Researchers examine antiviral responses in children infected with COVID-19 in South Brazil

The coronavirus disease 2019 (COVID-19) pandemic is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogen, a positive-sense RNA virus of the betacoronavirus subgenus. This is a highly contagious virus with severe disease outcomes, causing asymptomatic, mild or severe infection, which can be fatal in some critical cases. To date, SARS-CoV-2 has claimed more than 3 million lives worldwide. Epidemiological evidence has revealed that, in general, children are not severely infected by COVID-19. A very small percentage of children with comorbidities are severely infected.

In Brazil, the pediatric population, which includes children between 0-19 years of age, represents more than 25% of the country’s population. In this group, interestingly, only 1.9% of children had contracted the disease in the past twelve months, and the mortality rate has been recorded to be 0.5%. The percentage of children severely infected and hospitalized owing to the disease is 8.0%. Thereby, compared to all age groups, the clinical data reveals that the severity of the COVID-19 disease in this age group is significantly less, with a smaller number of hospitalizations and fatality.

Several hypotheses have been formulated to explain this phenomenon. One of the hypotheses is that milder disease in children is owing to the suppressed expression of the viral receptor ACE2, which leads to minimal viral replication in the host. A second theory suggests a differential immune response in children, while a third possibility could be the presence of neutralizing antibodies from a previous infection, mostly caused by seasonal coronaviruses. These antibodies could play an important role in cross-protection against SARS-CoV-2 induced disease. Scientists belonging to this school of thought further revealed that as children are the main reservoir for these seasonal viruses, there is a strong possibility of robust cross-protection. However, lack of enough data hinders further understanding of the differential mechanism by which SARS-CoV-2 infects the pediatric and adult population.

Several studies have been conducted to characterize the immune responses of COVID-19 infected adults. However, there is a research gap in regards to pediatric patients. This is mainly owing to the inadequacy of data which prevents a clear understanding of the striking differences between the pediatric and adult population being infected by COVID-19. This subject holds significant importance because it is a contributing factor for designing public policies such as the reopening of schools amidst the pandemic. Scientists also believe that understanding the mechanism owing to which children are not severely infected by the disease could help formulate novel therapeutic pathways for preventing COVID-19.

New research has been published on the medRxiv* preprint server, which focuses on the characterization of innate and adaptive immune responses in adult patients with different degrees of severity and also in pediatric patients with mild symptoms of COVID-19. In this study, researchers have developed an immune profile in children to understand the difference in COVID-19 infection in children and adults.

In the present study, plasma and peripheral blood mononuclear cells (PBMCs) were collected from 92 patients, which included 25 children, 34 adults with mild disease (AMD), and 33 adults with severe disease (ASD). The samples were obtained from the Hospital Moinhos de Vento and Hospital Restinga e Extremo Sul, southern Brazil. Detailed immune profiling was conducted for these samples via multi-parameter flow cytometry.

Researchers observed that children infected with COVID-19 had high viral load titers with high frequencies of dendritic cells (DCs). These cells influence adaptive immune response. The subpopulations of DCs, especially pDC, assist in the development of antiviral responses. The pDCs are recognized as one of the main sources of type I interferon. Previous studies have reported a decrease in the activation and number of DCs in COVID-19 infected adults. The expression of HLA-DR, a characteristic feature of mature DCs, was also found to be prominent. However, a reduction in CX3CR1, a chemokine receptor (also known as fractalkine receptor), was observed. Further, a reduced HLA-DR expression in children has been correlated with immune suppression and the occurrence of acute inflammatory conditions.

The current study has also reported that in pediatric patients, T cells and SARS-CoV-2 specific antibodies were at levels comparable to adults who are severely or mildly infected with SARS-CoV-2. A higher level of CD8+ TNFa+ T cell responses against Nucleocapsid (N) protein and Membrane (M) protein of the virus, i.e., more than for Spike peptides, was reported. However, this result does not match with the immune profile of an infected adult. Thereby, the present study suggested a differential immune response in children when compared to adults. The current research also highlights the role of both adaptive and innate immune systems in protecting children from COVID-19 disease.

One of the limitations of the present study is that it is only exploratory or descriptive, as it compares the immune response across different age groups. However, the study’s authors feel it is a valid approach due to the lack of comprehensive research in this area.

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

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