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1.
Clin Gastroenterol Hepatol ; 2021 Dec 20.
Article in English | MEDLINE | ID: covidwho-1588134

ABSTRACT

BACKGROUND & AIMS: We aimed to assess the safety and immunogenicity of inactivated whole-virion severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in patients with chronic liver diseases (CLD) in this study. METHODS: This was a prospective, multi-center, open-label study. Participants aged over 18 years with confirmed CLD and healthy volunteers were enrolled. All participants received 2 doses of inactivated whole-virion SARS-CoV-2 vaccines. Adverse reactions were recorded within 14 days after any dose of SARS-CoV-2 vaccine, laboratory testing results were collected after the second dose, and serum samples of enrolled subjects were collected and tested for SARS-CoV-2 neutralizing antibodies at least 14 days after the second dose. RESULTS: A total of 581 participants (437 patients with CLD and 144 healthy volunteers) were enrolled from 15 sites in China. Most adverse reactions were mild and transient, and injection site pain (n = 36; 8.2%) was the most frequently reported adverse event. Three participants had grade 3 aminopherase elevation (defined as alanine aminopherase >5 upper limits of normal) after the second dose of inactivated whole-virion SARS-CoV-2 vaccination, and only 1 of them was judged as severe adverse event potentially related to SARS-CoV-2 vaccination. The positive rates of SARS-CoV-2 neutralizing antibodies were 76.8% in the noncirrhotic CLD group, 78.9% in the compensated cirrhotic group, 76.7% in the decompensated cirrhotic group (P = .894 among CLD subgroups), and 90.3% in healthy controls (P = .008 vs CLD group). CONCLUSION: Inactivated whole-virion SARS-CoV-2 vaccines are safe in patients with CLD. Patients with CLD had lower immunologic response to SARS-CoV-2 vaccines than healthy population. The immunogenicity is similarly low in noncirrhotic CLD, compensated cirrhosis, and decompensated cirrhosis.

3.
Nurse Educ Today ; 109: 105256, 2021 Dec 24.
Article in English | MEDLINE | ID: covidwho-1586945

ABSTRACT

BACKGROUND: Key challenges for clinical education during the COVID-19 pandemic include how to continue teaching and learning, how to teach core clinical skills, and how to demonstrate professional and practical skills in various clinical situations. Therefore, nursing students need to learn how to assist with in-patient intubation, eliminate accumulated sputum overflow, and the basic techniques of sputum suction. OBJECTIVES: We proposed and investigated an approach to integrating online game-based learning with the watch-summarize-question strategy to improve nursing students' learning achievement, self-efficacy, learning engagement, and learning satisfaction in sputum suction skill training. DESIGN: A quasi-experimental study with pretest and posttest design. SETTINGS AND PARTICIPANTS: We randomly allocated 45 first-year nursing students to an experimental group (n = 21) or a control group (n = 24) at a school of nursing in a university. METHODS: The experimental group adopted the online game-based learning and watch-summarize-question strategy, while the control group used video-based learning. Participants were assessed on learning achievement of sputum suction skills, self-efficacy, learning engagement, and learning satisfaction before and after the intervention. RESULTS: The experimental group, which used the proposed approach, achieved statistically significant higher learning achievement, self-efficacy, learning engagement, and learning satisfaction than the control group. CONCLUSIONS: The integration of online game-based learning with the watch-summarize-question strategy demonstrated a positive impact on nursing students' sputum suction skill training. Nurse educators and researchers should consider integrating computer technology and teaching strategies to facilitate nursing education.

