Study detects SARS-CoV-2 BA.1/BA.2 recombinant in two epidemiologically linked cases

By Dr. Priyom Bose, Ph.D.Apr 5 2022Reviewed by Danielle Ellis, B.Sc.

Scientists have reported the continual evolution of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causal agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic, due to genomic mutations. Several SARS-CoV-2 variants have been identified worldwide, which have been classified as variants of concern (VOC) and variants of interest (VOI) by the World Health Organization.

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources

Background

The SARS-CoV-2 Omicron (B.1.1.529) variant has been characterized as a VOC. It has become the dominant circulating strain in many countries, replacing the previously circulating Delta variant. This variant was first identified in South Africa in November 2021, and soon it was transmitted to many parts of the world. Researchers detected three subvariants of Omicron, namely, BA.1, BA.1.1, and BA.2, in twenty-eight different continents within weeks of BA.1 being the dominant strain.

About the study

Previous studies have indicated the possibility of using incoming travelers for SARS-CoV-2 genomic surveillance. In a new study available on medRxiv* preprint server, researchers have focussed on detecting BA.1/BA.2 recombinant in travelers through surveillance. In this study, researchers used a next-generation sequencing method for their analysis.

Scientists observed that 198 out of 793 samples collected from travelers arriving in Hong Kong between November 15^th, 2021, and February 4^th, 2022, were SARS-CoV-2 real-time polymerase chain reaction reverse transcription (RT-PCR) positive. The authors conducted near-full genome sequencing of 180 positive samples. They found that most of the genomes belonged to either the Delta (58 samples) or the Omicron variant, including 66 samples belonging to BA.1, 28 with BA.1.1 infection, and 26 with BA.2.

Findings

Scientists reported that most of the identified BA.2 cases were from travelers coming from the Philippines and Nepal. This observation indicated that the subvariant might have initially established itself in these countries. The phylogenetic analysis conducted by the authors revealed that two additional nearly identical sequences formed a distinct branch in the Omicron clade. These two genomes, referred to as from patient 1 and patient 2, were identified from two epidemiologically linked cases.

Both the patients traveled together to Hong Kong in February 2022 from Europe. They tested SARS CoV-2 positive at the airport upon arrival. Patient 1 complained of having a sore throat and cough in late January 2022, while patient 2 was asymptomatic. Both the patients had received two doses of the COVID-19 vaccine developed by Pfizer-BioNTech. 

Owing to the unique topology of viral sequences from Patients 1 and 2, scientists hypothesized that both the patients were infected by a recombinant virus. To test this hypothesis, they used previously reported BA.1 and BA.2 single-nucleotide polymorphisms (SNPs) to analyze the new genomic sequences of patients 1 and 2. Scientists reported that the 5’ end sequences of the two patients contain only BA.1-specific SNPs, while the corresponding 3’ end sequences contain only BA.2-specific SNPs.

The authors conducted recombination analysis and confirmed the presence of only one breakpoint, which was present between nucleotide positions 20055-21618 in this recombinant. They observed phylogenetic similarities between this breakpoint and authentic BA.1 and BA.2 sequences. Scientists identified the location of the breakpoint of this recombinant virus to be near the 5’ ORF of the spike gene. Previous studies have also reported a breakpoint in this region, indicating that this region might be the hotspot for recombination. 

Researchers conducted extensive experiments to exclude any possibility that coinfection or contamination could generate biased recombinant observations. They observed that the minor allele frequencies (MAF) associated with BA.1-and BA.2- defining SNP positions were extremely low. This finding implies that these samples, i.e., from both patients 1 and 2, only contained a single virus population.

Additionally, scientists cloned an RT-PCR product spanning the recombination breakpoint using the patient 2 sample. They observed both BA.1-specific and BA.2-specific SNPs in the same plasmid clone, confirming that patients 1 and 2 were infected by a BA.1/BA.2 recombinant virus.

As the authors failed to find similar BA.1/BA.2 recombinant sequences in GISIAD or Genbank, this sequence could be a novel recombinant. They stated that both BA.1 and BA.2 subvariants are dominantly found in many parts of the world, which made detecting the geographical location where this recombination event occurred difficult.

Conclusion

The authors of this study stated that a high rate of transmission of the Omicron variant along with co-circulation of BA.1 and BA.2 subvariants in many parts of the world presents a greater possibility of generating novel recombinants. Even though the current global surveillance data has indicated the identified recombinant variant to be a sporadic case, the potential of the novel recombinants’ virus must not be underestimated. In the future, scientists recommended conducting more long-term genomic surveillance of SARS-CoV-2 at the global level. 

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources