Are You Immune? Why Immunity Is The Central Plot In Your Inner Covid Drama...

The questions seemed valid enough. After all, through Season 1, the India graph had moved at a gentle canter, with a low (official) fatality rate to boot. But as those ominous hoofbeats picked up in May, even that was discarded for a more fragmented picture. Some regions within India looked less (or more) at risk. Over 30 districts witnessed a wide spread, others experienced slower transmission. And seemingly inexplicable variations within that defied a universalising story. It still looks deadliest in Maharashtra, as the state exacts the highest toll. In Delhi, it looks more infectious but not as fatal as in Maharashtra and Gujarat. Kerala has a tremendous rec­overy rate; no other state has that.

Also Read | Our Live-in Virus: What Does the Real Covid Map Look Like?

But soon it became clear that one key playfield of variations existed at a still more micro level: not country, not region or ethnicity, but individual. Young Keralites in their 30s were dying in the Gulf, but back home in hilly Ranni, 93-year-old Thomas and his 88-year-old wife Mariyamma tested positive, even got critical and stayed so for days, then happily recovered바카라�defying everything in the COVID 101 handbook about the elderly being at higher risk. By now, this randomness is a leitmotif of the COVID story: you as a patient may have merely experienced an unpleasant fortnight (with your 바카라�pizza tasting like cardboard,바카라� as writer Karan Mahajan told The Atlantic), but your neighbour goes to the ICU, perhaps thence to the mortuary. Why? Two axioms stay with us: the new coronavirus has shown an extremely varying propensity and potential to infect, and an equally puzzling unpredictability about who recovers and who does not. And perhaps neither has to do with the virus per se. Some variation in recovery rates could owe to differing healthcare practices and treatment protocols (at state/hospital/country level). But the lens surely needed to be adjusted to another level of magnification바카라�because one key act in this grim drama unfolds inside the individual. This is where immunity comes in.

All other things being equal바카라�age, health, exposure to virus바카라�why does Person A get infected and Person B go unaffected? That바카라�s simply hard-wired innate immunity: a healthy body바카라�s first line of defence against pathogens, an in-built fortification. This inv­isible armoury of the body is by nature capable of warding off new enemies바카라�so the fact of this being a novel virus wouldn바카라�t matter. The innate system has non-specific barriers that work regardless of who the enemy is바카라�the body-castle바카라�s moat, drawbridge and mortar-fire repel Viking and Mongol alike. By contrast, adaptive (or acq­uired) immunity is like an active database of prior infections: it invests the body with a pathogen-specific immunological memory. An 85-year-old person바카라�s body thus carries the memory of a childhood measles infection, but is too slow to produce antibodies against a new enemy바카라�hence, more at risk. 바카라�This is why children are more protected: their immune systems are simply stronger. That wanes as you age,바카라� says Calcutta paediatrician Dr Aniruddha Maitra. A point of mystery: COVID-19 initially seemed to spare children altogether. Thus the famous 바카라�double peak바카라� seen in other infections바카라�older people and children being most vulnerable, healthy adults of median age being the hardiest바카라�was markedly absent here. But as the pandemic spread, even children are seen to be not entirely out of its sway. But regardless of age variation, think of a first layer of armour.

Also Read | The Mysterious World Of Viruses And Why You Can't Escape Them

Now, say the enemy penetrates that arm­our, via a Trojan horse, and you do get inf­ected. Why only a mild flu for X, and ICU for Y? Well, post-infection, innate immunity continues to work, now in collaboration with its brother-in-arms, adaptive immunity: it smells out the foreign invasion, and enlists its ally to produce the amm­unition바카라�the antibodies. Infla­mmation happens, like sirens going off, signalling for reinforcements to rush to the infected site. Usually, this is when you get fever with any flu, before the body recovers. This is where the critical twist in the plot comes. It바카라�s a cataclysmic breakdown of these normal immunity processes바카라�this complex wartime communication machinery바카라�that바카라�s now looming forth frighteningly as a final act. A sudden, little understood crumbling of the fortress. A gasping, shuddering death. The key episode, called a cyt­okine storm, is now linked to many a Covid fatality. 바카라�It바카라�s a centerpiece of COVID-19 pat­hology,바카라� writes Tufts University immunologist Alexander Poltorak. 바카라�The killer is not the virus but the immune response.바카라� Essentially, an exc­essive reaction or dysregulation of the host바카라�s immune system, akin to what happens with autoimmune disorders. The system goes into hyperactive mode, then goes berserk and launches a stunning mutiny against the body itself바카라�till the whole zeppelin comes flaming down. This happens when immunological agents fail in one key function바카라�recognising self-substances, and exempting them from attack, while it goes for those nasty 바카라�non-self바카라� macromolecules (the foreign pathogens).

