While debate continues on whether one dose of COVID-19 vaccine is sufficient, in some cases, with products designed to be provided in a two-dose series, a study maintains that a single shot is enough for patients who have recovered from novel coronavirus.

A letter to the editor published in the New England Journal of Medicine argues that a single shot of one of the first two COVID-19 vaccines granted emergency use authorization (EUA) might be sufficient to provide immunity to individuals who have previously been infected by the virus. Mount Sinai Hospital–led authors say this could help stretch vaccine supplies if they remain limited. The first two COVID-19 vaccines—mRNA vaccines from Pfizer-BioNTech and Moderna—received EUAs from the FDA in December 2020 and are recommended for two doses. A third product, an adenovirus vector vaccine, Janssen (Johnson & Johnson), got an EUA in February after this study was completed and requires only a single dose.

The study was previously published as a preprint on mdRxiv.

By not having to get the second dose of the mRNA vaccines, researchers point out that recovered COVID-19 patients also would be spared unnecessary side effects, which appear significantly more severe in people with some level of pre-existing immunity.

“We showed that the antibody response to the first vaccine dose in people with pre-existing immunity is equal to or even exceeds the response in uninfected people after the second dose,” explained coauthor Viviana Simon, MD, PhD, professor in the Departments of Microbiology and Medicine (Infectious Diseases) in the Icahn School of Medicine at Mount Sinai. “For that reason, we believe that a single dose of vaccine is sufficient for people who have already been infected by SARS-CoV-2 to reach immunity.”

In their study of 109 individuals with and without previous SARS-CoV-2 immunity, researchers determined that the first group developed antibodies within days of the first dose of vaccine at a rate 10 to 20 times higher than those who were uninfected, and at a more than tenfold rate after the second dose.

“These findings suggest that a single dose of vaccine elicits a very rapid immune response in individuals who have tested positive for COVID-19,” pointed out coauthor Florian Krammer, PhD, of Mount Sinai. “In fact, that first dose immunologically resembles the booster (second) dose in people who have not been infected.”

Systemic reactions were tested after the first dose of vaccine in a second group of 231 individuals, 83 of whom had tested positive for COVID-19, and 148 who had not.

Researchers found that, while the vaccines were generally well tolerated, injection-site symptoms—including pain, swelling, and reddening of the skin—were identified in both sub-groups. For recipients with pre-existing immunity, however, side effects occurred with a significantly higher frequency, including fatigue, headache, chills, fever, and muscle or joint pain.

In fact, the authors suggest that the intensity of the response to the first dose in people previously infected looks quite similar to the response from those not previously infected after the second dose. Researchers post that the reason for the stronger response in both groups is because immune cells have learned how to recognize the spike protein of the virus—the antigen that forms the basis for vaccination. Response is more vigorous and leads to stronger reactions to the vaccine.

In fact, Dr. Simon suggests using a serological assay to detect antibodies that might exist to the spike protein. “If the screening process determines the presence of antibodies due to previous infection, then a second shot of the coronavirus vaccine may not be necessary for the individual,” she concludes. “And if that approach were to translate into public health policy, it could not only expand limited vaccine supplies, but control the more frequent and pronounced reactions to those vaccines experienced by COVID-19 survivors.”

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