@article {814, title = {Aripiprazole as protector against COVID-19 mortality.}, journal = {Sci Rep}, volume = {14}, year = {2024}, month = {2024 May 29}, pages = {12362}, abstract = {

The relation of antipsychotics with severe Coronavirus Disease 19 (COVID-19) outcomes is a matter of debate since the beginning of the pandemic. To date, controversial results have been published on this issue. We aimed to prove whether antipsychotics might exert adverse or protective effects against fatal outcomes derived from COVID-19. A population-based retrospective cohort study (January 2020 to November 2020) comprising inpatients (15,968 patients) who were at least 18~years old and had a laboratory-confirmed COVID-19 infection. Two sub-cohorts were delineated, comprising a total of 2536 inpatients: individuals who either had no prescription medication or were prescribed an antipsychotic within the 15~days preceding hospitalization. We conducted survival and odds ratio analyses to assess the association between antipsychotic use and mortality, reporting both unadjusted and covariate-adjusted results. We computed the average treatment effects, using the untreated group as the reference, and the average treatment effect on the treated, focusing solely on the antipsychotic-treated population. Among the eight antipsychotics found to be in use, only aripiprazole showed a significant decrease in the risk of death from COVID-19 [adjusted odds ratio (OR) = 0.86; 95\% CI, 0.79-0.93, multiple-testing adjusted p-value < 0.05]. Importantly, these findings were consistent for both covariate-adjusted and unadjusted analyses. Aripiprazole has been shown to have a differentiated beneficial effect in protecting against fatal clinical outcome in COVID-19 infected individuals. We speculate that the differential effect of aripiprazole on controlling immunological pathways and inducible inflammatory enzymes, that are critical in COVID19 illness, may be associated with our findings herein.

}, keywords = {Adult, Aged, Aged, 80 and over, Antipsychotic Agents, Aripiprazole, COVID-19, COVID-19 Drug Treatment, Female, Humans, Male, Middle Aged, Retrospective Studies, SARS-CoV-2}, issn = {2045-2322}, doi = {10.1038/s41598-024-60297-y}, author = {Loucera-Mu{\~n}ecas, C and Canal-Rivero, M and Ruiz-Veguilla, M and Carmona, R and Bostelmann, G and Garrido-Torres, N and Dopazo, J and Crespo-Facorro, B} } @article {805, title = {Drug-target identification in COVID-19 disease mechanisms using computational systems biology approaches.}, journal = {Front Immunol}, volume = {14}, year = {2024}, month = {2023}, pages = {1282859}, abstract = {

INTRODUCTION: The COVID-19 Disease Map project is a large-scale community effort uniting 277 scientists from 130 Institutions around the globe. We use high-quality, mechanistic content describing SARS-CoV-2-host interactions and develop interoperable bioinformatic pipelines for novel target identification and drug repurposing.

METHODS: Extensive community work allowed an impressive step forward in building interfaces between Systems Biology tools and platforms. Our framework can link biomolecules from omics data analysis and computational modelling to dysregulated pathways in a cell-, tissue- or patient-specific manner. Drug repurposing using text mining and AI-assisted analysis identified potential drugs, chemicals and microRNAs that could target the identified key factors.

RESULTS: Results revealed drugs already tested for anti-COVID-19 efficacy, providing a mechanistic context for their mode of action, and drugs already in clinical trials for treating other diseases, never tested against COVID-19.

DISCUSSION: The key advance is that the proposed framework is versatile and expandable, offering a significant upgrade in the arsenal for virus-host interactions and other complex pathologies.

