SARS-CoV-2 Antibodies May Protect From Infection - But For How Long?

SARS-CoV-2 antibodies were associated with protection from infection in a laboratory database study, but the duration of protection is unknown, researchers say.

"Being antibody-positive is associated with a lower risk of new infection than being antibody-negative," Dr. Douglas Lowy of the National Cancer Institute in Bethesda told Reuters Health by email. "People who have been infected once are less likely to be infected a second time. However, protection is not complete, so there will be some people who experience another infection."

"Going forward, it will be important to determine the duration of protection, especially if waning of protection is associated with becoming antibody-negative," he said. "A potentially confounding issue is whether the virus strains in the US will change over time, and if they do, whether the protection against new infection by strains that are closely related to the first infection will also extend to variants that are less closely related."

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As reported in JAMA Internal Medicine, Dr. Lowy and colleagues created cohorts from a deidentified data set of commercial laboratory tests, medical and pharmacy claims, electronic health records, and hospital chargemaster data from December 1, 2018 through August 26, 2020. Patients were categorized as antibody-positive or antibody-negative according to their first SARS-CoV-2 antibody test in the database.

The primary end point was post-index diagnostic nucleic acid amplification test (NAAT) results; infection was defined as a positive diagnostic test post-index, measured in 30-day intervals (0-30, 31-60, 61-90, >90 days).

The cohort included more than three million patients (median age, 48; 56%, women). Of these, 88.3% had a negative index antibody result, and 11.6% were positive. Those with a negative result were somewhat older (mean age, 48 vs. 44).

Evidence of prior disease was 0.7% for the seronegative group, 18.4% for the seropositive group, and 6.7% for the sero-uncertain group, suggesting that seropositive individuals were more likely to have had symptoms of and/or a diagnosis of COVID-19 than those who were seronegative, although the majority of subjects in both groups had no evidence of prior infection in the observable data.

Of those with a positive result, 18.4% converted to seronegative during follow-up. Specifically, the ratio of positive NAAT results among those who had a positive versus a negative index antibody test was 2.85 at 0 to 30 days, 0.67 at 31 to 60 days, 0.29 at 61 to 90 days, and 0.10 at more than 90 days.

The authors conclude, "Patients with positive antibody test results were initially more likely to have positive NAAT results, consistent with prolonged RNA shedding, but became markedly less likely to have positive NAAT results over time, suggesting that seropositivity is associated with protection from infection. The duration of protection is unknown, and protection may wane over time."

Dr. Lowy noted, "Because some people may continue to shed viral RNA for a long time, we feel the most telling results are the rate of viral RNA positivity seen 90-120 days after the index antibody finding."

Regardless, he added, "Both antibody-positive and antibody-negative people should plan to be vaccinated when they are offered the opportunity to do so."

Dr. Ruth McDermott-Levy, Associate Professor of Nursing, Villanova University's Fitzpatrick College of Nursing in Pennsylvania, commented in an email to Reuters Health, "The data were only examined for an eight-month period. Further study of the longitudinal effects of antibody protection against the virus needs to occur."

"It is important to note, however, that there also were a small number of people who did test positive for COVID-19 despite having antibodies that indicated that they had prior exposure to the virus," she said.

"Overall, this study in an important addition to understanding of SAR-CoV-2 human infections," she added. "But, as the authors accurately point out, the safest way to have protection against COVID-19 is through vaccinations."

The study didn't examine B cells and doesn't address the potential reserves of antibody response they represent.

—Marilynn Larkin

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