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Immunity debt and immunity theft: the global resurgence of respiratory infections

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The recent resurgence of respiratory infections following the COVID-19 pandemic is a topic of great interest, with the prevalence of viral infections such as influenza and respiratory syncytial virus (RSV) on the rise around the globe.1 With COVID-19 still spreading rapidly in many countries,2 the collision of these viruses has been termed a ‘tripledemic’.3 The incidence of bacterial infections such as Streptococcus pneumoniae and group A Streptococcus have also been increasing.4

Whilst the mechanisms behind the rising incidence of these infections are unknown, current thought amongst experts are around the concepts of immunity debt versus immunity theft.


Implications of COVID-19 lockdowns

The prevalence of infectious diseases such as influenza and RSV decreased significantly during lockdowns,7 with a 93.4% reduction in RSV detection during winter 2020 in Australia.4 Researchers accurately predicted there would be a rise in viral infections following the NPIs imposed during the COVID-19 pandemic,8 with staggering surges in respiratory tract infections (RTIs) across the globe following the lifting of lockdowns in 2021.4,9,10 In 2022, compared to 2019, Germany saw a four-fold increase in the number of RTIs,9 with prevalence continuing to rise across Europe, with higher levels of fever and cough this past winter.11 Interestingly, there also appears to be a seasonal shift, with statistical data showing that the number of infections and hospital admissions post-pandemic were similar or even greater outside of the typical winter peaks,4 making immune health a consideration all year.


Immune system dysregulation

One of the most concerning long-term impacts of COVID-19 is the potential immune dysregulation that can persist after infection.13 Multiple studies have identified protein and genetic material from SARS-CoV-2 persisting in the body for over one year following contraction of COVID-19.13

Viral persistence may occur following acute infection if a virus is not completely cleared allowing for the continued viral replication and viral protein production to persist in tissues.13 These viral proteins are then released into circulation, interfering with immune responses, dysregulating the immune system, promoting inflammation, and activating latent viruses.13 Viral persistence can damage tissues by altering the differentiation of virus-specific T and B cells over time.13 A study demonstrated that immunological dysfunction persisted in patients with long COVID for 8 months after infection, with these patients demonstrating persistently highly activated innate immune cells and reduced naive T and B cells following infection.14

Remarkably, viral proteins have been found in tissues all over the body, including the reproductive system, cardiovascular system, brain, muscles, eyes, and lung tissue.15 Viral persistence has also been demonstrated with other viruses, such as Ebola virus, which can linger in tissues and cause chronic symptoms and new outbreaks.16


Nutrients and herbal medicines

Certain nutrients and herbal medicines can support the regulation of immune activity, providing protection from infections, relief of common symptoms, and accelerate recovery.

Key nutrients to enhance immune system health include zinc, vitamins C and D, probiotics, and quercetin, with specific therapeutic dosages recommended for protection against respiratory viruses (see Table 1).21 Together, these nutrients play a key role in immune system defence and restoration (see Table 2).21


Evidence clearly demonstrates the importance of regular physical activity, adequate sleep, and effective stress management for optimal immune system health. Lack of movement, poor sleep, and chronic stress can hinder immune function, promote inflammation, and increase the risk of infection from respiratory viruses.22

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1  Chuang YC, Lin KP, Wang LA, Yeh TK, Liu PY. The Impact of the COVID-19 Pandemic on Respiratory Syncytial Virus Infection: A Narrative Review. Infection and Drug Resistance [Internet]. 2023 Jan 30;16:661–75. Available from: https://www.dovepress.com/ the-impact-of-the-covid-19-pandemic-on-respiratory-syncytial-virus-inf-peer-reviewed-fulltext-article-IDR

2  Are EB, Song Y, Stockdale JE, Tupper P, Colijn C. COVID-19 endgame: From pandemic to endemic? Vaccination, reopening and evolution in low- and high-vaccinated populations. Journal of Theoretical Biology. 2023 Feb;559:111368.

3  Luo W, Liu Q, Zhou Y, Ran Y, Liu Z, Hou W, et al. Spatiotemporal variations of “triple-demic” outbreaks of respiratory infections in the United States in the post-COVID-19 era. BMC Public Health. 2023 Dec 7;23(1).

4  Principi N, Autore G, Ramundo G, Esposito S. Epidemiology of Respiratory Infections during the COVID-19 Pandemic. Viruses. 2023 May 13;15(5):1160–0.

5  Rubin R. From “Immunity Debt” to “Immunity Theft”—How COVID-19 Might Be Tied to Recent Respiratory Disease Surges. JAMA [Internet]. 2024 [cited 2024 Jan 14]; Available from: https://jamanetwork.com/journals/jama/fullarticle/2814028

6  Marshall JS, Warrington R, Watson W, Kim HL. An Introduction to Immunology and Immunopathology. Allergy, Asthma & Clinical Immunology. 2018 Sep;14(S2).

7  The Influence of COVID-19 on Influenza and Respiratory Syncytial Virus Activities. ProQuest [Internet]. 2022 [cited 2022 Nov 27];134. Available from: https://www.proquest.com/docview/2632745870/96097CD264734BC4PQ/7?account...

