Baltimore, MD—Antibody levels against SARS-CoV-2 were more durable in healthcare workers who were previously infected with the novel coronavirus and then received two doses of mRNA vaccine, according to a new study.

The three independent exposures to spike antigen led to higher levels of antibodies over an extended period of time than in individuals who only received the initial mRNA vaccine series, according to Johns Hopkins Medicine researchers. The research letter published in JAMA also pointed out that a longer interval between infection and first vaccine dose appeared to further enhance the antibody response.

“This finding adds to our understanding of how immunity against SARS-CoV-2 works, and builds upon an earlier study by our team that showed the mRNA vaccines yielded a robust antibody response, even if a person did not develop significant symptoms following vaccination or did not have a prior SARS-CoV-2 infection,” explained study senior author Aaron Milstone, MD, MHS, professor of pediatrics at the Johns Hopkins University School of Medicine and pediatric epidemiologist at Johns Hopkins Children’s Center.

To reach those conclusions, the study team enrolled a convenience sample of 3,500 healthcare workers from the Johns Hopkins Health System beginning in June 2020 and followed through September 3, 2021. Participants provided serum samples 90 days apart, and researchers collected SARS-CoV-2 polymerase chain reaction (PCR) test results and vaccination dates (inside and outside the health system) from electronic health records.

The study subjects also had a serum sample collected at least 14 days after receiving the second dose of an mRNA SARS-CoV-2 vaccine, with previous SARS-CoV-2 infection defined by the date of positive SARS-CoV-2 PCR test results prior to first vaccine dose. Investigators obtained immunoglobulin G (IgG) antibody measurements using an enzyme-linked immunosorbent assay (Euroimmun), estimating optical density ratios with a lower threshold of 1.23 and upper threshold of 11.00 based on assay saturation.

Slightly fewer than 4% of the 1,960 healthcare workers who provided serum samples showed evidence of previous infection: 41 with positive PCR results 90 or fewer days before vaccination and 32 with positive PCR results more than 90 days before vaccination. With a mean age of 40.4 years, most (80%) of the healthcare workers providing samples were women.

In explaining why they undertook the study, the authors noted, “Waning serum antibodies against SARS-CoV-2 have raised questions about long-term immunity. Lower antibody levels to SARS-CoV-2 spike protein are associated with breakthrough infections after vaccination, prompting consideration of booster doses. Prior infection may enhance protection from vaccination, stimulating inquiry about hybrid immunity. Our objective was to examine SARS-CoV-2 spike IgG antibodies in a longitudinal cohort, comparing antibody durability in individuals who received an mRNA SARS-CoV-2 vaccine with or without prior SARS-CoV-2 infection.”

Results indicate that among participants without previous SARS-CoV-2 infection, the adjusted median antibody measurements were 8.69 (95% CI, 8.56-8.80) at 1 month, 7.28 (95% CI, 7.15-7.40) at 3 months, and 4.55 (95% CI, 4.16-4.91) at 6 months after vaccination.

“Compared with participants without previous SARS-CoV-2 infection, those with prior infection maintained higher postvaccination adjusted median antibody measurements by an absolute difference of 1.25 (95% CI, 0.86-1.62) (relative difference, 14% [95% CI, 10%-19%]) at 1 month, 1.42 (95% CI, 0.98-1.86) (relative difference, 19% [95% CI, 13%-26%]) at 3 months, and 2.56 (95% CI, 1.66-4.08) (relative difference, 56% [95% CI, 35%-94%]) at 6 months,” the authors stated.

When the previously infected patients were vaccinated made a difference, the authors noted, adding, “Individuals with PCR-confirmed infection more than 90 days before vaccination had higher postvaccination adjusted antibody measurements, compared with those with PCR-confirmed infection less than or equal to 90 days before vaccination, of 10.52 (95% CI, 10.13-11.00) (absolute difference, 0.86 [95% CI, 0.28-1.48]; relative difference, 9% (95% CI, 3%-16%]) at 1 month and 9.31 (95% CI, 8.47-9.98) (absolute difference, 1.09 [95% CI, 0.17-1.92]; relative difference, 13% [95% CI, 2%-24%]) at 3 months.”

“This suggests that a longer interval between infection and first vaccine dose may enhance the antibody response,” Dr. Milstone said, adding that further investigation is needed to determine whether increased postvaccination durability in previously infected people is attributable to the number of exposures to the virus, the interval between exposures, or the interplay between natural or vaccine-derived immunity.

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