[] Ranjana Hawaldar[1]
Designation:
Consultant Pathologist
[] Sadhna Sodani[2]
Designation:
Associate Professor
[] Varsha Sodani[1]
Designation:
Consultant Sonologist
[] R K Sodani[1]
Designation:
Consultant Sonologist
Dept. of Pathologist & Cytopathologist, Sampurna Sodani Diagnostic Clinic Indore, Madhya Pradesh India
Dept. of Microbiology, MGM Medical College (Devi Ahilya University) Indore, Madhya Pradesh India
Abstract
Introduction: It is said that children are less affected by SARSCoV2 infection because of their young immune system, so they have relatively milder symptoms as compared to adults. So the true incidence of SARSCoV2 is not known in this age group. Serosurveys in the paediatric age group can give a much better estimate of the incidence of SARSCoV2 infection in asymptomatic and symptomatic children.
Objectives: The present study was undertaken to study the seroprevalence of SARSCoV2 antibodies in children below 18 years of age, by measuring the S1RBD domain of spike protein neutralizing IgG antibody levels.
Materials and Methods: This was a retrospective study carried out from August 2020 to August 2021 in a private diagnostic centre of Central India. 539 children of both genders from newborn babies upto 18 years of age were included in the study. US FDA Emergency Use Authorized [EUA], Atellica Solution SARS-CoV-2 IgG assay that detects anti S1-RBD antibodies including neutralizing IgG against SARS-CoV-2 was used for antibody estimation. Antibody level ≥1 was termed reactive or seropositive and below 1 were considered to be non reactive or seroneagtive
Results: There were 321 males and 218 females with a male to female ratio of 1.47 :1. 57% male children were seropositive while 61.9% female children showed seropositivity with an overall positivity rate of 58.99%.
Conclusion: The findings of our study suggest that chidren below 5 years and adolescents exhibit higher antibody responses as compared to children between 5-10 years of age. The results of our study would be of help in formulating surveillance and vaccination strategies for children and in implementing public safety guidelines.
Introduction
An unknown respiratory illness causing severe acute respiratory syndrome was first identified in Wuhan, China in December 2019, later named as SARSCoV2.1 This later spread to all parts of the world causing a global pandemic with two major peaks of infection in India causing considerable morbidity and mortality, both in adults as well as in paediatric population. However, exact data of paediatric population is still unclear. The SARSCoV2 disease has an incubation period of 5.2 days.2 The symptoms include fever, cough, breathlessness, easy fatigability and sometimes severe viral pneumonia and multiorgan failure. These symptoms may not be evident in children, specially in infants and toddlers. Asymptomatic or mildly symptomatic patients may not seek medical advice, so the true prevalence in this population is underestimated.3 It is said that children are less affected by SARSCoV2 infection because of their young immune system, so they have relatively milder symptoms as compared to adults.4, 5, 6, 7, 8, 9, 10 Because of the milder symptoms and also due to difficulty in taking nasopharyngeal and oropharyngeal swabs in children, the true incidence of SARSCoV2 is not known. Moreover, the sensitivity of the kit as well as the timing of sample collection also plays a major role. Hence, Serosurveys in the paediatric age group can give a much better estimate of the incidence of SARSCoV2 infection in asymptomatic and symptomatic children.
The present study was undertaken to study the seroprevalence of SARSCoV2 antibodies in children below 18 years of age, by measuring the S1RBD domain of spike protein neutralizing IgG antibody levels in children. Children under 18 years of age are still to be vaccinated in India due to ongoing studies on the efficacy of vaccines in this age group.
Materials and Methods
This was a retrospective study carried out from August 2020 to August 2021 in a private diagnostic centre of Central India. 539 children of both genders from newborn babies upto 18 years of age were included in the study. The patients were divided into < 5 years, 5-10 and 11-18 years of age. Blood was collected with thorough aseptic precautions, following standard blood collection protocols in serum separator tubes and processed within 2 hours of collection for Spike protein IgG antibodies.
US FDA Emergency Use Authorized [EUA], Atellica Solution SARS-CoV-2 IgG assay that detects anti S1-RBD antibodies including neutralizing IgG against SARS-CoV-2 was used for antibody estimation.
