On the Relationship between Asymptomatic Infections and Diseases


  • Martin Zach Department of Analytic Philosophy, Institute of Philosophy of the Czech Academy of Sciences, Prague, Czechia https://orcid.org/0000-0001-7181-0391




Host-microbe interaction, Immunology, Philosophy of science, Asymptomatic infection, Disease


Many microbes responsible for infectious diseases are known to run an asymptomatic course in a significant portion of the population. By highlighting the conceptual complexities of host-microbe interactions, this paper elucidates the fact that while many infections remain asymptomatic, this does not necessarily mean that such infections are of no concern for health. The paper builds on the so-called damage-response framework and considers several developments required to gain a more comprehensive perspective on infections and their relationship to diseases. Irrespective of their (short-term) clinical manifestation, infections leave an imprint with consequences for health. Finally, these considerations regarding host-microbe interactions must be incorporated into policy decisions and public understanding of health if we hope to handle future pandemics such as Covid-19 better.


Akdis, Cezmi A. 2021. “Does the Epithelial Barrier Hypothesis Explain the Increase in Allergy, Autoimmunity and Other Chronic Conditions?” Nature Reviews Immunology 21, no. 11: 739–751. https://doi.org/10.1038/s41577-021-00538-7.

Altmann, Daniel M., Emily M. Whettlock, Siyi Liu, Deepa J. Arachchillage, and Rosemary J. Boyton. 2023. “The Immunology of Long COVID.” Nature Reviews Immunology, 11 July: 1–17. https://doi.org/10.1038/s41577-023-00904-7.

Amoretti, Maria Cristina and Elisabetta Lalumera. 2020. “The Concept of Disease in the Time of COVID-19.” Theoretical Medicine and Bioethics 41, nos. 5–6: 203–221. https://doi.org/10.1007/s11017-021-09540-5.

Ayres, Janelle. 2016. "Ending the Arms Race with Infectious Diseases." TEDxSanDiego, 23 November. https://www.youtube.com/watch?v=7ZWTG0-eCEg.

———. 2020. “Surviving COVID-19: A Disease Tolerance Perspective.” Science Advances 6, no. 18, eabc1518. https://doi.org/10.1126/sciadv.abc1518.

Broadbent, Alex. 2014. “Disease as a Theoretical Concept: The Case of ‘HPV-Itis.’” Studies in History and Philosophy of Science Part C: Studies in History and Philosophy of Biological and Biomedical Sciences 48 (Part B): 250–257. https://doi.org/10.1016/j.shpsc.2014.07.010.

CDC (Centers for Disease Control and Prevention). 2022. “What Is Polio?” https://www.cdc.gov/polio/what-is-polio/index.htm.

Chen, Ingrid, Siân E. Clarke, Roly Gosling, Busiku Hamainza, Gerry Killeen, Alan Magill, Wendy O’Meara, Ric N. Price, and Eleanor M. Riley. 2016. “‘Asymptomatic’ Malaria: A Chronic and Debilitating Infection that Should Be Treated.” PLOS Medicine 13, no. 1, e1001942. https://doi.org/10.1371/journal.pmed.1001942.

Choutka, Jan, Viraj Jansari, Mady Hornig, and Akiko Iwasaki. 2022. “Unexplained Post-Acute Infection Syndromes.” Nature Medicine 28, no. 5: 911–923. https://doi.org/10.1038/s41591-022-01810-6.

Da Fonseca, Denise Morais, Timothy W. Hand, Seong Ji Han, Michael Y. Gerner, Arielle Glatman Zaretsky, Allyson L. Byrd, Oliver J. Harrison, et al. 2015. “Microbiota-Dependent Sequelae of Acute Infection Compromise Tissue-Specific Immunity.” Cell 163, no. 2: 354–366. https://doi.org/10.1016/j.cell.2015.08.030.

De Steenhuijsen Piters, Wouter A.A., Rebecca L. Watson, Emma M. de Koff, Raiza Hasrat, Kayleigh Arp, Mei Ling J.N. Chu, Pieter C.M. de Groot, et al. 2022. “Early-Life Viral Infections Are Associated with Disadvantageous Immune and Microbiota Profiles and Recurrent Respiratory Infections.” Nature Microbiology 7, no. 2: 224–237. https://doi.org/10.1038/s41564-021-01043-2.

