Transcriptional Differences for COVID-19 Disease Map Genes between Males and Females Indicate a Different Basal Immunophenotype Relevant to the Disease
Abstract
:1. Introduction
2. Material and Methods
2.1. Datasets
2.2. DeCovid Software
3. Results
3.1. DeCovid as a User-Friendly Tool to Explore Gene Expression of COVID-19 Related Genes in Healthy Individuals
3.2. DeCovid Shows Wide-Spread Gene Expression Differences in COVID-19 Disease Map Genes in Sex and Age Groups at Diverse Tissues and Cell Types
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- Mai, F.; Pinto, R.D.; Ferri, C. COVID-19 and cardiovascular diseases. J. Cardiol. 2020, 76, 453–458. [Google Scholar] [CrossRef] [PubMed]
- Zheng, Y.-Y.; Ma, Y.-T.; Zhang, J.-Y.; Xie, X. COVID-19 and the cardiovascular system. Nat. Rev. Cardiol. 2020, 17, 259–260. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Apicella, M.; Campopiano, M.C.; Mantuano, M.; Mazoni, L.; Coppelli, A.; Prato, S.D. COVID-19 in people with diabetes: Understanding the reasons for worse outcomes. Lancet Diabetes Endocrinol. 2020, 8, 782–792. [Google Scholar] [CrossRef]
- Fang, L.; Karakiulakis, G.; Roth, M. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? Lancet Respir. Med. 2020, 8, e21. [Google Scholar] [CrossRef]
- Dietz, W.; Santos-Burgoa, C. Obesity and its Implications for COVID-19 Mortality. Obesity 2020, 28, 1005. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lighter, J.; Phillips, M.; Hochman, S.; Sterling, S.; Johnson, D.; Francois, F.; Stachel, A. Obesity in Patients Younger than 60 Years Is a Risk Factor for COVID-19 Hospital Admission. Clin. Infect. Dis. 2020, 71, 896–897. [Google Scholar] [CrossRef] [Green Version]
- Iaccarino, G.; Grassi, G.; Borghi, C.; Ferri, C.; Salvetti, M.; Volpe, M. Age and Multimorbidity Predict Death Among COVID-19 Patients. Hypertension 2020, 76, 366–372. [Google Scholar] [CrossRef]
- Palaiodimos, L.; Kokkinidis, D.G.; Li, W.; Karamanis, D.; Ognibene, J.; Arora, S.; Southern, W.N.; Mantzoros, C.S. Severe obesity, increasing age and male sex are independently associated with worse in-hospital outcomes, and higher in-hospital mortality, in a cohort of patients with COVID-19 in the Bronx, New York. Metabolism 2020, 108, 154262. [Google Scholar] [CrossRef]
- Klein, S.L.; Dhakal, S.; Ursin, R.L.; Deshpande, S.; Sandberg, K.; Mauvais-Jarvis, F. Biological sex impacts COVID-19 outcomes. PLoS Pathog. 2020, 16, e1008570. [Google Scholar] [CrossRef]
- Sharma, G.; Volgman, A.S.; Michos, E.D. Sex Differences in Mortality From COVID-19 Pandemic. JACC Case Rep. 2020, 2, 1407–1410. [Google Scholar] [CrossRef]
- Grundy, E.J.; Suddek, T.; Filippidis, F.T.; Majeed, A.; Coronini-Cronberg, S. Smoking, SARS-CoV-2 and COVID-19: A Review of Reviews Considering Implications for Public Health Policy and Practice. Tob. Induc. Dis. 2020, 18. [Google Scholar] [CrossRef] [PubMed]
- Jamal, A. Current Cigarette Smoking Among Adults—United States, 2005–2015. MMWR Morb. Mortal. Wkly. Rep. 2016, 65. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wang, C.; Pan, R.; Wan, X.; Tan, Y.; Xu, L.; Ho, C.S.; Ho, R.C. Immediate Psychological Responses and Associated Factors during the Initial Stage of the 2019 Coronavirus Disease (COVID-19) Epidemic among the General Population in China. Int. J. Environ. Res. Public Health 2020, 17, 1729. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Takahashi, T.; Ellingson, M.K.; Wong, P.; Israelow, B.; Lucas, C.; Klein, J.; Silva, J.; Mao, T.; Oh, J.E.; Tokuyama, M.; et al. Sex differences in immune responses that underlie COVID-19 disease outcomes. Nature 2020, 1–6. [Google Scholar] [CrossRef]