Antibody level ≥1 was termed reactive or seropositive and below 1 were considered to be non reactive or seroneagtive. Dilution protocol as per the kit insert was used for Specimens that crossed measuring range of the assay.
Results
539 children from newborns upto 18 years of age of both genders were included in the study. There were 164 (30.4%) children under 5 years of age, 126(23.37%) between 5-10 years and 249(46.19%) between 11-18 years of age. The youngest child was a 2 days old newborn and the eldest was 18 years of age. There were 321 males and 218 females with a male to female ratio of 1.47:1. Table 1 shows the demographic data of patients.
33.8% males below 5 years of age were seropositive, followed by 25.6% between 5-10 years of age and 40.4% in 11-18 years age group. Similarly in females below 5 years of age, 29.6% were seropositive, followed by 24.4% in 5-10 years of age, and 45.9% in 11-18 years of age group.
57% male children(183/321) were seropositive while 61.9% female children(135/218) showed seropositivity with an overall positivity rate of 58.99%.(Table 2)
The mean antibody level below 5 years of age was 10.37 and 10.04 in males and females respectively. The mean antibody level in 5-10 years of age group was 5.92 in males and 6.34 in females. In 11-18 years age group, the mean antibody level was 9.38 in males and 4.52 in females.(Table 3)
The mean antibody level in seropositive patients below 5 years of age was 16.97,between 5-10 years age group was 8.24 and 16.34 in 11-18 years of age group.(Table 4)
Seropositive Data analysed month wise showed an increasing trend from August to December 2020 coinciding with First peak of SARSCoV2 infection with 44.4% seropositive rate in November 2020 and 68.2% in December 2020. The second rising trend was seen from May 2021 lasting upto July 2021 with 74%,72.9% and 79.6% seropositivity rate in May, June and July respectively. (Table 5)
Table 1
Demographic data of patients
View full table
Age (Years) | Male | Female | Total | % |
<5 | 107 | 57 | 164 | 30.40% |
5-10 | 72 | 54 | 126 | 23.37% |
11-18 | 142 | 107 | 249 | 46.19% |
Total | 321 | 218 | 539 | 100% |
Table 2
Total seropositive & seronegative patients in different age groups
View full table
Age (Years) | Male | Female | Total | ||
Reactive | Non Reactive | Reactive | Non Reactive | ||
<5 | 62 | 45 | 40 | 17 | 164 |
5-10 | 47 | 25 | 33 | 21 | 126 |
11-18 | 74 | 68 | 62 | 45 | 249 |
Total | 183 | 138 | 135 | 83 | 539 |
Table 3
Mean & median antibody level in different age groups
View full table
Age (Years) | Male | Female | ||
Mean | Median | Mean | Median | |
<5 | 10.4 | 4.34 | 10.0 | 5.71 |
5-10 | 5.92 | 3.56 | 6.34 | 2.27 |
11-18 | 9.38 | 1.61 | 4.52 | 1.89 |
Table 4
Mean reactive & non-reactive antibody in different age group
View full table
Age (Years) | Male | Female | ||
Reactive | Non-Reactive | Reactive | Non-Reactive | |
<5 | 17.0 | 0.1 | 14 | 0.2 |
5-10 | 8.75 | 0.12 | 9.84 | 0.13 |
11-18 | 16.32 | 0.15 | 6.91 | 0.43 |
Table 5
Month wise trend of antibody levels
View full table
Month | SeroPositivity | seroNegativity |
Aug 20 | 10.0% | 90.0% |
Sept 20 | 33.3% | 66.7% |
Oct 20 | 40.7% | 59.3% |
Nov 20 | 44.4% | 55.6% |
Dec 20 | 68.2% | 31.8% |
Jan 21 | 30.8% | 69.2% |
Feb 21 | 57.1% | 42.9% |
Mar 21 | 47.1% | 52.9% |
Apr 21 | 35.7% | 64.3% |
May 21 | 74.0% | 26.0% |
Jun 21 | 72.9% | 27.1% |
Jul 21 | 79.6% | 20.4% |
Aug 21 | 57.1% | 42.9% |
Discussion
Susceptibility of children to SARSCoV2 is still unclear but has important health policy implications and the decision to reopen the schools after a long time is largely based on the serosurveillance studies in different areas. Moreover, it has been predicted that a probable third wave of SARSCoV2 infection would affect the paediatric population the most. However, only a few serosurvey data are available in India in the paediatric population.
