Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread widely and rapidly over the whole world, causing millions of deaths and hundreds of millions of documented infections and illnesses.
Natural immunity is known to follow natural infection with the virus, though it wanes with time unless boosted by a single or two doses of a vaccine.
A new study looks at the period over which natural immunity may be expected to persist in children and adolescents and is available on the medRxiv* preprint server, while the article undergoes peer review.
Study: Durability of SARS-CoV-2 Antibodies from Natural Infection in Children and Adolescents. Image Credit: FamVeld/Shutterstock
The virus is a beta-coronavirus with a large 30 kilobase ribonucleic acid (RNA) genome. This encodes both structural and non-structural viral proteins, as well as several accessory proteins. The structural proteins include the spike protein that accomplishes the viral binding to the host cell angiotensin-converting enzyme 2 (ACE2) receptor, as well as the nucleocapsid protein that makes up the virus coat.
The spike antigen is used in all currently available vaccines, to stimulate the recipient’s immune response and induce the formation of protective antibodies to the virus. The Pfizer and Moderna vaccines, both developed on a nucleic acid platform, contain messenger RNA (mRNA) encoding the spike antigen in order to express it within the host cells. The effect of the vaccination will be to elicit anti-spike neutralizing antibodies in the recipient’s body.
Over the two years since its emergence, several variants of the virus have been identified, containing clusters of mutations that may confer increased infectivity, transmissibility, or pathogenicity. The presence of such potentially dangerous biological attributes causes such variants to be called variants of concern (VOCs).
This is true of the Delta variant, B.1.617.2, that appears to spread far more easily even than the Alpha (B.126.96.36.199) strain, itself much more transmissible than the wild-type virus or the D614G lineage. The reopening of schools has raised the question of whether this strain can cause surges of infection among children.
The current study was triggered by the paucity of data on the incidence of SARS-CoV-2 infection in this age group, especially given the largely asymptomatic nature of the infection. Secondly, it aimed at following the antibody response to the infection over time, by repeated sampling of the same cohort.
The investigators used data from the Texas Coronavirus Antibody Response Survey (Texas CARES) data. This project assesses seroprevalence at the population level prospectively over time, thus providing estimates of the incidence of infection and the durability of immunity.
The project began enrolment in October 2020, offering tests every two to three months, including serology tests for antibodies to the viral nucleocapsid (N) antigen that are found only following natural infection. The current study used data on those enrolled who were between the ages of 5 and 19 years.
What did the study show?
There were 159 participants who had completed all three tests, with the mean age being 12.5 years. Of these, 96% of those who showed anti-N antibodies at baseline were still seropositive after six months or more. Two children who were initially seropositive became negative after the first test.
There were 16 children, almost one in ten, who seroconverted during the course of testing. However, seroconversion did not vary by symptom severity or even by the presence of symptoms. Age, sex, or body mass index also failed to show any correlation with seroconversion.
Anti-N immunoglobulin (Ig) antibodies, namely, IgM, IgG, and IgA, all went up from baseline to the second test, about six months later, but then went down. About 60% of the children tested negative for anti-N antibodies induced by natural infection, by the time of the third test.
What are the implications?
The results indicated that while most children remained seropositive for the antibodies six months later, irrespective of age, sex, and symptom status, or severity of illness, the total duration of protection is unknown since there was no data on how many of these children had been infected before they were enrolled.
Secondly, the fact that over half the children were seronegative at six months indicates that even after natural infection, a majority of children remain vulnerable to the virus, their immunity apparently not having provided natural protection against reinfection.
This indicates that vaccination may be required to protect children against the virus even after natural infection. At present, the recommendations are for children aged 12 and older, and in younger children who have high-risk conditions.
It should be noted that not all scientists support the administration of the vaccine to children, who have been remarkably spared from serious illness and death from COVID-19. Children have not been demonstrated to be large-scale carriers of the virus to date, in schools or households.
A careful cost-benefit analysis must be carried out before making this sweeping recommendation to vaccinate all children aged 12 years or younger. Though, the US may soon extend the vaccine offer to infants above six months of age. More scientific evidence is required before such potentially injurious interventions are mandated or even advised in this age group.
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.
Messiah, S. E. et al. (2021). Durability of SARS-CoV-2 Antibodies from Natural Infection in Children and Adolescents. medRxiv preprint. doi: https://doi.org/10.1101/2021.11.21.21266484. https://www.medrxiv.org/content/10.1101/2021.11.21.21266484v1