Transmission of SARS-CoV-2 Omicron VOC subvariants BA.1 and BA.2: Evidence from Danish Households

Abstract

The Omicron SARS-CoV-2 variant of concern (VOC lineage B.1.1.529), which became dominant in many countries during early 2022, includes several subvariants with strikingly different genetic characteristics. Several countries, including Denmark, have observed the two Omicron subvariants: BA.1 and BA.2. In Denmark the latter has rapidly replaced the former as the dominant subvariant. Based on nationwide Danish data, we estimate the transmission dynamics of BA.1 and BA.2 following the spread of Omicron VOC within Danish households in late December 2021 and early January 2022. Among 8,541 primary household cases, of which 2,122 were BA.2, we identified a total of 5,702 secondary infections among 17,945 potential secondary cases during a 1-7 day follow-up period. The secondary attack rate (SAR) was estimated as 29% and 39% in households infected with Omicron BA.1 and BA.2, respectively. We found BA.2 to be associated with an increased susceptibility of infection for unvaccinated individuals (Odds Ratio (OR) 2.19; 95%-CI 1.58-3.04), fully vaccinated individuals (OR 2.45; 95%-CI 1.77-3.40) and booster-vaccinated individuals (OR 2.99; 95%-CI 2.11-4.24), compared to BA.1. We also found an increased transmissibility from unvaccinated primary cases in BA.2 households when compared to BA.1 households, with an OR of 2.62 (95%-CI 1.96-3.52). The pattern of increased transmissibility in BA.2 households was not observed for fully vaccinated and booster-vaccinated primary cases, where the OR of transmission was below 1 for BA.2 compared to BA.1. We conclude that Omicron BA.2 is inherently substantially more transmissible than BA.1, and that it also possesses immune-evasive properties that further reduce the protective effect of vaccination against infection, but do not increase its transmissibility from vaccinated individuals with breakthrough infections.

Insights on the mutational landscape of the SARS-CoV-2 Omicron variant receptor-binding domain

“…Omicron's antibody evasion mutations may largely negate this penalty, and it is plau-sible that such RBD down -RBD down interface mutations are only enabled in the context of Omicron's unique degree of immune escape. We also note that the Omicron BA.2 subvariant, which appears to have a transmission advantage, 47 features distinct RBD-RBD interface mutation S371F and additonal interface mutations T376A, D405N, and R408S. This observation further supports a relationship between mutations in this region and enhanced transmissibility.…”

Occurrence and significance of Omicron BA.1 infection followed by BA.2 reinfection

“…The Community track, TestCenter Denmark (TCDK) provides large scale testing for SARS-CoV-2 for all residents using RT-PCR through the free Danish universal health care system, providing easy access to testing facilities across the country. Since the end of 2021, surveillance of SARS-CoV-2 variants has been based on screening of ~15,000 positive samples per week using a variant-specific RT-PCR 9 and subsequent WGS as previously described 10 . Briefly, WGS was performed using Illumina technology using the ARTIC v3 amplicon sequencing panel (https://artic.network) with slight modifications.…”

Tracking SARS-CoV-2 Omicron diverse spike gene mutations identifies multiple inter-variant recombination events

“…BA.1 subvariant was more frequently detected than BA.2 during the early transmission phase. However, BA.2 is replacing BA.1 as the dominant epidemic subvariant in more and more countries over time 37 Through scanning 52,563 high-quality completed Omicron spike gene sequences, most Omicron spike mutations appear stable (frequency >99%). Eighteen core mutations (frequency >99%) of BA.1 subvariant exist in NTD (A67V, del69-70, T95I, G142D, del143-145), SD (underpinning subdomain) near the S1/S2 cleavage site (T547K, D614G, H655Y, N679K, P681H), and S2 (D796Y, N856K, Q954H, N969K, L981F)( Table1).…”