Coronaviruses consist of four structural proteins; Spike (S), membrane (M), envelop (E) and nucleocapsid (N). Spike is composed of a trans-membrane trimetric glycoprotein protruding from the viral surface, which determines the diversity of coronaviruses and host tropism. Spike comprises two functional subunits: S1 and S2 S1 subunit is responsible for binding to the host cell receptor and S2 subunit is for the fusion of the viral and cellular membranes.6

Angiotensin converting enzyme 2 (ACE2) was identified as a functional receptor for SARS-CoV . Structural and functional analysis showed that the spike for SARS-CoV-2 also bound to ACE2. ACE2 expression was high in lung, heart, ileum, kidney and bladder.7,8,9,10,11

In lung, ACE2 was highly expressed on lung epithelial cells. Whether or not SARS-CoV-2 binds to an additional target needs further investigation. Following the binding of SARS-CoV-2 to the host protein, the spike protein undergoes protease cleavage.12,13,14 After the cleavage at the S1/S2 cleavage site, S1 and S2 subunits remain non-covalently bound and the distal S1 subunit contributes to the stabilization of the membraneanchored S2 subunit at the prefusion state.9

The coronavirus spike is unusual among viruses because a range of different proteases can cleave and activate it .15 The characteristics unique to SARS-CoV-2 among corona viruses is the existence of furin cleavage site (“RPPA” sequence) at the S1/S2 site. 9 Although the S1/S2 site was also subjected to cleavage by other proteases such as transmembrane protease serine 2 (TMPRSS2) and cathepsin L. 14,16 , The ubiquitous expression of furin likely makes this virus very pathogenic.

In later stages of infection, when viral replication accelerates, epithelial-endothelial barrier integrity is compromised. In addition to epithelial cells, SARS-CoV-2 infects pulmonary capillary endothelial cells, accentuating the inflammatory response and triggering an influx of monocytes and neutrophils. Autopsy studies have shown diffuse thickening of the alveolar wall with mononuclear cells and macrophages infiltrating airspaces in addition to endothelialitis. Interstitial mononuclear inflammatory infiltrates and edema develop and appear as ground-glass opacities on computed tomographic imaging. Pulmonary edema filling the alveolar spaces with hyaline membrane formation follows, compatible with early-phase acute respiratory distress syndrome (ARDS).17 Bradykinin-dependent lung angioedema may contribute to disease.18

In severe COVID-19, fulminant activation of coagulation and consumption of clotting factors occur.19,20 A report from Wuhan, China, indicated that 71% of 183 individuals who died of COVID-19 met criteria for diffuse intravascular coagulation.19Inflamed lung tissues and pulmonary endothelial cells may result in microthrombi formation and contribute to the high incidence of thrombotic complications, such as deep venous thrombosis, pulmonary embolism, and thrombotic arterial complications (eg, limb ischemia, ischemic stroke, myocardial infarction) in critically ill patients.21 The development of viral sepsis, defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, may further contribute to multiorgan failure.

The role of the immune response in viral clearance and pathogenesis in the CNS has been well characterized. Both antibody and cell-mediated immune responses are required to protect against coronavirus infections. The CD8⁺  T and CD4⁺ T cells are primarily responsible for clearance of the virus during acute infection. Perforin-mediated mechanisms are necessary for clearance of virus from astrocytes and microglia, while gamma interferon (IFN-γ) has been implicated in clearance from oligodendrocytes.22

The life cycle of the virus with the host consists of the following 5 steps: Attachment, Penetration, Biosynthesis, Maturation and Release. Once viruses bind to host receptors (Attachment), they enter host cells through endocytosis or membrane fusion (Penetration). Once viral contents are released inside the host cells, viral RNA enters the nucleus for replication. Viral mRNA is used to make viral proteins (Biosynthesis). Then, new viral particles are made (Maturation) and Released.

All children of age between 0 to 18 years of either gender with RT-PCR positive for COVID19 infection

Children with RT-PCR negative results for COVID19 infection

-Fever - 3 -Sore Throat - 4 -Cough - 4

-Respiratory Difficulty - 2 -Diarrhoea - Nil -Rash - 1 -Jaundice - 1 -Seizure -1

Figure 3 showing symptoms with which the child presents to our setup. Most of the children were asymptomatic contacts of COVID19 RT-PCR positive patients and remained asymptomatic throughout the stay while 4 out of 26 patients were having sore throat with cough. 3 children were having fever out of which 2 children presented with respiratory difficulty. 1 child presented with fever, rash, jaundice and respiratory difficulty and seizures.

No oxygen therapy required - 24 Non invasive ventilation(NIV) - 1 Invasive ventilatory support(IV) - 1

Figure 4 represents number of children requiring oxygen therapy. 1 child was given continuous positive pressure ventilation, which was later tapered and shifted to nasal prongs and then weaned off from oxygen support. Another child was intubated and mechanically ventilated (Child couldnot survive and got expired within 24 hrs of mechanical ventilation). Majority of children (92.3%) did not require any oxygen support.

Table 3 shows number of children requiring antibiotic therapy. Antibiotics given to these children include azithromycin. Second line antibiotics added were meropenem and vancomycin in 2 of the cases.

Table 4 shows none of the pediatric COVID19 positive patient were given antivirals as most of our patients were asymptomatic and also there is paucity of data on the safety profile of antivirals in pediatric population.

Table 5 shows that mortality rate in pediatric population in our setup so far is 3.8% with 1 motality out of the 26 COVID19 RT-PCR positive pediatric patients. Distribution according to age shows 0% mortality in children less than 1 year of age in our setup so far.

In our study, the confirmation of COVID19 infection was done by RT-PCR.

Maximum number of children with COVID19 infection were in the age group of >1 to 18 years (92.3%) followed by age group of 1 month to 1 year of age(7.6%) and no child was found to be COVID19 positive in the age less than 1 month(0%) with mean age of presentation is 8.9 years(n=8.9). Number of male cases outnumbers the number of female cases(61.5 vs 38.4% %). 15.3% children of COVID19 infection presented to us with cough and sore throat as their presenting complaint, 11.5% children presented with fever, 7.6% children presented with respiratory difficulty.

None of the children presented with pain abdomen or diarrhoea. 1 out of 26 children was having fever along with rash, jaundice, seizures and respiratory difficulty. 7.6% children presented with respiratory difficulty requiring supportive oxygen therapy. 15.6% children were given antibiotic therapy with none of them were given antivirals or hydroxychloroquine. Regarding mortality rate and pattern, 1 out of 26 COVID19 RTPCR positive child died due to corona virus disease and its complications (mortality rate 3.8%) and none of the children who died were under 1 year of age. Parental understanding regarding the route of transmission and the ways to prevent transmission of infection like wearing of masks, regular handwashing, restraining onself from going to public places unless unavoidable circumstances, maintaining social distance of minimum 2 meters has worthwhile effect in preventing infection and thus disease spread to children at home and in contact.