4.
Cell Res ; 2021 Nov 26.
Article in English | MEDLINE | ID: covidwho-1537308

ABSTRACT

Host cellular receptors play key roles in the determination of virus tropism and pathogenesis. However, little is known about SARS-CoV-2 host receptors with the exception of ACE2. Furthermore, ACE2 alone cannot explain the multi-organ tropism of SARS-CoV-2 nor the clinical differences between SARS-CoV-2 and SARS-CoV, suggesting the involvement of other receptor(s). Here, we performed genomic receptor profiling to screen 5054 human membrane proteins individually for interaction with the SARS-CoV-2 capsid spike (S) protein. Twelve proteins, including ACE2, ASGR1, and KREMEN1, were identified with diverse S-binding affinities and patterns. ASGR1 or KREMEN1 is sufficient for the entry of SARS-CoV-2 but not SARS-CoV in vitro and in vivo. SARS-CoV-2 utilizes distinct ACE2/ASGR1/KREMEN1 (ASK) receptor combinations to enter different cell types, and the expression of ASK together displays a markedly stronger correlation with virus susceptibility than that of any individual receptor at both the cell and tissue levels. The cocktail of ASK-related neutralizing antibodies provides the most substantial blockage of SARS-CoV-2 infection in human lung organoids when compared to individual antibodies. Our study revealed an interacting host receptome of SARS-CoV-2, and identified ASGR1 and KREMEN1 as alternative functional receptors that play essential roles in ACE2-independent virus entry, providing insight into SARS-CoV-2 tropism and pathogenesis, as well as a community resource and potential therapeutic strategies for further COVID-19 investigations.

5.
Preprint in English | EuropePMC | ID: ppcovidwho-292008

ABSTRACT

Chest radiography (CXR) is the most widely-used thoracic clinical imaging modality and is crucial for guiding the management of cardiothoracic conditions. The detection of specific CXR findings has been the main focus of several artificial intelligence (AI) systems. However, the wide range of possible CXR abnormalities makes it impractical to build specific systems to detect every possible condition. In this work, we developed and evaluated an AI system to classify CXRs as normal or abnormal. For development, we used a de-identified dataset of 248,445 patients from a multi-city hospital network in India. To assess generalizability, we evaluated our system using 6 international datasets from India, China, and the United States. Of these datasets, 4 focused on diseases that the AI was not trained to detect: 2 datasets with tuberculosis and 2 datasets with coronavirus disease 2019. Our results suggest that the AI system generalizes to new patient populations and abnormalities. In a simulated workflow where the AI system prioritized abnormal cases, the turnaround time for abnormal cases reduced by 7-28%. These results represent an important step towards evaluating whether AI can be safely used to flag cases in a general setting where previously unseen abnormalities exist.

6.
Acta Obstet Gynecol Scand ; 2021 Nov 03.
Article in English | MEDLINE | ID: covidwho-1501369

ABSTRACT

INTRODUCTION: Conflicting reports of increases and decreases in rates of preterm birth (PTB) and stillbirth in the general population during the coronavirus disease 2019 (COVID-19) pandemic have surfaced. The objective of our study was to conduct a living systematic review and meta-analyses of studies reporting pregnancy and neonatal outcomes by comparing the pandemic and pre-pandemic periods. MATERIAL AND METHODS: We searched PubMed and Embase databases, reference lists of articles published up until August 14, 2021 and included English language studies that compared outcomes between the COVID-19 pandemic time period and the pre-pandemic time periods. Risk of bias was assessed using the Newcastle-Ottawa scale. We conducted random-effects meta-analysis using the inverse variance method. RESULTS: Forty-five studies with low-to-moderate risk of bias, reporting on 1 843 665 pregnancies during the pandemic period and 23 564 552 pregnancies during the pre-pandemic period, were included. There was significant reduction in unadjusted estimates of PTB (35 studies, unadjusted odds ratio [uaOR] 0.95, 95% CI 0.92-0.98), but not in adjusted estimates (six studies, adjusted OR [aOR] 0.95, 95% CI 0.80-1.13). This reduction was noted in studies from single centers/health areas (25 studies, uaOR 0.90, 95% CI 0.86-0.96) but not in regional/national studies (10 studies, uaOR 0.99, 95% CI 0.95-1.02). There was reduction in spontaneous PTB (six studies, uaOR 0.89, 95% CI 0.81-0.96) and induced PTB (five studies, uaOR 0.89, 95% CI 0.81-0.97). There was no difference in the odds of stillbirth between the pandemic and pre-pandemic time periods (24 studies, uaOR 1.11, 95% CI 0.97-1.26 and four studies, aOR 1.06, 95% CI 0.81-1.38). There was an increase in mean birthweight during the pandemic period compared with the pre-pandemic period (six studies, mean difference 17 g, 95% CI 7-28 g). The odds of maternal mortality were increased (four studies, uaOR 1.15, 95% CI 1.05-1.26); however, only unadjusted estimates were available and the result was mostly influenced by one study from Mexico. There was significant publication bias for the outcome of PTB. CONCLUSIONS: The COVID-19 pandemic may be associated with a reduction in PTB; however, referral bias cannot be excluded. There was no statistically significant difference in stillbirth between pandemic and pre-pandemic periods.

