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1.
Informatica ; 46(1):69-75, 2022.
Article in English | ProQuest Central | ID: covidwho-1879800

ABSTRACT

The quest to create a vaccine for covid-19 has rekindled hope for most people worldwide, with the anticipation that a vaccine breakthrough would be one step closer to the end of the deadly Covid-19. The pandemic has had a bearing on the use of Twitter as a communication medium to reach a wider audience. This study examines Covid-19 vaccine-related discussions, concerns, and Twitter-emerged sentiments about the Covid-19 vaccine rollout program. Natural Language Processing (NLP) techniques were applied to analyze Covid-19 vaccine-related tweets. Our analysis identified popular n-grams and salient themes such as "vaccine health information," "vaccine distribution and administration," "vaccine doses required for immunity," and "vaccine availability." We apply machine learning algorithms and evaluate their performance using the standard metrics, namely accuracy, precision, recall, and f1-score. Support Vector Machine (SVM) classifier proves to be the best fit on the dataset with 84.32% accuracy. The research demonstrates how Twitter data and machine learning methods can study the evolving public discussions and sentiments concerning the Covid-19 vaccine rollout program.

2.
Sustainability ; 13(18):10243, 2021.
Article in English | ProQuest Central | ID: covidwho-1765921

ABSTRACT

The International Maritime Organization (IMO) plays a significant role in global marine environmental governance, providing a forum of regulatory oversight for member states. Member states are the main actors of the IMO and exert considerable influence on the process of lawmaking. Among these member states, China is unique due to its multiple identities. There are various factors influencing interests behind China’s multiple identities, which fully engage the country in various shipping and maritime trade activities. This article examines China’s role in the IMO marine environmental regulatory governance. It identifies the impact of China on global ocean governance and indicates the development and reforms in the global governance system. China enacted the China Ocean Agenda 21 for its strategy of ocean development. Thus, China is the object of study in this examination of empirical research that collects submissions from 2001 to 2020 related to marine environmental governance. The findings reveal that the extent to which China participates in such governance has considerably increased, and although the contribution of China’s submissions is still in development, its role in the IMO is no longer merely that of a follower, and the efforts of the country have had a positive influence on the IMO’s marine environmental regulatory governance, including its legal instruments.

3.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-317971

ABSTRACT

Jianhui Nie, Qianqian Li, and Jiajing Wu contributed equally to this work. Pseudotyped viruses are useful virological tools due to their safety and versatility. Based on a VSV pseudotyped virus production system, we developed a pseudotyped virus-based neutralization assay against SARS-CoV-2 in biosafety level 2 facilities. This protocol includes production, titration of the SARS-CoV-2 S pseudotyped virus and neutralization assay based on it. Various types of samples targeting virus attachment and entry could be evaluated for their potency, including serum samples derived from animals and humans, monoclonal antibodies, fusion inhibitors (peptides or small molecules). If the pseudotyped virus stock has been prepared in advance, it will take 2 days to get the potency data for the candidate samples. Experience of handling cells is needed before implementing this protocol.

4.
Antiviral Res ; 198: 105254, 2022 02.
Article in English | MEDLINE | ID: covidwho-1654045

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a newly emerged infectious disease caused by a novel coronavirus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The rapid global emergence of SARS-CoV-2 highlights the importance and urgency for potential drugs to control the pandemic. The functional importance of RNA-dependent RNA polymerase (RdRp) in the viral life cycle, combined with structural conservation and absence of closely related homologs in humans, makes it an attractive target for designing antiviral drugs. Nucleos(t)ide analogs (NAs) are still the most promising broad-spectrum class of viral RdRp inhibitors. In this study, using our previously developed cell-based SARS-CoV-2 RdRp report system, we screened 134 compounds in the Selleckchemicals NAs library. Four candidate compounds, Fludarabine Phosphate, Fludarabine, 6-Thio-20-Deoxyguanosine (6-Thio-dG), and 5-Iodotubercidin, exhibit remarkable potency in inhibiting SARS-CoV-2 RdRp. Among these four compounds, 5-Iodotubercidin exhibited the strongest inhibition upon SARS-CoV-2 RdRp, and was resistant to viral exoribonuclease activity, thus presenting the best antiviral activity against coronavirus from a different genus. Further study showed that the RdRp inhibitory activity of 5-Iodotubercidin is closely related to its capacity to inhibit adenosine kinase (ADK).


Subject(s)
Antiviral Agents/pharmacology , COVID-19/drug therapy , Nucleic Acid Synthesis Inhibitors/pharmacology , SARS-CoV-2/drug effects , Tubercidin/analogs & derivatives , Cell Line , Deoxyguanosine/analogs & derivatives , Deoxyguanosine/pharmacology , Drug Evaluation, Preclinical/methods , HEK293 Cells , Humans , Microbial Sensitivity Tests , RNA, Viral/biosynthesis , RNA-Dependent RNA Polymerase/antagonists & inhibitors , SARS-CoV-2/genetics , Thionucleosides/pharmacology , Tubercidin/pharmacology , Vidarabine/analogs & derivatives , Vidarabine/pharmacology , Vidarabine Phosphate/analogs & derivatives , Vidarabine Phosphate/pharmacology
5.
Antiviral Res ; 196: 105209, 2021 12.
Article in English | MEDLINE | ID: covidwho-1520691

ABSTRACT

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative agent of Coronavirus Disease 2019 (COVID-19) pandemic. Despite intensive and global efforts to discover and develop novel antiviral therapies, only Remdesivir has been approved as a treatment for COVID-19. Therefore, effective antiviral therapeutics are still urgently needed to combat and halt the pandemic. Viral RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 demonstrates high potential as a reliable target for the development of antivirals. We previously developed a cell-based assay to assess the efficiency of compounds that target SARS-CoV-2 RdRp, as well as their tolerance to viral exoribonuclease-mediated proof-reading. In our previous study, we discovered that 2-((1H-indol-3-yl)thio)-N-phenyl-acetamides specifically targets the RdRp of both respiratory syncytial virus (RSV) and influenza A virus. Thus, we hypothesize that 2-((1H-indol-3-yl)thio)-N-phenyl-acetamides may also have the ability to inhibit SARS-CoV-2 replication by targeting its RdRp activity. In this research, we test a compound library containing 103 of 2-((1H-indol-3-yl)thio)-N-phenyl-acetamides against SARS-CoV-2 RdRp, using our cell-based assay. Among these compounds, the top five candidates strongly inhibit SARS-CoV-2 RdRp activity while exhibiting low cytotoxicity and resistance to viral exoribonuclease. Compound 6-72-2a is the most promising candidate with the lowest EC50 value of 1.41 µM and highest selectivity index (CC50/EC50) (above 70.92). Furthermore, our data suggests that 4-46b and 6-72-2a also inhibit the replication of HCoV-OC43 and HCoV-NL63 virus in a dose-dependent manner. Compounds 4-46b and 6-72-2a exhibit EC50 values of 1.13 µM and 0.94 µM, respectively, on HCoV-OC43 viral replication. However, higher concentrations of these compounds are needed to effectively block HCoV-NL63 replication. Together, our findings successfully identified 4-46b and 6-72-2a as promising inhibitors against SARS-CoV-2 RdRp.


Subject(s)
Acetamides/pharmacology , COVID-19/drug therapy , RNA-Dependent RNA Polymerase , Antiviral Agents/pharmacology , Drug Delivery Systems , Humans , RNA, Viral/biosynthesis , RNA-Dependent RNA Polymerase/antagonists & inhibitors , RNA-Dependent RNA Polymerase/drug effects , SARS-CoV-2/drug effects , Viral Proteins/antagonists & inhibitors , Viral Proteins/drug effects , Virus Replication/drug effects
6.
Hum Vaccin Immunother ; 17(12): 4999-5006, 2021 12 02.
Article in English | MEDLINE | ID: covidwho-1442977

