COVID-19 Virus Reinfections Rare, but Riskiest After Age 65

Damian McNamara

March 18, 2021

Editor's note: Find the latest COVID-19 news and guidance in Medscape's Coronavirus Resource Center.

The first large study of its kind reveals that SARS-CoV-2 reinfections remain rare, although people older than 65 are at higher risk.

When researchers analyzed test results of 4 million people in Denmark, they found that less than 1% of those who tested positive experienced reinfection.

Initial infection was associated with about 80% protection overall against getting SARS-CoV-2 again. However, among those older than 65, the protection plummeted to 47%.

Dr Daniela Michlmayr

"Not everybody is protected against reinfection after a first infection. Older people are at higher risk of catching it again," co–lead author Daniela Michlmayr, PhD, told Medscape Medical News. "Our findings emphasize the importance of policies to protect the elderly and of adhering to infection control measures and restrictions, even if previously infected with COVID-19."

Verifying the Need for Vaccination

"The findings also highlight the need to vaccinate people who had COVID-19 before, as natural immunity to infection ― especially among the elderly 65 and older ― cannot be relied upon," added Michlmayr, a researcher in the Department of Bacteria, Parasites, and Fungi at the Staten Serums Institut, Copenhagen, Denmark.

The population-based observational study was published online March 17 in The Lancet.

Dr David Hirschwerk

"The findings make sense, as patients who are immunocompromised or of advanced age may not mount an immune response that is as long-lasting," David Hirschwerk, MD, told Medscape Medical News when asked to comment. "It does underscore the importance of vaccination for people of more advanced age, even if they previously were infected with COVID.

"For those who were infected last spring and have not yet been vaccinated, this helps to support the value of still pursuing the vaccine," added Hirschwerk, an infectious disease specialist at Northwell Health in Manhasset, New York.

Evidence on reinfection risk was limited prior to this study. "Little is known about protection against SARS-CoV-2 repeat infections, but two studies in the UK have found that immunity could last at least 5 to 6 months after infection," the authors note.

Along with co–lead author Christian Holm Hansen, PhD, Michlmayr and colleagues found that 2.11% of 525,339 individuals tested positive for SARS-CoV-2 during the first surge in Denmark from March to May 2020. Within this group, 0.65% tested positive during a second surge from September to December.

By the end of 2020, more than 10 million people had undergone free polymerase chain reaction testing by the Danish government or through the national TestDenmark program.

Dr E. John Wherry

"My overall take is that it is great to have such a big dataset looking at this question," E. John Wherry, PhD, told Medscape Medical News. The findings support "what we've seen in previous, smaller studies."

Natural protection against reinfection of approximately 80% "is not as good as the vaccines, but not bad," added Wherry, director of the Institute for Immunology at the University of Pennsylvania, Philadelphia, Pennsylvania.

Age Alters Immunity?

"Our finding that older people were more likely than younger people to test positive again if they had already tested positive could be explained by natural age-related changes in the immune system of older adults, also referred to as immune senescence," the authors note.

The investigators found no significant differences in reinfection rates between women and men.

As with the previous research, this study also indicates that an initial bout with SARS-CoV-2 infection appears to confer protection for at least 6 months. The researchers found no significant differences between people who were followed for 3 to 6 months and those followed for 7 months or longer.

Variants Not Included

To account for possible bias among people who got tested repeatedly, Michlmayr and colleagues performed a sensitivity analysis in a subgroup. They assessed reinfection rates among people who underwent testing frequently and routinely ― nurses, doctors, social workers, and healthcare assistants ― and found that 1.2% tested positive a second time during the second surge.

A limitation of the study was the inability to correlate symptoms with risk for reinfection. Also, the researchers did not account for SARS-CoV-2 variants, noting that "during the study period, such variants were not yet established in Denmark; although into 2021 this pattern is changing."

Asked to speculate whether the results would be different had the study accounted for variants, Hirschwerk said, "It depends upon the variant, but certainly for the B.1.351 variant, there already has been data clearly demonstrating risk of reinfection with SARS-CoV-2 despite prior infection with the original strain of virus."

The emergence of SARS-CoV-2 variants of concern that could escape natural and vaccine-related immunity "complicates matters further," Rosemary J. Boyton, MBBS, and Daniel M. Altmann, PhD, both of Imperial College London, London, United Kingdom, write in an accompanying comment in The Lancet.

"Emerging variants of concern might shift immunity below a protective margin, prompting the need for updated vaccines. Interestingly, vaccine responses even after single dose are substantially enhanced in individuals with a history of infection with SARS-CoV-2," they add.

The current study confirms that "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," Boyton and Altmann note.

Cause for Alarm?

Despite evidence that reinfection is relatively rare, "many will find the data reported by Hansen and colleagues about protection through natural infection relatively alarming," Boyton and Altmann write in their commentary. The 80% protection rate from reinfection in general and the 47% rate among people aged 65 and older "are more concerning figures than offered by previous studies."

Vaccines appear to provide better quality, quantity, and durability of protection against repeated infection ― measured in terms of neutralizing antibodies and T cells ― compared with previous infection with SARS-CoV-2, Boyton and Altmann write.

More Research Needed

The duration of natural protection against reinfection remains an unanswered question, the researchers note, "because too little time has elapsed since the beginning of the pandemic."

Future prospective and longitudinal cohort studies coupled with molecular surveillance are needed to characterize antibody titers and waning of protection against repeat infections, the authors note. Furthermore, more answers are needed regarding how some virus variants might contribute to reinfection risk.

No funding for the study has been reported. Michlmayr, Hirschwerk, Wherry, Boyton, and Altmann have disclosed no relevant financial relationships.

Lancet. Published online March 17, 2021. Full text, Comment

Damian McNamara is a staff journalist based in Miami. He covers a wide range of medical specialties, including infectious diseases, gastroenterology and neurology. Follow Damian on Twitter: @MedReporter.

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