#16,684
Recombinant COVID viruses have only recently begun making headlines (see UKHSA, ECDC & WHO Now Monitoring Multiple Recombinant COVID Variants (XD, XE & XF)), but this evolutionary process has long been considered a potential pathway for creating new SARS-CoV-2 variants.
Recombination is the sharing of genetic material between similar genomes that simultaneously infect a single host. The resultant hybrid is called a recombinant.
During the first two years of the pandemic, the world was blanketed by relatively monolithic COVID viruses (all `Wild type', Alpha, or Delta). Recombinants were less likely to have a significant impact on viral fitness, and were harder to spot.
With the introduction of a radically different Omicron variant last fall (see Preprint: Mapping the Antigenic Diversification of SARS-CoV-2), recombinants became more easily identifiable.
That said, most variants end up becoming evolutionary failures.
They emerge, and may even flourish briefly, but are eventually overwhelmed by more biologically `fit' viruses. While SARS-CoV-2 has generated literally thousands of variants, only a handful (D614G, Alpha, Delta, Omicron, BA.2, etc.) have significantly affected the course of the pandemic.
As early as May of 2020 we were seeing signs of recombination (see More COVID-19 (SARS-CoV-2) Mutation Reports)); signs which grew stronger in 2021 with the emergence of both Alpha and Beta variants (see ECCMID: Dual Infection With COVID Variants (Alpha & Beta)).
Last summer, in UK SAGE: Can We Predict the Limits of SARS-CoV-2 Variants and their Phenotypic Consequences?, UK scientists discussed at length the unpredictable ramifications that new recombinant COVID variants could have on the future course of the pandemic.
Which is why - even though most variants quickly fade into obscurity - we need to monitor the emergence, and geographic spread, of new COVID variants closely.
All of which brings us to a dispatch - published this week in the CDC's EID Journal - on the detection of multiple recombinant BA.1/BA.2 SARS-CoV-2 viruses among travelers entering Hong Kong. I've only printed the Abstract and some excerpts, so follow the link to read it in its entirety.
I'll return with a brief postscript after the break.
Research Letter
Recombinant BA.1/BA.2 SARS-CoV-2 Virus in Arriving Travelers, Hong Kong, February 2022
Haogao Gu, Daisy Y.M. Ng, Gigi Y.Z. Liu, Samuel S.M. Cheng, Pavithra Krishnan, Lydia D.J. Chang, Sammi S.Y. Cheuk, Mani M.Y. Hui, Tommy T.Y. Lam, Malik Peiris, and Leo L.M. Poon
Abstract
We studied SARS-CoV-2 genomes from travelers arriving in Hong Kong during November 2021–February 2022. In addition to Omicron and Delta variants, we detected a BA.1/BA.2 recombinant with a breakpoint near the 5′ end of the spike gene in 2 epidemiologically linked case-patients. Continued surveillance for SARS-CoV-2 recombinants is needed.
The SARS-CoV-2 Omicron variant (Pango lineage B.1.1.529) emerged in November 2021. Within a few weeks, subvariants BA.1, BA.1.1, and BA.2 were detected in varying proportions on different continents, but BA.1 initially was dominant (1). By March 2022, these 3 subvariants accounted for >95% of sequences submitted to GISAID (https://www.gisaid.org). We previously demonstrated the feasibility of testing incoming travelers for SARS-CoV-2 genomic surveillance (2). We report detecting a BA.1/BA.2 recombinant SARS-CoV-2 subvariant in travelers arriving in Hong Kong, China.
Using our previously described next-generation sequencing method (2), we analyzed 198 (25%) of 793 SARS-CoV-2 reverse transcription PCR (RT-PCR)–positive samples collected from travelers arriving in Hong Kong during November 15, 2021–February 4, 2022 (Appendix Table 1). We randomly selected samples with cycle thresholds <30 and successfully deduced near-full genome sequences from 180 samples (mean coverage 97.6%; depth >100). Deduced genomes predominantly were Delta (n = 58) and Omicron (BA.1 = 66, BA.1.1 = 28, and BA.2 = 26) variants (Appendix Figures 1, 2).
Time distribution of these variants agrees with global surveillance data submitted to GISAID, confirming that travel hubs are useful sentinel sites to monitor SARS-CoV-2 circulation (2). Of note, the BA.2 cases we detected predominantly were imported from the Philippines and Nepal, indicating this subvariant might have become established in these countries before detection in Hong Kong.
In our phylogenetic analysis, 2 additional nearly identical sequences formed a distinct branch in the Omicron clade (Appendix Figure 2). We detected these sequences from 2 epidemiologically linked cases, patients 1 and 2, who were work colleagues and traveled together to Hong Kong on February 1, 2022, from Germany via the Netherlands. They tested SARS-CoV-2–positive by RT-PCR at the airport upon arrival (cycle thresholds 27 and 22). Patient 1 reported having a sore throat and cough since January 28, but patient 2 was asymptomatic.
Both patients had received 2 doses of Pfizer-BioNTech COVID-19 vaccine (Pfizer Inc., https://www.pfizer.comExternal Link); patient 1 received the second dose on November 1, 2021, and patient 2 received the second dose on June 22, 2021.
The distinct topology of viral sequences from these patients suggested that they were infected by a recombinant virus.
(SNIP)
We found no similar BA.1/BA.2 recombinant sequences in GISIAD or GenBank (as of March 7, 2022), suggesting a novel recombinant. The BA.1 region of this recombinant virus is genetically close to 3 BA.1 sequences detected in Europe and the United States (Figure, panel B), whereas its BA.2 region is identical to 19,555 BA.2 sequences from multiple continents. Because global cocirculation of BA.1 and BA.2 subvariants is high, pinpointing the geographic location where this recombination event occurred would be difficult.
Emerging Omicron subvariants could allow vaccine breakthrough and widespread reinfection. Previous studies reported detection of SARS-CoV-2 interlineage recombinants at the same time as different SARS-CoV-2 lineages were cocirculating (3; D. VanInsberghe et al., unpub. data, https://doi.org/10.1101/2020.08.05.238386; P. Colson et al., unpub. data; T. Peacock, unpub. data).The high transmissibility of Omicron (5,6) has led to wide cocirculation of BA.1 and BA.2 subvariants in many regions, which might provide ample opportunities to generate novel recombinants among these or other variants via coinfection events. Although current global surveillance data suggest that our recombinant might only be a sporadic case, the potential effects of novel recombinants should not be underestimated.
Of note, homologous recombination is common in animal and other human coronaviruses (7), and some recombination events could generate recombinants with enhanced virulence (8,9). Long-term global SARS-CoV-2 genomic surveillance will be needed to monitor for possible more virulent or transmissible strains.
Dr. Gu is a postdoctoral fellow at The University of Hong Kong, Hong Kong, China. His research interests focus on bioinformatics and virus evolution.
On Friday the UKHSA released their bi-weekly Technical Update (#40) on SARS-CoV-2, and announced they were now following several new COVID variants; V-22APR-01 (XD) and V-22APR-02 (XE), V-22APR-03 (Omicron sub-lineage BA.4), and V-22APR-04 (Omicron sub-lineage BA.5).
Despite some of the more hyperbolic posts on social media, we don't know enough about these variants to begin to make predictions about what they will do. They may all fade into viral oblivion, or there could be a contender or two in the bunch.
Time will tell.
But this procession of new variants should tell us that COVID continues to evolve, and as tired as we all are of this pandemic, we may not have seen COVID's last hurrah.