ABSTRACT

The mortality rate from COVID-19 appears to be higher in solid organ transplant (SOT) recipients when compared with other populations. Vaccination is a key strategy to prevent the COVID-19 pandemic. However, it is unclear how readily SOT recipients will get vaccinated against COVID-19. We conducted an internet-based survey to investigate the vaccination willingness among Chinese SOT recipients and further explore possible influencing factors. Eight hundred and thirteen respondents participated in the survey. Overall, 46 (5.7%) recipients were vaccinated against COVID-19, while 767 (94.3%) were not. Among those not vaccinated, 175 (22.8%) intended to be vaccinated, while 592 (77.2%) were categorized as vaccine-hesitant. The most common reason for vaccination hesitancy is fear of preexisting comorbidities, followed by fear of side effects and doctors' negative advice. Factors associated with vaccination willingness were as follows: with liver transplantation, the main source of information on COVID-19 vaccines was from medical doctors, scientists, and scientific journals, with at least college-level education, positive intention toward influenza vaccination during the current season, perceived importance of vaccination for SOT recipients, and having been vaccinated against influenza during the last season. Our survey indicated the necessity for SOT recipients to receive more comprehensive and accessible health education about vaccination and emphasized the critical role of transplantation physicians in promoting vaccine acceptance among SOT recipients. We hope that our survey results will help governments to better target communication in the ongoing COVID-19 vaccination campaign.


Subject(s)
COVID-19 , Influenza Vaccines , Organ Transplantation , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Pandemics/prevention & control , SARS-CoV-2 , Transplant Recipients , Vaccination
8.
Pacific-Basin Finance Journal ; 68:101608, 2021.
Article in English | ScienceDirect | ID: covidwho-1294113

ABSTRACT

By developing a machine learning-based measure of corporate big data strategies, this study empirically explores how stock markets respond to the COVID-19 pandemic and whether corporate big data strategies make firms immune to the pandemic effect. We find that except for information technology and health care sectors, firms in most sectors in China are negatively affected by the COVID-19 outbreak. Among these firms, an increase in the number of daily new confirmed cases in the city of a firm's headquarters is associated with a decrease in its stock prices, however, such a decline is attenuated for firms with a high emphasis on big data strategies. Our results are robust when we use COVID-19 cases at the whole country level.

9.
ACS Infect Dis ; 7(6): 1535-1544, 2021 06 11.
Article in English | MEDLINE | ID: covidwho-1243273

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a fatal respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The identification of potential drugs is urgently needed to control the pandemic. RNA dependent RNA polymerase (RdRp) is a conserved protein within RNA viruses and plays a crucial role in the viral life cycle, thus making it an attractive target for development of antiviral drugs. In this study, 101 quinoline and quinazoline derivatives were screened against SARS-CoV-2 RdRp using a cell-based assay. Three compounds I-13e, I-13h, and I-13i exhibit remarkable potency in inhibiting RNA synthesis driven by SARS-CoV-2 RdRp and relatively low cytotoxicity. Among these three compounds, I-13e showed the strongest inhibition upon RNA synthesis driven by SARS-CoV-2 RdRp, the resistance to viral exoribonuclease activity and the inhibitory effect on the replication of CoV, thus holding potential of being drug candidate for treatment of SARS-CoV-2.


Subject(s)
Quinazolines , Quinolines , RNA-Dependent RNA Polymerase/antagonists & inhibitors , SARS-CoV-2/drug effects , Humans , Quinazolines/pharmacology , Quinolines/pharmacology , RNA, Viral/biosynthesis
10.
Antiviral Res ; 190: 105078, 2021 06.
Article in English | MEDLINE | ID: covidwho-1198616

