Literature Overview

Pediatrics

Children are generally less affected by COVID-19 than adults. Numerous studies have found that COVID-19 is mostly a mild disease in children, with a substantial, yet not exactly known, amount of asymptomatic cases and very few fatal cases. In addition, a low proportion of infected children with COVID-19 has been reported during the pandemic (around 1-5% of the total case numbers), although it is possible that the number has been underestimated as initial testing was often focused on clearly symptomatic patients and children were promptly confined. Whether the lower proportion of COVID-19 pediatric cases consistently reported can be solely explained by a lower tendency to show clinical symptoms or whether it is also due to a lower susceptibility of children to infection or to a restricted exposure of children to the infection is a subject of ongoing research. Likewise, the role of children in transmission is still unknown, although the current evidence suggests that children have not been superspreaders of COVID-19.

Seroprevalence and transmission

Seroepidemiological investigations from different countries (such as Switzerland, Spain and Italy) that aimed at studying population-representative samples of individuals and not only medically attended cases found a significantly lower seroprevalence in children below 10 years of age than in older groups. It is not clear, however, whether these results reflect that children are less susceptible to the infection in general, that parents have restricted the exposure of their children before and after the confinement as well as during it to a greater extent than the average adult limits their exposure, or that the studies were conducted while schools and nurseries were closed and the exposure of children therefore restricted.

Household studies, which could offer a controlled setting to understand viral transmission independently of the implemented social distancing measures and school closures, have reached different conclusions. Some investigations using RT-PCR to identify cases show that children may have a lower susceptibility for SARS-CoV-2 infection while others suggest that children are at a similar risk of infection to the general population, although they are less likely to have severe symptoms. Our own research as part of the Kids Corona project in strictly quarantined family households from Barcelona during the pandemic, the first to study seroprevalence, indicates that children and adults appear to have similar probability to become infected by SARS-CoV-2.

Whether children infected with COVID-19 can transmit the disease is another key question. The school closures limited the collection of transmission data in children, and many of the available studies are based on very low case numbers, although increasingly, countries where schools have reopened are sharing experiences, and transmission studies in summer camps on a sufficient number of child index cases and their contacts are becoming available. So far, most countries with open schools or those where schools never closed have shown that SARS-CoV-2 infections and outbreaks are uncommon, with a few exceptions in high schools, and some found that the majority of cases were in staff with a low transmission rate among young children in a classroom. Our own research on more than 2,000 participants in summer camps with strict infection control measures, as part of the Kids Corona project, revealed a low infection rate with a local empirical reproduction number (R) almost six times lower than that of the general population and few secondary positives. This is in accordance with studies of households and family clusters from different countries worldwide, which have mostly shown that children are unlikely to be the primary source of infection. As in some other studies, we also observed that there was a high correlation between the incidence of infection in the general population and the number of index cases detected in camps from the same area, emphasizing the importance of controlling community transmission to protect educational settings.

Although some studies have shown that children can have viral loads similar to adults, and the virus has been detected by PCR in the stool of affected children for several weeks after symptoms have resolved, data on the actual transmission of the infection has been lacking. In addition, the study of the dynamics of transmission in non-controlled environments has not been yet conducted as children were confined and the reopening of educational settings is in the process of being done under strict infection control measures. The contacts from positive pediatric cases outside controlled environments are under study.

Based on the available studies, many researchers agree that the evidence so far does not show that children have been the drivers of the COVID-19 pandemic nor have they been superspreaders, unlike for other respiratory infections such as influenza. Preventive measures such as bubble groups, use of masks and frequent hand washing in educational settings together with sufficient contact tracing to reduce the spread of COVID-19 within the community can be useful mitigation strategies.

Clinical presentation

Study of the clinical data from pediatric cases often shows that children have some distinct epidemiological, clinical and radiological characteristics from those typically found in adults. Children can have a wide range of clinical symptoms and a large, still undetermined, number may be asymptomatic, which highlights the importance of extensive laboratory testing, as symptom screening alone could hinder the identification of COVID-19 pediatric cases.

Cough and fever are usually the most common clinical features, presented in over half of symptomatic children with COVID-19. However, it is not uncommon for children to also present with other respiratory symptoms such as sore throat, rhinorrhea, nasal congestion and shortness of breath (20-40% of cases) and gastrointestinal symptoms such as diarrhea, vomiting and/or abdominal pain (5-15%). Tachycardia, loss of smell or taste, myalgias, fatigue, hypoxemia and chest pain are other reported symptoms in pediatric cases of COVID-19.

Although severe COVID-19 illness in children is rare and outcomes are usually good, some complications triggered by SARS-CoV-2 such as multisystem inflammatory syndrome in children (MIS-C), also known as pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS), exist and can lead to serious illness in some previously healthy children and adolescents. MIS-C/PIMS-TS is an uncommon hyper-inflammatory response, similar but distinct to Kawasaki disease, that typically occurs 2 to 4 weeks after infection with SARS-CoV-2. The majority of children present with fever or chills, and frequently suffer shock with prominent cardiac dysfunction, although the syndrome has a range of clinical features including dermatologic, mucocutaneous, and gastrointestinal manifestations as well as neurological complications. Notably, patients do not present with respiratory symptoms. Pediatric patients usually recover quickly, although some need intensive care support and treatment with immunomodulatory agents, and a few deaths have been reported. A relatively high proportion of cases have occurred among Black, Asian and Minority Ethnic (BAME) persons. The mechanism by which SARS-CoV-2 may be associated with PIMS-TS remains elusive. We have described a series of 12 patients of PIMS-TS temporary associated with SARS-CoV-2 mimicking complete or incomplete Kawasaki disease in line with other recent observational data.

Mental health and well-care

Numerous observations and comments have remarked on the potentially serious consequences at different levels that lockdowns could have on children and families. In low or middle-income countries, the disruption of routine health service coverage may have led and may continue to lead to a rise in maternal and child mortality. Health professionals advise that national programs should keep providing essential maternal and child health services even at risk of COVID-19 transmission. Additionally, school closures aimed at slowing the spread of COVID-19 forced children in families with social needs to give up educational, nutritional and social support. Some organizations lobbied for support for children and families in need, and initiatives to mitigate negative impacts were started and have continued. However, the potential negative consequences of lockdowns are not restricted to disadvantaged families. Observations from different countries showed a decrease in routine pediatric vaccines, which could increase the risk of future outbreaks of vaccine-preventable diseases. Other concerns raised included the management of children with chronic diseases such as cancer, as even if these children have not been shown to be more vulnerable to COVID-19, their prognosis could be negatively affected in the long term because of alterations to pediatric cancer treatment. The psychological consequences of a prolonged lack of routine school programs, leisure activities and social contact are also another potential issue for all children. Several comments from the medical community highlighted the need of finding ways to overcome these potential negative consequences of lockdowns. Compounding this, the effectiveness of closing schools has not yet been proven and raises many concerns. While the debate on the efficacy of school closure is still open, the potential negative impact of this measure on children and families should be also considered and alternative strategies evaluated.