How a major COVID-19 outbreak occurred in a naïve and vaccinated population in Taiwan with a limited number of entry events

In a recent study posted to the medRxiv* preprint server, researchers explored the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome using high-throughput genome sequencing to provide novel insights into how the novel SARS-CoV-2 Omicron BA.2.3.7 variant enters and spreads among the otherwise naïve Taiwanese population.

Background

The coronavirus disease 2019 (COVID-19) pandemic originated in China, most likely from Wuhan, in late 2019. In response, the Taiwanese government introduced stringent travel restrictions for incoming passengers by sea and air, with long quarantine periods for those allowed to enter Taiwan. In addition, in Taiwan, several non-pharmaceutical interventions (NPIs) such as social distancing and mask-wearing were enforced. Until April 2022, only a few COVID-19 cases were reported in Taiwan; however, by June 2022, COVID-19 case counts had considerably increased in the country.

About the study

In the present study, researchers conducted genomic surveillance to assess the prevalence and spread of Omicron BA.2.3.7 in Taiwanese community-dwelling residents.

The team analyzed 2,405 polymerase chain reaction (PCR)-confirmed SARS-CoV-2-positive nasopharyngeal swab specimens from 2,339 persons. Blood samples were obtained from the coronavirus disease 2019 (COVID-19) patients enrolled from the NTU-HCH (national Taiwan university hospital’s Hsinchu branch), and SARS-CoV-2 ribonucleic acid (RNA) was extracted, amplified by reverse transcription PCR (RT-PCR) analysis, and subjected to whole-genome sequencing (WGS) analysis.

For the phylogenetic analysis, 2847 sequences, including 1,966 from NTU-HCH and 881 references (GISAID) sequences, were utilized for constructing the phylogenetic tree framework. Subsequently, 1,584 BA.2.3.7 sequences submitted to GISAID from the current study, with 228 BA.2.3.7 sequences deposited to GISAID by other groups, were analyzed in batches. The emergence of novel Omicron variants in Taiwan and the genomic evolution during the swift Omicron pool expansion between 22 February 22 and 6 June 2022 were assessed.

To investigate the global variant transmission, 249 BA.2.3.7, 282 global, and 403 additional sequences from Taiwan residents were retrieved from the GISAID (global initiative on sharing all influenza data) database up to July 2022. As a pilot study, 293 samples from 228 patients were analyzed, and most of the samples were obtained in 2021 from three hospitals in north Taiwan. The sequences were assembled and examined for significantly altered amino acids to determine signature mutations in the Omicron-infected samples.

Results

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BA.2.3.7 was detected as the prime causative variant of the 2022 SARS-CoV-2 outbreak among Taiwanese communities. The 1966 complete-length sequences of Omicron were uploaded to the GISAID database enabling the identification of three signature BA.2.3.7 mutations, i.e., L631F, K97E, and M322I detected in open reading frame 1a (ORF1a), spike (S) protein and nucleocapsid (N) protein, respectively, within the non-structural protein 2 (nsp2), S subunit 1 (S1) N-terminal domain (NTD) and at amino acid position 322, respectively, among 81% (n=1584) of Omicron sequences.

The signature changes occurred after the fourth sequenced batch, indicative of the rapid surge in COVID-19 cases due to the emerging BA.2.3.7 strain from hundreds to thousands over the course of the study period among Taiwanese (especially north Taiwan) communities. The proportion of sequences containing the signature changes increased from 62 % to 85% from the fourth batch to the fifth batch. By June 2022, the strain established considerable dominance among SARS-CoV-2 sequences.

Additionally., novel mutations (ORF1a:I1091T and G1251V) were detected in BA.2.3.7 with a remarkable increase over time, rapidly increasing the count of BA.2.3.7 infections across Taiwan, reported in four Taiwan locations, indicative of BA.2.3.7 as the causative variant for the SARS-CoV-2 outbreaks among Taiwanese community residents.

Most of the pilot study samples obtained in 2021 were assigned the Alpha variant. A remarkable increase in Omicron BA.2.3.7 infections was observed from week 4 onwards, and BA.2.3.7 variant percentage was persistently high for ≥10 weeks. The number of S:G1251V-positive sequences steadily increased from week 6 onwards and plateaued in the tenth week (between 26 April 26 2 and May). In the period between weeks 11 and 15, the ORF1a:T3224A proportion reduced, whereas the ORF1a:I1091T proportion concomitantly increased.

During the same period, Omicron BA.2.3.7 was also detected in other Asian Pacific countries such as Hong Kong, Singapore, Indonesia, Japan, Vietnam, Philippines, Thailand, Malaysia, and New Zealand. Among 44 BA.2.3.7 cases detected in Japan, 41 and two individuals had travel histories to Taiwan and Vietnam, respectively, indicative of silent outward BA.2.3.7 transmission from Taiwan. On the contrary, BA.2.3.7 forms <0.5% of sequences reported in the United States of America (USA), California, or globally.

Conclusion

Overall, the study findings highlighted the emergence, rapid spread, and persistence of BA.2.3.7 as the causative variant of community outbreaks in Taiwan. The findings could considerably impact socioeconomic and public health domains. Of note, the 2021 Alpha variant outbreak was relatively small and limited to cluster infection within New Taipei City, whereas the Omicron BA.2.3.7 outbreak between April and June 2022 exceeded 50,000 cases/day at the peak level.

*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.

Written by

Pooja Toshniwal Paharia

Dr. based clinical-radiological diagnosis and management of oral lesions and conditions and associated maxillofacial disorders.