7.
FEBS J ; 2021 Oct 19.
Article in English | MEDLINE | ID: covidwho-1476183

ABSTRACT

The ongoing outbreak of COVID-19 caused by SARS-CoV-2 has resulted in a serious public health threat globally. Nucleocapsid protein is a major structural protein of SARS-CoV-2 that plays important roles in the viral RNA packing, replication, assembly, and infection. Here, we report two crystal structures of nucleocapsid protein C-terminal domain (CTD) at resolutions of 2.0 Å and 3.1 Å, respectively. These two structures, crystallized under different conditions, contain 2 and 12 CTDs in asymmetric unit, respectively. Interestingly, despite different crystal packing, both structures show a similar dimeric form as the smallest unit, consistent with its solution form measured by the size-exclusion chromatography, suggesting an important role of CTD in the dimerization of nucleocapsid proteins. By analyzing the surface charge distribution, we identified a stretch of positively charged residues between Lys257 and Arg262 that are involved in RNA-binding. Through screening a single-domain antibodies (sdAbs) library, we identified four sdAbs targeting different regions of nucleocapsid protein with high affinities that have future potential to be used in viral detection and therapeutic purposes.

8.
Int J Lab Hematol ; 43(6): 1325-1333, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1462811

ABSTRACT

BACKGROUND: Multiple myeloma (MM) is a hematological malignancy. Coronavirus disease 2019 (COVID-19) infection correlates with MM features. This study aimed to identify MM prognostic biomarkers with potential association with COVID-19. METHODS: Differentially expressed genes (DEGs) in five MM data sets (GSE47552, GSE16558, GSE13591, GSE6477, and GSE39754) with the same expression trends were screened out. Functional enrichment analysis and the protein-protein interaction network were performed for all DEGs. Prognosis-associated DEGs were screened using the stepwise Cox regression analysis in the cancer genome atlas (TCGA) MMRF-CoMMpass cohort and the GSE24080 data set. Prognosis-associated DEGs associated with COVID-19 infection in the GSE164805 data set were also identified. RESULTS: A total of 98 DEGs with the same expression trends in five data sets were identified, and 83 DEGs were included in the protein-protein interaction network. Cox regression analysis identified 16 DEGs were associated with MM prognosis in the TCGA cohort, and only the cytochrome c oxidase subunit 6C (COX6C) gene (HR = 1.717, 95% CI 1.231-2.428, p = .002) and the nucleotide-binding oligomerization domain containing 2 (NOD2) gene (HR = 0.882, 95% CI 0.798-0.975, p = .014) were independent factors related to MM prognosis in the GSE24080 data set. Both of them were downregulated in patients with mild COVID-19 infection compared with controls but were upregulated in patients with severe COVID-19 compared with patients with mild illness. CONCLUSIONS: The NOD2 and COX6C genes might be used as prognostic biomarkers in MM. The two genes might be associated with the development of COVID-19 infection.