The realisation that there바카라�s a consistent pattern of Covid fatalities being linked to this inner suicidal drama has led to a reorientation of efforts across the world. That바카라�s why proposed/ongoing studies posted on the US National Library of Health바카라�s ClinicalTrials.gov bear titles that refer to therapeutic strategies targeted at critically ill patients who바카라�ve suffered or are close to an immunological burnout바카라�by modulating or suppressing their immunity processes. A Lancet study called immunosuppression 바카라�a double-edged sword바카라� because the body may be still vulnerable to any infection, and leaving it ber­eft of its armour is risky too. As a focus area, though, it has dawned. But first the macro-level, before we descend the steps.

Also Read | Did The Lockdown Work? What Did It Do? Would Have Happened Without It?

Are Indians immune?

바카라�Native immunity바카라� is actually just a synonym for innate immunity, but let바카라�s twist it to fit us 바카라�natives바카라�. Have Indians been conferred with an ability to take on all comers of the microscopic variety? Have we acquired a greater immunity by way of familiarity with viruses in general? Would that suffice to thwart a novel and tenacious one like Covid? The idea that prior exposure to other infections can create an all-purpose shield isn바카라�t entirely erroneous. There is such a thing as 바카라�cross-res­istance바카라�, which can work by altering the way receptor sites behave. But India바카라�s climbing numbers do not seem to offer any blanket comfort there. Why?

One reason could be that low nutrition levels enfeeble the delicate web acquired weaves in conjunction with innate. It바카라�s the latter바카라�s signalling apparatus바카라�a complex, multi-function communication grid involving constantly patrolling sentinel called neutrophils, our most abundant White Blood Cells, and proteins called cytokines바카라�that rec­ruit the good guys with the Bofors gun, the B-cells and T-cells. (Roughly, the first produces antibodies that lock onto antigens on the surface of pathogens, and calls upon phagocytes that eat them up; the latter kills infected cells). Micronutrient deficiency leaves this double-barrelled defence fortification starving at all levels. The internet is awash with preprints of studies linking, for instance, Covid morbidity with low Vitamin D levels (severe among the old in Italy, Spain et al). Elina Hypponen, an Australian nutritional and genetic epidemiology professor, offers preliminary support 바카라�in theory바카라� for the link, writing: 바카라�Nearly all immune cells have Vitamin D receptors (showing the interaction). The active Vitamin D hormone, calcitrol, helps regulate both innate and adaptive immunity. And deficiency is associated with immunity dysregulation.바카라� So, on that front, India fundamentally represents a vulnerable mass of humanity바카라�and it goes beyond vitamin deficiency. (see ).

What about BCG? Can vaccination against bacterial infections even conceivably work against a virus? Well, there바카라�s a new line of theory on 바카라�trained immunity바카라�바카라�the idea that, say, a vaccine can modify our innate system바카라�s pattern recognition receptors in such a way that they pick up similar antigens on even new enemies (antigens are surface structures on microbial bodies). But it begs further study바카라�. 바카라�As of now, there is only correlation,바카라� admits Dr Maitra. And as Lancet warned in another context, 바카라�correlation does not equal causation바카라�.

Also Read | 'We Have To Count Up To 60 Crore, That바카라�s When It Will Stop'

Despite India바카라�s recent surge in cases, some researchers are willing to give a chance to BCG, a mandatory booster for children in India to protect them against meningitis and disseminated TB. 바카라�While COVID-19 caused a lot of deaths in Spain, its neighbour, Portugal, witnessed a very low fatality. And Portugal is the only European country where BCG vaccination is still prevalent,바카라� says Dr Sudhir Bhandari, senior professor of medicine at Sawai Man Singh Medical College, Jaipur. 바카라�The BCG association, like that of hydroxychloroquine, arose because the early spread of Covid was a reverse image of these two, but there are multiple possible explanations for it without ascribing a causal link,바카라� says Ranchi-based radiologist Dr Manish Kumar.

 Many medical professionals anyway dismiss the notion of India (or any other country) collectively having a higher immunity, citing the interplay of several factors that inf­luence transmission and fatality. Dr Yadu Singh, Sydney-based cardiologist, for ins­tance, attributes Australia바카라�s 바카라�spectacular바카라� flattening of the curve (a mere 7,227 cases as of June 4, some 6,640 recovered, 102 deaths) to simply 바카라�good policies바카라�and civic sense바카라�, adding it has nothing to do with high immunity among Australians. But even if country-wise variations are possible, we바카라�re still in the grip of a story that evokes fear and awe: the perennially unravelling mysteries of Covid, and how your body can itself unravel, a deadly denouement where immunity is the tragic protagonist.

