empirical data analysis of each company, representing the economic impact of ordinary small and medium enterprises (SMEs) in construction.

6.
JAMA Netw Open ; 5(1): e2143781, 2022 01 04.
Artigo em Inglês | MEDLINE | ID: covidwho-1625088

RESUMO

Importance: Myopia progression has been found to be worsening during the COVID-19 pandemic. It is important to control the rapid myopia progression in this period. Objective: To analyze the association of COVID-19-related lockdown measures with myopia progression in schoolchildren and to compare the performance of defocus incorporated multiple segments (DIMS) lens with that of single vision lens (SVL) treatment in reducing myopia progression. Design, Setting, and Participants: This cohort study involved an exploratory, prespecified, comparison of 2 independent longitudinal studies performed at the same institute beginning in 2019. Data from Hong Kong schoolchildren (aged 7-13 years) were gathered and analyzed. Data analysis was performed from June to July 2021. Exposure: Schoolchildren in study 1 wore a DIMS lens for 18 months, and those in study 2 wore a SVL for 24 months. Main Outcomes and Measures: Cycloplegic spherical equivalent refraction and axial length were measured. Studies 1 and 2 started before the start of lockdown measures and continued throughout the lockdown. In both studies, periods of fewer and more COVID-19-related lockdown measures were identified. Because COVID-19 lockdown caused deviations from the visit schedule, myopia progression was normalized to 12-month change, which were compared between DIMS and SVL groups, also during the periods with less and more lockdown time. Results: There were 115 participants (58 girls [50.4%]; mean [SD] age, 10.3 [1.5] years) in the DIMS group; their mean (SD) baseline refraction was -4.02 (1.46) D. There were 56 participants (29 girls [51.8%]; mean [SD] age, 10.8 [1.5] years) in the SVL group; their mean (SD) baseline refraction was -2.99 (1.06) D. After controlling for the covariates, DIMS treatment was significantly associated with 34% less axial elongation (0.19 mm [95% CI, 0.16 to 0.22 mm] vs 0.30 mm [95% CI, 0.25 to 0.35 mm]; P < .001) and 46% less myopic progression after 12 months (-0.31 D [95% CI, -0.39 to -0.23 D] vs -0.57 D [95% CI, -0.69 to -0.45 D]; P = .001) compared with SVL treatment. In both the DIMS and SVL groups, more lockdown time was associated with significantly more spherical equivalent refraction (-0.54 D [95% CI, -0.64 to 0.44 D] vs -0.34 D [95% CI, -0.44 to -0.25 D]; P = .01) and axial length (0.29 mm [95% CI, 0.25 to 0.32 mm] vs 0.20 mm [95% CI, 0.16 to 0.24 mm]; P = .001) compared with less lockdown time. No significant interaction between treatment type and lockdown time was observed. Conclusions and Relevance: In this exploratory analysis, myopia progressed more rapidly in schoolchildren during the period when there were more COVID-19-related lockdown measures. However, optical treatment with DIMS was significantly associated with slower myopia progression compared with SVL treatment during the lockdown period.


Assuntos
Óculos , Miopia/terapia , COVID-19/epidemiologia , Criança , Progressão da Doença , Feminino , Humanos , Masculino , Miopia/fisiopatologia , Pandemias , Quarentena , Refração Ocular , SARS-CoV-2 , Isolamento Social
7.
Hepatology ; 74(4): 1750-1765, 2021 10.
Artigo em Inglês | MEDLINE | ID: covidwho-1274697

