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BUENOS AIRES, Argentina — When it comes to knowing how much time should pass between having COVID and getting a booster, there are no set rules or solid findings from comparative studies to look to. In light of the Omicron wave, there are currently, and will continue to be, millions of people in Ibero-America and throughout the world who will need this information.

“There’s no clear consensus,” Jarbas Barbosa, MD, PhD, assistant director of the Pan American Health Organization, told Medscape Spanish Edition. “Although the vaccine is totally safe to give a person who no longer has any symptoms, every country has its own recommendation as to when to give it. There are other factors at play as well, such as the availability of vaccines.”

The prevailing recommendation is to give the dose as soon as the person has recovered when they have the opportunity to access this vaccination. According to the Centers for Disease Control and Prevention (CDC), people with known current SARS-CoV-2 infection should defer any COVID-19 vaccination, including booster vaccination, “at least until recovery from the acute illness (if symptoms were present) and criteria to discontinue isolation have been met.”

Still, the CDC acknowledges that “information is lacking” about whether and how the amount of time since infection affects the immune response to vaccination.

“While there are a number of soft recommendations, there still haven’t been any randomized studies that have evaluated when the best time to vaccinate people after they’ve recovered from COVID is so as to stimulate the strongest immune response. So, we don’t have any solid, conclusive evidence. However, we know that giving the vaccine to someone after they’ve had the disease is highly effective and provides hybrid protection, something that’s highly desirable. So, people who have recovered from COVID-19 should get vaccinated,” noted Armelle Pérez-Cortés Villalobos, MD, a Mexican infectious disease specialist now based in Canada. She is also a member of the editorial board for Medscape Spain.

“My recommendation is in line with the CDC’s: people should get the vaccine at any time after the isolation and clinical recovery criteria have been met,” she added.

The Sooner, the Better?

For many experts in the region, “give the booster any time” turns into “the sooner the booster’s given, the better.”

“Once the requisite amount of time after the last dose has passed, the booster should be given as soon as the patient no longer has symptoms and their isolation has ended,” noted Wilfrido Clara, MD, MPH, a pediatrician and epidemiologist from El Salvador who works for the CDC, in Atlanta, Georgia. He went on to tell Medscape Spanish Edition that, in his opinion, patients treated with monoclonal antibodies only have to wait 90 days.

“When’s best? There’s no set rule. The CDC recommends that people wait at least until their symptoms have disappeared or 7 days since testing positive and after they’ve been fever-free for more than 24 hours. So, there’s no excuse. Get vaccinated!” as Alfredo Victoria, MD, epidemiologist at Ángeles Hospital Puebla, in Puebla, Mexico, urged on Instagram.

To cite one example, the procedures manual of the Costa Rican Department of Social Security states that the vaccine can be given “immediately after the individual has recovered from the illness.” This recommendation is applicable to the first, second, and third doses, as reported in an article in the country’s La Nación newspaper.

Chile was the first country in the region to start giving COVID-19 vaccine boosters. Jeannette Dabanch, MD, is an infectious disease specialist at the University of Chile’s Clinical Hospital in Santiago. She is also a member of the country’s Advisory Committee on Vaccines and Immunizations. As she told Medscape Spanish Edition, “In our booster recommendations, there’s no specific recommendation with respect to an interval after infection.”

According to the guidelines of Chile’s Ministry of Health, “a patient who has had COVID-19 and has recovered can get the vaccine.” And Dabanch supported that position. “There’s not a lot of evidence, but I believe that the findings of studies on reinfection, as well as the emergence of variants, justify vaccinating on shorter timelines as a matter of public policy.”

Other countries recommend longer intervals. In accordance with the advice of its Vaccine Advisory Committee, Colombia suggests that people wait 30 days from the onset of symptoms — or, for those who are asymptomatic, from the date of diagnosis — before getting the booster, said Leonardo Arregocés, MD, PhD, director of medicines and health technologies at the country’s Ministry of Health and Social Protection.

As reported in Madrid’s newspaper, El Mundo, Spain recommends that, after being diagnosed with COVID, people wait at least 4 weeks — and ensure that they have fully recovered — before getting vaccinated. The United Kingdom adopted the same guidance.

“It Is Confusing”

But the most patient country seems to be Argentina, which this year alone has had over 3 million confirmed new cases of COVID-19 (ie, almost one third of the total cases the country has recorded since the start of the pandemic). In a press conference on January 20 of this year, the country’s Minister of Health, Carla Vizzotti, MD, recommended that anyone who has recovered from COVID hold off on getting the booster for 90 days because “the immunity from natural infection is like a booster for our immune system”; the delay will allow “the dose, once it is given, to be more effective and to provide protection for a longer period of time.”

This interval is arbitrary (“it could have been 80 days, or 120 days”), but the recommendation is “reasonable,” said Pedro Cahn, MD, PhD, scientific director of the Huésped Foundation in Buenos Aires and one of the most prominent infectious disease specialists advising Argentina’s government during the pandemic. In his conversation with Medscape Spanish Edition, Cahn pointed out, “There aren’t any comparative studies. But we know that acute infection produces a rapid response of antibodies that lasts 4 months. So, while vaccinating immediately doesn’t cause anything bad to happen, this approach doesn’t take advantage of all of the benefits there are during that time period.”

This view was shared by Jorge Geffner, PhD, professor of immunology at the University of Buenos Aires School of Medicine. “The infection essentially acts as an additional dose. And if one immediately administers the third dose of the vaccine — which would be like a fourth dose — it’s very likely that there will be only a slight increase in the adaptive immune response. And so it makes sense to wait 60 or 90 days.”

Eduardo López, MD, infectious disease specialist and head of the Department of Medicine of the Ricardo Gutiérrez Children’s Hospital in Buenos Aires, took a position somewhere in the middle. “There’s no global agreement, and even the World Health Organization doesn’t indicate what the optimal interval would be. The idea we’re currently leaning toward is that if you space the doses out over a longer period of time, when you do give the booster, the antibody levels will increase more. But this is not shown to be true with Omicron. I would fall somewhere in the middle: after a person has been COVID-free for 1 month, the booster doses can be given whenever,” he stated on Radio Con Vos.

In a recent video discussion recorded for Medscape, a couple of renowned specialists from the United States shared the uncertainties they, too, have. Paul Sax, MD, clinical director of the Division of Infectious Diseases at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School in Boston, Massachusetts, pointed out that one of the most confusing aspects of COVID-19 — for doctors and for patients — is how durable protection is after natural infection. Part of the reason it’s so confusing is that it varies from person to person, there is not a “defined dose” like there is with a vaccine, and it also varies depending on the severity of the illness or even the variant involved.

“There are immunologists who feel like, yes, once you get infected, you can wait. You have 3 months at least and you’re not going to get reinfected. There are other immunologists who feel like the infection actually harms some of the immune responses and you should probably get vaccinated as soon as you can. I don’t think we have enough data to say what the optimal time to wait is,” noted Sax.

For his part, Paul Offit, MD, director of the Vaccine Education Center and professor of pediatrics in the Division of Infectious Diseases at Children’s Hospital of Philadelphia, Pennsylvania, agreed that this interval will be understood over time. “It does look like the so-called hybrid immunity, which is induced by a combination of natural infection and immunization, provides maybe a broader protection and possibly longer-lasting protection. We’ll see, but it is confusing,” he acknowledged.

Pérez-Cortés, Dabanch, Clara, Cahn, and Geffner have disclosed no relevant financial relationships.

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