Vaccination protects the young against COVID-19

COVID-19 remains a global health concern, and children and adolescents are equally affected. In fact, COVID-19 hospitalization rates in children increased during the Omicron era. [MMWR 2022;71:271-278] In children aged 5–11 years who were hospitalized during the predominance of Omicron, nearly 90 percent were unvaccinated. [MMWR 2022;71:574-581]

mRNA vaccines provide protection against COVID-19 hospitalizations in children aged 5–11 years. With its efficacy extending to infants aged 6–36 months, regulatory approval for children from 6 months onwards ensued. [www.cdc.gov/vaccines/acip/meetings/downloads/slides-2022-10-19-20/05-COVID-Oliver-508.pdf, accessed May 21, 2023; N Engl J Med 2022;10:1056/NEJMoa2209367]

Low vaccine uptake

However, COVID-19 vaccine uptake among the young is low, primarily because of safety, noted Professor Susanna Esposito from the University of Parma, Italy, in her presentation at ESPID 2023. “Many children have not yet initiated their COVID-19 vaccine primary series.”

 

In the US, about 40 percent of 12–17-year-olds have yet to complete their primary vaccines against COVID-19. In those aged <2, 2–4, and 5–11 years, vaccination rates for primary series were 4.6, 6.0, and 32.9 percent, respectively.

Looking at those who have received a bivalent booster vaccine, roughly 8 percent of 12–17-year-olds have received their shots. Rates were much lower in the younger age groups (0.6, 0.6, and 4.7 percent for ≤2, 2–4, and 5–11 years, respectively).

“Therefore, it is very important to discuss with parents about safety because this is a major issue that they have in relation to mRNA vaccines,” said Esposito.

Safety of mRNA vaccines

In a systematic review and meta-analysis, mRNA vaccines protect well against COVID-19 hospitalizations and are safe in children aged 5–11 years. Serious adverse events were low and even lower after booster vaccination. [Lancet Child Adolesc Health 2023;S2352-4642(23)00078-0]

The risk of myocarditis/pericarditis after COVID-19 vaccination among adolescents and young adult males within the first week following the second or booster dose of an mRNA vaccine has been reported. Nonetheless, Esposito said this was rare and most patients recovered fully at follow-up. [www.cdc.gov/vaccines/covid-19/clinical-considerations/myocarditis.html, accessed May 21, 2023] “An interval of 8 weeks between vaccine doses may further lower myocarditis risk,” she noted.

In males aged 12–17 years, the risk of adverse cardiac outcomes was 1.8–5.6 times higher after contracting the SARS-CoV-2 infection compared with those who have received a second shot of a COVID-19 mRNA vaccine. [MMWR 2022;71:517-523]

mRNA-1273.214 vs mRNA-1273

The safety of the mRNA-1273.214 bivalent primary series was compared against the original mRNA-1273 in children aged 6 months to 5 years. In terms of local reactions (eg, pain, erythema, swelling, and axillary swelling or tenderness), the rates were lower with the bivalent vs the original vaccine, but all reactions were grade 1/2 irrespective of vaccine type. Pain was the most dominant event in both groups, with the highest incidence reported after dose 2 (63 percent).

Looking at systemic reactions (eg, fever, irritability/crying, sleepiness, and loss of appetite), only 10 grade 4 events (fever) were reported with the original vaccine. Most reactions with both vaccines were grade 1/2. Grade 3 events tied to the bivalent series were only observed after dose 2.

Simliar trends in local and systemic reactions were seen with the booster shots. With respect to the bivalent booster, a few cases of grade 3 local reactions (eg, pain, swelling, and erythema) were reported. The most common grade 3 systemic reactions tied to the bivalent booster were irritability/crying (in participants aged 6–36 months) and fatigue and fever (in those aged 37 months to 5 years) [www.fda.gov/media/164810/download, accessed May 21, 2023]

COVID in the very young

Infants <1 year had the highest rate of intensive care admission or death due to SARS-CoV-2. [PLoS One 2021;16:e0246326] “We did not think COVID-19 was a problem for very young children, but after Delta and Omicron, we understand that it continues to be a significant disease,” said Dr Flor Muñoz-Rivas from the Texas Children’s Hospital, Houston, Texas, US, during her talk at ESPID 2023.

In the US, children <5 months of age have the highest risk of morbidity and mortality for COVID-19. Between August 1, 2021 and July 31, 2022, 821 infant (0–5 months) deaths from COVID-19 were reported, yielding a crude mortality rate of 1.0/100K population. [JAMA Netw Open 2023;6:e2253590] Hospitalizations were also a problem during the Omicron wave. After the ≥65-years age group, children aged 0–5 months were the most vulnerable to hospitalization.

“As we know, there is no vaccine for this population at the moment. So this is where maternal immunization [comes into play] as a way to protect infants in this very vulnerable period of time,” Muñoz-Rivas stressed.

Pregnant women have a very good response to vaccination. In one study, a very nice antibody response was seen in all groups of women evaluated after one vaccine dose. Responses improved after the second dose. [Am J Obstet Gynecol 2021;225:303.e1-303.e17] “There were equivalent immune responses in pregnant and lactating mothers vs nonpregnant women,” said Muñoz-Rivas.

Important questions

One of the pressing questions that mums had during the pandemic was whether breastmilk could still offer protection if they cannot get a COVID-19 vaccine during pregnancy.

Three antibodies transferred to breastmilk post-infection are IgA, IgG, and IgM. Despite serum declines over time, especially with IgM, there is persistence even up to 150 days, suggesting continued secretory Ig production and, therefore, ongoing protection. [Cell Rep 2021;37:109959] “Indeed, we can infer that there can be protection through breastmilk,” Muñoz-Rivas said.

What about getting vaccinated during the lactation period? “Questions arose regarding the safety of breastmilk when mums are receiving mRNA vaccines,” she shared.

In women who received COVID-19 mRNA vaccines, IgG, IgA, and IgM antibodies were present in blood following the first and second doses. [Cell Rep Med 2021;2:100468] “Secretory IgA and T cells targeting SARS-CoV-2 spike protein are transferred to the breastmilk upon mRNA activation,” Muñoz-Rivas added, thus providing an additional layer of protection to the babies.

In another study, there were no severe vaccine-related local and systemic reactions in both mums and babies, and no significant amounts of mRNA were present in breastmilk. [Front Immunol 2022;13852928]

COVID-19 mRNA boosters elicited a robust maternal antibody response and passive transfer of antibodies via the placenta and breastmilk. [Am J Obstet Gynecol MFM 2023:5:100830] “There was a very nice increase in antibodies in both breastmilk and plasma after booster vaccination. I think this is very supportive of booster vaccination in pregnancy,” said Muñoz-Rivas.

Takeaways

“Maternal vaccination and breastfeeding were able to protect infants too young to be vaccinated during a period of high vulnerability. mRNA vaccines are safe for pregnant women and during lactation. Boosters during pregnancy and lactation could enhance maternal and breastmilk immunity,” said Muñoz-Rivas. “Nursing is encouraged to potentially provide protection to the infant as well.”

“Healthy mum equals a healthy baby, and that includes immunization,” Muñoz-Rivas concluded.