RESUMO

BACKGROUND AND AIMS: We compared risk of acute liver injury and mortality in patients with COVID-19 and current, past, and no HBV infection. APPROACH AND RESULTS: This was a territory-wide retrospective cohort study in Hong Kong. Patients with COVID-19 between January 23, 2020, and January 1, 2021, were identified. Patients with hepatitis C or no HBsAg results were excluded. The primary outcome was mortality. Acute liver injury was defined as alanine aminotransferase or aspartate aminotransferase ≥2 × upper limit of normal (ULN; i.e., 80 U/L), with total bilirubin ≥2 × ULN (i.e., 2.2 mg/dL) and/or international normalized ratio ≥1.7. Of 5,639 patients included, 353 (6.3%) and 359 (6.4%) had current and past HBV infection, respectively. Compared to patients without known HBV exposure, current HBV-infected patients were older and more likely to have cirrhosis. Past HBV-infected patients were the oldest, and more had diabetes and cardiovascular disease. At a median follow-up of 14 (9-20) days, 138 (2.4%) patients died; acute liver injury occurred in 58 (1.2%), 8 (2.3%), and 11 (3.1%) patients with no, current, and past HBV infection, respectively. Acute liver injury (adjusted HR [aHR], 2.45; 95% CI, 1.52-3.96; P < 0.001), but not current (aHR, 1.29; 95% CI, 0.61-2.70; P = 0.507) or past (aHR, 0.90; 95% CI, 0.56-1.46; P = 0.681) HBV infection, was associated with mortality. Use of corticosteroid, antifungal, ribavirin, or lopinavir-ritonavir (adjusted OR [aOR], 2.55-5.63), but not current (aOR, 1.93; 95% CI, 0.88-4.24; P = 0.102) or past (aOR, 1.25; 95% CI, 0.62-2.55; P = 0.533) HBV infection, was associated with acute liver injury. CONCLUSION: Current or past HBV infections were not associated with more liver injury and mortality in COVID-19.


Assuntos
Lesão Pulmonar Aguda/epidemiologia , COVID-19/mortalidade , Hepatite B Crônica/epidemiologia , Lesão Pulmonar Aguda/sangue , Lesão Pulmonar Aguda/diagnóstico , Lesão Pulmonar Aguda/virologia , Adulto , Fatores Etários , Idoso , Alanina Transaminase , Aspartato Aminotransferases , COVID-19/complicações , COVID-19/diagnóstico , COVID-19/virologia , Feminino , Antígenos de Superfície da Hepatite B/isolamento & purificação , Vírus da Hepatite B/imunologia , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/complicações , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/virologia , Hong Kong/epidemiologia , Humanos , Masculino , Anamnese/estatística & dados numéricos , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco/estatística & dados numéricos , Fatores de Risco
8.
Open Forum Infect Dis ; 8(6): ofab205, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: covidwho-1261053

RESUMO

BACKGROUND: Liver injury in patients with coronavirus disease 2019 (COVID-19) is common and prognostic. Direct viral tropism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for angiotensin-converting enzyme 2 receptors in hepatocytes may be one of the mechanisms of liver injury. We aimed to determine the role of viral persistence of SARS-CoV-2, based on cycle threshold (Ct) value, in liver injury in COVID-19. METHODS: This was a territory-wide retrospective cohort study of all public hospitals in Hong Kong. Laboratory-confirmed COVID-19 was identified. Serial liver biochemistries and Ct values of SARS-CoV-2 RNA were analyzed. RESULTS: We identified 7622 COVID-19 patients (mean age, 47 years; 48.2% male) diagnosed from March 24 to January 1, 2021, who had serial liver biochemistries and Ct values. A total of 1363 (17.9%) COVID-19 patients had alanine transferase (ALT)/aspartate aminotransferase (AST) elevations with 2 temporal patterns-early (within first 14 days of symptom onset) and late (>14 days from symptom onset). COVID-19 patients with ALT/AST elevations had a lower Ct value at admission (23 vs 25; P < .001), day 5 (24 vs 26; P < .001), and day 20 (31 vs 32; P < .001) after admission, compared with those without ALT/AST elevations. COVID-19 patients with ALT/AST elevations had a longer duration from first positive to first negative reverse transcription polymerase chain reaction test for SARS-CoV-2 (13 vs 9 days; P < .001). ALT/AST elevation and presence of diabetes were independent risk factors of viral persistence. CONCLUSIONS: Liver injury in COVID-19 is linked to a higher SARS-CoV-2 viral load during the early phase of infection, signifying a possible direct viral injury to the liver. Prolonged viral persistence of SARS-CoV-2 is associated with liver injury.

