Among the many medical puzzles about COVID-19 that continue to confound experts: Why does one spouse contract COVID-19 while in many cases the other does not? Why does the African continent have far fewer COVID-19 cases and deaths per capita than the other continents? Why does Singapore have more COVID-19 cases per capita than the U.S. but less than one-tenth the per capita death rate? What protects better from future COVID-19 infection, previous infection or vaccination?
Some of the partial answers to these questions are obvious: In terms of prevention, both previous infection and vaccination protect better than either alone. Environmental factors and mitigation efforts play a role in how the virus spreads, while age, obesity and underlying health affect COVID-19’s severity. The novel characteristics of the virus and its variants — transmissibility and lethality — surely matter, as does chance, which invariably exerts itself in most medical mysteries.
But the real key to demystifying the COVID-19 pandemic is immunity — explaining why some individuals are able to resist infection, while others are susceptible, and still others are especially vulnerable. Unfortunately, even our best immunologists have little more than a rudimentary understanding of how immunity in COVID-19 works.
Immunity is basically how the body defends itself from germs, and it is a complicated phenomenon. We are born with certain types of immunity, we acquire some immunity through vaccination and some is developed through exposure to various infectious agents. One theory about why Africa has been relatively protected from COVID-19 is the outdoor population’s greater exposure to germs — the so-called hygiene hypothesis. The lower mortality from COVID-19 in East Asia may be the result of contact with earlier COVID-19-related coronaviruses in these countries, which would have conferred some protective immunity.
Some of our immunity is the result of producing antibodies to specific diseases. But immunity goes beyond that. While antibody levels in the blood can be measured, they do not always correlate well with whatever protection our immune systems actually deliver. Besides antibodies, certain white blood cells generate a different form of immunity. Also, there is a local immunity — the respiratory airways and gastrointestinal tract have cells designed to keep hostile invaders out. The interaction among all these components is extremely complex — like the pieces on a chessboard in the hands of a grandmaster.
A recent study published in the journal Nature gave an indication of how important immunity is during pandemics. The Black Death, caused by a specific plague bacterium, may have killed as many as 200 million people in Afro-Eurasia during the Middle Ages. It is the single greatest mortality event in human history. The Nature study analyzed the DNA of centuries-old skeletons and found that those with a certain genetic mutation were 40% more likely to survive the plague than other people were. That particular gene was essential to making proteins that primed the immune system to recognize the lethal plague bacterium. The study said, “Clarifying the dynamics that have shaped the human immune system is key to understanding how historical diseases contributed to disease susceptibility today.” It is humbling to think that our descendants will pass on mutations for centuries that may help people survive future COVID-19.
From a historical scientific standpoint, we are basically in the same primitive spot in medicine that we were in physics before quantum mechanics revolutionized the field. In the early years of the 20th century, Nobel laureate physicists J.J. Thomson and Ernest Rutherford proposed simple models of the atom based on the physics of Isaac Newton. Less than 20 years later, another Nobel laureate, Niels Bohr, changed physics forever with the Bohr atomic model, based on early quantum mechanics rather than classical Newtonian physics. While extremely complicated, the practical effects of the Bohr model, now obsolete itself, are evident in the development of atomic power and (regrettably) atomic weapons. Perhaps even more important was how quantum mechanics changed thinking about physics, science and the world in general.
Discovering the secrets of immunity and the reasons people respond to infections as they do will open up new vistas in medicine just as quantum mechanics did in physics. It will also guide us toward practical answers about the pandemic, including who benefits most from vaccination, which groups need the greatest protection, and what measures are likely to be effective in enhancing personal immunity. Some of what seems inexplicable today will one day be understandable.
Since biblical times, contagions have struck some humans while passing over others in ways we do not understand. When the final account of the COVID-19 pandemic is written, it will be the story of the essential trait of disease immunity.
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ABOUT THE WRITER
Dr. Cory Franklin is a retired intensive care physician.