Subject(s)
COVID-19/genetics , Computational Biology/methods , Gene Expression Profiling , Multiple Myeloma/genetics , SARS-CoV-2 , COVID-19/mortality , Datasets as Topic , Electron Transport Complex IV/genetics , Gene Expression Regulation, Neoplastic , Gene Expression Regulation, Viral , Gene Ontology , Humans , Kaplan-Meier Estimate , Microarray Analysis , Neoplasm Proteins/biosynthesis , Neoplasm Proteins/genetics , Nod2 Signaling Adaptor Protein/genetics , Prognosis , Proportional Hazards Models , Protein Interaction Maps/genetics
9.
J Am Coll Surg ; 232(5): 682-689.e5, 2021 05.
Article in English | MEDLINE | ID: covidwho-1454247

ABSTRACT

BACKGROUND: If Asian American and Pacific Islanders (AAPIs) are not recognized within patients in health services research, we miss an opportunity to ensure health equity in patient outcomes. However, it is unknown what the rates are of AAPIs inclusion in surgical outcomes research. STUDY DESIGN: Through a scoping review, we used Covidence to search MEDLINE, EMBASE, PsycINFO, Web of Science, Scopus, and CINAHL for studies published in 2008-2018 using NSQIP data. NSQIP was chosen because of its national scope, widespread use in research, and coding inclusive of AAPI patients. We examined the proportion of studies representing AAPI patients in the demographic characteristics and Methods, Results, or Discussion section. We then performed multivariable logistic regression to examine associations between study characteristics and AAPI inclusion. RESULTS: In 1,264 studies included for review, 62% included race. Overall, only 22% (n = 278) of studies included AAPI patients. Of studies that included race, 35% represented AAPI patients in some component of the study. We found no association between sample size or publication year and inclusion. Studies were significantly more likely to represent AAPI patients when there was a higher AAPI population in the region of the first author's institution (lowest vs highest tercile; p < 0.001). Studies with a focus on disparities were more likely to include AAPI patients (p = 0.001). CONCLUSIONS: Our study is the first to examine AAPI representation in surgical outcomes research. We found < 75% of studies examine race, despite availability within NSQIP. Little more than one-third of studies including race reported on AAPI patients as a separate group. To provide the best care, we must include AAPI patients in our research.


Subject(s)
Asian Americans/statistics & numerical data , Health Services Research/statistics & numerical data , Patient Selection , Specialties, Surgical/statistics & numerical data , Health Services Research/standards , Healthcare Disparities/statistics & numerical data , Humans , Patient Acceptance of Health Care/statistics & numerical data , Specialties, Surgical/organization & administration , Specialties, Surgical/standards , Treatment Outcome
10.
International Journal of Environmental Research and Public Health ; 17(11), 2020.
Article in English | CAB Abstracts | ID: covidwho-1409606

ABSTRACT

Background: COVID-19 has become one of the most serious global epidemics in the 21st Century. This study aims to explore the distribution of research capabilities of countries, institutions, and researchers, and the hotspots and frontiers of coronavirus research in the past two decades. In it, references for funding support of urgent projects and international cooperation among research institutions are provided. Method: the Web of Science core collection database was used to retrieve the documents related to coronavirus published from 2003 to 2020. Citespace.5.6.R2, VOSviewer1.6.12, and Excel 2016 were used for bibliometric analysis.

11.
Chem Eng J ; 429: 132332, 2022 Feb 01.
Article in English | MEDLINE | ID: covidwho-1401283

ABSTRACT

The ongoing outbreak of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has highlighted that new diagnosis technologies are crucial for controlling the spread of the disease. Especially in the resources-limit region, conveniently operated detection methods such as "naked-eye" detection are urgently required that no instrument is needed. Herein, we have designed a novel and facile strategy to fabricate covalent organic framework (COF) capsules, which can be utilized to establish a new colorimetric assay for naked-eye detection of SARS-CoV-2 RNA. Specifically, we employ the digestible ZIF-90 as the sacrificial template to prepare the hollow COF capsules for horseradish peroxidase (HRP) encapsulation. The fabricated COF capsules can provide an appropriate microenvironment for the enzyme molecules, which may improve the conformational freedom of enzymes, enhance the mass transfer, and endow the enzyme with high environmental resistance. With such design, the proposed assay exhibits outstanding analytical performance for the detection of SARS-CoV-2 RNA in the linear range from 5 pM to 50 nM with a detection limit of 0.28 pM which can go parallel to qTR-PCR analysis. Our method also possesses excellent selectivity and reproducibility. Moreover, this method can also be served to analyze the clinical samples, and can successfully differentiate COVID-19 patients from healthy people, suggesting the promising potential in clinical diagnosis.