An evolving death

The Covid infection was initially thought to be a merely respiratory phenomenon, aff­ecting only the alveoli in the lungs바카라�and bringing on pneumonia. That바카라�s still the primary effect: the lung바카라�s ACE2 receptors are the most abundant, most strategically placed, most amenable to hosting the virus. But it바카라�s becoming clear that it often causes a 바카라�multi-system disorder바카라�, says Dr Maitra바카라�an all-pervasive attack on several fronts. Heart, guts, liver, kidney, brain...all cells can get inf­ected because most organs have ACE2 rec­eptors. A captured heart can go into myo­carditis, an inflamed liver produces an enz­yme glut. Most benignly, the gut lining; an altered gut flora equilibrium leads to the loss of appetite and/or diarrhoea common to many diseases. The UK officially added the loss of taste and smell as part of Covid symptoms on May 18바카라�either as a presenting symptom, signalling an early onset stage, or independently, without other symptoms. Indeed, isolated anosmia and ageusia are now seen as a tool to screen potential spreaders, for these are often associated with a milder form of the virus바카라�patients 바카라�10 times less likely바카라� to go on to be critical. The reasons for anosmia/ageusia are not understood yet. One view is that ACE2 is also present in cortical neurons, making them potential targets. Another is that it바카라�s likely to be a secondary effect바카라�the nervous system, for instance, is dependent on blood oxygen to function properly바카라�rather than a direct infection of the nerves, as in, say, forms of meningitis or encephalitis.

Also Read | What is ICMR? The History And Geography of Disease Control

This brings us to another potentially crucial site: blood. It was controversially proposed in a ChemRxiv preprint by two Chinese scholars and then reiterated by Italian pharmacologist Annalisa Chiusolo that the Covid virus manages to plug on to red blood cells, crack open the haemoglobin and release the enclosed iron. This was then linked to all the obs­erved chain of catastrophic effects: anaemia, excess iron choking the kidney; silent hypoxia (from a hindered exchange of oxygen and carbon dioxide) starving all organs, inc­luding the brain; thrombosis, with all its usual effects (heart attack, stroke) et al. Blood was also a putative candidate to explain Covid바카라�s rainbow effect: the all-pervasive nature of its attack on the body. The theory is hotly disputed, even if Ebola too famously wrought havoc on blood systems in unexplained ways. The idea that the virus cracks open haemoglobin molecules (haemolysis) may or may not endure. Then where do we take all that stunning variety of symptoms? Well, recent understanding inserts a vital first step: immunity-gone-awry. Once that happens, your body-castle turns into a house of cards and caves in. That바카라�s cause; haemolysis, thrombosis et al are effect ().

So the real twist in the plot is when your body starts eating itself. An uncontrolled immunological self-immolation. And it바카라�s cytokines that do the arson. 바카라�Small proteins important in immunological processes바카라� and produced by white blood cells are called macrophages, their job is to 바카라�trigger inflammation바카라� and 바카라�recruit바카라� other immunological elements to fight infection. Why they dysfunction is because Covid manages to 바카라�silence바카라� this inflammatory res­ponse, and grows in the body in what an Atlantic article called 바카라�stealth mode바카라�. When the body realises belatedly that it has been totally besieged, the immune system goes into overdrive: cytokine storm. A mass attack ensues on infected cells. The lungs fill with a sea of dead cells, a kind of biological sludge that leads to organ failure. The blood clots all over, blood vessels leak, BP plummets because of vasodilation, anaemia occurs. Somewhere along this disastrous slope, they start turning on even healthy body cells. Just like any other autoimmune disorder, it바카라�s an aberrant overreaction that some people have. Including, it바카라�s now known, a subset of the children who get infected. Why only they have it is one of the mysteries of science. Thus, from a struggling country down to a self-immolating cell, the view is different at each step down the baoli. And the last step promises a pool of water with no clear reflections. 

Vox PoP

Dr Ramanan Laxminarayan
Director, Center for Disease Dynamics, Economics and Policy, Washington

Are we more immune? Does BCG, heat바카라�any of that matter? Does having a younger population?

Younger population, yes. Not the others, of course. There is no difference in immunity, I think the only difference is that we got the epidemic later바카라�India, Pakistan, Bangladesh all got it later. Remember, at one point in the global curve of number of cases, we were at number 39. Today, we바카라�ve caught up바카라�. So there바카라�s no question of us being more immune, it is just how countries managed their lockdown. There is no escaping the virus.