Our study showed an overall seropositivity rate of 58.99% in children upto 18 years of age. The youngest patient was a 2-day-old newborn. Males were more affected than females with a seropositivity rate of 57.5% in males and 42.5% in females out of the total seropositive children. The mean antibody level below 5 years and in 11-18 years age did not show much difference. However, the seropositivity in 5-10 years of age was less compared to under 5 years and in 11-18 years of age. The reason for this is unclear and needs further studies to arrive at a conclusion.
In a study conducted by Thomas Waterfield et al. in United Kingdom from April to July 2020, they reported that the presence of antibody and the mean antibody titre was not influenced by age.11 They concluded that the children demonstrated similar antibody titre in response to SARSCoV 2 irrespective of age. Similarly, Silvia Bloise et al. in their study also did not find any significant difference in IgG levels related to age, gender and other clinical manifestations.12 However, in their study they reported significantly lower antibody levels in children as compared to adults.
In the study by Brittany K. Smith et al. in Missouri USA, the authors reported an overall positivity rate of 1.71% in paediatric population with a significantly lower seropositivity rate in children below 5 years of age.13 Danilo B et al. conducted a study in the household contacts of known SARSCoV2 infected patients and found that 52.3% of the paediatric contacts had detectable level of IgG antibodies.14 Similarly Ludwig Knabl et al demonstrated a seropositivity rate of 27.1% in children below 18 years of age.15 In a large multicentric population based seroepidemiological study in India, the interim result of serological prevalence of SARSCoV2 antibody among children 2-17 years of age, between 15th March 2021 to 10th June 2021, showed an overall prevalence rate of 55.7%. 16 Our study correlated with this study. He S. Yang et al studied the association of age with SARSCoV2 antibody response and found that adolescents showed higher median antibody levels.17
Understanding the pathophysiology behind the response to SARSCov2 in paediatric population as compared to adults is much needed. The exact mechanism is still under study but possibility of an attenuated immune response in children resulting in better tolerance to SARSCo2 virus cannot be ruled out.18 Some studies have proposed that children may show milder disease manifestations as compared to adults as they are less exposed to environmental pollutants and have few comorbid conditions.19 Few other studies have postulated that innate immune memory may be generated on exposure to SARSCoV2 in children who have taken live attenuated vaccines such as Measles, Mumps, Rubella etc. which may play a protective role against the SARSCoV2 virus.20 In a few studies from China, USA and other countries, it has been suggested that young children and adolescents especially children below 10 years of age may have milder symptoms as compared to adolescents.19, 20, 21
Our study has certain limitations as this was a retrospective study and relied mainly on the data available to us. We did not have sufficient data on the symptoms as children may not be able to elucidate their symptoms as clearly as adults. Another limitation is that the sample size is small. Moreover, we cannot definitely state that the seronegative children are true seronegative or the antibody has waned or that some children may be able to fight the virus infection due to innate immunity without mounting a detectable level of antibody response which might have affected the results of the study.
Conclusion
The findings of our study suggest that children below 5 years and adolescents exhibit higher antibody responses as compared to children between 5-10 years of age. The results of our study would be of help in formulating surveillance and vaccination strategies for children and in implementing public safety guidelines. Large multicentric population based studies in children including those without any overt symptoms or contact history are required as schools have started reopening after a long gap and safety of children is of utmost concern for parents as well as for all the stakeholders. This will also help in curbing the impending probable third wave.
Source of Funding
None.