12.
Sci Rep ; 11(1): 15523, 2021 09 01.
Article in English | MEDLINE | ID: covidwho-1392879

ABSTRACT

Chest radiography (CXR) is the most widely-used thoracic clinical imaging modality and is crucial for guiding the management of cardiothoracic conditions. The detection of specific CXR findings has been the main focus of several artificial intelligence (AI) systems. However, the wide range of possible CXR abnormalities makes it impractical to detect every possible condition by building multiple separate systems, each of which detects one or more pre-specified conditions. In this work, we developed and evaluated an AI system to classify CXRs as normal or abnormal. For training and tuning the system, we used a de-identified dataset of 248,445 patients from a multi-city hospital network in India. To assess generalizability, we evaluated our system using 6 international datasets from India, China, and the United States. Of these datasets, 4 focused on diseases that the AI was not trained to detect: 2 datasets with tuberculosis and 2 datasets with coronavirus disease 2019. Our results suggest that the AI system trained using a large dataset containing a diverse array of CXR abnormalities generalizes to new patient populations and unseen diseases. In a simulated workflow where the AI system prioritized abnormal cases, the turnaround time for abnormal cases reduced by 7-28%. These results represent an important step towards evaluating whether AI can be safely used to flag cases in a general setting where previously unseen abnormalities exist. Lastly, to facilitate the continued development of AI models for CXR, we release our collected labels for the publicly available dataset.


Subject(s)
COVID-19/diagnostic imaging , Radiographic Image Interpretation, Computer-Assisted/methods , Tuberculosis/diagnostic imaging , Adult , Aged , Algorithms , Case-Control Studies , China , Deep Learning , Female , Humans , India , Male , Middle Aged , Radiography, Thoracic , United States
13.
Eur J Med Chem ; 215: 113286, 2021 Apr 05.
Article in English | MEDLINE | ID: covidwho-1385487

ABSTRACT

Covalent drugs have been intensively studied in some very important fields such as anti-tumor and anti-virus, including the currently global-spread SARS-CoV-2. However, these drugs may interact with a variety of biological macromolecules and cause serious toxicology, so how to reactivate the inhibited targets seems to be imperative in the near future. Organophosphate was an extreme example, which could form a covalent bound easily with acetylcholinesterase and irreversibly inhibited the enzyme, causing high toxicology. Some nucleophilic oxime reactivators for organophosphate poisoned acetylcholinesterase had been developed, but the reactivation process was still less understanding. Herein, we proposed there should be a pre-reactivated pose during the reactivating process and compounds whose binding pose was easy to transfer to the pre-reactivated pose might be efficient reactivators. Then we refined the previous reactivators based on the molecular dynamic simulation results, the resulting compounds L7R3 and L7R5 were proven as much more efficient reactivators for organophosphate inhibited acetylcholinesterase than currently used oximes. This work might provide some insights for constructing reactivators of covalently inhibited targets by using computational methods.


Subject(s)
Acetylcholinesterase/chemistry , Cholinesterase Reactivators/chemistry , Acetylcholinesterase/metabolism , Cholinesterase Inhibitors/chemistry , Cholinesterase Reactivators/metabolism , Humans , Kinetics , Molecular Dynamics Simulation , Organophosphorus Compounds/chemistry , Proof of Concept Study , Protein Binding
14.
Int J Environ Res Public Health ; 18(16)2021 08 12.
Article in English | MEDLINE | ID: covidwho-1354964

ABSTRACT

The outbreak of the COVID-19 has brought upon unprecedented challenges to nearly all people around the globe. Yet, people may differ in their risks of social, economic, and health well-being. In this research, we take a gender-difference approach to examine whether and why women suffered greater emotional and life distress than men at the early stage of the COVID-19 outbreak in China. Using a large nationwide Chinese sample, we found that compared to men, women reported higher levels of anxiety and fear, as well as greater life disturbance during the COVID-19 pandemic. Importantly, that women suffered more was partly explained by their higher level of pathogen disgust sensitivity. Our findings highlight the important consequences of gender differences in response to the threat of the COVID-19 pandemic and suggest that policymakers pay more attention to gender inequalities regarding COVID-19 responses.


