The World Cannot say anymore that Children are not the face of COVID-19 The Urgency to Detect, Respond to MICS, and Care for children in 2021

Covid 19 pandemic has been showing disastrous effects across the world, since December 2019, affecting 220 countries, over 197 million cases and 4.2 million deaths by end July 2021, and huge economic loss, Political blame games and vaccine diplomacy and many social security measures. The pandemic also has exposed the limitation of Public Health capacities across the world. By now we know that Children of all ages can be affected. The fact that exact data of number of children affected or their proportion of the total infections or deaths, is not readily available even at subnational levels, indicates that they have not been the face of the Pandemic. In the initial months the symptoms and signs of the disease were very mild in children, until in May 2020, when a few cases of critical illness called Multisystem infl ammatory syndrome in children were fi rst reported in UK/USA. Very few cases of mucor mycosis a fungal infection after recovering from Covid 19 are also being reported among children across the world. As of now available data indicates that children under the age of 18 years represent about 8.5% of reported cases and the symptomatic children are fewer and usually mild, and deaths were negligible compared to other age groups. The complications of MICS and lack of vaccine are the two major hurdles in protecting the lives of the children as of now. The indirect impact is the Orphanhood due the death of millions of COVID-19-associated deaths of the parents, poverty due to diminished earning by the parents losing jobs or working for low wages, interruption in education due to closure of schools, increase in malnutrition in poor countries due to disruption of nutrition programs and mental health of the children for want of peer interactions and the tensions of online learning. After about one and half year analysis of the available data indicates that the Covid 19 Pandemic affects the world’s children in three ways through: 1. infection with the virus and its complications like MICS and Mucor mycosis 2. the socioeconomic effects of the virus and related public health measures to suppress transmission and control the pandemic by the national and provincial Governments and 3. the risk that the virus and its response poses to the longer-term efforts to achieve the economic revival, efforts for Sustainable Development Goals (SDGs) and ensuring the realization of the rights of all children as committed by the national governments. Working with UNICEF India, for over 17 years, the author in this article tries to look at the data available and assess the impact of covid 19 pandemic on the children in short and long terms. Materials & methods: The author has reviewed the Covid 19 pandemic world dash boards, Periodical press and TV media reports, sub-national data of age and sex distribution of cases, small studies on the cases and deaths of Covid 19and it’s complications and reports on the various development partners on the issue of child related SDGs. Review Article The World Cannot say anymore that Children are not the face of COVID-19 The Urgency to Detect, Respond to MICS, and Care for children in 2021

Multisystem Syndrome (PIMS) was fi rst reported in UK/USA in April 2020 [5]. MIS-C is triggered by the virus that causes COVID-19, therefore It can occur in children who have not had any common symptoms of COVID-19, such as fever, sore throat, or cough. "Most children with MIS-C will have antibodies to the SARS-CoV-2 virus, indicating their body has been infected previously. Pre-existing medical conditions like diabetes, immune suppression conditions are known as risk factor for severe disease and intensive care admission in children.
In USA indicates about 10.5% of a total of fourteen million were in the age group between 0 and 14 years of age [6]. The US has reported more than 4,000 such cases and 36 deaths from the disease so far. UK had reported that children contributed about 10% up to 26 July out of 5,745,526 positive cases 8,601 per 100,000 population and 129303 deaths [5]

Magnitude of the Infection and complication Problem in Indian children
While offi cial sources report that India has seen 317 million cases and 424,000 deaths. Various national and States Health Missions reported proportion of child cases between 8-11% and deaths -3-5% out of the total [3,7,8]  Infl ammatory Syndrome (MICS) and very few had Mucor mycosis popularly known as black fungus a fungal infection maiming faces of many due to extraction of eyeballs, nose, jaws etc. For many others the effect will be lifelong though they did not exhibit any signs and symptoms or suffered mild illness due to loosing parents or impoverishing of the families.
The aftereffects of the pandemics on children will be more damaging in the poorest countries, the poorest families, and on already disadvantaged people.    [11]. The authors attribute the reduced ACE-2 expression in the children's nasal epithelium as responsible for reduced SARS-CoV-2 susceptibility among children [7].

