An analysis of more than two-thirds of people in Denmark found that less than 1% who were infected during the country's spring wave of COVID-19 got reinfected during a winter surge. Although the Danes' "natural immunity" remained stable for at least six months, older people were at much higher risk of reinfection than the rest of the population.

In a paper published March 17 in The Lancet, Danish researchers reported that people 65 or older who already had the contagious disease were slightly more than half as likely to get it again compared with their uninfected peers, while risk of reinfection among the overall infected population fell by about 81%. 

The findings align with previous research on post-infection immunity, and the researchers emphasized the need to rely on other forms of protection for older populations, such as vaccines.

Like much of Europe, Denmark underwent two waves of the COVID-19 pandemic: an initial surge in the spring of 2020, and a much larger one in the following fall and early winter. As of March 17, the country has experienced about 223,000 cases and nearly 2,400 deaths, with one of Europe's lowest mortality rates at about 41 deaths per 100,000 people.

The researchers from the Status Serum Institute — the Danish equivalent to the U.S. Centers for Disease Control and Prevention — took advantage of Denmark's large national COVID-19 testing program, which in 2020 administered 10.6 million tests to nearly 4 million people in a country of 5.8 million. They could identify the date and result of any individual's tests and track their infection status through the year.

The study is the largest of its kind by sample size, making use of testing data from millions of Danes. Its first analysis looked at the 530,000 people who got tested between March and May during the first wave and between September and December during the second. In addition, a cohort analysis took data from about 2.4 million people and found similar results for protection strength and stability.

Of the 11,000 people who tested positive for COVID-19 in the spring, only 72 got it again, representing a 0.65% reinfection rate. The infected group had a protection rate of 80.5% against reinfection, meaning they were one-fifth as likely to develop COVID-19 as people who had previously tested negative for the disease. 

Similar or somewhat higher levels of protection have been found in previous studies, such as a preprint U.K. study that found reduced reinfection risk of 83%, and a preprint Qatar study that said the figure was 95%. (Neither paper has yet been peer-reviewed or published in a scientific journal.)

However, in the new study, that protection rate fell to 47.1% among people 65 or older. Those in the age group benefited much less from natural immunity, or resistance to the virus following a previous infection, than the general post-infection population.

In comparison, the efficacy of the Pfizer-BioNTech COVID-19 vaccine was found to be 95% effective at preventing the disease during Phase III trials, while the Moderna vaccine was 94.1% effective. 

"The public-health message of this is that vaccination is certainly a good idea," said Steen Ethelberg, a senior researcher at Statens Serum Institut and an author of the paper. "The elderly segment in society, who also are likely to have more serious consequences if they get ill, should be protected by the vaccination since they do not appear to be protected, even if they had the infection."

The less effective protection in previously infected older people appears to be simply a result of their weaker immune systems, according to the researchers, as similar trends have been found in other diseases. As far as is known, the effect is not caused by any coronavirus-specific reasons, according to Ethelberg.

The results also advocate for vaccination of all previously infected people, according the researchers, because the natural protection they developed "cannot be relied on."

"Personally, I would rather get vaccinated" than contract COVID-19, Ethelberg said. In addition to avoiding the illness, "I might also be better protected from future illnesses with a vaccination."

The study also found that the protective effects did not weaken with time, meaning that natural immunity persists for at least six months, a finding that is consistent with previous results. More time will need to pass for scientists to learn how much longer it lasts, though protection from the related SARS and MERS viruses has been found to stick around for about two to three years, according to the paper.

Listing their research's limitations, the Danish scientists said their analyses could not distinguish between symptomatic and asymptomatic people with COVID-19. The paper also analyzed only the original strain of the novel coronavirus and not other variants, some of which are more contagious. Denmark is already working to suppress the highly contagious B.1.1.7 or "U.K." variant, which was introduced to the country in January and triggered another lockdown.

Ethelberg said he is interested in ongoing and future research that will reveal how long post-infection immunity to COVID-19 lasts, and how effective it is against other coronavirus variants. Other studies may investigate how COVID-19 immunity works in the body, a topic that was outside the scope of his observational study.

The study, "Assessment of protection against reinfection with SARS-CoV-2 among 4 million PCR-tested individuals in Denmark in 2020: a population-level observational study," published March 17 in The Lancet, was authored by Christian Hansen, Statens Serum Institut and London School of Hygiene & Tropical Medicine; Daniela Michlmayr, Statens Serum Institut and European Centre for Disease Prevention and Control; Sophie Gubbels, Statens Serum Institut; and Kâre Mølbak and Steen Ethelberg, Statens Serum Institut.