Hospitalization and Mortality Risk for COVID-19 Cases With SARS-CoV-2 AY.4.2 (VUI-21OCT-01) Compared to Non-AY.4.2 Delta Variant Sublineages

Nyberg, Tommy; Harman, Katie; Zaidi, Asad; Seaman, Shaun; Andrews, Nick; Nash, Sophie; Charlett, André; Groves, Natalie; Gallagher, Eileen; Gharbia, Saheer; Chand, Meera; Thelwall, Simon; Angelis, Daniela De; Dabrera, Gavin; Presanis, Anne M.

doi:10.1093/infdis/jiac063

Cited by 9 publications

(9 citation statements)

References 18 publications

(15 reference statements)

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“…It is therefore reassuring that the BA.2 sub-lineage, despite being more transmissible than BA.1 4 , may be associated with no greater risk of severe outcomes than Omicron BA.1. These patterns are analogous with previous findings for the AY.4.2 sub-lineage of the Delta variant, which had higher transmissibility but lower or similar severity risks compared to other Delta sub-lineages 14 .…”

Section: Discussionsupporting

confidence: 90%

Hospitalisation and mortality risk of SARS-COV-2 variant omicron sub-lineage BA.2 compared to BA.1 in England

Webster¹,

Nyberg

Sinnathamby³

et al. 2022

Nat Commun

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The Omicron variant of SARS-CoV-2 became the globally dominant variant in early 2022. A sub-lineage of the Omicron variant (BA.2) was identified in England in January 2022. Here, we investigated hospitalisation and mortality risks of COVID-19 cases with the Omicron sub-lineage BA.2 (n = 258,875) compared to BA.1 (n = 984,337) in a large cohort study in England. We estimated the risk of hospital attendance, hospital admission or death using multivariable stratified proportional hazards regression models. After adjustment for confounders, BA.2 cases had lower or similar risks of death (HR = 0.80, 95% CI 0.71–0.90), hospital admission (HR = 0.88, 95% CI 0.83–0.94) and any hospital attendance (HR = 0.98, 95% CI 0.95–1.01). These findings that the risk of severe outcomes following infection with BA.2 SARS-CoV-2 was slightly lower or equivalent to the BA.1 sub-lineage can inform public health strategies in countries where BA.2 is spreading.

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Section: Discussionsupporting

confidence: 90%

Hospitalisation and mortality risk of SARS-COV-2 variant omicron sub-lineage BA.2 compared to BA.1 in England

Webster¹,

Nyberg

Sinnathamby³

et al. 2022

Nat Commun

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“…Most of these studies are therefore consistent with our results. Our estimate that AY.4.2 is associated with approximately the sample severity as other Delta sublineages is inconsistent with an analysis of the English population which found that confirmed AY.4.2 cases are associated with lower hospitalisation risk than cases associated with non-AY.4.2 Delta [34]. This inconsistency between our study and others may be explained by differences in the adjustment variables used, or because the larger sample size in Nyberg et al 2022 [33] allowed precise isolation of a small negative effect, with their effect estimate falling within our credible interval.…”

Section: Discussioncontrasting

confidence: 99%

Inconsistent directions of change in case severity across successive SARS-CoV-2 variant waves suggests an unpredictable future