Didierlaurent, Arnaud, John Goulding, Seema Patel, Robert Snelgrove, Lionel Low, Magali Bebien, Toby Lawrence, et al. 2008. “Sustained Desensitization to Bacterial Toll-Like Receptor Ligands after Resolution of Respiratory Influenza Infection.” Journal of Experimental Medicine 205, no. 2: 323–329. https://doi.org/10.1084/jem.20070891.

Divangahi, Maziar, Peter Aaby, Shabaana Abdul Khader, Luis B. Barreiro, Siroon Bekkering, Triantafyllos Chavakis, Reinout van Crevel, et al. 2020. “Trained Immunity, Tolerance, Priming and Differentiation: Distinct Immunological Processes.” Nature Immunology 22, no. 1: 2–6. https://doi.org/10.1038/s41590-020-00845-6.

Doolan, Denise L., Carlota Dobaño, and J. Kevin Baird. 2009. “Acquired Immunity to Malaria.” Clinical Microbiology Reviews 22, no. 1: 13–36. https://doi.org/10.1128/cmr.00025-08.

Eberl, Gérard. 2016. “Immunity by Equilibrium.” Nature Reviews Immunology 16, no. 8: 524–532. https://doi.org/10.1038/nri.2016.75.

Feehan, Karen T. and Derek W. Gilroy. 2019. “Is Resolution the End of Inflammation?” Trends in Molecular Medicine 25, no. 3: 198–214. https://doi.org/10.1016/j.molmed.2019.01.006.

Fuller, Jonathan. 2018. “What Are Chronic Diseases?” Synthese 195, 7: 3197–3220. https://doi.org/10.1007/s11229-017-1368-1.

Goulding, John, Robert Snelgrove, José Saldana, Arnaud Didierlaurent, Mary Cavanagh, Emily Gwyer, Jeremy Wales, Erika L. Wissinger, and Tracy Hussell. 2007. “Respiratory Infections: Do We Ever Recover?” Proceedings of the American Thoracic Society 4,no. 8: 618–625. https://doi.org/10.1513/pats.200706-066TH.

Griffin, Diane E. 2022. “Why Does Viral RNA Sometimes Persist after Recovery from Acute Infections?” PLOS Biology 20, no. 6, e3001687. https://doi.org/10.1371%2Fjournal.pbio.3001687.

Hayes, Kelly S., Laura J. Cliffe, Alison J. Bancroft, Simon P. Forman, Seona Thompson, Cath Booth, and Richard K. Grencis. 2017. “Chronic Trichuris Muris Infection Causes Neoplastic Change in the Intestine and Exacerbates Tumour Formation in APC Min/+ Mice.” PLOS Neglected Tropical Diseases 11, no. 6, e0005708. https://doi.org/10.1371/journal.pntd.0005708.

Hesslow, Germund. 1993. “Do We Need a Concept of Disease?” Theoretical Medicine 14, no. 1: 1–14. http://dx.doi.org/10.1007/BF00993984.

Hussell, Tracy. 2016. “Heterologous Immunity Meets Tissue-Specific Training.” Nature Reviews Immunology 16, no. 5, 275. https://doi.org/10.1038/nri.2016.41.

Jenkins, Stephen J. and Judith E. Allen. 2021. “The Expanding World of Tissue-Resident Macrophages.” European Journal of Immunology 51, no. 8: 1882–1896. https://doi.org/10.1002/eji.202048881.

Leavitt, Judith W. 1992. “‘Typhoid Mary’ Strikes Back: Bacteriological Theory and Practice in Early Twentieth-Century Public Health.” Isis 83, no. 4: 608–629. https://doi.org/10.1086/356292.

Lemoine, Maël. 2013. “Defining Disease beyond Conceptual Analysis: An Analysis of Conceptual Analysis in Philosophy of Medicine.” Theoretical Medicine and Bioethics 34, no. 4: 309–325. https://doi.org/10.1007/s11017-013-9261-5.

———. Forthcoming 2024. Basic Concepts of Medical Science. Cambridge: Cambridge University Press.

