Clinical severity of SARS-CoV-2 Omicron BA.4 and BA.5 lineages in South Africa

Wolter, Nicole; Jassat, Waasila; Walaza, Sibongile; Welch, Richard; Moultrie, Harry; Groome, Michelle; Amoako, Daniel G.; Everatt, Josie; Scheepers, Cathrine; Tebeila, Naume; Chiwandire, Nicola; Plessis, Mignon du; Govender, Nevashan; Ismail, Arshad; Glass, Allison; Mlisana, Koleka; Stevens, Wendy; Treurnicht, Florette K.; Subramoney, Kathleen; Makatini, Zinhle; Hsiao, Marvin; Parboosing, Raveen; Wadula, Jeanette; Hussey, Hannah; Davies, Mary‐Ann; Boulle, Andrew; Gottberg, Anne von; Cohen, Cheryl

doi:10.21203/rs.3.rs-1792132/v1

Cited by 9 publications

(19 citation statements)

References 11 publications

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“…While some South African studies have suggested that Omicron BA.4 and BA.5 had similar disease severity to Omicron BA.1 and BA.2 (16,21), our data indicate a lower risk of mortality in the Omicron BA.4/BA.5 wave compared to the Omicron BA.1/BA.2 wave. Immunological observations from South Africa point to considerable immune escape of Omicron BA.4 and BA.5 from Omicron BA.1 elicited immunity, but much less so in those with vaccination (15).…”

Section: Discussioncontrasting

confidence: 84%

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Trends in Cases, Hospitalisation and Mortality Related to the Omicron BA.4/BA.5 Sub-Variants in South Africa

Jassat

Karim

Ozougwu

et al. 2022

Preprint

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Introduction: The Omicron BA.1/BA.2 wave in South Africa had lower hospitalisation and mortality than previous SARS-CoV-2 variants and was followed by an Omicron BA.4/BA.5 wave. This study compared admission incidence risk across waves, and the risk of mortality in the Omicron BA.4/BA.5 wave, to the Omicron BA.1/BA.2 and Delta waves. Methods: Data from South Africa's national hospital surveillance system, SARS-CoV-2 case linelist and Electronic Vaccine Data System were linked and analysed. Wave periods were defined when the country passed a weekly incidence of 30 cases/100,000 people. Mortality rates in the Delta, Omicron BA.1/BA.2 and Omicron BA.4/BA.5 wave periods were compared by post-imputation random effect multivariable logistic regression models. Results: In-hospital deaths declined 6-fold from 37,537 in the Delta wave to 6,074 in the Omicron BA.1/BA.2 wave and a further 7-fold to 837 in the Omicron BA.4/BA.5 wave. The case fatality ratio (CFR) was 25.9% (N=144,798), 10.9% (N=55,966) and 7.1% (N=11,860) in the Delta, Omicron BA.1/BA.2, and Omicron BA.4/BA.5 waves respectively. After adjusting for age, sex, race, comorbidities, health sector and province, compared to the Omicron BA.4/BA.5 wave, patients had higher risk of mortality in the Omicron BA.1/BA.2 wave (adjusted odds ratio [aOR] 1.43; 95% confidence interval [CI] 1.32-1.56) and Delta (aOR 3.22; 95% CI 2.98-3.49) wave. Being partially vaccinated (aOR 0.89, CI 0.86-0.93), fully vaccinated (aOR 0.63, CI 0.60-0.66) and boosted (aOR 0.31, CI 0.24-0.41); and prior laboratory-confirmed infection (aOR 0.38, CI 0.35-0.42) were associated with reduced risks of mortality. Conclusion: Overall, admission incidence risk and in-hospital mortality, which had increased progressively in South Africa's first three waves, decreased in the fourth Omicron BA.1/BA.2 wave and declined even further in the fifth Omicron BA.4/BA.5 wave. Mortality risk was lower in those with natural infection and vaccination, declining further as the number of vaccine doses increased.

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Section: Discussioncontrasting

confidence: 84%

“…Omicron sub-variants are more transmissible than previous VOCs, with greater immune escape, with BA.4/BA.5 showing reduced neutralization from antibodies induced by BA.1 infection, more so in the unvaccinated (14,15). Early data showed that Omicron BA.4/BA.5 waves had reduced severity in South Africa (16) and the United States (17).…”

Section: Introductionmentioning

confidence: 99%

Trends in Cases, Hospitalisation and Mortality Related to the Omicron BA.4/BA.5 Sub-Variants in South Africa

Jassat

Karim

Ozougwu

et al. 2022

Preprint

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“…Consistent with a smaller recent study in South Africa, 9 we did not identify evidence of differential severity of infections with the BA.4/BA.5 and BA.2 lineages in either unadjusted analyses comparing all incident cases or adjusted analyses controlling for measured characteristics of cases with each lineage. Previous analyses within our study population 4 and South Africa 16 have likewise established equivalent severity of BA.1 and BA.2 infections.…”

