The connection between age and virulence of SARS-CoV-2 variants of concern

A severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was first reported in 2019 in Wuhan, China. The rapid outbreak of SARS-CoV-2 has caused the coronavirus disease 2019 (COVID-19) pandemic, which has claimed more than 4.7 million lives worldwide.

Several studies have shown that as compared to adults, children are less affected by SARS-CoV-2. These studies also revealed that children who contracted SARS-CoV-2 were mostly asymptomatic.

Study: Age-Specific Changes in Virulence Associated with SARS-CoV-2 Variants of Concern. Image Credit: TommyStockProject /


Owing to mutations, many SARS-CoV-2 variants have emerged that have been categorized as variants of concern (VOC) and variants of interest (VOI) by the United States Centers for Disease Control and Prevention (CDC). VOCs exhibited greater virulence and infectivity compared to the original SARS-CoV-2 strain.

One VOC of interest has been the SARS-CoV-2 Delta strain, which has been found to evade vaccine-induced immunity, as well as immune protection elicited after natural infection. As with any other VOC, the Delta strain also has a high rate of transmission and rate of mortality.

During the summer of 2021, both the United Kingdom as well as the United States experienced a tremendous surge in pediatric hospitalizations related to COVID-19. As the Delta variant was the dominant circulating strain in both countries, scientists linked the increase in the COVID-19 pediatric cases with the emergence of this strain.

However, the surge in pediatric infections could be related to the increased infectivity of this strain. Scientists failed to determine if the Delta strain infected children with more virulence than the original SARS-CoV-2 strain or other VOCs, such as the Alpha and Beta strains.

About the study

It is important to understand the reason behind the heterogeneity in the effects of SARS-CoV-2 VOCs by age. A new study published on the medRxiv* preprint server focuses on determining the existence of an age-related heterogeneity in the severity of COVID-19.

This retrospective study included a cohort of people residing in Ontario (Canada) and who had tested positive for COVID-19. These individuals were further screened to assess for VOCs between  February 7, 2021, and August 30, 2021.

The researchers categorized detected cases as N501Y-positive VOC, probable Delta VOC, and VOC undetected. An age-specific logistic regression model was constructed to determine the effects of these categories of VOCs on infection severity by using hospitalization, admission to the intensive care unit (ICU), and mortality as outcome variables. The models were adjusted according to sex, health unit, time, comorbidities, vaccination status, immune compromise, long-term care residence, healthcare worker status, and pregnancy.

Study findings

In this study, the researchers found that Delta VOC infection is more virulent as compared to the infection caused by both N501Y-positive VOC and non-VOC SARS-CoV-2 strains. In fact, individuals infected with the Delta strain showed a higher risk of ICU admission, hospitalization, and death in both younger and older age groups when compared to other VOCs.

The current study found that the Delta strain elevated hospitalization risk in children who were below 10 years by a factor of 2.5 compared to non-VOC strains. Importantly, an inverse relationship between age and relative enhancement in the risk of mortality with the Delta VOC was observed. This meant that the younger age groups showed a greater increase in their relative risk of death than the older age groups.

However, in the case of other VOCs, such age specificity was not observed. The authors of this study emphasized that their results do not indicate that other VOCs are not a threat to older age groups. In both N501Y-positive and Delta VOC strains, a significant increase in the risk of severe infection was reported in older individuals.


The present study has several limitations. Firstly, the relative numbers of severely infected COVID-19 cases in children are rare, making accurate estimation difficult. The researchers also failed to make proper categorization between age groups.

Owing to this, determining the differential effect of the SARS-CoV-2 variants between teens and younger ager groups was not possible. Another limitation was the extent to which the frequency with which the COVID-19 tests were conducted was dynamic.


The authors did not find conclusive evidence that enhanced virulence of SARS-CoV-2 VOCs is targeted to a specific age group. They show that the relative virulence of Delta VOC is inversely related to age.

Severe outcomes are relatively rare in teens and children, making estimation difficult. In the future, more studies using a larger cohort are essential to derive solid conclusions.

*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.