9.
ACS Omega ; 6(19): 12557-12566, 2021 May 18.
Artigo em Inglês | MEDLINE | ID: covidwho-1246318

RESUMO

An extensive search for active therapeutic agents against the SARS-CoV-2 is being conducted across the globe. While computational docking simulations remain a popular method of choice for the in silico ligand design and high-throughput screening of therapeutic agents, it is severely limited in the discovery of new candidate ligands owing to the high computational cost and vast chemical space. Here, we present a de novo molecular design strategy that leverages artificial intelligence (AI) to discover new therapeutic agents against SARS-CoV-2. A Monte Carlo tree search algorithm combined with a multitask neural network surrogate model for expensive docking simulations, and recurrent neural networks for rollouts, is used in an iterative search and retrain strategy. Using Vina scores as the target objective to measure binding to either the isolated spike protein (S-protein) at its host receptor region or to the S-protein/angiotensin converting enzyme 2 receptor interface, we generate several (∼100's) new therapeutic agents that outperform Food and Drug Administration (FDA) (∼1000's) and non-FDA molecules (∼million). Our AI strategy is broadly applicable for accelerated design and discovery of chemical molecules with any user-desired functionality.

10.
J Am Soc Nephrol ; 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: covidwho-1197445

RESUMO

BACKGROUND: Severe acute respiratory syndrome (SARS) and coronavirus disease 2019 (COVID-19) are closely related. The effect of AKI on the clinical outcomes of these two conditions is unclear. METHODS: This retrospective, territory-wide cohort study used an electronic public healthcare database in Hong Kong to identify patients with SARS or COVID-19 by diagnosis codes, virologic results, or both. The primary endpoint was a composite of intensive care unit admission, use of invasive mechanical ventilation, and/or death. RESULTS: We identified 1670 patients with SARS and 1040 patients with COVID-19 (median ages, 41 versus 35 years, respectively). Among patients with SARS, 26% met the primary endpoint versus 5.3% of those with COVID-19. Diabetes mellitus, abnormal liver function, and AKI were factors significantly associated with the primary endpoint among patients with either SARS or COVID-19. Among patients with SARS, 7.9%, 2.1%, and 3.7% developed stage 1, stage 2, and stage 3 AKI, respectively; among those with COVID-19, 6.6%, 0.4%, and 1.1% developed stage 1, stage 2, and stage 3 AKI, respectively. In both groups, factors significantly associated with AKI included diabetes mellitus and hypertension. Among patients with AKI, those with COVID-19 had a lower rate of major adverse clinical outcomes versus patients with SARS. Renal function recovery usually occurred within 30 days after an initial AKI event. CONCLUSIONS: AKI rates were higher among patients with SARS than those with COVID-19. AKI was associated with major adverse clinical outcomes for both diseases. Patients with diabetes mellitus and abnormal liver function were also at risk of developing severe consequences after SARS and COVID-19 infection.

