In a recent study published in the Journal of the Pediatric Infectious Diseases Society, researchers characterized the children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection, determined the number of reinfections, and characterized the intervals between two infections in the patient population.

Study: SARS-CoV-2 Reinfection With Different SARS-CoV-2 Variants in Children, Ohio, United States. Image Credit: FamVeld/Shutterstock.com

Background

Studies from the early stages of the coronavirus disease 2019 (COVID-19) pandemic suggested that protection from infection-acquired immunity can last longer than six months, and reinfections were infrequent.

Nevertheless, growing data show increased rates of reinfection linked to SARS-CoV-2 Omicron variants, with shorter reinfection intervals among Omicron variants.

About the study

In the present study, researchers characterized SARS-CoV-2 reinfections in children. Individuals aged 21 or younger testing SARS-CoV-2-positive by nucleic acid amplification (NAAT) or antigen testing between March 14, 2020, and September 30, 2022, at any area of the Nationwide Children’s Hospital (NCH) system were included.

Reinfection was defined as two positive tests at least 90 days apart, with reinfection occurring before January 2022 or two positive tests at least 45 days after for those after January 2022.

Samples positive by NAAT between January 2021 and September 2022 were identified. A convenience sample was selected from these for variant typing by mutation-specific reverse-transcription polymerase chain reaction (RT-PCR) assays.

Positive samples were screened for SARS-CoV-2 Alpha, Delta, or Omicron BA.1. An H655Y assay was developed for screening SARS-CoV-2 Omicron BA.2 or BA.4/5.

When samples were unavailable (for variant typing), the predominant SARS-CoV-2 variant at sampling was assumed to be present in specimens. Demographic data, testing site, and hospitalization and vaccination status were obtained from electronic health records (EHRs).

Kruskal-Wallis and chi-squared tests were performed to analyze continuous and categorical variables, respectively.

Findings

Overall, the researchers documented 27,244 positive tests during the study period. Of these, 541 reinfected patients were identified and included for analysis; 539 patients had two infections, and two cases had three infections.

Patients median age at the time of the second infection was 7.85. Fifty-six patients were less than one year old. Nearly half of the reinfected patients were males.

EHRs were available/accessible for 529 patients. Most patients (54%) had an underlying condition, with chronic respiratory distress being the most prevalent at 16%.

Around 13% were obese or overweight; genetic/neurologic disorders were observed in 13% of subjects. Twenty-seven subjects were immunocompromised. Hospitalization rates were higher in primary infections (6%).

Vaccination status was available for 69 patients only, all of whom were fully vaccinated before the reinfection. Of these, 16 were boosted at least two weeks before the second infection. Three were hospitalized, and two were admitted to the intensive care unit (ICU).

The median time between two positive tests was 229 days. Most reinfections (93%) occurred at least 90 days apart, while 7% occurred within 90 days of the first infection.

Three patients had samples available from first and second infections for variant typing. They were infected with SARS-CoV-2 Delta and later by Omicron BA.1 within 90 days. Over 1,800 samples were tested for variant surveillance.

Six reinfections were recorded before the Delta variant identification, which increased to 45 by mid-December 2021, and sharply spiked until early February 2022, reaching 263 before BA.2 emerged.

The number of reinfections continued to increase and reached 541 in September 2022. Reinfections accounted for 0.14%, 0.73%, 2.4%, 6.9%, and 6.4% of the cumulative infections during pre-Delta, Delta, BA.1, BA.2, and BA.4/5 periods, respectively. BA.1-reinfected patients were significantly older than those infected with other variants.

No significant differences were observed by variant type in gender and hospitalization/ICU admission rates during the second infection.

The median time between two infections was significantly different by variant type. Of the two female children with three infections, one was nine years old and had no underlying conditions; the other was obese and aged 6.6. They were not hospitalized for COVID-19.

Conclusions

In sum, the researchers documented SARS-CoV-2 reinfections in pediatric patients and identified 541 reinfected cases. The findings indicate shorter intervals between reinfections and higher reinfection rates with SARS-CoV-2 Omicron variants. Hospitalization rates were lower for reinfections.

Reinfection rates increased after the emergence of SARS-CoV-2 Delta, although a significant surge in reinfections was not observed until January 2022.

Notably, one-third of patients reinfected with BA.2 or BA.4/5 had a prior BA.1 infection, suggesting that BA.1 infection may not protect against reinfection. Although different variants caused most primary and secondary infections, six patients were reinfected with the same variant (Delta).

Above all, given the continued viral evolution and increasing vaccination rates, the surveillance of reinfections and assessment of the associated risk and disease burden in children is warranted.