Subject(s)
COVID-19 , Disgust , Anxiety/epidemiology , Female , Humans , Male , Pandemics , SARS-CoV-2
15.
CMAJ ; 193(30): E1164-E1172, 2021 08 03.
Article in English | MEDLINE | ID: covidwho-1352715

ABSTRACT

BACKGROUND: Conflicting reports have emerged for rates of preterm births and stillbirths during the COVID-19 pandemic. Most of these reports did not account for natural variation in these rates. We aimed to evaluate variations in preterm birth and stillbirth rates before and during the COVID-19 pandemic in Ontario, Canada. METHODS: We conducted a retrospective cohort study using linked population health administrative databases of pregnant people giving birth in any hospital in Ontario between July 2002 and December 2020. We calculated preterm birth and stillbirth rates. We assessed preterm birth at 22-28, 29-32 and 33-36 weeks' gestation, and stillbirths at term and preterm gestation. We used Laney control P' charts for the 18-year study period (6-mo observation periods) and interrupted time-series analyses for monthly rates for the most recent 4 years. RESULTS: We evaluated 2 465 387 pregnancies, including 13 781 that resulted in stillbirth. The mean preterm birth rate for our cohort was 7.96% (range 7.32%-8.59%). From January to December 2020, we determined that the preterm birth rate in Ontario was 7.87%, with no special cause variation. The mean stillbirth rate for the cohort was 0.56% (range 0.48%-0.70%). From January to December 2020, the stillbirth rate was 0.53%, with no special cause variation. We did not find any special cause variation for preterm birth or stillbirth subgroups. We found no changes in slope or gap between prepandemic and pandemic periods using interrupted time-series analyses. INTERPRETATION: In Ontario, Canada, we found no special cause variation (unusual change) in preterm birth or stillbirth rates, overall or by subgroups, during the first 12 months of the COVID-19 pandemic compared with the previous 17.5 years.


Subject(s)
COVID-19/epidemiology , Infant Mortality/trends , Premature Birth/epidemiology , Stillbirth/epidemiology , Cohort Studies , Comorbidity , Female , Gestational Age , Humans , Infant , Infant, Newborn , Infant, Premature , Interrupted Time Series Analysis , Ontario , Pregnancy , Retrospective Studies
16.
PLoS One ; 16(8): e0249872, 2021.
Article in English | MEDLINE | ID: covidwho-1341484

ABSTRACT

This paper analyzes the application of various telemedicine services in Gansu Province, China during the COVID-19 epidemic, and summarizes the experiences with these services. In addition, the satisfaction levels of patients and doctors with the application of telemedicine in COVID-19 were investigated, the deficiencies of telemedicine in Gansu were determined, and recommendations for modification were proposed. Coronavirus Disease 2019 (COVID-19) has broken out in China, and Gansu Province in Northwest of China has not been spared. To date, there are 91 local COVID-19 cases and 42 imported cases. 109 hospitals were selected as designated hospitals during the COVID-19 outbreak, and most of them were secondary hospitals. However, it was unsatisfactory that the ability of medical services is relatively low in most of secondary hospitals and primary hospitals. Therefore, we helped the secondary hospitals cope with COVID-19 by means of remote consultation, long-distance education, telemedicine question and answer (Q&A). Our practical experience shows that telemedicine can be widely used during the COVID-19 epidemic, especially in developing countries and areas with lagging medical standards.