- Davies, N.G.; Klepac, P.; Liu, Y.; Prem, K.; Jit, M.; Eggo, R.M. Age-dependent effects in the transmission and control of COVID-19 epidemics. Nat. Med. 2020, 26, 1205–1211. [Google Scholar] [CrossRef]
- Yin, Y.; Wunderink, R.G. MERS, SARS and other coronaviruses as causes of pneumonia. Respirology 2018, 23, 130–137. [Google Scholar] [CrossRef] [Green Version]
- Park, J.-E.; Jung, S.; Kim, A.; Park, J.-E. MERS transmission and risk factors: A systematic review. BMC Public Health 2018, 18, 574. [Google Scholar] [CrossRef] [Green Version]
- Viasus, D.; Paño-Pardo, J.R.; Pachón, J.; Campins, A.; López-Medrano, F.; Villoslada, A.; Fariñas, M.C.; Moreno, A.; Rodríguez-Baño, J.; Oteo, J.A.; et al. Factors associated with severe disease in hospitalized adults with pandemic (H1N1) 2009 in Spain. Clin. Microbiol. Infect. 2011, 17, 738–746. [Google Scholar] [CrossRef] [Green Version]
- Ostaszewski, M.; Mazein, A.; Gillespie, M.E.; Kuperstein, I.; Niarakis, A.; Hermjakob, H.; Pico, A.R.; Willighagen, E.L.; Evelo, C.T.; Hasenauer, J.; et al. COVID-19 Disease Map, building a computational repository of SARS-CoV-2 virus-host interaction mechanisms. Sci. Data 2020, 7, 136. [Google Scholar] [CrossRef]
- GTEx Consortium. The Genotype-Tissue Expression (GTEx) project. Nat. Genet. 2013, 45, 580–585. [Google Scholar] [CrossRef]
- Robinson, M.D.; McCarthy, D.J.; Smyth, G.K. edgeR: A Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 2010, 26, 139–140. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Benjamini, Y.; Hochberg, Y. Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing. J. R. Stat. Soc. Series B (Methodol.) 1995, 57, 289–300. [Google Scholar] [CrossRef]
- Yu, G.; Wang, L.-G.; Han, Y.; He, Q.-Y. clusterProfiler: An R Package for Comparing Biological Themes Among Gene Clusters. Omics J. Integr. Biol. 2012, 16, 284–287. [Google Scholar] [CrossRef] [PubMed]
- Baig, A.M.; Khaleeq, A.; Ali, U.; Syeda, H. Evidence of the COVID-19 Virus Targeting the CNS: Tissue Distribution, Host–Virus Interaction, and Proposed Neurotropic Mechanisms. ACS Chem. Neurosci. 2020, 11, 995–998. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chaussabel, D.; Pascual, V.; Banchereau, J. Assessing the human immune system through blood transcriptomics. BMC Biol. 2010, 8, 84. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cueni, L.N.; Detmar, M. The Lymphatic System in Health and Disease. Lymphat. Res. Biol. 2008, 6, 109–122. [Google Scholar] [CrossRef]
- Shi, S.; Su, M.; Shen, G.; Hu, Y.; Yi, F.; Zeng, Z.; Zhu, P.; Yang, G.; Zhou, H.; Li, Q.; et al. Matrix metalloproteinase 3 as a valuable marker for patients with COVID-19. J. Med. Virol. 2020. [Google Scholar] [CrossRef]
- Hadjadj, J.; Yatim, N.; Barnabei, L.; Corneau, A.; Boussier, J.; Smith, N.; Péré, H.; Charbit, B.; Bondet, V.; Chenevier-Gobeaux, C.; et al. Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients. Science 2020, 369, 718–724. [Google Scholar] [CrossRef]