Maizels, Rick M. and Henry J. McSorley. 2016. “Regulation of the Host Immune System by Helminth Parasites.” Journal of Allergy and Clinical Immunology 138, no. 3: 666–675. https://doi.org/10.1016%2Fj.jaci.2016.07.007.

Maziarz, Mariusz and Martin Zach. 2020. “Agent‐Based Modelling for SARS‐ CoV‐2 Epidemic Prediction and Intervention Assessment: A Methodological Appraisal.” Journal of Evaluation in Clinical Practice 26, no. 5: 1352–1360. https://doi.org/10.1111/jep.13459.

———. 2021. “Assessing the Quality of Evidence from Epidemiological Agent-Based Models for the COVID-19 Pandemic.” History and Philosophy of the Life Sciences 43, no. 1, 10. https://doi.org/10.1007/s40656-020-00357-4.

Medzhitov, Ruslan, David S. Schneider, and Miguel P. Soares. 2012. “Disease Tolerance as a Defense Strategy.” Science 335, no. 6071: 936–941. https://doi.org/10.1126/science.1214935.

Méthot, Pierre-Olivier and Samuel Alizon. 2014. “What Is a Pathogen? Toward a Process View of Host-Parasite Interactions.” Virulence 5, no. 8: 775–785. https://doi.org/10.4161/21505594.2014.960726.

Meyerowitz, Eric A., Aaron Richterman, Isaac I. Bogoch, Nicola Low, and Muge Cevik. 2021. “Towards an Accurate and Systematic Characterisation of Persistently Asymptomatic Infection with SARS-CoV-2.” Lancet Infectious Diseases 21, no. 6: e163–e169. https://doi.org/10.1016/S1473-3099(20)30837-9.

Motwani, Madhur P., Justine Newson, Simon Kwong, Angela Richard-Loendt, Romain Colas, Jesmond Dalli, and Derek W. Gilroy. 2017. “Prolonged Immune Alteration Following Resolution of Acute Inflammation in Humans.” PLOS ONE 12, no. 10, e0186964. https://doi.org/10.1371/journal.pone.0186964.

Murphy, Dominic. 2020. “Concepts of Disease and Health.” In The Stanford Encyclopedia of Philosophy (Spring 2021 Edition), edited by Edward N. Zalta. https://plato.stanford.edu/archives/spr2021/entries/health-disease/.

Naik, Shruti and Elaine Fuchs. 2022. “Inflammatory Memory and Tissue Adaptation in Sickness and in Health.” Nature 607, no. 7918: 249–255. https://doi.org/10.1038/s41586-022-04919-3.

Netea, Mihai G., Jorge Domínguez-Andrés, Luis B. Barreiro, Triantafyllos Chavakis, Maziar Divangahi, Elaine Fuchs, Leo A.B. Joosten, et al. 2020. “Defining Trained Immunity and Its Role in Health and Disease.” Nature Reviews Immunology 20, no. 6: 375–388. https://doi.org/10.1038/s41577-020-0285-6.

Olive, Andrew J. and Christopher M. Sassetti. 2018. “Tolerating the Unwelcome Guest: How the Host Withstands Persistent Mycobacterium Tuberculosis.” Frontiers in Immunology 9 (September), 2094. https://doi.org/10.3389%2Ffimmu.2018.02094.

Pirofski, Liise-anne and Arturo Casadevall. 2002. “The Meaning of Microbial Exposure, Infection, Colonisation, and Disease in Clinical Practice.” Lancet Infectious Diseases 2, no. 10: 628–635. https://doi.org/10.1016/s1473-3099(02)00398-5.

Rakoff-Nahoum, Seth, Justin Paglino, Fatima Eslami-Varzaneh, Stephen Edberg, and Ruslan Medzhitov. 2004. “Recognition of Commensal Microflora by Toll-Like Receptors Is Required for Intestinal Homeostasis.” Cell 118, no. 2: 229–241. https://doi.org/10.1016/j.cell.2004.07.002.

Reiss, Julian and Rachel A. Ankeny. 2016. “Philosophy of Medicine.” In The Stanford Encyclopedia of Philosophy, edited by Edward N. Zalta. https://plato.stanford.edu/archives/spr2022/entries/medicine/.

