Researchers at a hospital in Washington D.C. found a new mutant strain of the virus in a neonatal patient with high viral loads. According to the authors, this strain could be spreading in the United States mid-Atlantic population and needs monitoring.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over 107 million individuals worldwide and has caused more than 2.36 million deaths. However, many early reports suggested that most infected children were either asymptomatic or had only mild symptoms.
As more reports came in, it was seen that children were more susceptible to a new manifestation of the disease, multi-system inflammatory syndrome in children (MIS-C). At the Children’s National Hospital in Washington, D. C., the number of pediatric and young adults seeking care has been similar to the general COVID-19 case trends in the United States (U.S.) East Coast. Although there were several hundred patients who were hospitalized, no children deaths occurred at the hospital.
COVID-19 patients were tested using commercial RT-PCR to confirm a diagnosis. Samples from some patients were also sent for genome sequencing. The researchers found a new virus variant from the sample of a neonatal patient who had high loads of viral RNA. This is probably one of the earliest virus variants identified in the U.S. mid-Atlantic region. The results are published in a research paper posted to the medRxiv* preprint server.
*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
Viral genome sequencing of children’s samples
The authors analyzed the genome of 27 samples and found the strains in the children to be similar to those found in adults. Using the Phylogenetic Assignment of Named Global Outbreak LINeages (PANGOLIN) tool, they found that the virus in the children of the Washington metro area was likely of European origin of the G.H. clade.
About 92% of the viral genomes sequenced had the D614G spike protein variant. Five patients had identical viral genome sequences, with one showing MIS-C symptoms. These sequences had the S193I nucleoprotein variant and the T371I non-structural protein 2 variant, different from other sequences in the G.H. clade.
Even though the five patients had identical genome sequences, they had different disease outcomes, suggesting it is challenging to form correlations between the viral and human phenotypes. Other variables such as initial viral dose, environment, and genetics could play a role in disease progression and MIS-C.
In a neonatal patient admitted to the hospital in September 2020 with high viral load and fever, the team found a nonsynonymous amino acid substitution (alters amino acid sequence) on the spike protein N679S, next to the cleavage site at residue 681, a new variant of the virus. This sequence also had the D614G variant.
An initial search on the GISAID database revealed six sequences with this variant, all deposited by labs in Virginia and Maryland. By January 2021, more samples with the variant were seen from Australia, Japan, and Brazil, and from Delaware in the United States (U.S.). These sequences belonged to the G.R. clade but had different lineages. All the U.S. samples were of the same lineage.
Monitoring of the new variant is important
Observing this variant in the U.S. in a short time window without any known person-to-person transmission suggests more cases with this viral strain may be present in the mid-Atlantic region. As of January 12, there were about 828,000 cases in Delaware, Maryland, Washington D.C., and Virginia, but only 0.36% of the viral genomes were sequenced, just above the national average of 0.3%, but much lower than the about 5% of the samples sequenced in the United Kingdom (U.K.).
The high level of genome sequencing in the U.K. indicates the importance of high throughput sequencing technologies and quick data sharing, which will allow more such discoveries that can be acted upon. The US Centers for Disease Control (CDC) plans to fund further sequencing, which will allow sequencing of about 0.4% of the cases.
The single observation of the N679S variant is not sufficient to demonstrate a relationship between the variant and high viral loads or infection in very young children. But, this strain will require continued monitoring as it is likely spreading in the U.S. mid-Atlantic region. Since the spike protein not only affects infectivity but is also a target for vaccines, testing this variant for vaccine efficacy is also important.
*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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