- Ragab, D.; Salah Eldin, H.; Taeimah, M.; Khattab, R.; Salem, R. The COVID-19 Cytokine Storm; What We Know So Far. Front. Immunol. 2020, 11. [Google Scholar] [CrossRef]
- Dunkelberger, J.R.; Song, W.-C. Complement and its role in innate and adaptive immune responses. Cell Res. 2010, 20, 34–50. [Google Scholar] [CrossRef] [Green Version]
- Amara, U.; Rittirsch, D.; Flierl, M.; Bruckner, U.; Klos, A.; Gebhard, F.; Lambris, J.D.; Huber-Lang, M. Interaction Between the Coagulation and Complement System. Adv. Exp. Med. Biol. 2008, 632, 71–79. [Google Scholar] [PubMed] [Green Version]
- Java, A.; Apicelli, A.J.; Liszewski, M.K.; Coler-Reilly, A.; Atkinson, J.P.; Kim, A.H.J.; Kulkarni, H.S. The complement system in COVID-19: Friend and foe? JCI Insight 2020, 5. [Google Scholar] [CrossRef] [PubMed]
- Fang, S.; Wang, H.; Lu, L.; Jia, Y.; Xia, Z. Decreased complement C3 levels are associated with poor prognosis in patients with COVID-19: A retrospective cohort study. Int. Immunopharmacol. 2020, 89, 107070. [Google Scholar] [CrossRef] [PubMed]
- Zhao, Y.; Nie, H.-X.; Hu, K.; Wu, X.-J.; Zhang, Y.-T.; Wang, M.-M.; Wang, T.; Zheng, Z.-S.; Li, X.-C.; Zeng, S.-L. Abnormal immunity of non-survivors with COVID-19: Predictors for mortality. Infect. Dis. Poverty 2020, 9. [Google Scholar] [CrossRef] [PubMed]
- Risitano, A.M.; Mastellos, D.C.; Huber-Lang, M.; Yancopoulou, D.; Garlanda, C.; Ciceri, F.; Lambris, J.D. Complement as a target in COVID-19? Nat. Rev. Immunol. 2020, 20, 343–344. [Google Scholar] [CrossRef] [Green Version]
- Mastaglio, S.; Ruggeri, A.; Risitano, A.M.; Angelillo, P.; Yancopoulou, D.; Mastellos, D.C.; Huber-Lang, M.; Piemontese, S.; Assanelli, A.; Garlanda, C.; et al. The first case of COVID-19 treated with the complement C3 inhibitor AMY-101. Clin. Immunol. 2020, 215, 108450. [Google Scholar] [CrossRef]
- Cugno, M.; Meroni, P.L.; Gualtierotti, R.; Griffini, S.; Grovetti, E.; Torri, A.; Panigada, M.; Aliberti, S.; Blasi, F.; Tedesco, F.; et al. Complement activation in patients with COVID-19: A novel therapeutic target. J. Allergy Clin. Immunol. 2020, 146, 215–217. [Google Scholar] [CrossRef]
- Boxx, G.M.; Cheng, G. The Roles of Type I Interferon in Bacterial Infection. Cell Host Microbe 2016, 19, 760–769. [Google Scholar] [CrossRef] [Green Version]
- Huber, J.P.; Farrar, J.D. Regulation of effector and memory T-cell functions by type I interferon. Immunology 2011, 132, 466–474. [Google Scholar] [CrossRef]
- Fingleton, B. Matrix metalloproteinases as regulators of inflammatory processes. Biochim. Biophys. Acta (BBA) Mol. Cell Res. 2017, 1864, 2036–2042. [Google Scholar] [CrossRef]
- Medzhitov, R. Origin and physiological roles of inflammation. Nature 2008, 454, 428–435. [Google Scholar] [CrossRef] [PubMed]
- Eba, H.; Murasawa, Y.; Iohara, K.; Isogai, Z.; Nakamura, H.; Nakamura, H.; Nakashima, M. The anti-inflammatory effects of matrix metalloproteinase-3 on irreversible pulpitis of mature erupted teeth. PLoS ONE 2012, 7, e52523. [Google Scholar] [CrossRef] [Green Version]
- Mouton, A.J.; Rivera Gonzalez, O.J.; Kaminski, A.R.; Moore, E.T.; Lindsey, M.L. Matrix Metalloproteinase-12 as an endogenous resolution promoting factor following myocardial infarction. Pharmacol. Res. 2018, 137, 252–258. [Google Scholar] [CrossRef]
