ABSTRACT
As transportation system plays a vastly important role in combatting newly-emerging and severe epidemics like the coronavirus disease 2019 (COVID-19), the vehicle routing problem (VRP) in epidemics has become an emerging topic that has attracted increasing attention worldwide. However, most existing VRP models are not suitable for epidemic situations, because they do not consider the prevention cost caused by issues such as viral tests and quarantine during the traveling. Therefore, this paper proposes a multi-objective VRP model for epidemic situations, named VRP4E, which considers not only the traditional travel cost but also the prevention cost of the VRP in epidemic situations. To efficiently solve the VRP4E, this paper further proposes a novel algorithm named multi-objective ant colony system algorithm for epidemic situations, termed MOACS4E, together with three novel designs. First, by extending the efficient “multiple populations for multiple objectives” framework, the MOACS4E adopts two ant colonies to optimize the travel and prevention costs respectively, so as to improve the search efficiency. Second, a pheromone fusion-based solution generation method is proposed to fuse the pheromones from different colonies to increase solution diversity effectively. Third, a solution quality improvement method is further proposed to improve the solutions for the prevention cost objective. The effectiveness of the MOACS4E is verified in experiments on 25 generated benchmarks by comparison with six state-of-the-art and modern algorithms. Moreover, the VRP4E in different epidemic situations and a real-world case in the Beijing-Tianjin-Hebei region, China, are further studied to provide helpful insights for combatting COVID-19-like epidemics.
ABSTRACT
Background: The COVID-19 pandemic poses an imminent threat to humanity, especially for those who have comorbidities. Evidence of COVID-19 and COPD comorbidities is accumulating. However, data revealing the molecular mechanism of COVID-19 and COPD comorbid diseases is limited. Methods: We got COVID-19/COPD -related genes from different databases by restricted screening conditions (top500), respectively, and then supplemented with COVID-19/COPD-associated genes (FDR<0.05, ;LogFC;≥1) from clinical sample data sets. By taking the intersection, 42 co-morbid host factors for COVID-19 and COPD were finally obtained. On the basis of shared host factors, we conducted a series of bioinformatics analysis, including protein-protein interaction analysis, gene ontology and pathway enrichment analysis, transcription factor-gene interaction network analysis, gene-microRNA co-regulatory network analysis, tissue-specific enrichment analysis and candidate drug prediction. Results: We revealed the comorbidity mechanism of COVID-19 and COPD from the perspective of host factor interaction, obtained the top ten gene and 3 modules with different biological functions. Furthermore, we have obtained the signaling pathways and concluded that dexamethasone, estradiol, progesterone, and nitric oxide shows effective interventions. Conclusion: This study revealed host factor interaction networks for COVID-19 and COPD, which could confirm the potential drugs for treating the comorbidity, ultimately, enhancing the management of the respiratory disease.
ABSTRACT
Background: Coronavirus Disease 2019 (COVID-19) caused by the enveloped RNA virus SARS-CoV-2 primarily affects the respiratory and gastrointestinal tracts.SARS-CoV-2 was isolated from faecal samples and active viral replication was reported in human intestinal cells. The human gut also harbors an enormous amount of resident viruses (collectively known as virome) that play a role in regulating host immunity and pathophysiology.Understanding gut virome perturbation that underlies SARS-CoV-2 infection and severity is an unmet need.Methods: We enrolled 98 COVID-19 patients with varying disease severity (3 asymptomatic, 53 mild, 34 moderate, 5 severe, 3 critical) and 78 non-COVID-19 controls matched for gender and co-morbidities. All study subjects had faecal specimens sampled at inclusion. Blood specimens were sampled for COVID-19 patients at admission to test for inflammatory markers and white cell counts. Among COVID-19 cases, 37 (38%) patients had serially faecal samples collected 2 to 3 times per week from time of hospitalization until after discharge. Using shotgun metagenomics sequencing, we sequenced and profiled the faecal RNA and DNA virome respectively. We investigated alterations and longitudinal dynamics of the gut virome in association with disease severity and blood parameters.Findings: Patients with COVID-19 showed underrepresentation of P epper mild mottle virus (RNA virus) and multiple bacteriophage lineage s (DNA viruses) and enrichment of environment-derived eukaryotic DNA viruses in faecal samples, compared to non-COVID-19 subjects. Such gut virome dysbiosis persisted up to 30 