Dynamics of Reverse Transcription-Polymerase Chain Reaction and Serologic Test Results in Children with SARS-CoV-2 Infection

Abstract

Objectives: To determine the time to reverse transcription-polymerase chain reaction (RT-PCR) negativity after the first positive RT-PCR test, factors associated with longer time to RT-PCR negativity, proportion of children seroconverting after proven severe acute respiratory syndrome coronavirus 2 infection, and factors associated with the lack of seroconversion.

Study design: The Epidemiological Study of Coronavirus in Children of the Spanish Society of Pediatrics is a multicenter study conducted in Spanish children to assess the characteristics of coronavirus disease 2019. In a subset of patients, 3 serial RT-PCR tests on nasopharyngeal swab specimens were performed after the first RT-PCR test, and immunoglobulin G serology for severe acute respiratory syndrome coronavirus 2 antibodies was performed in the acute and follow-up (<14 and ≥14 days after diagnosis) phase.

Results: In total, 324 patients were included in the study. The median time to RT-PCR negativity was 17 days (IQR, 8-29 days), and 35% of patients remained positive more than 4 weeks after the first RT-PCR test. The probability of RT-PCR negativity did not differ across groups defined by sex, disease severity, immunosuppressive drugs, or clinical phenotype. Globally, 24% of children failed to seroconvert after infection. Seroconversion was associated with hospitalization, persistence of RT-PCR positivity, and days of fever.

Conclusions: Time to RT-PCR negativity was long, regardless of the severity of symptoms or other patient features. This finding should be considered when interpreting RT-PCR results in a child with symptoms, especially those with mild symptoms. Seroprevalence and postimmunization studies should consider that 11 in 4 infected children fail to seroconvert.

Keywords: COVID-19; RT-PCR; SARS-CoV-2; children; dynamics; seroconversion; serology.

Figure 1

A, C_t over time. The line represents an inference of the trajectory of C_ts until negativity. Negative values are presented as a C_t of 45. Negative values beyond 60 days are not presented. B, Box-and-whiskers distributions of C_t across weeks. Most of the samples had a high C_t value. At diagnosis, the median C_t was 38.5 (IQR, 35.5-40.0).

Figure 3

Flowchart of patients with serologic follow-up. Overall, at least 22/93 (23.6%) children with a recent RT-PCR positive test and available serum specimens did not develop detectable IgG SARS-CoV-2 antibodies. N/A, not applicable.

Figure 4

Probability of RT-PCR test negativity in all 324 participants.

Figure 2

Probability of RT-PCR negativity by A, severity, B, immunosuppressive medication or C, phenotype. PICU, pediatric intensive care unit; URTI, upper respiratory tract infection.