- Davey, A.; McAuley, D.F.; O’Kane, C.M. Matrix metalloproteinases in acute lung injury: Mediators of injury and drivers of repair. Eur. Respir. J. 2011, 38, 959–970. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Solun, B.; Shoenfeld, Y. Inhibition of metalloproteinases in therapy for severe lung injury due to COVID-19. Med. Drug Discov. 2020, 7, 100052. [Google Scholar] [CrossRef] [PubMed]
- Oliva, M.; Muñoz-Aguirre, M.; Kim-Hellmuth, S.; Wucher, V.; Gewirtz, A.D.H.; Cotter, D.J.; Parsana, P.; Kasela, S.; Balliu, B.; Viñuela, A.; et al. The impact of sex on gene expression across human tissues. Science 2020, 369, 6509:eaba3066. [Google Scholar] [CrossRef]
- Blanco-Melo, D.; Nilsson-Payant, B.E.; Liu, W.-C.; Uhl, S.; Hoagland, D.; Møller, R.; Jordan, T.X.; Oishi, K.; Panis, M.; Sachs, D.; et al. Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19. Cell 2020, 181, 1036–1045.e9. [Google Scholar] [CrossRef]
- Channappanavar, R.; Fehr, A.R.; Vijay, R.; Mack, M.; Zhao, J.; Meyerholz, D.K.; Perlman, S. Dysregulated Type I Interferon and Inflammatory Monocyte-Macrophage Responses Cause Lethal Pneumonia in SARS-CoV-Infected Mice. Cell Host Microbe 2016, 19, 181–193. [Google Scholar] [CrossRef] [Green Version]
- Strope, J.D.; Chau, C.H.; Figg, W.D. Are sex discordant outcomes in COVID-19 related to sex hormones? Semin. Oncol. 2020, 47, 335–340. [Google Scholar] [CrossRef]
- Scully, E.P.; Haverfield, J.; Ursin, R.L.; Tannenbaum, C.; Klein, S.L. Considering how biological sex impacts immune responses and COVID-19 outcomes. Nat. Rev. Immunol. 2020, 20, 442–447. [Google Scholar] [CrossRef]
Analysis | Whole Blood | Kidney-Cortex | Stomach | Lung | Heart Left-Ventricle | Brain-Cortex | Spleen | Lymphocytes |
---|---|---|---|---|---|---|---|---|
Sex: p < 0.05; FC > 0.5 | 77 | 93 | 56 | 47 | 57 | 47 | 91 | 65 |
Sex: p < 0.05 | 438 | 184 | 213 | 179 | 252 | 270 | 480 | 193 |
Age: p < 0.05; FC > 0.5 | 104 | 69 | 76 | 41 | 51 | 45 | 99 | 104 |
Age: p < 0.05 | 330 | 184 | 408 | 180 | 183 | 799 | 515 | 315 |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Liu, T.; Balzano-Nogueira, L.; Lleo, A.; Conesa, A. Transcriptional Differences for COVID-19 Disease Map Genes between Males and Females Indicate a Different Basal Immunophenotype Relevant to the Disease. Genes 2020, 11, 1447. https://doi.org/10.3390/genes11121447
Liu T, Balzano-Nogueira L, Lleo A, Conesa A. Transcriptional Differences for COVID-19 Disease Map Genes between Males and Females Indicate a Different Basal Immunophenotype Relevant to the Disease. Genes. 2020; 11(12):1447. https://doi.org/10.3390/genes11121447
Chicago/Turabian StyleLiu, Tianyuan, Leandro Balzano-Nogueira, Ana Lleo, and Ana Conesa. 2020. "Transcriptional Differences for COVID-19 Disease Map Genes between Males and Females Indicate a Different Basal Immunophenotype Relevant to the Disease" Genes 11, no. 12: 1447. https://doi.org/10.3390/genes11121447
APA StyleLiu, T., Balzano-Nogueira, L., Lleo, A., & Conesa, A. (2020). Transcriptional Differences for COVID-19 Disease Map Genes between Males and Females Indicate a Different Basal Immunophenotype Relevant to the Disease. Genes, 11(12), 1447. https://doi.org/10.3390/genes11121447