Reinfection with SARS-CoV-2 in children

Until the last few months, the coronavirus disease 2019 (COVID-19) pandemic has had the least impact on children. However, much remains to be understood about how infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affects children and how well prior infection protects them against reinfection.

Study: Burden of SARS-CoV-2 and protection from symptomatic second infection in children. Image Credit: Rimma Bondarenko/Shutterstock

This is all the more important as they are likely to receive the vaccine last among all groups. A new preprint examines these questions in a cohort of children in Nicaragua’s Managua.

Background

Children mostly have a mild or asymptomatic infection with SARS-CoV-2, but a few have developed severe symptoms like breathlessness or multi-system inflammatory syndrome (MIS-C). This is more common in the youngest and oldest children and those with comorbidities. These are also at the highest risk for post-acute sequelae of COVID-19 (PASC), also termed “long covid’, though the risk is far smaller than for adults.

SARS-CoV-2 infections among children have mostly been studied in the context of hospitalized children, thus largely missing out on asymptomatic and mild infections in this age group. Most such studies have been performed in high-income countries, limiting the generalizability.

An earlier study indicates that even if sterilizing immunity wanes rapidly, the prior infection may continue at a stable level, such that the virus may become endemic. This may result in infections eventually becoming only as severe as the currently circulating seasonal endemic human coronavirus infections. The big question is, how long will this take to occur?

Research is also going on to understand how various degrees of severity of disease are linked to sequelae and subsequent protective immunity to reinfection. Moreover, the impact of the recently emerging variants of concern on clinical illness in children remains to be assessed. The current study, published on the medRxiv* preprint server, attempts to answer these questions.

What did the study show?

The study used data from The Nicaraguan Pediatric Influenza Cohort, collected from March 1, 2020, through October 15, 2021. It was designed to be a prospective study and included almost 2,000 non-immunocompromised children aged 0-14 years.

Children with prior infection had to have a positive anti-SARS-CoV-2 receptor-binding domain (RBD) and spike antibody test, or a real-time confirmation of infection by reverse transcriptase-polymerase chain reaction (RT-PCR) at least 60 days earlier than the current episode. All symptomatic cases had to have been confirmed by RT-PCR, with a history of hospitalization within 28 days of the onset of symptoms.

All cases were classified as subclinical, mild, moderate, or severe. Those with respiratory symptoms were considered to have a moderate illness, while those who required hospitalization were said to have a severe illness.

Reinfection was defined as having a positive RT-PCR test following the confirmation of earlier infection by a positive enzyme-linked immunosorbent assay (ELISA) and/or a positive PCR test at 60 or more days after a prior positive PCR result. All children with a positive ELISA test who showed no evidence of current infection were retrospectively assessed for severity of infection.

In the lull period from August 1, 2020, to February 15, 2021, no case was considered to be COVID-19 in the absence of a clear epidemiologic link to a source of infection.

In this study, half the children were seropositive during the study period, with ~200 PCR-positive COVID-19 cases. Of these, 12 children had to be hospitalized for the illness. The disease incidence was greatest among those younger than two years, at 16 per 1,000 person-years. This was three times as high as in any other age group and twice as high as the overall incidence of 7.7 cases per 100 person-years.  

About one in five of the symptomatic infections occurred in previously infected children, with a slightly higher incidence among the older children. Up to the age of 5 years, 60% of children were protected against symptomatic reinfection, vs. 64% and ~50% in those aged 5-9 years and 10-14 years, respectively.

All reinfections occurred in 2021 and were caused by the Gamma and Delta variants of concern (VOC) of SARS-CoV-2, which began to circulate widely in this country at this period. The same trends with age were observed as with the overall group.

The incidence of infection among children appears to be high, with over half the children seroconverting over the study period. Most were mild or asymptomatic infections, but children under the age of two years were at a higher risk for severe illness, at five times the rate of children aged 5-9 years. Overall, however, only 6% developed severe illness, for an incidence of 0.4 per 100 person-years.

About a tenth of those with confirmed COVID-19 had long covid, mostly relating to respiratory symptoms lasting for 28 days or more. These included a runny nose, cough, and sometimes a stuffy nose or sore throat. One child under the age of 2 had rapid breathing.

What are the implications?

These findings bear out earlier reports that COVID-19 is less frequent and severe in children than adults. Only a small proportion of all SARS-CoV-2 infections in this age group are detected by PCR, underlining the need for community-based prospective studies to understand the course of these infections.

The increased frequency of long covid in the under-5 and the oldest children may be due to the higher incidence of symptomatic and severe infection in these groups. The lowest protection appeared to be in children below the age of 10 years. Unlike earlier studies, about one in ten children with confirmed infection had long covid, and most had respiratory issues rather than general symptoms.

The results also show that symptomatic reinfection is relatively common, making up over a fifth of all confirmed infections in children. Some of these were severe illnesses. This points to the need to monitor severity in pediatric SARS-CoV-2 infections and a safe vaccine for the youngest children to prevent long covid and severe reinfections.

*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.