Section: Tablesupporting

confidence: 89%

“…As BA.4/BA.5 lineages harbor the Δ69-70 amino acid deletion in the S protein, S-gene target failure (SGTF) has been proposed elsewhere as a proxy for distinguishing BA.4/BA.5 from BA.2 lineages. 9,10 Within a sample of cases KPSC randomly selected for sequencing throughout 2022, 99.6% (243/244) of BA.4 cases and 99.0% (406/410) of BA.5 cases exhibited SGTF. In contrast, SGTF did not occur in 97.8% (2,000/2,046) of BA.2 cases, validating the use of SGTF to distinguish contemporaneous infections with the BA.4/BA.5 and BA.2 lineages.…”

Section: Methodsmentioning

confidence: 99%

“…4,8 Following the initial peak in BA.1 infections within the US from December, 2021 to February, 2022, multiple Omicron lineages have driven subsequent surges in cases. Although not associated with enhanced severity or risk of breakthrough infection after vaccination or natural infection, 4,9 the BA.2 lineage (and associated BA.2.12.1 sublineage) surpassed BA.1 in incident cases within the US beginning in March, 2022. Subsequently, the BA.4 and BA.5 lineages have become dominant globally.…”

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confidence: 91%

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Association of SARS-CoV-2 BA.4/BA.5 Omicron lineages with immune escape and clinical outcome

Lewnard¹,

Hong²,

Tartof³

2022

Preprint

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Expansion of the SARS-CoV-2 BA.4/BA.5 Omicron lineages in populations with prevalent immunity from prior infection and vaccination has raised concerns about the association of these lineages with immune escape. Here we show that COVID-19 vaccination and documented prior infection are associated with reduced protection against infection with BA.4/BA.5. Compared to time-matched BA.2 cases, BA.4/BA.5 cases had 9% (95% confidence interval: 2-17%) and 27% (15-41%) higher adjusted odds of having received 3 and 4 COVID-19 vaccine doses, respectively, and 55% (39-71%) higher adjusted odds of documented infection ≥90 days previously. However, BA.4/BA.5 infection was not associated with differential risk of emergency department presentation, hospital admission, or intensive care unit admission following an initial outpatient diagnosis. This finding held after correcting for potential exposure misclassification resulting from unascertained prior infections. Despite increased risk of BA.4/BA.5 breakthrough infection observed among previously vaccinated or infected individuals, the reduced severity associated with prior (BA.1 and BA.2) Omicron lineages has persisted with BA.4/BA.5.

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Clinical severity of Omicron subvariants BA.1, BA.2, and BA.5 in a population‐based cohort study in British Columbia, Canada

Russell

Klaver

Harrigan

et al. 2022

Journal of Medical Virology

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The SARS‐CoV‐2 variant Omicron emerged in late 2021. In British Columbia (BC), Canada, and globally, three genetically distinct subvariants of Omicron, BA.1, BA.2, and BA.5, emerged and became dominant successively within an 8‐month period. SARS‐CoV‐2 subvariants continue to circulate in the population, acquiring new mutations that have the potential to alter infectivity, immunity, and disease severity. Here, we report a propensity‐matched severity analysis from residents of BC over the course of the Omicron wave, including 39,237 individuals infected with BA.1, BA.2, or BA.5 based on paired high‐quality sequence data and linked to comprehensive clinical outcomes data between December 23, 2021 and August 31, 2022. Relative to BA.1, BA.2 cases were associated with a 15% and 28% lower risk of hospitalization and intensive care unit (ICU) admission (aHRhospital = 1.17; 95% confidence interval [CI] = 1.096–1.252; aHRICU = 1.368; 95% CI = 1.152–1.624), whereas BA.5 infections were associated with an 18% higher risk of hospitalization (aHRhospital = 1.18; 95% CI = 1.133–1.224) after accounting for age, sex, comorbidities, vaccination status, geography, and social determinants of health. Phylogenetic analysis revealed no specific subclades associated with more severe clinical outcomes for any Omicron subvariant. In summary, BA.1, BA.2, and BA.5 subvariants were associated with differences in clinical severity, emphasizing how variant‐specific monitoring programs remain critical components of patient and population‐level public health responses as the pandemic continues.

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Clinical severity of SARS-CoV-2 Omicron BA.4 and BA.5 lineages in South Africa

Cited by 9 publications

References 11 publications

Trends in Cases, Hospitalisation and Mortality Related to the Omicron BA.4/BA.5 Sub-Variants in South Africa

Trends in Cases, Hospitalisation and Mortality Related to the Omicron BA.4/BA.5 Sub-Variants in South Africa

Association of SARS-CoV-2 BA.4/BA.5 Omicron lineages with immune escape and clinical outcome

Clinical severity of Omicron subvariants BA.1, BA.2, and BA.5 in a population‐based cohort study in British Columbia, Canada

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