New SARS-CoV-2 Variant Featuring N679S Mutation Alarmingly Found In A Newborn Child Exhibiting Seizures In The United States!
A new SARS-CoV-2 Variant N679S
has been found in a new born child exhibiting seizures in the United States and according to physicians and medical researchers from the Children’s National Hospital-Center for Genetic Medicine Research, George Washington University School of Medicine and Health Sciences, Children’s Hospital of Los Angeles and the University of Southern California, alarmingly there are more emerging cases of patients being detected with the new mutation variant and exhibiting various unusual medical conditions! At the same time numerous other variants with S193I nucleoprotein mutation and the T371I non-structural protein 2 mutation are also being found in other pediatric patients in the United States.
Scientists are warning that contrary to the norm of coronaviruses, the SARS-CoV-2 virus is mutating at a rapid phase suddenly and more and more variants are emerging as the virus is fighting to survive. It is of critical need that more resources are dedicated towards constant profiling and monitoring of the viral genome in the various populations.
The study team present an analysis of viral genomes acquired from pediatric patients presenting to Children's National Hospital in Washington D.C, including 24 with primary SARS CoV2 infection and 3 with Multisystem Inflammatory Syndrome in Children (MIS-C) undergoing treatment at the facility.
Detailed viral genome analysis using next generation sequencing indicated that approximately 81% of the analyzed strains were of the GH clade, 7% of the cases belonged to the GR clade, and 12% of the cases belonged to S, V, or G clades.
Importantly one sample, acquired from a neonatal patient exhibiting seizures, presented with the highest viral RNA load of all patients evaluated at our center. Viral sequencing of this sample identified a SARS-CoV-2 spike variant, S:N679S
The similarity of the regional sequences suggests transmission and persistence of the SARS-CoV-2 variant within the Capitol region, raising the importance of increasing the frequency of SARS-CoV-2 genomic surveillance.
Most significantly, this variant in the SARS-CoV-2 spike protein was identified in a febrile neonate who was hospitalized with COVID-19. This patient exhibited the highest viral RNA load of any COVID-19 patient tested at our center. Viral sequencing identified a spike protein variant, S:N679S, which is proximal to the cleavage site at residue 681. The SARS-CoV-2 surface spike is a protein trimer (three subunits) which serves as the key target for antibody therapies and vaccine development.
Further study of viral sequences from the GISAID database revealed eight related sequences from the US mid-Atlantic region. The identification of this variant in a very young patient, its critical location in the spike polyprotein, and the evidence that it has been detected in other patients in our region underscores the need for increased viral sequencing to monitor variant prevalence and emergence, which may have a direct impact on recommended public health measures and vaccination strategies.
The study findings were published on a preprint server and are currently being peer reviewed.
The study team from the hospital in Washington D.C. found the new mutant strain of the virus in a neonatal patient with high viral loads. According to the study team, this strain alarmingly could be spreading in the United States mid-Atlantic population and needs monitoring.
The SARS-CoV-2 has infected almost 108 million individuals worldwide and has caused more than 2.37 million deaths.
Many early reports suggested that most infected children were either asymptomatic or had only mild symptoms.
However 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).
It was found that 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.
Most COVID-19 patients were tested using commercial RT-PCR to confirm a diagnosis. Samples from some patients were also sent for genome sequencing.
The study team 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 study team 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.
It was found that 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.
It was observed that 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.
Importantly 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.
A preliminary 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.
Alarmingly 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.).
Importantly 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.
Although 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, this variant 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.
Many experts believe that there are many more such new variants emerging exhibiting various types of human phenotypes but has yet to be discovered or identified due to insufficient genomic sequencings being done in the United States and also in countries like India, Thailand, Indonesia, Malaysia, Myanmar etc.
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