Evaluating the Correlation of SARS-CoV-2 Reverse-transcription Polymerase Chain Reaction Cycle Threshold Values at Diagnosis with Subsequent COVID-19 Disease Severity and Humoral Immune Responses in Children: A Prospective Observational Study

Background and Objective: Few studies in adults and none in children have analyzed simultaneously, the correlation of SARS-CoV-2 reverse-transcription polymerase chain reaction (RT-PCR) cycle threshold (Ct) value (inversely correlated to viral load) at diagnosis, with subsequent disease severity and antibody responses. A correlation could potentially inform treatment and vaccination decisions in advance. Materials and Methods: This prospective observational study was conducted from February 2021 to January 2022 in children below 16 years who tested RT-PCR test positive for SARS-CoV-2, including multisystem inflammatory syndrome in children. Disease severity was stratified as per standard definitions. Ct values were analyzed at diagnosis; IgG antibodies to S and N2 were quantified using a binding antibody test, 4–6 weeks after diagnosis. Multivariable analyses factored in potential effect modifiers such as age, gender, time from onset of symptoms to RT-PCR testing, time from RT-PCR to antibody testing, and immunocompromised state. Results: Of the 79 (47 male: 32 female) children who completed the study, 23 (29%) were asymptomatic, 47 (59%) had mild-to-moderate disease, 9 (11.4%) had severe disease; and 30/79 (38%) had comorbidities. The mean Ct/standard deviation (SD) value of the study population was 27.94 (±6.8); with mean Ct/SD values of 30.71 (±4.82), 26.25 (±6.82), and 29.69 (±8.5) in asymptomatic, mild-to–moderate, and severe disease, respectively. Although differences were observed between disease groups in mean Ct values and anti-N antibody titers using multiple-comparison correction, multivariable analyses showed no statistically significant correlation between Ct values, disease severity, and antibody titers. Conclusions: In children, SARS-CoV-2 Ct value at diagnosis independently predicts neither subsequent disease course/severity nor antibody response after 4–6 weeks.