• Research suggests that a first infection with SARS-CoV-2 provides only 47% protection against a second infection for those aged 65 years and over, compared with 80% protection across all age groups.
• These findings underscore the importance of physical distancing and vaccinations, even among those who have already had COVID-19.
• The study found that the level of protection against reinfection remained stable for more than 6 months.
• However, it did not take into account new variants of the virus, infection with which may provide less immunity against reinfection.

A key factor that will determine how soon life can return to normal after the pandemic is how easily people can reacquire SARS-CoV-2, which is the virus that causes COVID-19.

Proven cases of reinfection have been extremely rare, but the most comprehensive population-based study to date suggests that the risks may be greater than scientists initially thought.

The study, which drew from a register of millions of polymerase chain reaction (PCR) tests carried out in Denmark during 2020, found that an initial infection provided around 80% protection across all age groups.

However, among individuals aged 65 years and older, protection against reinfection dropped to 47%.

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“Since older people are also more likely to experience severe disease symptoms, and sadly die, our findings make clear how important it is to implement policies to protect the elderly during the pandemic,” says senior study author Prof. Steen Ethelberg, Ph.D., of the Statens Serum Institut in Copenhagen, Denmark.

“Given what is at stake,” he adds, “the results emphasize how important it is that people adhere to measures implemented to keep themselves and others safe, even if they have already had COVID-19.”

Scientists know that the immune systems of older adults respond less strongly to infections and vaccinations. This is known as immunosenescence.

Mass testing

Early in the pandemic, Denmark offered free and relatively fast PCR testing for anyone who wanted it, regardless of their symptoms.

As a result, 4 million people (more than two-thirds of the population) underwent a total of 10.6 million tests during 2020.

This allowed the researchers to determine what proportion of individuals who tested positive in the first wave of infections (from March 1 to May 31, 2020) would go on to test positive again in the second wave (September 1 to December 31, 2020).

Out of 11,068 individuals who tested positive in the first wave, only 72 (0.65%) tested positive again during the second wave.

After adjusting for other variables, the researchers saw that this equated to an overall protection against repeat infection of 80.5% for all age groups.

In a second analysis, the researchers widened their focus to first infections and reinfections that occurred at any time during the year. This confirmed a similar degree of overall protection of 78.8%.

However, among those aged 65 years and older, a first infection provided only 47.1% protection against a second infection.

On a more positive note, overall levels of immunity against reinfection appeared to persist for at least 6 months.

“The closely related coronaviruses SARS and MERS have both been shown to confer immune protection against reinfection lasting up to 3 years, but ongoing analysis of COVID-19 is needed to understand its long-term effects on [people’s] chances of [catching the infection] again,” says study co-author Daniela Michlmayr, Ph.D., who is also from the Statens Serum Institut.

The results of the study now appear in The Lancet.

Cause for concern

In an accompanying comment article, Prof. Rosemary J. Boyton and Daniel M. Altmann, from Imperial College London in the United Kingdom, write that many people will find the results of the study “relatively alarming.”

“Only 80% protection from reinfection in general, decreasing to 47% in people aged 65 years and older are more concerning figures than offered by previous studies,” they write.

They conclude:

“These data are all confirmation, if it were needed, that for SARS-CoV-2, the hope of protective immunity through natural infections might not be within our reach, and a global vaccination program with high efficacy vaccines is the enduring solution.”

The authors of the new study acknowledge some limitations of their research.

For instance, most of the PCR tests took place before the emergence of new, more transmissible strains of the virus. These strains may be better at evading existing immunity and, therefore, increase the risk of reinfection.

The researchers also note that people who know that they have already had the virus once may be less likely to seek testing again and less likely to take precautions such as wearing a face mask.

However, when the researchers refocused their analysis on healthcare professionals — who have a high risk of infection but are more likely to follow infection control guidelines — protection against reinfection was 81.1%. This is almost the same as that for the general population.

There is also a theoretical possibility that after a person tests positive, the virus could linger in their body for several months. This could account for some of the second positive tests.

However, when the researchers restricted their comparison to tests at least 4 months apart in the first and second waves of the pandemic, the apparent protection from reinfection remained about the same, at 82.8%.

Crucially, the study does not shed any light on whether a first infection protects a person from experiencing a severe second infection (as opposed to one with few or no symptoms).

The Danish register usually only records people’s test results, not their symptoms.

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