12.
Clin Infect Dis ; 72(10): e466-e475, 2021 05 18.
Artigo em Inglês | MEDLINE | ID: covidwho-811336

RESUMO

BACKGROUND: The case-fatality ratios (CFR) of coronavirus disease 2019 (COVID-19) and severe acute respiratory syndrome (SARS) appeared to differ substantially. We aimed to compare the CFR and its predictors of COVID-19 and SARS patients using a territory-wide cohort in Hong Kong. METHODS: This was a territory-wide retrospective cohort study using data captured from all public hospitals in Hong Kong. Laboratory-confirmed COVID-19 and SARS patients were identified. The primary endpoint was a composite endpoint of intensive care unit admission, use of mechanical ventilation, and/or death. RESULTS: We identified 1013 COVID-19 patients (mean age, 38.4 years; 53.9% male) diagnosed from 23 January to 14 April 2020 and 1670 SARS patients (mean age, 44.4 years; 44.0% male) from March to June 2003. Fifty-five (5.4%) COVID-19 patients and 432 (25.9%) SARS patients had reached the primary endpoint in 30 days. By 30 June 2003, 286 SARS patients had died (CFR, 17.1%). By 7 June 2020, 4 COVID-19 patients had died (CFR, 0.4%). After adjusting for demographic and clinical parameters, COVID-19 was associated with a 71% lower risk of primary endpoint compared with SARS (adjusted hazard ratio, 0.29; 95% confidence interval, .21-.40; P < .0001). Age, diabetes mellitus, and laboratory parameters (high lactate dehydrogenase, high C-reactive protein, and low platelet count) were independent predictors of the primary endpoint in COVID-19 patients, whereas use of antiviral treatments was not associated with primary endpoint. CONCLUSIONS: The CFR of COVID-19 was 0.4%. Age and diabetes were associated with worse outcomes, whereas antiviral treatments were not.


Assuntos
COVID-19 , Síndrome Respiratória Aguda Grave , Adulto , Estudos de Coortes , Feminino , Hong Kong/epidemiologia , Hospitalização , Humanos , Masculino , Estudos Retrospectivos , SARS-CoV-2 , Síndrome Respiratória Aguda Grave/epidemiologia
13.
J Phys Chem Lett ; 11(17): 7058-7065, 2020 Sep 03.
Artigo em Inglês | MEDLINE | ID: covidwho-712970

RESUMO

The current pandemic demands a search for therapeutic agents against the novel coronavirus SARS-CoV-2. Here, we present an efficient computational strategy that combines machine learning (ML)-based models and high-fidelity ensemble docking studies to enable rapid screening of possible therapeutic ligands. Targeting the binding affinity of molecules for either the isolated SARS-CoV-2 S-protein at its host receptor region or the S-protein:human ACE2 interface complex, we screen ligands from drug and biomolecule data sets that can potentially limit and/or disrupt the host-virus interactions. Top scoring one hundred eighty-seven ligands (with 75 approved by the Food and Drug Administration) are further validated by all atom docking studies. Important molecular descriptors (2χn, topological surface area, and ring count) and promising chemical fragments (oxolane, hydroxy, and imidazole) are identified to guide future experiments. Overall, this work expands our knowledge of small-molecule treatment against COVID-19 and provides a general screening pathway (combining quick ML models with expensive high-fidelity simulations) for targeting several chemical/biochemical problems.


Assuntos
Antivirais/farmacologia , Betacoronavirus/efeitos dos fármacos , Aprendizado de Máquina , Simulação de Acoplamento Molecular , Antivirais/metabolismo , Avaliação Pré-Clínica de Medicamentos , Humanos , Ligação de Hidrogênio , Conformação Proteica , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/metabolismo
14.
Gut ; 70(4): 733-742, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: covidwho-638266