Covid 19 infection and its immediate and late complications
Another analysis of data ending April 2021 had put the proportion of cases among 0-20 yrs. age group at 8.6%

Sero-prevalence of antibodies
A latest national serosurvey conducted between 20 June to 7 July 2021 conducted across 70 districts in 21 states among about 28975 people over the age of 6 years, indicated an overall positivity of 67.6% with desegregated fi gures of 69.2% among women as against 65.8% among men. The age wise positivity was between 57.2% lowest among 6-9-year-olds and 77.6% highest among 45-60-year-old persons. The urban population has roughly 3% higher antibodies. This is indicative that nearly one third of the population is susceptible. The seroprevalence of antibodies was 85.2% among 7252 health workers out of the population surveyed. The seroprevalence has jumped from 0.7% a year ago to 67.6%.

MICS-made us not to think Covid-19 is mild among children!
While in the fi rst phase of Covid 19, administrators, and program mangers thought that Covid 19 was mild and negligible till February 2021. A new study suggests that Covid-19 may have turned severe and even deadly for thousands of children in India. Figures released by the Indian Academy of Paediatrics Intensive Care Chapter show that there were more than 2,000 cases of Multisystem Infl ammatory Syndrome in Children (MIS-C) reported in the country by early 2021 [11,12]. MIS is a condition in which a patient develops fever and infl ammation in multiple organs such as the heart, lungs, and brain. In more than 60 per cent cases, MIS affects the heart, with symptoms such as redness of eyes, rashes, low blood pressure, highgrade fever and stomach-ache or acute gastroenteritis and lower respiratory tract infection [11][12][13]. The condition is not life-threatening but has huge debilitating effects on children. It is the result of a reaction to an antigen made in the body to combat Covid-19 and the antibodies produced in the body of the children. These antibodies can cause allergies in their body. Government data on MICS is silent. With the onslaught of the second phase of the pandemic since April 2021 this number is expected to be over 5000 by now [13] Figure 7.

Mucor mycosis among children
The contribution of Children in Mucor mycosis cases is negligible. Rajasthan, in the last four months, has reported over 3,000 cases of mucormycosis and 167 deaths, of which only fi ve cases were among children and one of them died within two days of hospitalisation. Similarly, four children with mucormycosis infection lost an eye in Mumbai. Most often these cases where Covid 19 antibodies were detected and not the confi rmed disease.

Karnataka
As of 29th July 21, the home state of the author had reported around 3 million cases (29,48,700) cases and 36,491 deaths.     in July, the highest for any month since the pandemic began Figures 8,9. An analysis of fi rst 112 860 cases in Karnataka had indicated that 73,797 (65.39%) cases were males and 39,063 (34.61%) females COVID-19 patients. While the lowest distribution by sex was in male (1.28%) and female (2.19%) patients were found among 0 to 4 years age category (Figure 8), the Highest infected male (37.21%) and female (37.99%) patients was within 18 to 35 years age category. The difference between gender among age categories was found to be statistically signifi cant (p<0.001) [13].

MICS in karnataka
IAP Karnataka reported having seen 2856 cases of MICs till 25th July 2021 of which 825 were from Bengaluru City [13]. 225 died and another 124 left the hospital against advice which we assume also died due to Mucor mycosis till June 17. This amounts a case fatality rate of 12.2%, as against half of them (6.68%) recovering &majority of the cases were still under treatment.

Mucor mycosis case in karnataka
Two cases of Mucormycosis were reported in early June 21, fi rst a 11-year-old girl from Bellary and a 14-year-old boy from Chitradurga district. Both were suffering from 'acute juvenile diabetes', which came to light when they were taken to a hospital following contracting the coronavirus disease. This is out of a total of 1,370 cases and 51 people have lost their lives in Karnataka [14]     Among adolescents, a rise in disease-related mortality is likely, with nearly 6,000 additional deaths from malaria, Tuberculosis (TB), HIV/AIDS and typhoid [15].
On the education front as schools across the country remain closed, and remote learning was disrupted in several states especially at sub-district levels, 420 million children in ROSA and 247 million children in Indian elementary and secondary education were away from these safe spaces, just when they need them most. In addi tion, many children do not have access to digital learning. Learning loss will therefore continue for children in India. A recent study commissioned by the National Commission for Protection of Child Rights (NCPCR) highlights that while 29.7% children feel that the pandemic has "very much" had a negative impact, 43.7% think it has had a "partial" negative impact on their education. Students across age groups think that their education has suffered due to the pandemic and somehow online learning has not been good enough. Study had covered 5,811 participants 3,491 schoolgoing children, 1,534 parents and 786 teachers from 60 schools, across six cities, including some metros, and their adjoining areas selected from across regions in the country. The study also brings forth a concern and the need for proper oversight and stricter enforcement on social media as 37.8% and 24.3% of 10-yearold children surveyed had Facebook and Instagram accounts, respectively, in contravention to the guidelines laid down by various social networking platforms. Social media platforms contain and disperse a variety of content, that can be violent or vulgar content to instances of online abuse and bullying of children which is neither appropriate nor conducive for children [16,17].
The second phase surge is having dire consequences for children whose access to essential health, social, protection and education services is being constrained. Grief, fear, uncertainty,

