Pulitzer Prize-winning writer (“Emperor of Maladies”) and U.S.-based immunologist, Siddhartha Mukherjee, does an extraordinary job of accounting for the reasons behind the current pandemic’s death and infection disparities across the globe.
It’s a deep mystery that the death and positivity rate toll in the world’s poorest nations have been unexpectedly low, while Europe and the United States have been ravaged. 1/2 a million Americans have died of Covid-19 and the number continues to climb though the viral lethality seems to be on the decline as we speak.
Mukherjee digs up several entangling factors behind this mystery and comes up with the analogy of Agatha Christies’ famed “Murder on the Orient Express.” Citing an overt dependency on the “Ockham’s razor” principle of solving scientific puzzles (“epistemology” not just “epidemiology” needs to be considered in scientific knowledge-gathering as well: It’s not just that “what” of the matter, but the “how” we get to the matter on hand), Mukherjee says that the arriving at the most “parsimonious” or simplest of answers to the questions of the intricate vagaries of human cellular composition will not hold because the human body is not the Newtonian bodies in motion or rest. The human body and its “socio-cellular” ecology is darn complex to yield to the scrutiny led by the the Ockham inquiry principle. Mukherjee suggests we chuck the “razor” and embrace the “quilt” instead. Detective Poirot was shell-shocked upon discovering that the entire village entered into a quilted tangle of complicity to murder the man aboard the Orient Express. So a vast quilt of reasons could be behind the most profoundest of all “epidemiological mysteries” and shall we say, murderous, of our times:
“The usual trend of death from infectious diseases—malaria, typhoid, diphtheria, H.I.V.—follows a dismal pattern. Lower-income countries are hardest hit, with high-income countries the least affected. But if you look at the pattern of covid-19 deaths reported per capita—deaths, not infections—Belgium, Italy, Spain, the United States, and the United Kingdom are among the worst off. The reported death rate in India, which has 1.3 billion people and a rickety, ad-hoc public-health infrastructure, is roughly a tenth of what it is in the United States. In Nigeria, with a population of some two hundred million, the reported death rate is less than a hundredth of the U.S. rate. Rich countries, with sophisticated health-care systems, seem to have suffered the worst ravages of the infection. Death rates in poorer countries—particularly in South Asia and large swaths of sub-Saharan Africa—appear curiously low. (South Africa, which accounts for most of sub-Saharan Africa’s reported covid-19 deaths, is an important exception.)”
Among the intertwining causes is the statistico-bureaucratic one: Deaths due to Covid-19 have been vastly underreported in many countries, including India, where folks have died at home rather than in hospital ICU beds. However, delving into the cellular matrix of the human body, Mukherjee says that the presence of “cross-reactive T-cells” in Sub Saharan African bodies and subcontinental South Asian bodies could also have played a vital role in the low Covid 19 death rates in the world’s poorer nations.
What are “Cross-reactive T-cells?” and how do they resist pathogenic invasions of our cellular systems more effectively than antibodies?
Honestly, here I stumbled to grasp the knowledge that was being generously shared with us lay persons in the non-scientific world. So, I’m putting the entire information as is:
“Other researchers are exploring whether acquired differences in human immunology might play a role. Acquired, or adaptive, immunity involves two principal kinds of cells: B cells make antibodies against pathogens, and T cells hunt for cells infected by a pathogen. B cells can be imagined as sharpshooters that target a virus with well-aimed bullets, while T cells are gumshoe detectives that go door to door, seeking viruses that are hidden inside cells.
Both B cells and T cells have an unusual capacity: after generating an immune response, some of them may become long-lived passengers in our blood, and carry the “memory” of an already encountered pathogen. These so-called memory cells are triggered when the pathogen reappears, and they can swiftly raise forces to fight it.
At the La Jolla Institute for Immunology, in California, researchers led by Shane Crotty and Alessandro Sette were studying the B- and T-cell responses to the coronavirus through samples of human blood plasma. To quantify the level of immunological activity against the virus, Crotty and Sette wanted a “negative control”—that is, samples of plasma that were collected before the pandemic.
But there was a peculiarity in the data: in more than forty per cent of pre-pandemic samples, the researchers found evidence that the new coronavirus was somehow triggering a T-cell response. These T cells were acting as if they’d recognized a virus they had assuredly never before encountered.
Sette, who was born in Italy, wears blue-rimmed spectacles, and rides his motorcycle to the lab where he works. “A negative control is supposed to be negative,” he told me, stabbing his finger in the air. “We were totally surprised.” He lifted his hands emphatically and waved them around, his ash-gray sweater stretching over his torso. “But the cross-reactivity is always there. We’ve repeated it. Other labs have confirmed the data. The number varies by geography and by the population—twenty per cent, forty per cent—but it’s always there.”
Why is that? Part of the answer may have to do with how T cells recognize pathogens. It’s natural to think of our memory T cells as brandishing a criminal’s mug shot. But what they “remember” is more like the curve of a nostril, the shape of an ear—distinctive snippets of a larger protein picture. Now, suppose a former intruder’s much worse cousin shows up; it’s a fresh face, but it shares a family trait—maybe those batwing ears—that could alert at least some of the memory T cells. Could the novel coronavirus share such traits with previously circulating pathogens?
He told me about an island in Italy, Isola del Giglio, that, he thought, might have been swept by a respiratory infection a few years ago. “But, when covid-19 came and swept through Italy, the Giglio islanders were all spared,” Sette said. “It may just be a story, but it makes you wonder whether one infection might protect you from another, perhaps via cross-reactive T cells.”
Here’s what I understand this to say: cross-reactive T cells will identify an invader from a fragment that resembles a previous invader, and I mean even the tiniest of a tear from a fragment of a fragment will be recognized by cross-reactive T cells as a lethal pathogen and raise the alarm or fight the pathogen.
An antibody, on the other hand, is more “discriminating” in pattern recognition methodologies. An antibody will not rush at a prior invaders “criminal cousin” based on traces of similarity. The invading pathogen has to be more fully formed for antibodies to recognize its criminal intent and hence raise the alarm to go and fight.
Thank you, Dr. Mukherjee for this. Leaves me with a question: Are the Covid 19 vaccines we are being injected with at present sufficient to battle Covid 19 and its increasingly lethal variants?