Is Natural Immunity Inviolable?

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The obvious answer is NO, otherwise no one would suffer immune related illness and death.

The ability of your immune system to respond, repel and return to homeostasis after insult has many influencing factors. Yet our long history of survival as a species indicates that our immune response is adaptive and sustaining, subject to its challenges being manageable. This incredible plasticity involves ‘immunological trade-offs’ and shapes disease outcomes at individual and population scales. These ‘trade-offs’ mainly exist at a cellular level and impact the survivability of every organism. They may also be intentional behaviours that impact daily decisions or carefully mediated, innate behaviours.

Whilst current focus is on the ‘insult’, others study the capability of the innate immune defences and the creation of a memory-based response triggered via exposure or vaccination. There is a large health generation opportunity understanding how all aspects can be manipulated in the sustainability of immunocompetence. For Immunocompetence depends on adequate protein energy nutrition as well as multiple micronutrients[1]. Yet ensuring and sustaining immune defences has a cost.

These can be summarised into two main categories, representing the stage on which they act.

  1. The evolutionary costs involved in evolving an efficient immune system[2], and
  2. The costs of maintaining and using this immune system to successfully combat parasites, pathogens and environmental events that pose a significant threat to the integrity of self.

Due to the inherent biological costs in immunity, and variation between the adaptive value of a particular immune response, an optimal immune defence will vary both temporally and spatially. i.e it will wax and wane, with related benefits and risks to the host.

Immune responses vary significantly across individuals and are not solely determined by their genetics. A particular immune response will be genetically encoded to some degree (mainly in the innate immune responses), but will also be a product of such things as diet[3], gender[4], age[5], stress levels[6], and past or ongoing biotic interactions[7], including viruses, dysbiosis[8] and parasites[9].

Implicit as a confounder around these factors are environmental influences, including the lived environment, the eaten or consumed elements, as well as the social and psychological experiences each person contends with. Medicine and science is increasingly taking a big picture approach to human health and over 230 medical journals[10] published a matching editorial on the 6th September 2021 stating: Climate crisis is the “greatest” health threat[11]. In effect elevating climate ahead of our current challenges with viral infection.

Post Covid-19 Immunity (natural or induced?)

Freely circulating viruses, especially coronaviruses and influenza viruses, which encode their genetic instructions using the molecule RNA, mutate frequently[12] and randomly[13] due to copying errors introduced as they replicate in their human host cells. This results in variants, and at the time of writing the most common variant of concern is Delta. This is unlikely to be the last but is currently estimated to be the most easily transmissible[14] and most dangerous[15] to health to date.

A recurring question is, does catching Sars-Cov-2 and surviving, confer a genuine immunological benefit that may provide long term resilience[16]. A pre-paper published on Israeli data (on the medRxiv site) indicates that it does, indicating the remarkable capability of our immune system to adapt to insults[17].

Dr Eric Topol a well-respected physician-scientist at Scripps Research reported on the paper stating “We continue to underestimate the importance of natural infection immunity … especially when [infection] is recent”. “And when you bolster that with one dose of vaccine, you take it to levels you can’t possibly match with any vaccine in the world right now.”

For many infectious diseases, naturally acquired immunity is now known to be more powerful than vaccine-induced immunity and it often lasts a lifetime. Other coronaviruses that cause the serious human diseases severe acute respiratory syndrome[18] and Middle East respiratory syndrome[19] and endemic human coronaviruses trigger robust and persistent immune responses. But taking the decision to deliberately infect yourself and/or others is not proposed to be a rational use of limited resources, including immune and societal (as a higher infectiousness simply means a greater number will display symptoms).

Waning Immunity

Natural post infective and vaccine induced effectiveness are not monoliths. Staying safe from a pathogen depends on host and pathogen alike; a change in either can chip away at the barriers that separate the two without obliterating them, which to some extent is what we see with what are called breakthrough events, where the level of neutralising antibodies have declined[20]. As the infectious threat passes, our immune response contracts; frontline B and T cells, no longer needed in their amped-up state, start to die off. All of these B cells can continue to broaden and intensify[21] their virus-vanquishing powers for months after a vaccine or pathogen leaves the body[22], in a sped-up form of antibody evolution[23]. Populations[24] of memory T cells[25], can hide out for many months[26] or years in tissues, waiting to strike again, acting as vital memory defences. Neutralising antibodies also have varied individual immune longevity and are part of the immune systems most effective response to subsequent exposure[27].

Neutralising antibodies are naturally occurring antibodies that play an important role in the immune system. They work alongside binding antibodies that signal the presence of a pathogen in the body so that white blood cells can locate and kill it. They are responsible for blocking the entry of a pathogen into a cell so that it is firstly unable to infect healthy cells, and secondly, it is unable to replicate and cause severe infection.

