INTRODUCTION:
SARS Coronavirus-2 (SARS CoV-2) causing the COVID-19 pandemic has undergone continuous genetic and antigenic evolution from the Wuhan strain (Wu Hu-1) to numerous variants of concern (VOC)-Alpha, Beta, Delta and recently, Omicron, resulting in global waves of infection. VOC have shown higher replication efficiency, enhanced ACE2 receptor binding and ability to evade immunity induced by natural infection or vaccination.1 Mutations resulting in increased replication fitness lead to higher viral loads of delta VOC as compared to Wu Hu-1 and alpha variants.2 Recently emerged variants (Omicron and its sub-lineages) have shown a higher replicative fitness than delta.3
The infection spectrum (asymptomatic to severe) of SARS CoV-2 is similar in children and adults, but children have fewer symptoms,4 recover faster, with better prognosis and fewer deaths overall.5 Children rarely manifest a hyper-inflammatory severe illness - multisystem inflammatory syndrome in children (MIS-C).6 It is based on this notion of milder paediatric illness that covid-19 vaccines (Wu Hu-1-based or bivalent boosters) have been widely approved for use globally in adults and children >12 years of age.7
Real-time RT-PCR (rRT-PCR), the diagnostic modality of choice for COVID-19 provides a Ct value readout that may be used as a metric of virus load.8 Ct values correlate poorly with severity,9 but have shown improved relationship, with differences between variants.10 Children have higher respiratory virus loads compared to adults,11 but loads do not correlate with severity.12 Presence of SARS CoV-2 specific antibody (IgM/IgG) anti-spike antibodies indicates virus exposure and if neutralising are considered a correlate of protection.13 Levels of antibody correlate with severe disease in adults.14 Children, respond to infection with a robust, long-lasting immune response, which is skewed towards the spike protein compared to nucleoprotein (unlike in adults), irrespective of illness severity.15 Few studies have reported the relationship of Ct value, antibody response and clinical severity among adults and very limited among children.16
To understand antibody dynamics in paediatric SARS CoV-2 infection, we recruited PCR positive children across the infection spectrum (asymptomatic to severe disease including MIS-C) during the wild-type and delta waves in India. Sera were tested for antibodies to SARS CoV-2 nucleoprotein(anti-N) and spike(anti-S) proteins. We examined the relationship of virus load at detection, clinical severity on antibody levels (anti-N and anti-S) 4-6 weeks after infection. We observed differences in virus load and antibody response between wild-type and delta variants in mild-to-moderate disease.