Long Covid 19 symptoms
A Paediatrician and his team, at the Gemelli University Hospital in Rome, interviewed 129 children aged 6-16 years, diagnosed with COVID-19 between March and November 2020 and reported that more than one-third had one or two lingering symptoms like Insomnia, fatigue, muscle pain and persistent cold-like complaints for four months or more after infection. Even children who'd had mild initial symptoms, or were asymptomatic, also showed long-lasting effects [19]. The UK Offi ce for National Statistics' latest report estimates that out of 500,000 UK children tested positive for covid-19 since March 2020, at least 12.9 % of UK children aged 2 to 11, and 14.5 % of children aged 12 to 16, had symptoms fi ve weeks after their fi rst infection [20]. The symptoms reported number up to include fatigue, muscle and joint pain, headache, insomnia, respiratory problems, and heart palpitations, gastrointestinal problems, nausea, dizziness, seizures, hallucinations, and testicular pain [18].
The biggest long-term disaster for children is the Orphanhood due the death of COVID-19-associated deaths.

Status of Covid 19 vaccination for children
Currently hypothesized explanations for an evidently less severe impact of COVID-19 on children globally includes the protective cross-immunity provided by other common childhood vaccines. There is a strong basis to hypothesize that immune response to the SARS-CoV-2 virus in children is different than in adults, resulting in differences in the levels of severity of symptoms and outcomes of the disease in different age groups [23]. Further investigations are desired on at least 3 childhood vaccines: BCG, MMR, and HEP-A for their potential protective role against the SARS-CoV-2 virus [23].
After the completion of a search of 13 articles published in 2020, and a narrative review imply that the potential relationship between childhood vaccination and COVID-19 based on the potential genomic and immunological protective effects of heterologous immunity, and / or based on observational associations of cross-immunity among vaccines and other prior endemic diseases.
Salman and Salem suggest that cross-immunogenicity of childhood vaccines for multiple viruses could potentially be a reason for the relatively milder infection and severity of COVID-19 among children. Most routine viral vaccines are either inactivated or killed viruses that stimulate T Helper 1 cells (CD4+) to secrete many different types of cytokines as interferon gamma, interleukin-2 (IL-2), and IL-12, improving the cytotoxicity of natural killer cells to recognize and destroy cells infected with new cross-reactive viruses. For example, warts that are caused by Human Papilloma Virus (HPV) could be ameliorated using intralesional MMR vaccine [24].
In many coun tries, children are routinely vaccinated against several bacterial and viral diseases. Vaccines may have non-specifi c physiologic effects when they alter the immune response to unrelated organisms, called heterologous immunity. The non-specifi c effects of vaccines are usually more pronounced in girls and appear to be maximal in the fi rst 6 months of life when passed maternal immunity is further supplemented by newly introduced vaccines, starting at 2 months. There are several theories as to why heterologous immunity may occur [25].
Neutralizing antibodies produced against the foregoing vaccine-preventable microbes might cross-react with the antigenic epitopes of the spike (S) and nucleocapsid (N) proteins and prevent COVID-19 in children [26].
An investigation of the above hypothesis, using the BLAST search tool, showed no signifi cant sequence similarity between these proteins and those in the childhood vaccine-preventable microbes, inferring that memory T-cells, rather than vaccine neutralizing antibodies, may be involved in the protection of children against COVID-19 owing to them having a larger number of naive T-cells that can be programmed to protect them against the disease [27].
Potentially, the low immunity in children that doesn't exaggerate the immune response against the virus as in the case of adults, could explain the lesser severity of SARS-CoV-2 in this age group. Children have less adults-like memory cells specifi c to other circulating coronaviruses and therefore, are less capable to mount a devastating and vigorous cell-mediated attack on alveoli and interstitial tissue of the lung upon new infection [28].
The low immunity in children that doesn't exaggerate the immune response against the virus as in the case of adults, could explain the lesser severity of SARS-CoV-2 in this age group. Children have less adults-like memory cells specifi c to other circulating coronaviruses and therefore, are less capable to mount a devastating and vigorous cell-mediated attack on alveoli and interstitial tissue of the lung upon new infection Recently GOI, had informed the Delhi High Court that clinical trials of COVID-19 vaccines for children under 18 years of age were to get completed soon. AIIMS, Delhi is one of the trial centres for the vaccine for those below 18 years. As per sources, the results of clinical trials are expected to come in one month after the completion of trials of all age groups. The trial is conducted in three phases by segregating children into categories according to their age. The fi rst trial was started in the age group of 12-18 years followed by the age group of 6-12 years and 2-6 years which are currently undergoing trials. The second dose of Covaxin has already been administered to children in the age group of 6-12 years. As part of its COVID-19 vaccination trials for children, Bharat Biotech is likely to administer the second dose of Covaxin to children aged between 2-and 6-years next week, to children who have already received the fi rst dose of the vaccine.