Sachs, David H. 2003. “Tolerance: Of Mice and Men.” Journal of Clinical Investigation 111, no. 12: 1819–1821. https://doi.org/10.1172/JCI18926.

Schneider, David S. 2021. “Immunology’s Intolerance of Disease Tolerance.” Nature Reviews Immunology 21, no. 10: 624–625. https://doi.org/10.1038/s41577-021-00619-7.

Schneider, David S. and Janelle S. Ayres. 2008. “Two Ways to Survive Infection: What Resistance and Tolerance Can Teach Us about Treating Infectious Diseases.” Nature Reviews Immunology 8, no. 11: 889–895. https://doi.org/10.1038/nri2432.

Sholl, Jonathan. 2015. “Escaping the Conceptual Analysis Straitjacket: Pathological Mechanisms and Canguilhem’s Biological Philosophy.” Perspectives in Biology and Medicine 58, no. 4: 395–418. https://doi.org/10.1353/pbm.2015.0032.

Snelgrove, Robert J., Alexandra Godlee, and Tracy Hussell. 2011. “Airway Immune Homeostasis and Implications for Influenza-Induced Inflammation.” Trends in Immunology 32, no. 7: 328–334. https://doi.org/10.1016/j.it.2011.04.006.

Soares, Miguel P., Luis Teixeira, and Luis F. Moita. 2017. “Disease Tolerance and Immunity in Host Protection against Infection.” Nature Reviews Immunology 17, no. 2: 83–96. https://doi.org/10.1038/nri.2016.136.

Sollid, Ludvig M. 2022. “Epstein-Barr Virus as a Driver of Multiple Sclerosis.” Science Immunology 7, 70, eabo7799. https://doi.org/10.1126/sciimmunol.abo7799.

Sollid, Ludvig M. and Bana Jabri. 2013. “Triggers and Drivers of Autoimmunity: Lessons from Coeliac Disease.” Nature Reviews Immunology 13, no. 4: 294–302. https://doi.org/10.1038/nri3407.

Spinney, Laura. 2022. “Pandemics Disable People: The History Lesson that Policymakers Ignore.” Nature 602, no. 7897: 383–385. https://doi.org/10.1038/d41586-022-00414-x.

Swenson, Kai E., Stephen J. Ruoss, and Erik R. Swenson. 2021. “The Pathophysiology and Dangers of Silent Hypoxemia in COVID-19 Lung Injury.” Annals of the American Thoracic Society 18, no. 7: 1098–1105. https://doi.org/10.1513/annalsats.202011-1376cme.

Urbanowski, Michael E., Elizabeth A. Ihms, Kristina Bigelow, André Kübler, Paul T. Elkington, and William R. Bishai. 2018. “Repetitive Aerosol Exposure Promotes Cavitary Tuberculosis and Enables Screening for Targeted Inhibitors of Extensive Lung Destruction.” Journal of Infectious Diseases 218, no. 1: 53–63. https://doi.org/10.1093/infdis/jiy127.

Weinberg, Robert A. 2014. The Biology of Cancer. 2nd ed. New York: Garland Science.

Welsh, Raymond M. and Liisa K. Selin. 2002. “No One Is Naive: The Significance of Heterologous T-Cell Immunity.” Nature Reviews Immunology 2, no. 6: 417–426. https://doi.org/10.1038/nri820.

Yong, Ed. 2020. “Immunology Is Where Intuition Goes to Die.” The Atlantic, 5 August. https://www.theatlantic.com/health/archive/2020/08/covid-19-immunity-is-the-pandemics-central-mystery/614956.

Zach, Martin and Gregor P. Greslehner. 2022. “Towards an Extended View of Immunity: A Philosophical Perspective.” Anaesthesia Critical Care & Pain Medicine 41, no. 6, 101156. https://doi.org/10.1016/j.accpm.2022.101156.

———. 2023. “Understanding Immunity: An Alternative Framework beyond Defense and Strength.” Biology & Philosophy 38, no. 1: 1–25. https://doi.org/10.1007/s10539-023-09893-2.




How to Cite

Zach, M. (2023). On the Relationship between Asymptomatic Infections and Diseases . Philosophy of Medicine, 4(1). https://doi.org/10.5195/pom.2023.171



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