The Myth of Immune-Boosters
Artificial immune boosting may not be the right strategy to fight against COVID-19. Staying calm, maintaining social distancing and hygiene and using protective gear will help us in the long run.
The human immune system (inherited from gazillions of its preceding species in evolution) consists of a rather well-endowed immune response network. A network composed of cells (neutrophils, eosinophils, T cells, B cells, macrophages, and other cells) and non-cellular molecules (cytokines, leukotrienes, enzymes, etc.) form a formidable resistance, which intensely and strategically defend the wonderful bulwark that the human body is. This network however is useful and wonderful so long as it starts and ends on cue and does not overstay its welcome or overdo what is expected of it. In other words, balance is the key. “Immune boosting” would therefore mean artificially getting it all excited and ready to fight. Fight it must but only when it is necessary against a defined adversary, as much and as long as it requires to reinstate a desired state of health.
Not The Myth of Immune-Boosters Artificial immune boosting may not be the right strategy to fight against COVID-19. Staying calm, maintaining social distancing and hygiene and using protective gear will help us in the long run. more. Not less. This well-orchestrated response by a disciplined battalion of the immune army requires a band of welltrained scouts, elite strategists, and some seriously effective mobilisation of foot soldiers (granulocytes), mounted soldiers (antibody-dependant cell cytotoxicity), archers (inflammatory mediators and their receptors), powerful cannons (histamine, bradykinin), missiles (IL-6, IL-1, TNF-α, IFN-γ, chemokines), and target-locked nukes (antibodies). This arsenal in the immune repertoire (as is apparent from the analogies) must be kept under check. If not, tremendous and uncontrolled bombardment by its own defence system shall devastate the body’s ramparts (auto-immune response). We do not want that to happen under any circumstances because that will be disastrous! Now, to define "boosting" we revisit the original task, that of keeping the body in a state of preparedness but not draw first blood. Thus, (i) a "well-oiled" group of scouts (cells that are part of the first line of defence in our innate immune network and generally shoot from the hips but do manage to come back with useful information about a novel enemy) must be maintained such that even if an insidious attack is able to breach the body’s security system, it will not be allowed to penetrate too deep; (ii) the level of co-ordination among this network of immune players (innate and acquired immunity, long-term and short-term immunity, memory-directed immune stratification and new game plan against an unforeseen intruder) must be clear and specific such that no confusion (usually created by an intruder to set off false alarms) maybe unduly provoked. Thus, no immunosuppressant, no immunedepletion to red herring signals staged by sneaky pathogenic microbes maybe unduly evoked; and (iii) when the time comes, action is swift and lethal and cleanly eliminates the intruder. At last we come to the main point of this long prologue—SARS-CoV-2 and its pet scourge COVID-19. SARS-CoV-2 enters the human cell via a membranebound enzyme angiotensin converting enzyme 2 (ACE-2) and a transmembrane serene protease 2 that its spike protein combines efficiently with to initiate a smooth endocytosis reaction and the viral payload gains unobstructed entry into the cell. The receptor-binding spike making up its corona is the key to the host cell’s aforementioned lock. The dropletborne virus enters through the lung and quickly infiltrates circulation via its chosen portal and spreads systemically. ACE-2 being a blood pressure regulator, for the host humans, COVID-19 that may start with all the hallmarks of pneumonia, quickly and silently takes over multiple organs entering their cells via the endothelial lining of blood vessels, all of which express its chosen receptor protein. And all hell breaks loose! A severe “cytokine storm” starting with low levels of IFN-γand high levels of IL-6, TNF-α, IL-1β, CCL2, CCL3, CCL5 in huge amounts like a tsunami of powerful missiles by the body’s own defence
system completely overwhelms the immune system. This is what kills us—a total failure of our espionage system (scout cells), all the trained commandos, the diplomats, the strategists, and the entire security is breached and arson of the main weapon’s manufacturing units of the body leads to mayhem. Complete immune depletion due to foolish and explosive squandering of precious defensive resources turns into our own nemesis. And a final fatal blow jeopardises the thing called life from the poor human host. Thus, immune boosting, I feel, maybe accomplished simply by leading a balanced life—good nutrition (building, repairing and maintaining all the important faculties of the body and not just the immune system since it is not an isolated one), optimum and enjoyable activities (moderate exercise such as walking, swimming, yoga, pranayam and intellectually or creatively stimulating tasks that generate the happy 'hormones') and sufficient and quality sleep (that recharges, replenishes and regenerates the expenditure in the aforementioned enterprises). Ayurvedic knowledge (curcumin in turmeric, fisetin in apple and strawberry, piperine in black pepper, etc.), local and seasonal food (raw fruits and coloured vegetables high in flavonoids, phenolic compounds rich in anti-oxidants), clean lifestyle sans the redundant practices (avoiding nothing but excess), and effective armament (of offensive attack against the infectious agents) supplemented by western medicine (antiviral drugs such as avifavir, ritonavir, remdesivir, and others like hydroxychloroquine and azithromycine combination therapy, convalescent plasma therapy, intravenous immunoglobulin (IVIG) by recombinant DNA technology and support from ventilator, extracorporeal membrane oxygenation (ECMO) and excellent supportive care) may yet save us even if that wicked and troublesome rogue virus the SARS-CoV-2 manages to gain entry. A vaccine (such as Moderna’s mRNA1273 or Oxford University’s ChAdOx1, which are in various stages of clinical trial) may take long to come and offer a shield against COVID-19. And while we are at it, may I warn against frivolous advertisements claiming immune boosting because there is nothing to gain from a “boosted” immunity other than expediting and intensifying a pro-inflammatory disease like COVID-19. We do not want our immunity to be unnecessarily boosted. We want it to stay calm and in a state of preparedness so that it will not be fooled and respond to provocation and spend itself unnecessarily. We want the casualties of war (immune maintenance and immune surveillance circuits) to be efficiently replenished, replaced and regenerated and rejuvenated to remain healthy and balanced. We want capacity to generate and maintain a diverse immune weaponry, not necessarily in a state of preparedness but skilled and fit and there in case they are called into action. And most importantly, we want the regulatory mechanisms to remain alert and effective such that even if we need to go into a well-thought-out war (innate and acquired immunity including but not limited to inflammation and T and B cell-mediated cytotoxicity or humoral response, the designated cells with very specific and specialised immune functions, signalling peptides, receptors that regulate intercellular cross-talk, etc.) they are efficiently regulated and brought down to normal levels when it is over. Thus, balance is the key to a healthy ability to mount anti-viral immunity, rather than “boosting” it. I’d say, stay calm, stay safe, and stay alert, but most importantly, stay clean (social distancing, protective gear, hygiene) and “immune boosting” or not, we shall be able to keep the COVID-19 at bay. Dr Ena Ray Banerjee is Professor, Dept of Zoology, University of Calcutta, Immunology and Regenerative Medicine Research Unit, Translational Outcomes Research. Email: erb@caluniv.ac.in
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