One of the most perplexing and enduring mysteries of the pandemic is also one of the most fundamental questions about viruses. How can the same virus that kills so many go entirely unnoticed in others?
The mystery is hardly unique to COVID-19. SARS, MERS, influenza, Ebola, dengue, yellow fever, chikungunya, West Nile, Lassa, Japanese encephalitis, Epstein-Barr, and polio can all be deadly in one person but asymptomatic in the next.
But for most of human existence, we didn’t know that viruses could infect us asymptomatically. We didn’t know how to look for them, or even that we should. The tools of modern science have slowly made the invisible visible: Antibody surveys that detect past infection, tests that find viral DNA or RNA even in asymptomatic people, and mathematical models all show that viruses are up to much more than making us sick. Scientists now think that for viruses, a wide range of disease severity is the norm rather than the exception.
A virus, after all, does not necessarily wish its host ill. A dead host is a dead end. The viruses best adapted to humans have co-evolved over millions of years to infect but rarely sicken us. Human cytomegalovirus is a prime example, a virus so innocuous that it lives in obscurity despite infecting most of the world’s population. (Odds are that you have it.) Infections with human cytomegalovirus are almost always asymptomatic because it has evolved a suite of tricks to evade the human immune system, which nevertheless tries its best to hunt the virus down. By the time humans reach old age, up to a quarter of our killer T cells are devoted to fighting human cytomegalovirus. Pathogens and immune systems are in constant battle, with one just barely keeping the other in check. In the rare instances when human cytomegalovirus turns deadly—usually in an immunocompromised patient—it’s because this equilibrium did not hold.