That’s why post-infective and post vaccine infections, when they do happen, tend to be milder[28], shorter[29], and less likely to spread to other people[30]. It also means that the concepts of infection and disease need to be viewed individually.

For whilst it is normal for immune responses to wane, those who have had either a vaccine, have recovered from infection or both, are far more able to respond to future exposures with reduced risk of serious outcomes. Neither makes us impervious, they just ensure a better equipped ability to mount an immune response. There may also be a subsequent development when prior infected people receive a vaccination, known as “hybrid vigor immunity”. Overall, hybrid immunity to SARS-CoV-2 appears to be impressively potent[31]. The synergy is primarily observed for the antibody response more so than the T cell response after vaccination, although the enhanced antibody response depends on memory T cells.

But as explained, immune responses both pre and post infection of vaccination:

(i) do vary in nature, (ii) can be costly, (iii) optimality of immunity will rarely be achieved and only transiently, and (iv) observed immune defences will depend on both historical and contemporary factors (in particular nutrition status) within an individual’s environment.

Non-Pharma Option Update

Two interesting articles appeared in the early part of September 2021. The first published in the proceeding of the National Academy of Sciences reviewed whether any existing medication or allied therapeutic may confer effectiveness against Sars-Cov-2[32]. Various drugs were tested to see if they may induce the death of the Sars-Cov-2 virus. Interestingly the authors reported the following.

Most noteworthy, the screening identified bovine lactoferrin, a safe and widely available dietary supplement, with multimodal efficacy in multiple cell systems, including non-transformed and physiologically relevant iAEC2s. Our study is the only repurposing discovery effort that included several proteins (like lactoferrin), as conventional high-throughput screening is generally limited to small molecules in DMSO. Lactoferrin gene expression was shown to be highly up-regulated in response to SARS-CoV-1 infection, and in addition to enhancing natural killer cell and neutrophil activity, lactoferrin blocks SARS-CoV-1 attachment through binding to heparan sulphate proteoglycans.

First, it strongly inhibited cellular binding of SARS-CoV-2 to cells via competition with heparan sulphate.

Second, it modulated host cell innate immune responses through increased expression of interferon-stimulated genes and TNFα. Through heightening the innate immune response of host cells, orally administered lactoferrin could be effective in resolving the GI symptoms that are present in COVID-19 patients with a mechanism similar to norovirus infection.

Third, in addition, lactoferrin was previously shown to decrease the production of IL-6, which is one of the key players of the “cytokine storm” produced by SARS-CoV-2 infection.

Bovine lactoferrin, widely available as 250-mg gelatine capsules for oral administration, may represent a promising therapy for preexposure and postexposure prophylaxis.

The other paper as a pre-published article, sought to qualify various discussions around whether wearing a suitable mask, correctly, offers advantages to the wearer and or anyone nearby. There have been various studies conducted to see if a clear picture can be determined.

Out on the 1st September 2021  A Cluster-Randomized Trial in Bangladesh which tracked more than 340,000 adults across 600 villages in rural Bangladesh, is by far the largest randomised study supporting the effectiveness of masks at limiting the spread of coronavirus infections[33]. Offering the best evidence yet that widespread wearing of surgical masks can limit the spread of the coronavirus in communities[34].

The randomly assigned pro-masking policy reduced the number of confirmed, symptomatic COVID-19 cases in the intervention group by nearly 10 percent, relative to the control group. That might not sound like a huge effect. But the intervention increased masking from 14 percent to only 43 percent; 100 percent masking would have likely had a much larger effect. The discussions will no doubt continue. But community-wide usage of surgical masks clearly reduces the spread of the coronavirus, especially in the unventilated indoor environments where it seems to spread most efficiently.

The Power of Putting Yourself in Someone Else’s Shoes

It is hard for a well-informed person to appreciate the depth of someone else’s ignorance. You see there is a ‘curse of knowledge’. Lots of us have expertise in particular areas. Becoming an expert in something means not simply that we understand more, but that we become more and more fascinated by nuance and complexity. That’s when the curse of knowledge kicks in, and we start to forget what it’s like not to know what we know.

Try to keep that in mind when people state that nutrition is irrelevant for immunity, or that natural immunity is inviolable.


[1] Calder, P.C. Nutrition and immunity: lessons for COVID-19. Nutr. Diabetes 11, 19 (2021).

[2] McKean KA, Yourth CP, Lazzaro BP, Clark AG. The evolutionary costs of immunological maintenance and deployment. BMC Evol Biol. 2008;8:76. Published 2008 Mar 3.