days after disease resolution. Faecal virome in SARS-CoV-2 infection harboured more stress-, inflammation- and virulence-associated gene encoding capacities including those pertaining to bacteriophage integration, DNA repair, and metabolism and virulence associated with their bacterial host. Human faecal baseline abundance of 9 virus species (1 RNA virus, Pepper chlorotic spot virus, and 8 DNA virus species) inversely correlated with disease severity of COVID-19. These viruses were also inversely associated with blood levels of pro-inflammatory proteins, white cells and neutrophils. Among the 9 COVID-19 severity-associated virus species, 4 showed inverse correlation with age; 5 showed persistent lower abundance both during disease course and after disease resolution relative to non-COVID-19 subjects. Interpretation: Both enteric RNA and DNA viromes were perturbed in COVID-19, which prolonged even after disease resolution. Gut virome may calibrate host immunity and regulate severity to SARS-CoV-2 infection. Our observation that gut viruses inversely correlated with both severity of COVID-19 and host age partly explains that older subjects are prone to severe and unfavorable COVID-19 outcomes. Our data altogether highlight the significance of human gut virome in COVID-19 disease course and potentially therapeutics.Funding Statement: This work was supported by The D. H. Chen Foundation, Center for Gut Microbiota Research (Faculty of Medicine, The Chinese University of Hong Kong) and Health and Medical Research Fund (Hong Kong, China).Declaration of Interests: None.Ethics Approval Statement: This study was approved by the Joint Chinese University of Hong Kong–New Territories East Cluster Clinical Research Ethics Committees (Reference number: 2020.076). All subjects provided informed consent to participate in this study and agreed for publication of the research results.
Subject(s)
Metabolic Diseases , Gastrointestinal Neoplasms , COVID-19 , Cluster HeadacheABSTRACT
Background: Coronavirus Disease 2019 (COVID-19) caused by the enveloped RNA virus SARS-CoV-2 primarily affects the respiratory and gastrointestinal tracts. SARS-CoV-2 was isolated from faecal samples and active viral replication was reported in human intestinal cells. The human gut also harbors an enormous amount of resident viruses (collectively known as the virome) that play a role in regulating host immunity and disease pathophysiology. Understanding gut virome perturbation that underlies SARS-CoV-2 infection and severity is an unmet need.Methods: We enrolled 98 COVID-19 patients with varying disease severity (3 asymptomatic, 53 mild, 34 moderate, 5 severe, 3 critical) and 78 non-COVID-19 controls matched for gender and co-morbidities. All subjects had faecal specimens sampled at inclusion. Blood specimens were collected for COVID-19 patients at admission to test for inflammatory markers and white cell counts. Among COVID-19 cases, 37 (38%) patients had serial faecal samples collected 2 to 3 times per week from time of hospitalization until after discharge. Using shotgun metagenomics sequencing, we sequenced and profiled the faecal RNA and DNA virome. We investigated alterations and longitudinal dynamics of the gut virome in association with disease severity and blood parameters.Results: Patients with COVID-19 showed underrepresentation of Pepper mild mottle virus (RNA virus) and multiple bacteriophage lineages (DNA viruses) and enrichment of environment-derived eukaryotic DNA viruses in faecal samples, compared to non-COVID-19 subjects. Such gut virome alterations persisted up to 30 days after disease resolution. Faecal virome in SARS-CoV-2 infection harboured more stress-, inflammation- and virulence-associated gene encoding capacities including those pertaining to bacteriophage integration, DNA repair, and metabolism and virulence associated with their bacterial host. Baseline fecal abundance of 10 virus species (1 RNA virus, Pepper chlorotic spot virus, and 9 DNA virus species) inversely correlated with disease COVID-19 severity. These viruses inversely correlated with blood levels of pro-inflammatory proteins, white cells and neutrophils. Among the 10 COVID-19 severity-associated DNA virus species, 4 showed inverse correlation with age; 5 showed persistent lower abundance both during disease course and after disease resolution relative to non-COVID-19 subjects.Conclusions: Both enteric RNA and DNA virome in COVID-19 patients were different from non-COVID-19 subjects, which persisted after disease resolution of COVID-19. Gut virome may calibrate host immunity and regulate severity to SARS-CoV-2 infection. Our observation that gut viruses inversely correlated with both severity of COVID-19 and host age may partly explain that older subjects are prone to severe and worse COVID-19 outcomes. Altogether our data highlight the importance of human gut virome in severity and potentially therapeutics of COVID-19.