Confirmed cases of SARS-CoV-2 reinfection have been very rare, and fortunately most of them have been mild. But how and why reinfection occurs—and what these cases mean for ending the global COVID-19 pandemic—remains a mystery.

In a recent paper in Clinical Infectious Diseases, Mass General physician-investigators Arthur Y. Kim, MD, and Rajesh T. Gandhi, MD, summarize what is known about SARS-CoV-2 reinfection so far and what key questions remain. Here are five things to know:

Humans experience a full spectrum of immunity after exposure to viruses and other disease-causing pathogens including:

• Sterilizing immunity that fully protects against reinfection
• Partial immunity that reduces the likelihood, severity and duration of
subsequent infections
• No protective immunity
• An enhanced immune response that can paradoxically increase disease severity through inflammation

Based on what scientists have learned from studying other coronaviruses such as the common cold, reports of reinfection of SARS-CoV-2 are not surprising, Drs. Kim and Gandhi write.

In a study of the common cold coronavirus HCoV 229E, human participants who were re-exposed to the virus after recovering did get infected again, but the presence of detectable virus in their systems was shorter and none developed cold symptoms.

Similar results occurred in a study of SARS-CoV-2 re-exposure in macaque monkeys earlier this year. Previously infected monkeys had brief periods of detectable virus upon reexposure, but did not have prolonged infections or severe disease.

In nearly all reinfection cases reported in humans so far, the first infection was asymptomatic or mild.

This may be because a higher percentage of individuals worldwide have experienced a mild form of COVID-19 —thus skewing the results in that direction. It may also be that individuals with severe disease develop a stronger immune response over the course of their illness that provides longer protection.

The best way to identify cases of reinfection is by capturing and sequencing two different genetic strains of the virus in the same individual. Public health authorities will need to provide the laboratory support to store and sequence patient specimens in order to identify reinfection cases.

Scientists and health officials need to work together to learn more about reinfection frequency, why some people may be more susceptible to reinfection, and how long immune protection will last after infection or vaccination. It will be critical to determine whether re-infected patients are likely to infect others.

Top image caption: This scanning electron microscope image shows SARS-CoV-2 (round magenta objects) emerging from the surface of cells cultured in the lab. SARS-CoV-2, also known as 2019-nCoV, is the virus that causes COVID-19. The virus shown was isolated from a patient in the U.S. Image captured and colorized at NIAID’s Rocky Mountain Laboratories (RML) in Hamilton, Montana. Credit: NIAID

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