[3] Calder, P.C. Nutrition and immunity: lessons for COVID-19. Eur J Clin Nutr 75, 1309–1318 (2021).

[4] Ortona E, Pierdominici M and Rider V (2019) Editorial: Sex Hormones and Gender Differences in Immune Responses. Front. Immunol. 10:1076.

[5] Haynes L (2020) Aging of the Immune System: Research Challenges to Enhance the Health Span of Older Adults. Front. Aging 1:602108.

[6] Ravi M, Miller AH, Michopoulos V. The Immunology of Stress and the Impact of Inflammation on the Brain and Behavior. BJPsych Adv. 2021 May;27(Suppl 3):158-165.

[7] Lazar V, Ditu L-M, Pircalabioru GG, Gheorghe I, Curutiu C, Holban AM, Picu A, Petcu L and Chifiriuc MC (2018) Aspects of Gut Microbiota and Immune System Interactions in Infectious Diseases, Immunopathology, and Cancer. Front. Immunol. 9:1830.

[8]  Yeoh YK, Zuo T, Lui GC, et al Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19 Gut 2021;70:698-706.

[9] Tara J Cepon-Robins, Theresa E Gildner, Old friends meet a new foe: A potential role for immune-priming parasites in mitigating COVID-19 morbidity and mortality, Evolution, Medicine, and Public Health, Volume 2020, Issue 1, 2020, Pages 234–248,

[10] Full list of authors and signatories to climate emergency editorial September 2021

[11] Atwoli L, Baqui A H, Benfield T, Bosurgi R, Godlee F, Hancocks S et al. Call for emergency action to limit global temperature increases, restore biodiversity, and protect health BMJ 2021; 374 :n173

[12] Duffy S (2018) Why are RNA virus mutation rates so damn high? PLoS Biol 16(8): e3000003.

[13] Fleischmann WR Jr. Viral Genetics. In: Baron S, editor. Medical Microbiology. 4th edition. Galveston (TX): University of Texas Medical Branch at Galveston; 1996. Chapter 43. Available from:

[14] Delta’s rise is fuelled by rampant spread from people who feel fine. Nature News 19.8.2021

[15] How Dangerous Is the Delta Variant (B.1.617.2) American Society for Microbiology July 30, 2021

[16] Having SARS-CoV-2 once confers much greater immunity than a vaccine—but vaccination remains vital. Scienceinside, Meredith Wadman 26.8.2021

[17] Sivan Gazit, Roei Shlezinger, Galit Perez, Roni Lotan, Asaf Peretz, Amir Ben-Tov, Dani Cohen, Khitam Muhsen, Gabriel Chodick, Tal Patalon Comparing SARS-CoV-2 natural immunity to vaccine-induced immunity: reinfections versus breakthrough infections medRxiv 2021.08.24.21262415;

[18] Wu LP, Wang NC, Chang YH, et al. Duration of antibody responses after severe acute respiratory syndrome. Emerg Infect Dis. 2007;13(10):1562-1564.

[19] Huang, A.T., Garcia-Carreras, B., Hitchings, M.D.T. et al. A systematic review of antibody mediated immunity to coronaviruses: kinetics, correlates of protection, and association with severity. Nat Commun 11, 4704 (2020).

[20] Bergwerk M, Gonen T, Lustig Y, Amit S, Lipsitch M, Cohen C, Mandelboim M, Gal Levin E, Rubin C, Indenbaum V, Tal I, Zavitan M, Zuckerman N, Bar-Chaim A, Kreiss Y, Regev-Yochay G. Covid-19 Breakthrough Infections in Vaccinated Health Care Workers. N Engl J Med. 2021 Jul 28:NEJMoa2109072.

[21] Gaebler, C., Wang, Z., Lorenzi, J.C.C. et al. Evolution of antibody immunity to SARS-CoV-2. Nature 591, 639–644 (2021).

[22] Turner, J.S., O’Halloran, J.A., Kalaidina, E. et al. SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses. Nature 596, 109–113 (2021).

[23] The Body Is Far From Helpless Against Coronavirus Variants. The virus is evolving, but the antibodies that fight it can change, too. By Katherine J. Wu The Atlantic Feb 12 2021

[24] Dan JM, Mateus J, Kato Y, Hastie KM, Yu ED, Faliti CE, Grifoni A, Ramirez SI, Haupt S, Frazier A, Nakao C, Rayaprolu V, Rawlings SA, Peters B, Krammer F, Simon V, Saphire EO, Smith DM, Weiskopf D, Sette A, Crotty S. Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection. Science. 2021 Feb 5;371(6529):eabf4063..