Subject(s)
COVID-19/epidemiology , COVID-19/therapy , Telemedicine/organization & administration , China/epidemiology , Disease Outbreaks , Education, Distance/organization & administration , Education, Distance/statistics & numerical data , Education, Medical, Continuing/methods , Education, Medical, Continuing/organization & administration , Education, Medical, Continuing/statistics & numerical data , Education, Nursing, Continuing/methods , Education, Nursing, Continuing/organization & administration , Education, Nursing, Continuing/statistics & numerical data , Epidemics , Geography , Health Services Accessibility/organization & administration , Health Services Accessibility/statistics & numerical data , Humans , Physician-Patient Relations , Remote Consultation/instrumentation , Remote Consultation/methods , Remote Consultation/organization & administration , Remote Consultation/statistics & numerical data , SARS-CoV-2/physiology , Software , Telemedicine/instrumentation , Telemedicine/methods
17.
Int J Nanomedicine ; 16: 4959-4984, 2021.
Article in English | MEDLINE | ID: covidwho-1334842

ABSTRACT

Antiviral drugs (AvDs) are the primary resource in the global battle against viruses, including the recent fight against corona virus disease 2019 (COVID-19). Most AvDs require multiple medications, and their use frequently leads to drug resistance, since they have poor oral bioavailability and low efficacy due to their low solubility/low permeability. Characterizing the in vivo metabolism and pharmacokinetic characteristics of AvDs may help to solve the problems associated with AvDs and enhance their efficacy. In this review of AvDs, we systematically investigated their structure-based metabolic reactions and related enzymes, their cellular pharmacology, and the effects of metabolism on AvD pharmacodynamics and pharmacokinetics. We further assessed how delivery systems achieve better metabolism and pharmacology of AvDs. This review suggests that suitable nanosystems may help to achieve better pharmacological activity and pharmacokinetic behavior of AvDs by altering drug metabolism through the utilization of advanced nanotechnology and appropriate administration routes. Notably, such AvDs as ribavirin, remdesivir, favipiravir, chloroquine, lopinavir and ritonavir have been confirmed to bind to the severe acute respiratory syndrome-like coronavirus (SARS-CoV-2) receptor and thus may represent anti-COVID-19 treatments. Elucidating the metabolic and pharmacokinetic characteristics of AvDs may help pharmacologists to identify new formulations with high bioavailability and efficacy and help physicians to better treat virus-related diseases, including COVID-19.


Subject(s)
Antiviral Agents/administration & dosage , Antiviral Agents/pharmacokinetics , COVID-19/metabolism , Drug Delivery Systems , SARS-CoV-2/drug effects , Antiviral Agents/metabolism , Antiviral Agents/pharmacology , COVID-19/drug therapy , Humans
18.
Journal of Third Military Medical University ; 43(8):722-729, 2021.
Article in English | GIM | ID: covidwho-1302828

ABSTRACT

ObjectiveTo investigate whether hypocalcemia is associated with poor prognosis in COVID-19 patients. MethodsA retrospective analysis was performed on 2 651 COVID-19 patients admitted to Wuhan Huoshenshan Hospital from February 4, 2020 to April 11, 2020. They were divided into low and normal calcium groups according to their serum calcium level lower than 2.11 mmol/L or not. Their basic demographic characteristics, results of laboratory tests, treatment, complications and outcomes were analyzed and compared between the 2 groups. COX regression model was used to analyze whether low calcium is an independent risk factors for poor outcomes in COVID-19 patients. ResultsThe low calcium group had significantly higher ratios of mechanical ventilation, extracorporeal membrane oxygenation (ECMO) and ICU occupancy (P<0.05);obviously higher incidences of sepsis, shock, hypoproteinemia, respiratory failure, coagulation disorders, acute kidney injury, acute myocardial injury, acute respiratory distress syndrome (ARDS), and even mortality (P<0.05);and remarkably longer length of hospital stay (P<0.001) when compared with the normal calcium group. The blood calcium level of mild and common, severe, and critical COVID-19 patients was 2.17 (2.11, 2.24), 2.13 (2.04, 2.21), and 2.03 (1.89, 2.18) mmol/L, respectively, and significant differences were seen among the patients (P<0.05). The calcium level was in a decreasing trend with the severity of COVID-19 (P<0.05). The calcium level was statistically lower in the dead patients than those survival [1.97 (1.87, 2.03) vs 2.17 (2.09, 2.23), P<0.001]. Multivariate Cox regression analysis indicated that serum calcium concentration <2.11 mmol/L was an independent risk factor for poor prognosis of COVID-19 (HR=5.695, 95%CI :2.363-13.725, P<0.001). ConclusionLow blood calcium level is an independent risk factor for poor prognosis in COVID-19 patients. Correction for hypocalcemia may be an important strategy to improve the prognosis of COVID-19 patients.