RESUMO

OBJECTIVE: Data on serial liver biochemistries of patients infected by different human coronaviruses (HCoVs) are lacking. The impact of liver injury on adverse clinical outcomes in coronavirus disease 2019 (COVID-19) patients remains unclear. DESIGN: This was a retrospective cohort study using data from a territory-wide database in Hong Kong. COVID-19, severe acute respiratory syndrome (SARS) and other HCoV patients were identified by diagnosis codes and/or virological results. Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) elevation was defined as ALT/AST ≥2 × upper limit of normal (ie, 80 U/L). The primary end point was a composite of intensive care unit (ICU) admission, use of invasive mechanical ventilation and/or death. RESULTS: We identified 1040 COVID-19 patients (mean age 38 years, 54% men), 1670 SARS patients (mean age 44 years, 44% men) and 675 other HCoV patients (mean age 20 years, 57% men). ALT/AST elevation occurred in 50.3% SARS patients, 22.5% COVID-19 patients and 36.0% other HCoV patients. For COVID-19 patients, 53 (5.1%) were admitted to ICU, 22 (2.1%) received invasive mechanical ventilation and 4 (0.4%) died. ALT/AST elevation was independently associated with primary end point (adjusted OR (aOR) 7.92, 95% CI 4.14 to 15.14, p<0.001) after adjusted for albumin, diabetes and hypertension. Use of lopinavir-ritonavir ±ribavirin + interferon beta (aOR 1.94, 95% CI 1.20 to 3.13, p=0.006) and corticosteroids (aOR 3.92, 95% CI 2.14 to 7.16, p<0.001) was independently associated with ALT/AST elevation. CONCLUSION: ALT/AST elevation was common and independently associated with adverse clinical outcomes in COVID-19 patients. Use of lopinavir-ritonavir, with or without ribavirin, interferon beta and/or corticosteroids was independently associated with ALT/AST elevation.


Assuntos
Alanina Transaminase/sangue , Antivirais , Aspartato Aminotransferases/sangue , Tratamento Farmacológico da COVID-19 , COVID-19 , Fígado , Corticosteroides/administração & dosagem , Corticosteroides/efeitos adversos , Adulto , Antivirais/administração & dosagem , Antivirais/efeitos adversos , COVID-19/sangue , COVID-19/complicações , COVID-19/diagnóstico , Combinação de Medicamentos , Feminino , Hong Kong/epidemiologia , Hospitalização/estatística & dados numéricos , Humanos , Fígado/efeitos dos fármacos , Fígado/virologia , Testes de Função Hepática/métodos , Testes de Função Hepática/estatística & dados numéricos , Lopinavir/administração & dosagem , Lopinavir/efeitos adversos , Masculino , Estudos Retrospectivos , Ribavirina/administração & dosagem , Ribavirina/efeitos adversos , Ritonavir/administração & dosagem , Ritonavir/efeitos adversos , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença
15.
Lancet Gastroenterol Hepatol ; 5(8): 776-787, 2020 08.
Artigo em Inglês | MEDLINE | ID: covidwho-611744

RESUMO

The COVID-19 pandemic has spread rapidly worldwide. It is common to encounter patients with COVID-19 with abnormal liver function, either in the form of hepatitis, cholestasis, or both. The clinical implications of liver derangement might be variable in different clinical scenarios. With growing evidence of its clinical significance, it would be clinically helpful to provide practice recommendations for various common clinical scenarios of liver derangement during the COVID-19 pandemic. The Asia-Pacific Working Group for Liver Derangement during the COVID-19 Pandemic was formed to systematically review the literature with special focus on the clinical management of patients who have been or who are at risk of developing liver derangement during this pandemic. Clinical scenarios covering the use of pharmacological treatment for COVID-19 in the case of liver derangement, and assessment and management of patients with chronic hepatitis B or hepatitis C, non-alcoholic fatty liver disease, liver cirrhosis, and liver transplantation during the pandemic are discussed.


Assuntos
Infecções por Coronavirus/epidemiologia , Hepatopatias/terapia , Pandemias , Pneumonia Viral/epidemiologia , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Betacoronavirus , COVID-19 , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Humanos , Hepatopatias/etiologia , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico , Fatores de Risco , SARS-CoV-2
16.
Emerg Infect Dis ; 26(7): 1575-1579, 2020 07.
Artigo em Inglês | MEDLINE | ID: covidwho-76568

RESUMO

During the early phase of the coronavirus disease epidemic in Hong Kong, 1,715 survey respondents reported high levels of perceived risk, mild anxiety, and adoption of personal-hygiene, travel-avoidance, and social-distancing measures. Widely adopted individual precautionary measures, coupled with early government actions, might slow transmission early in the outbreak.


Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19 , Infecções por Coronavirus/prevenção & controle , Feminino , Hong Kong/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , SARS-CoV-2 , Adulto Jovem
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