}, keywords = {Computer Simulation, COVID-19, drug repositioning, Humans, SARS-CoV-2, Systems biology}, issn = {1664-3224}, doi = {10.3389/fimmu.2023.1282859}, author = {Niarakis, Anna and Ostaszewski, Marek and Mazein, Alexander and Kuperstein, Inna and Kutmon, Martina and Gillespie, Marc E and Funahashi, Akira and Acencio, Marcio Luis and Hemedan, Ahmed and Aichem, Michael and Klein, Karsten and Czauderna, Tobias and Burtscher, Felicia and Yamada, Takahiro G and Hiki, Yusuke and Hiroi, Noriko F and Hu, Finterly and Pham, Nhung and Ehrhart, Friederike and Willighagen, Egon L and Valdeolivas, Alberto and Dugourd, Aur{\'e}lien and Messina, Francesco and Esteban-Medina, Marina and Pe{\~n}a-Chilet, Maria and Rian, Kinza and Soliman, Sylvain and Aghamiri, Sara Sadat and Puniya, Bhanwar Lal and Naldi, Aur{\'e}lien and Helikar, Tom{\'a}{\v s} and Singh, Vidisha and Fern{\'a}ndez, Marco Fari{\~n}as and Bermudez, Viviam and Tsirvouli, Eirini and Montagud, Arnau and No{\"e}l, Vincent and Ponce-de-Leon, Miguel and Maier, Dieter and Bauch, Angela and Gyori, Benjamin M and Bachman, John A and Luna, Augustin and Pi{\~n}ero, Janet and Furlong, Laura I and Balaur, Irina and Rougny, Adrien and Jarosz, Yohan and Overall, Rupert W and Phair, Robert and Perfetto, Livia and Matthews, Lisa and Rex, Devasahayam Arokia Balaya and Orlic-Milacic, Marija and Gomez, Luis Cristobal Monraz and De Meulder, Bertrand and Ravel, Jean Marie and Jassal, Bijay and Satagopam, Venkata and Wu, Guanming and Golebiewski, Martin and Gawron, Piotr and Calzone, Laurence and Beckmann, Jacques S and Evelo, Chris T and D{\textquoteright}Eustachio, Peter and Schreiber, Falk and Saez-Rodriguez, Julio and Dopazo, Joaquin and Kuiper, Martin and Valencia, Alfonso and Wolkenhauer, Olaf and Kitano, Hiroaki and Barillot, Emmanuel and Auffray, Charles and Balling, Rudi and Schneider, Reinhard} } @article {801, title = {Evaluation of a combined detection of SARS-CoV-2 and its variants using real-time allele-specific PCR strategy: an advantage for clinical practice.}, journal = {Epidemiol Infect}, volume = {151}, year = {2023}, month = {2023 Nov 24}, pages = {e201}, abstract = {

This study aimed to assess the ability of a real-time reverse transcription polymerase chain reaction (RT-PCR) with multiple targets to detect SARS-CoV-2 and its variants in a single test. Nasopharyngeal specimens were collected from patients in Granada, Spain, between January 2021 and December 2022. Five allele-specific RT-PCR kits were used sequentially, with each kit designed to detect a predominant variant at the time. When the Alpha variant was dominant, the kit included the HV69/70 deletion, E and N genes. When Delta replaced Alpha, the kit incorporated the L452R mutation in addition to E and N genes. When Omicron became dominant, L452R was replaced with the N679K mutation. Before incorporating each variant kit, a comparative analysis was carried out with SARS-CoV-2 whole genome sequencing (WGS). The results demonstrated that RT-PCR with multiple targets can provide rapid and effective detection of SARS-CoV-2 and its variants in a single test. A very high degree of agreement (96.2\%) was obtained between the comparison of RT-PCR and WGS. Allele-specific RT-PCR assays make it easier to implement epidemiological surveillance systems for effective public health decision making.

}, keywords = {Alleles, COVID-19, COVID-19 Testing, Humans, Real-Time Polymerase Chain Reaction, SARS-CoV-2, Sensitivity and Specificity}, issn = {1469-4409}, doi = {10.1017/S095026882300184X}, author = {Chaves-Blanco, Luc{\'\i}a and de Salazar, Adolfo and Fuentes, Ana and Vi{\~n}uela, Laura and Perez-Florido, Javier and Dopazo, Joaquin and Garc{\'\i}a, Federico} } @article {797, title = {A second update on mapping the human genetic architecture of COVID-19.}, journal = {Nature}, volume = {621}, year = {2023}, month = {2023 Sep}, pages = {E7-E26}, keywords = {COVID-19, Human Genetics, Humans}, issn = {1476-4687}, doi = {10.1038/s41586-023-06355-3} } @article {762, title = {Assessing the Impact of SARS-CoV-2 Lineages and Mutations on Patient Survival.}, journal = {Viruses}, volume = {14}, year = {2022}, month = {2022 Aug 27}, abstract = {

OBJECTIVES: More than two years into the COVID-19 pandemic, SARS-CoV-2 still remains a global public health problem. Successive waves of infection have produced new SARS-CoV-2 variants with new mutations for which the impact on COVID-19 severity and patient survival is uncertain.

