Kinetics of Viral Clearance and Antibody Production Across Age Groups in Children with Severe Acute Respiratory Syndrome Coronavirus 2 Infection

Abstract

Objectives To improve understanding of transition from viral infection to viral clearance, and antibody response in pediatric patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Study design This retrospective analysis of children tested for SARS-CoV-2 by reverse transcription (RT) polymerase chain reaction (PCR) and immunoglobulin G antibody at a quaternary-care, free-standing pediatric hospital between March 13, 2020, and June 21, 2020, included 6369 patients who underwent PCR testing and 215 patients who underwent antibody testing. During the initial study period, testing focused primarily on symptomatic children; the later study period included asymptomatic patients who underwent testing as preadmission or preprocedural screening. We report the proportion of positive and negative tests, time to viral clearance, and time to seropositivity. Results The rate of positivity varied over time due to viral circulation in the community and transition from targeted testing of symptomatic patients to more universal screening of hospitalized patients. Median duration of viral shedding (RT-PCR positivity) was 19.5 days and time from RT-PCR positivity to negativity was 25 days. Of note, patients aged 6 through 15 years demonstrated a longer time of RT-PCR positivity to negativity, compared with patients aged 16 through 22 years (median 32 vs 18 days, P = .015). Median time to seropositivity, by chemiluminescent testing, from RT-PCR positivity was 18 days, whereas median time to reach adequate levels of neutralizing antibodies (defined as comparable with 160 titer by plaque reduction neutralization testing) was 36 days. Conclusions The majority of patients demonstrated a prolonged period of viral shedding after infection with SARS CoV-2. It is unknown whether this correlates with persistent infectivity. Only 17 of 33 patients demonstrated adequate neutralizing antibodies during the time frame of specimen collection. It remains unknown whether immunoglobulin G antibody against spike structured proteins correlates with immunity, and how long antibodies and potential protection persist.

Clinical characteristics of COVID-19 in neonates and young infants

“…However, the substantial number of infants who received iv antibiotics until the exclusion of bacterial co-infection justifies the increasing concern of a possible negative impact of the virus on antibiotic stewardship. Interestingly, in contrast to what has been reported for older children with COVID-19 [13], 5 infants had positive PCR for more than 3 weeks although with high Ct values which was suggestive that the virus was not transmissible [14].…”

“…Interestingly, in contrast to what has been reported for older children with COVID-19 [ 13 ], 5 infants had positive PCR for more than 3 weeks although with high Ct values which was suggestive that the virus was not transmissible [ 14 ].…”

Particularities of the Evolution of SARS-CoV-2 Infection in Children

“…The mean time from RT-PCR positive to RT-PCR negative was 26.5 days, consistent with the study conducted by Bahar B. [24].…”

Virological Characteristics of Hospitalized Children With SARS-CoV-2 Infection

“…Some of the hypotheses proposed to explain these differences include: 1) underexpression of ACE-2, the binding receptor for SARS-CoV-2 spike (S) protein in children, 2) lower respiratory tract viral load (VL) levels in children compared to adults, and 3) pre-existing cross-reactive immunity conferred by exposure to seasonal coronaviruses [20][21][22] . Pediatric data so far has focused predominantly on the description of demographic and clinical characteristics of hospitalized children with SARS-CoV-2 14,23,24 , with very limited information on virological characteristics 25,26 , particularly in children with asymptomatic and mild infections. Defining the virological characteristics of children with SARS-CoV-2 infection is important to facilitate identification of biomarkers of severe infection and adverse outcomes, understand transmission dynamics within families and communities and for development of effective management and prevention strategies.…”