Short stories can afford to come with a twist in the end. But epics are fated to contain twists at every turn, at every level of the labyrinth of nested stories. COVID-19 is proving to be one such gigantic and perplexing hall of mirrors: the logic unfolding in a sub-plot at Level 5 can alter the main narrative frame바카라and then twist again. Immunity is a word that바카라s been lurking around like a minor character with a walk-on part in the story from the beginning. There was at first that partly naïve optimism in the idea that Indians, on account of exposure to a rich bouquet of pathogens, have a kind of all-purpose 바카라native immunity바카라바카라a Teflon coating against Covid. As the new coronavirus plugged into India as a collective host, that was soon quietly replaced with a more modest, and perhaps illusorily durable, hypothesis. That if the virus strains were the same as were lacerating Italy, the UK and US, Indians looked at least more immune than the West. Could it have something to do with blood groups and variable vulnerability thereof? Was it the wall-to-wall coverage of BCG vaccination?
Are You Immune? Why Immunity Is The Central Plot In Your Inner Covid Drama...
The coronavirus has shown an extremely varying potential to infect and a puzzling unpredictability about who recovers and who does not
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.
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 recovered바카라defying 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 바카라pizza 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 magnification바카라because one key act in this grim drama unfolds inside the individual. This is where immunity comes in.
All other things being equal바카라age, health, exposure to virus바카라why does Person A get infected and Person B go unaffected? That바카라s simply hard-wired innate immunity: a healthy body바카라s first line of defence against pathogens, an in-built fortification. This invisible armoury of the body is by nature capable of warding off new enemies바카라so the fact of this being a novel virus wouldn바카라t matter. The innate system has non-specific barriers that work regardless of who the enemy is바카라the body-castle바카라s 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 person바카라s body thus carries the memory of a childhood measles infection, but is too slow to produce antibodies against a new enemy바카라hence, more at risk. 바카라This 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 바카라double peak바카라 seen in other infections바카라older people and children being most vulnerable, healthy adults of median age being the hardiest바카라was 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.
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 ammunition바카라the 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. It바카라s a cataclysmic breakdown of these normal immunity processes바카라this complex wartime communication machinery바카라that바카라s 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. 바카라It바카라s a centerpiece of COVID-19 pathology,바카라 writes Tufts University immunologist Alexander Poltorak. 바카라The killer is not the virus but the immune response.바카라 Essentially, an excessive reaction or dysregulation of the host바카라s 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 itself바카라till the whole zeppelin comes flaming down. This happens when immunological agents fail in one key function바카라recognising self-substances, and exempting them from attack, while it goes for those nasty 바카라non-self바카라 macromolecules (the foreign pathogens).
The realisation that there바카라s a consistent pattern of Covid fatalities being linked to this inner suicidal drama has led to a reorientation of efforts across the world. That바카라s why proposed/ongoing studies posted on the US National Library of Health바카라s ClinicalTrials.gov bear titles that refer to therapeutic strategies targeted at critically ill patients who바카라ve suffered or are close to an immunological burnout바카라by modulating or suppressing their immunity processes. A Lancet study called immunosuppression 바카라a 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.
Are Indians immune?
바카라Native immunity바카라 is actually just a synonym for innate immunity, but let바카라s twist it to fit us 바카라natives바카라. 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 isn바카라t entirely erroneous. There is such a thing as 바카라cross-resistance바카라, which can work by altering the way receptor sites behave. But India바카라s 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. It바카라s the latter바카라s signalling apparatus바카라a complex, multi-function communication grid involving constantly patrolling sentinel called neutrophils, our most abundant White Blood Cells, and proteins called cytokines바카라that 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 바카라in theory바카라 for the link, writing: 바카라Nearly 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 humanity바카라and it goes beyond vitamin deficiency. (see ).
What about BCG? Can vaccination against bacterial infections even conceivably work against a virus? Well, there바카라s a new line of theory on 바카라trained immunity바카라바카라the idea that, say, a vaccine can modify our innate system바카라s 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. 바카라As of now, there is only correlation,바카라 admits Dr Maitra. And as Lancet warned in another context, 바카라correlation does not equal causation바카라.
Despite India바카라s 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. 바카라While 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. 바카라The 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 Australia바카라s 바카라spectacular바카라 flattening of the curve (a mere 7,227 cases as of June 4, some 6,640 recovered, 102 deaths) to simply 바카라good policies바카라and civic sense바카라, adding it has nothing to do with high immunity among Australians. But even if country-wise variations are possible, we바카라re 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 lungs바카라and bringing on pneumonia. That바카라s still the primary effect: the lung바카라s ACE2 receptors are the most abundant, most strategically placed, most amenable to hosting the virus. But it바카라s becoming clear that it often causes a 바카라multi-system disorder바카라, says Dr Maitra바카라an 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 18바카라either 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 virus바카라patients 바카라10 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 it바카라s likely to be a secondary effect바카라the nervous system, for instance, is dependent on blood oxygen to function properly바카라rather than a direct infection of the nerves, as in, say, forms of meningitis or encephalitis.
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 Covid바카라s 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. That바카라s 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 it바카라s cytokines that do the arson. 바카라Small proteins important in immunological processes바카라 and produced by white blood cells are called macrophages, their job is to 바카라trigger inflammation바카라 and 바카라recruit바카라 other immunological elements to fight infection. Why they dysfunction is because Covid manages to 바카라silence바카라 this inflammatory response, and grows in the body in what an Atlantic article called 바카라stealth 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, it바카라s an aberrant overreaction that some people have. Including, it바카라s 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, heat바카라any 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 later바카라India, Pakistan, Bangladesh all got it later. Remember, at one point in the global curve of number of cases, we were at number 39. Today, we바카라ve caught up바카라. So there바카라s no question of us being more immune, it is just how countries managed their lockdown. There is no escaping the virus.