ABSTRACT

Antiviral therapeutics is one effective avenue to control and end this devastating COVID-19 pandemic. The viral RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 has been recognized as a valuable target of antivirals. However, the cell-free SARS-CoV-2 RdRp biochemical assay requires the conversion of nucleotide prodrugs into the active triphosphate forms, which regularly occurs in cells yet is a complicated multiple-step chemical process in vitro, and thus hinders the utility of this cell-free assay in the rapid discovery of RdRp inhibitors. In addition, SARS-CoV-2 exoribonuclease provides the proof-reading capacity to viral RdRp, thus creates relatively high resistance threshold of viral RdRp to nucleotide analog inhibitors, which must be examined and evaluated in the development of this class of antivirals. Here, we report a cell-based assay to evaluate the efficacy of nucleotide analog compounds against SARS-CoV-2 RdRp and assess their tolerance to viral exoribonuclease-mediated proof-reading. By testing seven commonly used nucleotide analog viral polymerase inhibitors, Remdesivir, Molnupiravir, Ribavirin, Favipiravir, Penciclovir, Entecavir and Tenofovir, we found that both Molnupiravir and Remdesivir showed the strong inhibition of SARS-CoV-2 RdRp, with EC50 value of 0.22 µM and 0.67 µM, respectively. Moreover, our results suggested that exoribonuclease nsp14 increases resistance of SARS-CoV-2 RdRp to nucleotide analog inhibitors. We also determined that Remdesivir presented the highest resistance to viral exoribonuclease activity in cells. Therefore, we have developed a cell-based SARS-CoV-2 RdRp assay which can be deployed to discover SARS-CoV-2 RdRp inhibitors that are urgently needed to treat COVID-19 patients.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/drug therapy , Drug Discovery , RNA-Dependent RNA Polymerase/antagonists & inhibitors , SARS-CoV-2/drug effects , SARS-CoV-2/enzymology , A549 Cells , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/pharmacology , Alanine/analogs & derivatives , Alanine/pharmacology , COVID-19/virology , Cell Survival/drug effects , Exoribonucleases/antagonists & inhibitors , HEK293 Cells , High-Throughput Screening Assays , Humans , RNA, Viral/genetics , SARS-CoV-2/genetics , Viral Nonstructural Proteins/antagonists & inhibitors
11.
Cell Discov ; 7(1): 21, 2021 Apr 06.
Article in English | MEDLINE | ID: covidwho-1171946

ABSTRACT

The origin and intermediate host for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is yet to be determined. Coronaviruses found to be closely related to SARS-CoV-2 include RaTG13 derived from bat and two clusters (PCoV-GD and PCoV-GX) of coronaviruses identified in pangolin. Here, we studied the infectivity and antigenicity patterns of SARS-CoV-2 and the three related coronaviruses. Compared with the other three viruses, RaTG13 showed almost no infectivity to a variety of cell lines. The two pangolin coronaviruses and SARS-CoV-2 showed similar infectious activity. However, in SARS-CoV-2-susceptible cell lines, the pangolin coronaviruses presented even higher infectivity. The striking difference between the SARS-CoV-2 and pangolin coronaviruses is that the latter can infect porcine cells, which could be partially attributed to an amino acid difference at the position of 498 of the spike protein. The infection by SARS-CoV-2 was mainly mediated by Furin and TMPRSS2, while PCoV-GD and PCoV-GX mainly depend on Cathepsin L. Extensive cross-neutralization was found between SARS-CoV-2 and PCoV-GD. However, almost no cross-neutralization was observed between PCoV-GX and SARS-CoV-2 or PCoV-GD. More attention should be paid to pangolin coronaviruses and to investigate the possibility of these coronaviruses spreading across species to become zoonoses among pigs or humans.

12.
Cell ; 184(9): 2362-2371.e9, 2021 04 29.
Article in English | MEDLINE | ID: covidwho-1139468

ABSTRACT

The 501Y.V2 variants of SARS-CoV-2 containing multiple mutations in spike are now dominant in South Africa and are rapidly spreading to other countries. Here, experiments with 18 pseudotyped viruses showed that the 501Y.V2 variants do not confer increased infectivity in multiple cell types except for murine ACE2-overexpressing cells, where a substantial increase in infectivity was observed. Notably, the susceptibility of the 501Y.V2 variants to 12 of 17 neutralizing monoclonal antibodies was substantially diminished, and the neutralization ability of the sera from convalescent patients and immunized mice was also reduced for these variants. The neutralization resistance was mainly caused by E484K and N501Y mutations in the receptor-binding domain of spike. The enhanced infectivity in murine ACE2-overexpressing cells suggests the possibility of spillover of the 501Y.V2 variants to mice. Moreover, the neutralization resistance we detected for the 501Y.V2 variants suggests the potential for compromised efficacy of monoclonal antibodies and vaccines.


