In every epidemic, some die, others become ill and recover, and the luckiest live through infection without symptoms. In today’s pandemic, we are seeing this play out before our eyes. Although the initial epidemiological data show that Covid-19 is more severe in older people, men and those with pre-existing conditions such as heart and lung disease, not everyone with severe disease has these risk factors. And not everyone at risk has the same symptoms, prognosis or outcome.

Why do people manifest such differences? And why is it not possible to predict an individual’s experience? To address this complex question, it is important to first get our terminology right. “Infection” means acquisition of the coronavirus after exposure to it. Infection is not synonymous with exposure — or with disease. Disease is a clinical state associated with cough, fever and other symptoms that ranges from mild to severe. These symptoms arise from damage to tissues and the immune system. Death occurs when there is so much damage that the body cannot maintain blood oxygenation and other necessary functions.

In past epidemics, death and survival were attributed to providence or fortune. Modern medicine and science provide a better understanding of why infection can lead to such different outcomes. Among individuals in the same risk group — the same age, say — differences in infection outcome can result from five different variables outside their control.The first of these is microbial dosage or inoculum, the number of viral particles that cause infection. Small numbers of viral particles are more likely to be contained effectively by the body’s defenses. Then, infection may cause no symptoms or only mild disease. In contrast, a large number of particles can lead to increased viral growth, overwhelming the immune system and causing more severe disease.

Finally, people’s immune status — especially their history of prior infectious diseases — crucially determines how they respond to a new infection. The immune system remembers previous encounters with microbes, and that affects how it fights and responds to new ones. In the case of dengue, infection with one type of the virus can make the individual more susceptible to infection with a different type of the same virus. In other situations, a recent infection with a virus can affect susceptibility to an unrelated new infection. For example, having had the flu before coronavirus infection could change the course of Covid-19 disease in unpredictable ways. When a person’s immune system has no memory of an infectious agent, it may be unable to rapidly respond, and this may allow the invader to escape detection, giving it more time to cause damage.

In this regard, today’s situation is similar to past pandemics in which the matter of who would live and who would die was also mysterious — and led people to attribute outcomes to fortune or supernatural intervention. However, Covid-19 is different than the 1918 flu, in that today a robust scientific establishment can quickly analyze what’s happening and help figure out how best to prevent and treat infections. Science is humanity’s lifeline. In the days ahead, physicians, scientists, epidemiologists and many more will work hard to understand individual susceptibility to coronavirus. The Covid-19 pandemic will teach us a great deal of new science that will make us better prepared for the next outbreak.