8  Cohen R, Ashman M, Taha MK, Varon E, Angoulvant F, Levy C, et al. Pediatric Infectious Disease Group (GPIP) position paper on the immune debt of the COVID-19 pandemic in childhood, how can we fill the immunity gap? Infectious Diseases Now [Internet]. 2021 Aug 1;51(5):418–23. Available from: https://www.sciencedirect.com/science/article/pii/S2666991921001123

9  Maison N, Omony J, Rinderknecht S, Kolberg L, Meyer-Bühn M, Erika von Mutius, et al. Old foes following news ways?— Pandemic-related changes in the epidemiology of viral respiratory tract infections. Infection. 2023 Aug 29; Mondal - https:// www.ncbi.nlm.nih.gov/pmc/articles/PMC8872472/

10  Virgili F, Petrarca L, Conti MG, Midulla F, Nenna R. Acute bronchiolitis in Post-COVID era: is the immunity debt paid off. Clin Case Rep Int. 2023; 7. 2023;1473.

11  Respiratory infectious diseases on the rise across WHO European Region [Internet]. www.who.int. Available from: https://www. who.int/europe/news/item/15-12-2023-respiratory-infectious-diseases-on-the-rise-across-who-european-region

12  MSc (Res) SJY. Immunity Debt vs. Theft: What Explains the Post-Lockdown Infection Rebounds? [Internet]. Microbial Instincts. 2023 [cited 2024 Mar 23]. Available from: https://medium.com/microbial-instincts/immunity-debt-vs-theft-what-expla... post-lockdown-infection-rebounds-2a218283936e

13  Proal AD, VanElzakker MB, Aleman S, Bach K, Boribong BP, Buggert M, et al. SARS-CoV-2 reservoir in post-acute sequelae of COVID-19 (PASC). Nature Immunology [Internet]. 2023 Oct 1;24(10):1616–27. Available from: https://www.nature.com/articles/ s41590-023-01601-2

14  Phetsouphanh C, Darley DR, Wilson DB, Howe A, Munier CML, Patel SK, et al. Immunological dysfunction persists for 8 months following initial mild-to-moderate SARS-CoV-2 infection. Nature Immunology [Internet]. 2022 Jan 13;23(2):210–6. Available from: https://www.nature.com/articles/s41590-021-01113-x.pdf

15  Davis HE, McCorkell L, Vogel JM, Topol EJ. Long COVID: major findings, mechanisms and recommendations. Nature Reviews Microbiology. 2023 Mar;21(3):133-46.

16 Chen B, Julg B, Mohandas S, Bradfute SB. Viral persistence, reactivation, and mechanisms of long COVID. eLife. 2023 May 4;12.

17 Boyce L. LibGuides: COVID Impacts: Immune Dysfunction [Internet]. libguides.mskcc.org. Available from: https://libguides. mskcc.org/CovidImpacts/Immune

18 Jiang Y, Zhao T, Zhou X, Xiang Y, Gutierrez‐Castrellon P, Ma X. Inflammatory pathways in COVID‐19: Mechanism and therapeutic interventions. MedComm. 2022 Aug;3(3).

19 Files JK, Boppana S, Perez MD, Sarkar S, Lowman KE, Qin K, et al. Sustained cellular immune dysregulation in individuals recovering from SARS-CoV-2 infection. The Journal of Clinical Investigation [Internet]. 2021 Jan 4;131(1). Available from: https:// pubmed.ncbi.nlm.nih.gov/33119547/

20 Davitt E, Davitt C, Mazer MB, Areti SS, Hotchkiss RS, Remy KE. COVID-19 disease and immune dysregulation. Best Practice & Research Clinical Haematology [Internet]. 2022 Sep 1 [cited 2023 Apr 21];35(3):101401. Available from: https://www. sciencedirect.com/science/article/pii/S1521692622000561

21 Blackmores. Immunity Guide [Internet]. www.blackmoresinstitute.org. [cited 2024 Mar 15]. Available from: https://www. blackmoresinstitute.org/immunity-guide

22 Monye I, Adelowo AB. Strengthening immunity through healthy lifestyle practices: Recommendations for lifestyle interventions in the management of COVID‐19. Lifestyle Medicine. 2020 Oct 3;

23 Cristofori F, Dargenio VN, Dargenio C, Miniello VL, Barone M, Francavilla R. Anti-Inflammatory and Immunomodulatory Effects of Probiotics in Gut Inflammation: A Door to the Body. Frontiers in Immunology [Internet]. 2021 Feb 26;12. Available from: https:// www.ncbi.nlm.nih.gov/pmc/articles/PMC7953067/

24 Mazziotta C, Tognon M, Martini F, Torreggiani E, Rotondo JC. Probiotics Mechanism of Action on Immune Cells and Beneficial Effects on Human Health. Cells. 2023 Jan 2;12(1):184.

25 Harper A, Vijayakumar V, Ouwehand AC, ter Haar J, Obis D, Espadaler J, et al. Viral Infections, the Microbiome, and Probiotics. Frontiers in Cellular and Infection Microbiology [Internet]. 2021 Feb 12 [cited 2021 Jul 17];10. Available from: https://www.ncbi.nlm. nih.gov/pmc/articles/PMC7907522/

26 Vijay A, Valdes AM. Role of the gut microbiome in chronic diseases: a narrative review. European Journal of Clinical Nutrition [Internet]. 2021 Sep 28;76:1–13. Available from: https://www.nature.com/articles/PMC8477631/

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