Conflict of Interest
None
References
1
N Zhu D Zhang W Wang X Li B Yang J Song China Novel Coronavirus Investigating and Research Team. 2020. A novel coronavirus from patients with pneumonia in China, 2019N Engl J Med 2019382872733
2
HA Rothan SN Byrareddy The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreakJ Autoimmun202010910243310.1016/j.jaut.2020.102433
3
CC Lai YH Liu CY Wang YH Wang SC Hsueh MY Yen Asymptomatic carrier state, acute respiratory disease, and pneumoniadue to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2):facts and mythsJ Microbiol Immunol Infect20205340412
4
J Yasuhara T Kuno H Takagi N Sumitomo Clinical characteristics of COVID-19 in children: a systematic reviewPediatr Pulmonol20205510256575
5
MJ Jeng Coronavirus disease 2019 in children: current statusJ Chin Med Assoc202083652733
6
X Lu L Zhang H Du J Zhang Y Y Li J Qu Chinese Pediatric Novel Coronavirus Study Team. 2020. SARS-CoV-2 infection in childrenN Engl J Med20203821716635
7
Z Wu JM Mcgoogan Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72314 cases from the Chinese Center for Disease Control and PreventionJAMA202032313123942
8
JFW Chan S Yuan KH Kok KKWTo H Chu J Yang A familial cluster of pneumoniaassociated with the 2019 novel coronavirus indicating person-to person transmission: a study of a family clusterLancet202039551423
9
NS Mehta OT Mytton EWS Mullins TA Fowler CL Falconer OB Murphy SARS-CoV-2 (COVID-19): what do we know about children? A systematic reviewClin Infect Dis2020719246979
10
X Cui T Zhang J Zheng J Zhang P Si Y Xu Children with coronavirus disease2019: a review of demographic, clinical, laboratory, and imaging features in pediatric patientsJ Med Virol2020929150110
11
T Waterfield C Watson R Moore K Ferris C Tonry A Watt Seroprevalence of SARS-CoV-2 antibodies in children: a prospective multicentre cohort studyArch Dis Child202110676806
12
S Bloise A Marcellino A Testa A Dilillo S Mallardo S Isoldi Serum IgG levels in children 6 months after SARS-CoV-2 infection and comparison with adultsEur J Pediatr202118011333542
13
BK Smith AB Janowski JE Danis IB Harvey H Zhao YN Dai Seroprevalence of SARS-CoV-2 Antibodies in Children and Adults in St. Louis, Missouri, USAmSphere202161120720
14
D Buonsenso P Valentini CD Rose D Pata D Sinatti D Speziale Seroprevalence of anti-SARS-CoV-2 IgG antibodies in children with household exposure to adults with COVID-19: Preliminary findingsPediatr Pulmonol202156613747
15
L Knabl T Mitra J Kimpel A Rössler A Volland A Walser High SARS-CoV-2 seroprevalence in children and adults in the Austrian ski resort of IschglCommun Med (London)20211410.1038/s43856-021-00007-1
16
P Misra S Kant R Guleria SK Rai Serological prevalence of SARS-CoV-2 antibody among children and young age (between age 2-17 years) group in India: An interim result from a large multi-centric population-based seroepidemiological study202110.1101/2021.06.15.21258880
17
HS Yang V Costa SE Racine-Brzostek KP Acker YJ Chen Z Karbaschi Association of Age With SARS-CoV-2 Antibody ResponseJAMA Netw Open202143e21430210.1001/jamanetworkopen.2021.4302
18
S Elahi Neonatal and children’s immune system and COVID-19: biased immune tolerance versus resistancestrategyJ Immunol2020205819907
19
PI Lee YL Hu PY Chen YC Huang PR Hsueh Are children less susceptible to COVID-19?J Microbiol Immunol Infect20205333712
20
P L Fidel M C Noverr Could an unrelated live attenuated vaccine serve as a preventive measure to dampen septic inflammation associated with COVID-19 infection? mBio2020113e0090720
21
P Zimmermann N Curtis Coronavirus infections in children including COVID-19: an overview of the epidemiology, clinical features, diagnosis, treatment and prevention options in childrenPediatr Infect Dis J202039535568
Keywords
Original Research Article
Keywords
SARSCoV2
SARSCoV2 IgG antibody
Seropositivity
Paediatric population
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