Pascall

Vink

Mollett

et al. 2022

Preprint

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Objective To determine how the severity of successively dominant SARS-CoV-2 variants has changed over the course of the COVID-19 pandemic. Design Prospective cohort analysis. Setting Community- and hospital- sequenced COVID-19 cases in the NHS Greater Glasgow and Clyde (NHS GG&C) Health Board (1.2 million people). Participants All sequenced non-nosocomial adult COVID-19 cases in NHS GG&C identified to be infected with the relevant SARS-CoV-2 lineage during the following analysis periods. B.1.177/Alpha analysis: 1st November 2020 - 30th January 2021 (n = 1640). Alpha/Delta analysis: 1st April - 30th June 2021 (n = 5552). AY.4.2 Delta/non-AY.4.2 Delta analysis: 1st July - 31st October 2021 (n = 9613). Non-AY.4.2 Delta/Omicron analysis: 1st - 31st December 2021 (n = 3858). Main outcome measures Admission to hospital, admission to ICU, or death within 28 days of first positive COVID-19 test Results In the B.1.177/Alpha analysis, 300 of 807 (37.2%) B.1.177 cases were recorded as hospitalised or having a more severe outcome, compared to 232 of 833 (27.9%) Alpha cases. After adjusting for the following covariates: age, sex, time of positive test, comorbidities and partial postcode, the cumulative odds ratio was 1.51 (95% central credible interval 1.08-2.11) for Alpha versus B.1.177. In the Alpha/Delta analysis, 113 of 2104 (5.4%) Alpha cases were recorded as hospitalised or having a more severe outcome, compared to 230 of 3448 (6.7%) Delta cases. After adjusting for the above covariates plus number of vaccine doses and reinfection, the cumulative odds ratio was 2.09 (95% central credible interval 1.42-3.08) for Delta versus Alpha. In the non-AY.4.2 Delta/AY.4.2 Delta analysis, 845 of 8644 (9.8%) non-AY.4.2 Delta cases were recorded as hospitalised or having a more severe outcome, compared to 101 of 969 (10.4%) AY.4.2 Delta cases. After adjusting for the previously stated covariates, the cumulative odds ratio was 0.99 (95% central credible interval 0.76-1.27) for AY.4.2 Delta versus non-AY.4.2 Delta. In the non-AY.4.2 Delta/Omicron analysis, 30 of 1164 (2.6%) non-AY.4.2 Delta cases were recorded as hospitalised or having a more severe outcome, compared to 26 of 2694 (1.0%) Omicron cases. After adjusting for the previously listed covariates, the median cumulative odds ratio was 0.49 (95% central credible interval 0.22-1.06) for Omicron versus non-AY.4.2 Delta. Conclusions The direction of change in disease severity between successively emerging SARS-CoV-2 variants of concern was inconsistent. This heterogeneity in virulence between variants, coupled with independent evolutionary emergence, demonstrates that severity associated with future SARS-CoV-2 variants is inherently unpredictable.

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“…29 This and other studies, 28,29 however, were restricted to short time periods where both variants co-circulated and, hence, do not capture subsequent changes such as a reduction in severity later in the Delta period with the AY.4.2 sub-variant compared with the earlier non-AY.4.2 one. 30 Moreover, survival studies restricted to discrete periods are subject to biases inherent to health seeking and treatment practices. In this sense, estimates of the increase severity of Delta over Alpha from patients seeking a PCR test are constrained by test-seeking behaviours in the population during the early phase of Delta transmission.…”

Section: Discussionmentioning

confidence: 99%

Epidemiological drivers of transmissibility and severity of SARS-CoV-2 in England

Perez‐Guzman

Knock

Imai

et al. 2023

Preprint

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As the SARS-CoV-2 pandemic progressed, distinct variants emerged and dominated in England. These variants, Wildtype, Alpha, Delta, and Omicron were characterized by variations in transmissibility and severity. We used a robust mathematical model and Bayesian inference framework to analyse epidemiological surveillance data from England. We quantified the impact of non-pharmaceutical interventions (NPIs), therapeutics, and vaccination on virus transmission and severity. Each successive variant had a higher intrinsic transmissibility. Omicron (BA.1) had the highest basic reproduction number at 8.1 (95% credible interval (CrI) 6.8-9.3). Varying levels of NPIs were crucial in controlling virus transmission until population immunity accumulated. Immune escape properties of Omicron decreased effective levels of protection in the population by a third. Furthermore, in contrast to previous studies, we found Alpha had the highest basic infection fatality ratio (2.8%, 95% CrI 2.3-3.2), followed by Delta (2.0%, 95% CrI 1.5-2.4), Wildtype (1.2%, 95% CrI 1.0-1.3), and Omicron (0.6%, 95% CrI 0.4-0.8). Our findings highlight the importance of continued surveillance. Long-term strategies for monitoring and maintaining effective immunity against SARS-CoV-2 are critical to inform the role of NPIs to effectively manage future variants with potentially higher intrinsic transmissibility and severe outcomes.

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Hospitalization and Mortality Risk for COVID-19 Cases With SARS-CoV-2 AY.4.2 (VUI-21OCT-01) Compared to Non-AY.4.2 Delta Variant Sublineages

Cited by 9 publications

References 18 publications

Hospitalisation and mortality risk of SARS-COV-2 variant omicron sub-lineage BA.2 compared to BA.1 in England

Hospitalisation and mortality risk of SARS-COV-2 variant omicron sub-lineage BA.2 compared to BA.1 in England

Inconsistent directions of change in case severity across successive SARS-CoV-2 variant waves suggests an unpredictable future

Epidemiological drivers of transmissibility and severity of SARS-CoV-2 in England

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