Subject(s)
COVID-19/immunology , COVID-19/virology , Immune Evasion , SARS-CoV-2/pathogenicity , Angiotensin-Converting Enzyme 2/metabolism , Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/immunology , Antigens, Viral/immunology , Cell Line, Tumor , HEK293 Cells , Humans , Mutation/genetics , SARS-CoV-2/genetics
13.
Acta Pharm Sin B ; 11(6): 1555-1567, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1082559

ABSTRACT

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has become one major threat to human population health. The RNA-dependent RNA polymerase (RdRp) presents an ideal target of antivirals, whereas nucleoside analogs inhibitor is hindered by the proofreading activity of coronavirus. Herein, we report that corilagin (RAI-S-37) as a non-nucleoside inhibitor of SARS-CoV-2 RdRp, binds directly to RdRp, effectively inhibits the polymerase activity in both cell-free and cell-based assays, fully resists the proofreading activity and potently inhibits SARS-CoV-2 infection with a low 50% effective concentration (EC50) value of 0.13 µmol/L. Computation modeling predicts that RAI-S-37 lands at the palm domain of RdRp and prevents conformational changes required for nucleotide incorporation by RdRp. In addition, combination of RAI-S-37 with remdesivir exhibits additive activity against anti-SARS-CoV-2 RdRp. Together with the current data available on the safety and pharmacokinetics of corilagin as a medicinal herbal agent, these results demonstrate the potential of being developed into one of the much-needed SARS-CoV-2 therapeutics.

15.
Cell Res ; 31(4): 404-414, 2021 04.
Article in English | MEDLINE | ID: covidwho-1054016

ABSTRACT

The newly identified Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has resulted in a global health emergency because of its rapid spread and high mortality. The molecular mechanism of interaction between host and viral genomic RNA is yet unclear. We demonstrate herein that SARS-CoV-2 genomic RNA, as well as the negative-sense RNA, is dynamically N6-methyladenosine (m6A)-modified in human and monkey cells. Combined RIP-seq and miCLIP analyses identified a total of 8 m6A sites at single-base resolution in the genome. Especially, epidemic strains with mutations at these identified m6A sites have emerged worldwide, and formed a unique cluster in the US as indicated by phylogenetic analysis. Further functional experiments showed that m6A methylation negatively regulates SARS-CoV-2 infection. SARS-CoV-2 infection also triggered a global increase in host m6A methylome, exhibiting altered localization and motifs of m6A methylation in mRNAs. Altogether, our results identify m6A as a dynamic epitranscriptomic mark mediating the virus-host interaction.


Subject(s)
Adenosine/analogs & derivatives , Genome, Viral , SARS-CoV-2/genetics , Adenosine/metabolism , Animals , COVID-19/pathology , COVID-19/virology , Cell Line , Chlorocebus aethiops , DNA Methylation , Gene Expression Regulation , Host-Pathogen Interactions , Humans , Mutagenesis, Site-Directed , Phylogeny , RNA, Messenger/genetics , SARS-CoV-2/classification , SARS-CoV-2/isolation & purification , SARS-CoV-2/physiology , Vero Cells , Virus Replication
16.
SciFinder; 2020.
Preprint | SciFinder | ID: ppcovidwho-5137

ABSTRACT

A review. It invades human body mainly through binding to angiotensin-converting enzyme 2 (ACE2) receptors mediated by spike protein. ACE2 is closely related to NCP infection, it is not only a key target of SARS-CoV-2 infection, ACE2 expression is an important factor affecting disease severity and mortality of NCP patients as well. Therefore, a number of marketed and in-development drugs targeting ACE2 renin-angiotensin system (RAS), such as angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), recombinant human ACE2, type II transmembrane serine proteases (TMSPSS2) inhibitors and specific neutralizing antibodies, etc. may be feasible strategies for the treatment of NCP. In addition, based on the available evidence,it is not recommended to withdraw ACEI/ARB in confirmed or suspected cases of mild NCP with hypertension so as to avoid blood pressure fluctuation.