Conclusion, future of children
Children are amongst the least at-risk population for Covid-19 severe disease. it is becoming increasingly apparent that many children with symptomatic and asymptomatic covid-19 are experiencing long-term effects, many months after the initial infection.
While keeping an eye on MICS in children, an overzealous attempt to protect the health of our children, may end up depriving them from the quality and holistic learning.
Children, although less directly affected by the virus, are paying a heavy price through the indirect effects of the crisis, including poor diet, mental health impact, social isolation, addiction to screens and lack of schooling and health care, particularly among vulnerable groups The pandemic has exposed the vulnerability of global food systems with a proportionate impact on the health and nutrition of vulnerable families particularly children and a deterioration in diet quality.
Many children in developing countries do not have access to digital learning. Learning loss will therefore continue for children in India and other countries. The second phase surge has increased screen time for children at the cost of sports and peer interactions and is having dire consequences on children whose access to essential health, social, protection & education is being constrained.
Neither there is any vaccine readily available, nor vaccination of children should unduly infl uence by any perceived urgency or external narrative. Encouraging news is that Zydus Cedilla's India-anti-Covid jab ZyCoV-D secured regulatory approval on Friday 20 August 2021 for emergency use. Pfi zer, Moderna, Covishield and Covaxin have started their clinical trials in phased manner for children between 12-18, 6-12, and 2-6-years old children and even younger 2 years to six months old.

War forwards
• Almost half of children who contract covid-19 may have lasting symptoms, which should factor into decisions on reopening schools. Based on localized rates of disease transmission the safe reopening of schools should be a top priority, ensuring that the risk of COVID-19 exposure and transmission is minimized. Standard precautionary steps of limits on class size, alternating school days, a ban on assemblies and other group events, together with on arrival temperature checks, and use of face masks and hand hygiene be made mandatory.
• Prioritize the continuity of child-centred services, with a particular focus on equity of access particularly in relation to nutrition programmes, immunization and other maternal and new-born care, and communitybased child protection programmes. Ensure sustainable food systems for an affordable and nutritionally adequate diet for all levels of society.
• Psychosocial and economic support can help families to nurture children bereft of caregivers and help to ensure that institutionalisation is avoided. These data show the need for an additional pillar of our response: prevent, detect, respond, and care for children.Rebalance the combination of interventions to minimize the impact of standard physical distancing and lockdown strategies on children in low-income countries and communities and expand social protection programmes to reach the most vulnerable children.
• Provide practical support to parents and caregivers, including how to talk about the pandemic with children, how to manage their own mental health and the mental health of their children, and tools to help support their children's learning.
• There is also the need for fi nancial support for poor families through providing work, increased daily wages and where that cannot be assured cash transfers.