Study Suggests a Potential Link Between SARS-CoV-2 Mutations, Disease Severity in Children

November 20, 2020

When it comes to children, it is becoming clear that coronavirus disease 2019 (COVID-19) impacts them more than was initially thought, and a study published in Open Forum Infectious Diseases has, for the first time, found a possible link between specific viral mutations and severity of the disease.

Xiaowu Gai, PhD, Children’s Hospital Los Angeles, Los Angeles, California, and colleagues performed whole genome sequencing on respiratory specimens collected on all children who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between March 13, 2020, to June 16, 2020 (n = 141). Viral genetic variations across the SARS-CoV-2 genome were identified and investigated to evaluate genomic correlates of disease severity.

Genomic analysis revealed a mean pairwise difference of 10.8 single nucleotide variants (SNVs), and the majority (55.4%) of SNVs led to an amino-acid change in the viral proteins. The D614G mutation in the spike protein was present in 99.3% of the isolates. The calculated viral mutational rate of 22.2 substitutions/year contrasts the 13.5 substitutions/year observed in California isolates without the D614G mutation. Phylogenetic clade 20C was associated with severe cases of COVID-19 (odds ratio = 6.95; P = .0467).

Epidemiological investigation revealed major representation of 3 of 5 major Nextstrain clades (20A, 20B and 20C) consistent with multiple introductions of SARS-CoV-2 in Southern California.

The study also found that children who were symptomatic (P = .0007) and children aged younger than 5 years (P = .0004) had higher viral loads.

“This study is very unique because in addition to having this large pool of genomic data, we’re really looking at what it all means,” said Jennifer Dien Bard, PhD, Children’s Hospital Los Angeles. “How can we trace this virus? How do the genomics correlate with clinical outcomes? These kinds of studies just aren’t out there yet, so we’re trying to fill that need.”

“Larger studies will be required to confirm that 1 subgroup of SARS-CoV-2 leads to worse prognosis, but this study is a clear example highlighting the importance of examining the genetics of the virus,” said Dr. Gai. “These are the puzzle pieces that will help us get ahead of this pandemic.”


SOURCE: Children’s Hospital Los Angeles