17.
SciFinder; 2020.
Preprint | SciFinder | ID: ppcovidwho-4393

ABSTRACT

A review. The coronavirus disease 2019 is caused by COVID-19 virus infection, with fever, fatigue, and dry cought as the mian clin. manifestations. It is highly contagious. Its etiol. is infection of epidemic toxin and it falls into the category of pestilence in TCM. The location of disease is in the lung and spleen and the incidence is mostly related to "cold, damp, heat, toxin and stasis" and other factors. Different experts have different views on the disease. From the perspective of TCM, the paper simply reviewed the recognition of etiol., pathomechanism and first-line treatment method, so as to make trivial contributin to the clin. practice of TCM.

19.
Nat Protoc ; 15(11): 3699-3715, 2020 11.
Article in English | MEDLINE | ID: covidwho-797534

ABSTRACT

Pseudotyped viruses are useful virological tools because of their safety and versatility. On the basis of a vesicular stomatitis virus (VSV) pseudotyped virus production system, we developed a pseudotyped virus-based neutralization assay against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in biosafety level 2 facilities. Compared with the binding antibody test, the neutralization assay could discriminate the protective agents from the antibody family. This protocol includes production and titration of the SARS-CoV-2 S pseudotyped virus and the neutralization assay based on it. Various types of samples targeting virus attachment and entry could be evaluated for their potency, including serum samples derived from animals and humans, monoclonal antibodies and fusion inhibitors (peptides or small molecules). If the pseudotyped virus stock has been prepared in advance, it will take 2 days to get the potency data for the candidate samples. Experience in handling cells is needed before implementing this protocol.


Subject(s)
Antibodies, Neutralizing/analysis , Betacoronavirus/immunology , Coronavirus Infections/virology , Genetic Techniques , Pneumonia, Viral/virology , Animals , COVID-19 , Female , HEK293 Cells , Humans , Mice , Pandemics , SARS-CoV-2
20.
Front Pharmacol ; 11: 1275, 2020.
Article in English | MEDLINE | ID: covidwho-769285

ABSTRACT

OBJECTIVE: This study was designed to evaluate the efficacy of remote medication management of rivaroxaban by pharmacists for geriatric patients with nonvalvular atrial fibrillation during the COVID-19 pandemic. METHODS: A single-site, prospective cohort study was conducted among patients with non-valvular atrial fibrillation who received rivaroxaban therapy from July 2019 to December 2019. Patients in the pharmacist-led education and follow-up service (PEFS) group were managed remotely by a pharmacist. In contrast, those in the usual care (UC) group were managed by other providers. Data of routine blood tests, coagulation function tests, which also included cardiac function parameters were collected. The number and type of provider encounters, interventions related to rivaroxaban therapy, the occurrence of thromboembolism or bleeding, and the time of the first outpatient visit after discharge were recorded. RESULTS: A total of 600 patients were recruited, and results of 381 patients were analyzed in the end, of which 179 patients were from the PEFS group and 202 were from the UC group. There was no significant difference between the two groups in terms of the occurrence ratio of systemic thrombosis, heart failure (LVEF < 40%), and left atrial dilation, which was defined as enlargement of left atrial diameter (LAD) > 40 mm. The cumulative incidences of bleeding complications, such as gastrointestinal tract and skin ecchymosis, were significantly higher in the UC group (12.4% vs. 6.1%, P=0.038; 4.5% vs. 0.6%, P=0.018). There was no significant difference after pharmacist intervention in terms of thrombosis occurrence ratio between the two groups (P = 0.338, HR: 0.722, 95% CI: 0.372-1.405). Remote instruction by a pharmacist reduced outpatient service frequency within the first 30 days after discharge (23.7% vs. 1.1%, P < 0.001). However, more patients in the PEFS group presented for the first outpatient revisit later than 40 days post-discharge (12.8% vs. 21.3%, P < 0.001). CONCLUSION: Remote pharmacist-led medication instruction of rivaroxaban could reduce bleeding complications of the gastrointestinal tract and skin ecchymosis and postpone the first outpatient revisit after discharge.

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