[25] Painter MM, Mathew D, Goel RR, et al. Rapid induction of antigen-specific CD4+ T cells is associated with coordinated humoral and cellular immunity to SARS-CoV-2 mRNA vaccination [published online ahead of print, 2021 Aug 13]. Immunity. 2021;S1074-7613(21)00308-3.

[26]  Durable Humoral and Cellular Immune Responses Following Ad26.COV2.S  Vaccination for COVID-19

Dan H. Barouch, Kathryn E. Stephenson, Jerald Sadoff, Jingyou Yu, Aiquan Chang, Makda Gebre, Katherine McMahan, Jinyan Liu, Abishek Chandrashekar, Shivani Patel, Mathieu Le Gars, Anne Marit de Groot, Dirk Heerwegh, Frank Struyf, Macaya Douoguih, Johan van Hoof, Hanneke Schuitemaker medRxiv 2021.07.05.21259918;

[27] Chia WN, Zhu F, Ong SWX, Young BE, Fong SW, Le Bert N, Tan CW, Tiu C, Zhang J, Tan SY, Pada S, Chan YH, Tham CYL, Kunasegaran K, Chen MI, Low JGH, Leo YS, Renia L, Bertoletti A, Ng LFP, Lye DC, Wang LF. Dynamics of SARS-CoV-2 neutralising antibody responses and duration of immunity: a longitudinal study. Lancet Microbe. 2021 Jun;2(6):e240-e249. doi: 10.1016/S2666-5247(21)00025-2. Epub 2021 Mar 23. Erratum in: Lancet Microbe. 2021 May;2(5):e179..

[28] Your Vaccinated Immune System Is Ready for Breakthroughs. Getting COVID-19 when you’re vaccinated isn’t the same as getting COVID-19 when you’re unvaccinated. By Katherine J. Wu July 26 2021 The Atlantic

[29] Virological and serological kinetics of SARS-CoV-2 Delta variant vaccine-breakthrough infections: a multi-center cohort study Po Ying Chia, Sean Wei Xiang Ong, Calvin J Chiew, Li Wei Ang, Jean-Marc Chavatte, Tze-Minn Mak, Lin Cui, Shirin Kalimuddin, Wan Ni Chia, Chee Wah Tan, Louis Yi Ann Chai, Seow Yen Tan, Shuwei Zheng, Raymond Tzer Pin Lin, Linfa Wang, Yee-Sin Leo, Vernon J Lee, David Chien Lye, Barnaby Edward Young

medRxiv 2021.07.28.21261295

[30] Virological characteristics of SARS-CoV-2 vaccine breakthrough infections in health care workers

Marc C. Shamier, Alma Tostmann, Susanne Bogers, Janet de Wilde, Jeroen IJpelaar, Willemijn A. van der Kleij, Herbert de Jager, Bart L. Haagmans, Richard Molenkamp, Bas. B. Oude Munnink, Carsten van Rossum, Janette Rahamat-Langendoen, Nannet van der Geest, Chantal P. Bleeker-Rovers, Heiman Wertheim, Marion P.G. Koopmans, Corine H. GeurtsvanKessel medRxiv 2021.08.20.21262158;

[31] Crotty, S. Hybrid Immunity, Science, Vol 372, issue 6549, pp 1392-1393 Jun 2021

[32] Carmen Mirabelli, Jesse W. Wotring, Charles J. Zhang, Sean M. McCarty, Reid Fursmidt, Carla D. Pretto, Yuanyuan Qiao, Yuping Zhang, Tristan Frum, Namrata S. Kadambi, Anya T. Amin, Teresa R. O’Meara, Jason R. Spence, Jessie Huang, Konstantinos D. Alysandratos, Darrell N. Kotton, Samuel K. Handelman, Christiane E. Wobus, Kevin J. Weatherwax, George A. Mashour, Matthew J. O’Meara, Arul M. Chinnaiyan, Jonathan Z. Sexton. Morphological cell profiling of SARS-CoV-2 infection identifies drug repurposing candidates for COVID-19. Proceedings of the National Academy of Sciences Sep 2021, 118 (36) e2105815118

[33] The Impact of Community Masking on COVID-19: A Cluster-Randomized Trial in Bangladesh. Jason Abaluck Laura H. KwongAshley StyczynskiAshraful HaqueMd Alamgir KabirEllen Bates-JefferysEmily CrawfordJade Benjamin-ChungSalim BenhachmiShabib RaihanShadman RahmanNeeti ZamanStephen LubyMushfiq Mobarak, Mohammad Ashraful HaqueMd Alamgir KabirEllen Bates-JefferysShabib RaihanShadman RahmanNeeti Zaman

Working Paper. September 01, 2021

[34] Largest study of masks yet details their importance in fighting Covid-19 By Denise Chow Sept 2, 2021 NBC News

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