METHODS: A total of 764 SARS-CoV-2 genomes, sequenced from COVID-19 patients, hospitalized from 19th February 2020 to 30 April 2021, along with their clinical data, were used for survival analysis.

RESULTS: A significant association of B.1.1.7, the alpha lineage, with patient mortality (log hazard ratio (LHR) = 0.51, C.I. = [0.14,0.88]) was found upon adjustment by all the covariates known to affect COVID-19 prognosis. Moreover, survival analysis of mutations in the SARS-CoV-2 genome revealed 27 of them were significantly associated with higher mortality of patients. Most of these mutations were located in the genes coding for the S, ORF8, and N proteins.

CONCLUSIONS: This study illustrates how a combination of genomic and clinical data can provide solid evidence for the impact of viral lineage on patient survival.

}, keywords = {COVID-19, Genome, Viral, Humans, mutation, Pandemics, Phylogeny, SARS-CoV-2}, issn = {1999-4915}, doi = {10.3390/v14091893}, author = {Loucera, Carlos and Perez-Florido, Javier and Casimiro-Soriguer, Carlos S and Ortuno, Francisco M and Carmona, Rosario and Bostelmann, Gerrit and Mart{\'\i}nez-Gonz{\'a}lez, L Javier and Mu{\~n}oyerro-Mu{\~n}iz, Dolores and Villegas, Rom{\'a}n and Rodr{\'\i}guez-Ba{\~n}o, Jes{\'u}s and Romero-G{\'o}mez, Manuel and Lorusso, Nicola and Garcia-Le{\'o}n, Javier and Navarro-Mar{\'\i}, Jose M and Camacho-Martinez, Pedro and Merino-Diaz, Laura and Salazar, Adolfo de and Vi{\~n}uela, Laura and Lepe, Jose A and Garc{\'\i}a, Federico and Dopazo, Joaquin} } @article {736, title = {COVID19 Disease Map, a computational knowledge repository of virus-host interaction mechanisms.}, journal = {Mol Syst Biol}, volume = {17}, year = {2021}, month = {2021 10}, pages = {e10387}, abstract = {

We need to effectively combine the knowledge from surging literature with complex datasets to propose mechanistic models of SARS-CoV-2 infection, improving data interpretation and predicting key targets of intervention. Here, we describe a large-scale community effort to build an open access, interoperable and computable repository of COVID-19 molecular mechanisms. The COVID-19 Disease Map (C19DMap) is a graphical, interactive representation of disease-relevant molecular mechanisms linking many knowledge sources. Notably, it is a computational resource for graph-based analyses and disease modelling. To this end, we established a framework of tools, platforms and guidelines necessary for a multifaceted community of biocurators, domain experts, bioinformaticians and computational biologists. The diagrams of the C19DMap, curated from the literature, are integrated with relevant interaction and text mining databases. We demonstrate the application of network analysis and modelling approaches by concrete examples to highlight new testable hypotheses. This framework helps to find signatures of SARS-CoV-2 predisposition, treatment response or prioritisation of drug candidates. Such an approach may help deal with new waves of COVID-19 or similar pandemics in the long-term perspective.

