In the early stages of the COVID-19 pandemic, the Pediatric data from across the globe stated a milder illness in children contracting the infection. As the pandemic runs its course, there are increasing concerns over the palpable threat of unidentified risks to children. In our study, we have witnessed a pattern similar to what has been previously described in other continents. However, the seemingly anonymous risk of an evolving disease pattern that could change course to a more life-threatening illness must be addressed based on such epidemiological and clinical data. The prime intention is to ensure an improved perception of the disease and better vigilance in handling it and containing its spread.
As of midnight, 25th May 2020, India had already recorded a total of 138,845 cases of COVID-19 with Maharashtra state leading the pack with number of cases accounting for 36.17% (50,231) of the total. Of these, children up to the age of 20 years account to only 10.54%. Pune had a total of 443 cases were less than 20 years of age, with one recorded death.
Majority of the children in this study were detected in the government declared containment zones of Pune thus highlighting the significance of improving vigilance while attending to children coming from these areas. Majority of the children reported exposure to a positive close contact, a family member in most cases, indicating the current community transmission considering that 98% of children had no history of travel.
About two-third children met the criteria for residing in an overcrowded home thus highlighting the increased risk of transmission of SARS-CoV-2 in lower socio-economic groups with them carrying a disproportionate burden of the disease. Though the disease was seen in all age groups (Table 3), children less than five years of age accounted for 48% of all the cases. This can be attributed to the inability of this age group to comprehend and follow social distancing norms and the need for parents to constantly handle the children to attend to their dispositions.
About 58% of the children were asymptomatic and were detected as a part of screening when one of the family members tested positive indicating the covert nature of the virus. 40% were mildly symptomatic. Pediatric observational studies published early in the pandemic across China in February 2020 reported similar findings with fever being the most common symptom followed by cough and sore throat.6,7,8 However, as the pandemic progressed, newer ‘atypical’ manifestations were witnessed across different continents in the form of cutaneous exanthems,9,10 encephalitis,11,12 and myocarditis.13,14
In this study, all 50 (100%) cases recovered completely with no morbidities. The adult COVID-19 mortality rate worldwide is 6.2% at present, with the mortality rate in children less than 18 years being much lesser at <1%.15 Various hypotheses have been suggested to explain the milder course of disease in children as compared to adults starting with constant exposure to multiple viral infections which helps the immune system response when infected with SARS-CoV-2. Children as opposed to adults have lesser co-morbidities and healthier respiratory tracts.16 SARS-CoV-2 uses nasal angiotensin-converting enzyme-2 (ACE2) as a portal of entry to host.17 Lower ACE2 expression in nasal cavity may also help explain why COVID-19 is less prevalent in children.18
Almost all children in our study were vaccinated with BCG and 64% of them were completely vaccinated according to universal immunization program. Immunization of children with BCG is also thought to confer protection against the virus. Adults with COVID-19 have been found to have lymphopenia and reduced number of cytotoxic CD8+ T cells19 which as per some studies may be prevented by BCG vaccination induced stimulation of the CD4+ and CD8+ T-cell capabilities thus helping in destroying the virus-infected cells.20 However, countries like Iceland where BCG is not a part of routine vaccination policy have not seen significant morbidity or mortality in COVID-19, questioning the cross protectivity of BCG vaccine in SARS-CoV-2 infection.21 The available epidemiologic data has also formed a base for postulation of the Rubella component of MMR vaccine conferring protection against SARS-CoV-2 infection. Also, the previous consideration of live measles vaccine as a base for other Coronavirus vaccines including SARS due to possible cross-over reactivity has formed the basis to encourage further research on the role of MMR against SARS-CoV-2.22
Malnutrition has been deemed a risk factor in adult COVID-19.23 In children, malnutrition is known to foster infections; however in this study, majority of the children were well nourished with respect to weight for age criteria. Also, only one (2%) child had underlying Type I Diabetes Mellitus and rest were free of co-morbidities thus maybe reducing the burden of severe disease.
The hematological profile of adult with COVID-19 has demonstrated leucopenia with associated neutrophilia, lymphopenia, eosinopenia and thrombocytopenia. Also, higher Neutrophil-to-Lymphocyte ratios (NLR), Lymphocyte-to-Monocyte Ratios (LMR) and Platelet-to-Lymphocyte ratios (PLR) have been associated with severe disease and used for prognostication.24,25,26,27 Leucopenia, however, was seen in only three (6%) of our children and there was no evidence of lymphopenia, thrombocytopenia or eosinopenia. Low NLR, LMR and PLR seen in our study correlated with asymptomatic or milder form of disease.
High CRP values have now become synonymous with severe COVID-19 infection among adults as seen in majority of the studies.28,29,30 Mean CRP in our study was found to be 10.98mg/dl. CRP as high as 153.77mg/dl were seen in asymptomatic children while CRP as low as 4.59mg/dl was seen in the severe case suggesting a milder immune response. Trends in CRP values may be used as a surrogate of inflammation in COVID-19 infection.
Early studies from China stated that despite COVID-19 pneumonia in children being mild, chest computed tomography (CT) scan can present with characteristic changes of subpleural ground-glass opacities and consolidations of lung with surrounding halo.31 Early detection of lung lesions on CT as an alternative for diagnosis to the COVID-19 nucleic acid test from pharyngeal swab samples due to lack of adequate sensitivity was also proposed. In our study, we did not perform CT chest for any children. However, of the 20 children for whom a chest radiograph was done in view of persistent fever and cough, only one showed minimal lower zone infiltrates (<50%) despite normal respiratory examination and oxygen saturation.
Repeat RT-PCR of nasopharyngeal swab was done on day 14 and 15 to check for infectivity status of the child. All the children except one were tested negative by RT-PCR for both the days. For the child who tested positive for one swab, a repeat swab was negative after three days, thus indicating that clearance of viral load may vary in different individuals. Similar findings were seen in other studies as well.32,33 The degree of infectivity of these individuals after 14 days remains questionable as RT-PCR detects genetic fragments of the virus and cannot distinguish between dead or live virus.34 In such scenarios, doing a viral culture may be the plausible method of detecting live virus and demonstrating continued infectivity. As performing a viral culture is difficult and requires advanced laboratory facilities, using GeneXpert platform with Ct values ≥ 24 may also be beneficial for predicting lack of infectivity.35
Recently an alarming rise in the number of Pediatric and adolescent Kawasaki Disease and a multisystemic hyper-inflammatory syndrome associated with COVID-19 requiring admission to intensive care units have been reported in Europe as well as North America as the pandemic has progressed.36, 37, 38 An acute onset illness accompanied by a hyperinflammatory syndrome, leading to multi-organ failure and shock has been described. Initial hypotheses suggest association with COVID-19 either as a direct manifestation or an antibody positive post-infectious immune mediated response based on initial laboratory testing. The management in these cases included anti-inflammatory therapy, parenteral immunoglobulin and steroids. This makes it imperative to characterize this particular syndrome and its risk factors, to understand causality, and devise therapeutic strategies.
In conclusion, all age groups remain vulnerable to COVID-19. Our study re-iterates the milder disease pattern in children with COVID-19 in the early phase of the pandemic with majority being asymptomatic and mildly symptomatic. The epidemiological pattern indicates an ongoing community transmission of the disease. With a high proportion of asymptomatic and mild cases there is difficulty in identifying pediatric patients with COVID-19 infection. Even asymptomatic and mildly symptomatic patients may have high CRP despite showing no leucopenia, lymphopenia or thrombocytopenia early in the disease and normal leucocyte indices. Chest radiographs are normal in most mild cases but may occasionally show occasional infiltrates despite no clinical findings. All these factors put together create a potentially precarious situation of ongoing unchecked community spread of the virus, thus laying the foundation for increasing severity of illness and post-infectious immune-mediated syndromes. Public health policies must hence be directed to ensuring safe social distancing amongst children and adolescents taking into consideration the re-opening of day-care centers and schools which may emerge as a source of an uncontrollable spread of disease once the lockdown is lifted.
Limitations of the study: Being a study in the initial phase of the pandemic with lockdown in place, it may not cover the entire spectrum of clinical presentations, severity and magnitude of SARS-CoV-2 in children from different geographical areas.
Key Message: Majority of COVID-19 cases in children are asymptomatic and mildly symptomatic
What is already known? There is no Indian data available in the pediatric population with respect to the epidemiological and clinical characteristics of COVID-19.
What this study adds? Majority of Indian children with COVID-19 have a milder course of disease in the initial stages of the pandemic.