Risk of SARS-CoV-2 reinfection in children compared to adults

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak of coronavirus disease 2019 (COVID-19) led to the emergence of numerous studies meant to identify the immune correlates of this infection. Earlier, it has been found that infected and recovered adults were susceptible to reinfection, though rarely in the first phase of the outbreak.

Study: Risk of SARS-CoV-2 reinfections in children: prospective national surveillance, January 2020 to July 2021, England. Image Credit: Oleksandr Yakoniuk/Shutterstock

Recently, however, increasing rates of breakthrough infections and reinfections following vaccination and recovery from natural infection, respectively, point to waning immunity and immune escape due to the generation of new virus variants.

More data is required, especially in children largely neglected due to the low incidence of infection and symptomatic disease in this age group. A new study used national testing data over the first two years of the pandemic to estimate the reinfection risk in children relative to adults when exposed to both Alpha and Delta variants. This shows that reinfections were rare among children and mostly mild.

Background

Earlier studies showed a strong immune response among children following exposure to SARS-CoV-2, both humoral and cell-mediated adaptive immune responses having been observed. The immune attack is directed mostly against the viral spike, but most cases are mild or asymptomatic, with the immunity persisting for 12 months or more.

This exceeds the period of active immunity in adults and seems to protect against newer variants of the virus. Adults have been vaccinated on a large scale in many countries, with early success in bringing down the incidence of new COVID-19 cases and hospitalizations. Still, waning immunity has seen a rise in breakthrough infections over time.

This has been aggravated by the rise of the new Delta variant that is much more infectious than earlier strains, which can evade natural and vaccine-induced immunity. The current study, available on the medRxiv* preprint server, aimed to explore the rate and risk of SARS-CoV-2 reinfections in children.

In England, SARS-CoV-2 testing was limited to symptomatic cases presenting at healthcare facilities. Presently, community testing is available freely, leading to about 100,000 tests being done each day in June 2020. This data was mined for the current study to understand reinfection risk in children over the first 19 months of the pandemic, while both Alpha and Delta variants were circulating.

What did the study show?

In England, during summer 2020, a low rate of infections then saw a rise just before the onset of Autumn, with the peak occurring in December 2020. This has been attributable to the emergence and rapid spread of the Alpha variant from November 2020 onwards. This was followed by a national lockdown, which saw cases declining rapidly.

During this period, few reinfections occurred in children, mirroring the low reinfection number at the community level. In March 2021, a six-fold rise in primary cases led to a small increase in reinfections as well, with a further sharp rise in May 2021.

In May 2021, infections rose again to a peak, as restrictions were relaxed simultaneously with the emergence and spread of the Delta variant. Therefore, reinfection rates followed the same trend as community infection rates with this variant. School closures led to a fall in primary infections and reinfections over the summer holidays.

The researchers found that the reinfection risk was in proportion to the risk of exposure to the virus. Most reinfections occurred during the time of maximum community transmission, at the time when the Delta virus was rampant.

Reinfections with the Alpha variant occurred mostly in those over 80 years of age, but the age distribution changed with increasing adult vaccination rates. By the time the Delta variant was circulating, younger adults less than 40 years of age were the major target of reinfection, these being largely unvaccinated or vaccinated with one dose.

In adolescents, July 2021 saw peak reinfection rates with the Delta wave, at 5.5 per 100,000, compared to <2 and <1 among children aged 5-11 years and <5 years, respectively. This followed similar trends among people aged 50-59 years who had received two doses of the COVID-19 vaccine in three of four cases. At least 93% had received one dose of the vaccine at this point.

The children were less prone to reinfection than adults, but the risk went up with age. The risk of adverse outcomes among children, including hospitalizations and intensive care admissions, was low with reinfections. In children, no deaths were reported to occur within 28 days of reinfection.

Throughout the study, primary infection rates were highest in infants but lowest among those aged 1-2 years. The pattern was reversed with reinfections, as described above.

The overall rate of reinfection was almost 70/100,000, but in adults, it was ~75 vs. ~21 per 100,000 in children. The rates were ~700 overall for reinfections, at 730 and ~340 per 100,000 in adults and children, respectively. Less than 5% of reinfected children needed hospital admission, and almost three-quarters of these had underlying medical conditions recorded at admission.

More reinfections among children were asymptomatic, at half, compared to infections, at 37%. Only four children had required ICU admission, and all were admitted during both primary infection and reinfection, with severe medical conditions. Thus, the exact contribution of SARS-CoV-2 to the severe phenotype is not clear.

There were 53 deaths within two months of the first positive COVID-19 test where this infection was recorded as the cause of death, all following primary infection.

What are the implications?

The study underlines the uncommon and mild phenotype of SARS-CoV-2 reinfections in children in England, reflecting the rates of community transmission. Most of them were related to the spread of the Delta variant in summer 2021. Despite the obvious limitations of using testing data, such as the reduced chances of testing among children due to the asymptomatic or very mild phenotype of primary infection or reinfection, the study also included the twice-weekly rapid home testing data from secondary schools, which could have led to lower rates of spread and higher rates of reporting among older children (11-16 years).

Exposure risks varied with the variant and the activity profiles, adults showing a different pattern from children. Testing probabilities also fluctuated over the study period. Nonetheless, the study successfully estimated the risk of reinfection over 19 months and compared it with that in adults. The high rates of infection among infants below the age of 1 year are probably due to newborns being tested after birth and testing being carried out at the time of presentation with fever or signs of infection.

A history of prior SARS-CoV-2 infection with one dose of the vaccine seems to confer broad and lasting immunity to reinfection. Even more importantly, to severe disease and death due to the infection, among children just as among adults. Further research will help uncover the risk of long COVID-19 in this age group.

 *Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.