Among the many uncertainties that remain about Covid-19 is how the human immune system responds to infection and what that means for the spread of the disease.
Immunity after any infection can range from lifelong and complete to nearly nonexistent. So far, however, only the first glimmers of data are available about immunity to SARS-CoV-2, the coronavirus that causes Covid-19.
What can scientists, and the decision makers who rely on science to inform policies, do in such a situation? The best approach is to construct a conceptual model — a set of assumptions about how immunity might work — based on current knowledge of the immune system and information about related viruses.
At the moment, cases of Covid-19 have been undercounted because of limited testing — perhaps by a factor of 10 in some places, like Italy as of late last month
No human-challenge experiments have been conducted to study immunity to SARS and MERS. But measurements of antibodies in the blood of people who have survived those infections suggest that defences persist for some time: two years for SARS, according to one study, and almost three years for MERS, according to another one.
However, the neutralising ability of these antibodies — a measure of how well they inhibit virus replication — was already declining during the study periods.
These studies form the basis for an educated guess at what might happen with Covid-19 patients. After being infected with SARS-CoV-2, most individuals will have an immune response, some better than others.
That response, it may be assumed, will offer some protection over the medium term — at least a year — and then its effectiveness might decline.
Other evidence supports this model. A recent peer-reviewed study led by a team published data from 12 patients showing that they had developed antibodies after infection with SARS-CoV-2.
Several of my colleagues and students and I have statistically analysed thousands of seasonal coronavirus cases in the United States and used a mathematical model to infer that immunity over a year or so is likely for the two seasonal coronaviruses most closely related to SARS-CoV-2 — an indication perhaps of how immunity to SARS-CoV-2 itself might also behave.
If it is true that infection creates immunity in most or all individuals and that the protection lasts a year or more, then the infection of increasing numbers of people in any given population will lead to the build-up of so-called herd immunity.
As more and more people become immune to the virus, an infected individual has less and less chance of coming into contact with a person susceptible to infection. Eventually, herd immunity becomes pervasive enough that an infected person on average infects less than one other person; at that point, the number of cases starts to go down.
At the moment, cases of Covid-19 have been undercounted because of limited testing — perhaps by a factor of 10 in some places, like Italy as of late last month.
If the undercounting is around this level in other countries as well, then a majority of the population in much (if not all) of the world still is susceptible to infection, and herd immunity is a minor phenomenon right now.
One concern has to do with the possibility of reinfection. South Korea’s Centers for Disease Control and Prevention recently reported that 91 patients who had been infected with SARS-CoV-2 and then tested negative for the virus later tested positive again.
If some of these cases were indeed reinfections, they would cast doubt on the strength of the immunity the patients had developed.
An alternative possibility, which many scientists think is more likely, is that these patients had a false negative test in the middle of an ongoing infection, or that the infection had temporarily subsided and then re-emerged.
For now, it is reasonable to assume that only a minority of the world’s population is immune to SARS-CoV-2, even in hard-hit areas. How could this tentative picture evolve as better data come in? Early hints suggest that it could change in either direction.
It is possible that many more cases of Covid-19 have occurred than have been reported, even after accounting for limited testing. Experimental and statistical evidence suggests that infection with one coronavirus can offer some degree of immunity against distinct but related coronaviruses.
Whether some people are at greater or lesser risk of infection with SARS-CoV-2 because of a prior history of exposure to coronaviruses is an open question.
And then there is the question of immune enhancement: Through a variety of mechanisms, immunity to a coronavirus can in some instances exacerbate an infection rather than prevent or mitigate it.
Such mechanisms are still being studied for coronaviruses, but concern that they might be at play is one of the obstacles that have slowed the development of experimental vaccines against SARS and MERS. Guarding against enhancement will also be one of the biggest challenges facing scientists trying to develop vaccines for Covid-19.
The good news is that research on SARS and MERS has begun to clarify how enhancement works, suggesting ways around it, and an extraordinary range of efforts is underway to find a vaccine for Covid-19, using multiple approaches.
More science on almost every aspect of this new virus is needed, but in this pandemic, as with previous ones, decisions with great consequences must be made before definitive data are in.
Given this urgency, the traditional scientific method — formulating informed hypotheses and testing them by experiments and careful epidemiology — is hyper-accelerated. Given the public’s attention, that work is unusually on display.
In these difficult circumstances, I can only hope that this article will seem out of date very shortly — as much more is soon discovered about the coronavirus than is known right now.
Marc Lipsitch is the professor of epidemiology at the department of Immunology and Infectious Diseases, Harvard