19.
Front Med (Lausanne) ; 8: 687220, 2021.
Article in English | MEDLINE | ID: covidwho-1291017

ABSTRACT

Purpose: The coronavirus disease (COVID-19) pandemic poses a global threat, and identification of its prognostic biomarkers could prove invaluable. Fibrinogen (FIB) could be one such indicator as coagulation and fibrinolysis abnormalities are common among COVID-19 patients. We examined the role of FIB levels in the prognosis of COVID-19. Methods: This retrospective cohort study enrolled 1,643 COVID-19 patients from the Leishenshan Hospital in Wuhan, China. The follow-up was conducted from February 8, 2020 to April 15, 2020. The cohort was divided into three groups according to the FIB level on admission, and associations with mortality and disease severity were determined using Cox and logistic regression analyses, respectively. Further, Kaplan-Meier (K-M) analyses by log-rank tests were used to assess the survival of patients with varying FIB levels. Results: Patients with FIB < 2.2 g/L [hazard ratio (HR): 9.02, 95% confidence interval (CI): 1.91-42.59, P = 0.006] and >4.2 g/L (HR: 4.79, 95% CI: 1.14-20.20, P = 0.033) showed higher mortality risks compared to those with FIB between 2.2 and 4.2 g/L. The survival curves showed similar results in K-M analyses (P < 0.001). Additionally, an elevated FIB level was associated with a greater risk of developing critical disease (odds ratio: 2.16, 95% CI: 1.04-4.46, P = 0.038) than a FIB level within the normal range. Conclusion: Abnormal FIB levels may be associated with mortality risk among COVID-19 patients and could predict critical disease development. Thus, assessment of FIB levels may assist in determining the prognosis of COVID-19 patients.

20.
Math Biosci Eng ; 18(5): 5409-5426, 2021 06 18.
Article in English | MEDLINE | ID: covidwho-1282673

ABSTRACT

After a major outbreak of the coronavirus disease (COVID-19) starting in late December 2019, there were no new cases reported in mainland China for the first time on March 18, 2020, and no new cases reported in Hong Kong Special Administrative Region on April 20, 2020. However, these places had reported new cases and experienced a second wave since June 11, 2020. Here we develop a stochastic discrete-time epidemic model to evaluate the risk of COVID-19 resurgence by analyzing the data from the beginning of the outbreak to the second wave in these three places. In the model, we use an input parameter to represent a few potential risks that may cause a second wave, including asymptomatic infection, imported cases from other places, and virus from the environment such as frozen food packages. The effect of physical distancing restrictions imposed at different stages of the outbreak is also included in the model. Model simulations show that the magnitude of the input and the time between the initial entry and subsequent case confirmation significantly affect the probability of the second wave occurrence. Although the susceptible population size does not change the probability of resurgence, it can influence the severity of the outbreak when a second wave occurs. Therefore, to prevent the occurrence of a future wave, timely screening and detection are needed to identify infected cases in the early stage of infection. When infected cases appear, various measures such as contact tracing and quarantine should be followed to reduce the size of susceptible population in order to mitigate the COVID-19 outbreak.


Subject(s)
COVID-19 , Data Analysis , Contact Tracing , Humans , Quarantine , SARS-CoV-2
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