}, keywords = {Antiviral Agents, Computational Biology, Computer Graphics, COVID-19, Cytokines, Data Mining, Databases, Factual, Gene Expression Regulation, Host Microbial Interactions, Humans, Immunity, Cellular, Immunity, Humoral, Immunity, Innate, Lymphocytes, Metabolic Networks and Pathways, Myeloid Cells, Protein Interaction Mapping, SARS-CoV-2, Signal Transduction, Software, Transcription Factors, Viral Proteins}, issn = {1744-4292}, doi = {10.15252/msb.202110387}, author = {Ostaszewski, Marek and Niarakis, Anna and Mazein, Alexander and Kuperstein, Inna and Phair, Robert and Orta-Resendiz, Aurelio and Singh, Vidisha and Aghamiri, Sara Sadat and Acencio, Marcio Luis and Glaab, Enrico and Ruepp, Andreas and Fobo, Gisela and Montrone, Corinna and Brauner, Barbara and Frishman, Goar and Monraz G{\'o}mez, Luis Crist{\'o}bal and Somers, Julia and Hoch, Matti and Kumar Gupta, Shailendra and Scheel, Julia and Borlinghaus, Hanna and Czauderna, Tobias and Schreiber, Falk and Montagud, Arnau and Ponce de Leon, Miguel and Funahashi, Akira and Hiki, Yusuke and Hiroi, Noriko and Yamada, Takahiro G and Dr{\"a}ger, Andreas and Renz, Alina and Naveez, Muhammad and Bocskei, Zsolt and Messina, Francesco and B{\"o}rnigen, Daniela and Fergusson, Liam and Conti, Marta and Rameil, Marius and Nakonecnij, Vanessa and Vanhoefer, Jakob and Schmiester, Leonard and Wang, Muying and Ackerman, Emily E and Shoemaker, Jason E and Zucker, Jeremy and Oxford, Kristie and Teuton, Jeremy and Kocakaya, Ebru and Summak, G{\"o}k{\c c}e Ya{\u g}mur and Hanspers, Kristina and Kutmon, Martina and Coort, Susan and Eijssen, Lars and Ehrhart, Friederike and Rex, Devasahayam Arokia Balaya and Slenter, Denise and Martens, Marvin and Pham, Nhung and Haw, Robin and Jassal, Bijay and Matthews, Lisa and Orlic-Milacic, Marija and Senff Ribeiro, Andrea and Rothfels, Karen and Shamovsky, Veronica and Stephan, Ralf and Sevilla, Cristoffer and Varusai, Thawfeek and Ravel, Jean-Marie and Fraser, Rupsha and Ortseifen, Vera and Marchesi, Silvia and Gawron, Piotr and Smula, Ewa and Heirendt, Laurent and Satagopam, Venkata and Wu, Guanming and Riutta, Anders and Golebiewski, Martin and Owen, Stuart and Goble, Carole and Hu, Xiaoming and Overall, Rupert W and Maier, Dieter and Bauch, Angela and Gyori, Benjamin M and Bachman, John A and Vega, Carlos and Grou{\`e}s, Valentin and Vazquez, Miguel and Porras, Pablo and Licata, Luana and Iannuccelli, Marta and Sacco, Francesca and Nesterova, Anastasia and Yuryev, Anton and de Waard, Anita and Turei, Denes and Luna, Augustin and Babur, Ozgun and Soliman, Sylvain and Valdeolivas, Alberto and Esteban-Medina, Marina and Pe{\~n}a-Chilet, Maria and Rian, Kinza and Helikar, Tom{\'a}{\v s} and Puniya, Bhanwar Lal and Modos, Dezso and Treveil, Agatha and Olbei, Marton and De Meulder, Bertrand and Ballereau, Stephane and Dugourd, Aur{\'e}lien and Naldi, Aur{\'e}lien and No{\"e}l, Vincent and Calzone, Laurence and Sander, Chris and Demir, Emek and Korcsmaros, Tamas and Freeman, Tom C and Aug{\'e}, Franck and Beckmann, Jacques S and Hasenauer, Jan and Wolkenhauer, Olaf and Wilighagen, Egon L and Pico, Alexander R and Evelo, Chris T and Gillespie, Marc E and Stein, Lincoln D and Hermjakob, Henning and D{\textquoteright}Eustachio, Peter and Saez-Rodriguez, Julio and Dopazo, Joaquin and Valencia, Alfonso and Kitano, Hiroaki and Barillot, Emmanuel and Auffray, Charles and Balling, Rudi and Schneider, Reinhard} } @article {745, title = {Real world evidence of calcifediol or vitamin D prescription and mortality rate of COVID-19 in a retrospective cohort of hospitalized Andalusian patients.}, journal = {Sci Rep}, volume = {11}, year = {2021}, month = {2021 12 03}, pages = {23380}, abstract = {

COVID-19 is a major worldwide health problem because of acute respiratory distress syndrome, and mortality. Several lines of evidence have suggested a relationship between the vitamin D endocrine system and severity of COVID-19. We present a survival study on a retrospective cohort of 15,968 patients, comprising all COVID-19 patients hospitalized in Andalusia between January and November 2020. Based on a central registry of electronic health records (the Andalusian Population Health Database, BPS), prescription of vitamin D or its metabolites within 15-30~days before hospitalization were recorded. The effect of prescription of vitamin D (metabolites) for other indication previous to the hospitalization was studied with respect to patient survival. Kaplan-Meier survival curves and hazard ratios support an association between prescription of these metabolites and patient survival. Such association was stronger for calcifediol (Hazard Ratio, HR = 0.67, with 95\% confidence interval, CI, of [0.50-0.91]) than for cholecalciferol (HR = 0.75, with 95\% CI of [0.61-0.91]), when prescribed 15~days prior hospitalization. Although the relation is maintained, there is a general decrease of this effect when a longer period of 30~days prior hospitalization is considered (calcifediol HR = 0.73, with 95\% CI [0.57-0.95] and cholecalciferol HR = 0.88, with 95\% CI [0.75, 1.03]), suggesting that association was stronger when the prescription was closer to the hospitalization.

}, keywords = {Calcifediol, COVID-19, Female, Humans, Kaplan-Meier Estimate, Male, Retrospective Studies, Spain, Survival Analysis, Vitamin D}, issn = {2045-2322}, doi = {10.1038/s41598-021-02701-5}, author = {Loucera, Carlos and Pe{\~n}a-Chilet, Maria and Esteban-Medina, Marina and Mu{\~n}oyerro-Mu{\~n}iz, Dolores and Villegas, Rom{\'a}n and L{\'o}pez-Miranda, Jos{\'e} and Rodr{\'\i}guez-Ba{\~n}o, Jes{\'u}s and T{\'u}nez, Isaac and Bouillon, Roger and Dopazo, Joaquin and Quesada Gomez, Jose Manuel} } @article {689, title = {COVID-19 Disease Map, building a computational repository of SARS-CoV-2 virus-host interaction mechanisms.}, journal = {Sci Data}, volume = {7}, year = {2020}, month = {2020 05 05}, pages = {136}, keywords = {Betacoronavirus, Computational Biology, Coronavirus Infections, COVID-19, Databases, Factual, Host Microbial Interactions, Host-Pathogen Interactions, Humans, International Cooperation, Models, Biological, Pandemics, Pneumonia, Viral, SARS-CoV-2}, issn = {2052-4463}, doi = {10.1038/s41597-020-0477-8}, author = {Ostaszewski, Marek and Mazein, Alexander and Gillespie, Marc E and Kuperstein, Inna and Niarakis, Anna and Hermjakob, Henning and Pico, Alexander R and Willighagen, Egon L and Evelo, Chris T and Hasenauer, Jan and Schreiber, Falk and Dr{\"a}ger, Andreas and Demir, Emek and Wolkenhauer, Olaf and Furlong, Laura I and Barillot, Emmanuel and Dopazo, Joaquin and Orta-Resendiz, Aurelio and Messina, Francesco and Valencia, Alfonso and Funahashi, Akira and Kitano, Hiroaki and Auffray, Charles and Balling, Rudi and Schneider, Reinhard} } @article {713, title = {Drug repurposing for COVID-19 using machine learning and mechanistic models of signal transduction circuits related to SARS-CoV-2 infection.}, journal = {Signal Transduct Target Ther}, volume = {5}, year = {2020}, month = {2020 12 11}, pages = {290}, keywords = {Computational Chemistry, COVID-19, drug repositioning, Humans, Machine Learning, Molecular Docking Simulation, Molecular Targeted Therapy, Proteins, SARS-CoV-2, Signal Transduction}, issn = {2059-3635}, doi = {10.1038/s41392-020-00417-y}, author = {Loucera, Carlos and Esteban-Medina, Marina and Rian, Kinza and Falco, Matias M and Dopazo, Joaquin and Pe{\~n}a-Chilet, Maria} }