Clinical severity of SARS-CoV-2 Omicron BA.4 and BA.5 lineages compared to BA.1 and Delta in South Africa

Wolter, Nicole; Jassat, Waasila; Walaza, Sibongile; Welch, Richard; Moultrie, Harry; Groome, Michelle; Amoako, Daniel G.; Everatt, Josie; Bhiman, Jinal N.; 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, Jeannette; Hussey, Hannah; Davies, Mary‐Ann; Boulle, Andrew; Gottberg, Anne von; Cohen, Cheryl

doi:10.1038/s41467-022-33614-0

Cited by 74 publications

(66 citation statements)

References 18 publications

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“…During the first weeks following BA.4/BA.5 emergence in South Africa, BA.4/BA.5 infections did not differ in severity from BA.1 infections, although statistical power in these analyses was constrained ( n =1,806 BA.4/BA.5 cases analyzed) and data on cases’ clinical comorbidities and healthcare-seeking behavior were not available to fully support causal inference addressing the role of infecting variant. 9 Consistent with this finding, risk of hospital admission during the BA.4/BA.5 and BA.1 waves in South Africa did not differ within analyses of all diagnosed cases. 23 Whereas a population-based study in Denmark suggested moderately increased risk of hospital admission among BA.5 cases as compared to BA.2 cases, 21 this analysis did not include adjustment for potentially relevant confounders including individuals’ healthcare-seeking behavior and calendar time.…”

Section: Discussionsupporting

confidence: 70%

“…As BA.4/BA.5 lineages harbor the Δ69-70 amino acid deletion in the S protein, SGTF has been proposed elsewhere as a proxy for distinguishing BA.4/BA.5 from BA.2 lineages. 9,10 Analyses of a randomly selected subset of SARS-CoV-2 specimens submitted for whole-genome sequencing supported this approach, with the S gene target identified in 97.7% (2,600/2,660) of BA.2 specimens and absent from 99.4% (347/349) of BA.4 specimens and 97.5% (977/1,002) of BA.5 specimens.…”

Section: Methodsmentioning

confidence: 85%

“…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, leading to persisting clinical burden and extended timetables for implementation of COVID-19 mitigation measures. Although not associated with enhanced severity or risk of breakthrough infection after vaccination or natural infection, 4,9 the BA.2 lineage 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.…”

mentioning

confidence: 90%

“…[4][5][6][7] Thus, whereas expansion of the Omicron variant was associated with surges in COVID-19 hospitalizations and deaths, the proportion of Omicron cases resulting in severe illness has been lower than that experienced with prior variants and during periods with lower population-level immunity 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, leading to persisting clinical burden and extended timetables for implementation of COVID-19 mitigation measures. Although not associated with enhanced severity or risk of breakthrough infection after vaccination or natural infection, 4,9 the BA.2 lineage 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.…”

mentioning

confidence: 92%

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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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Section: Discussionsupporting

confidence: 70%

Section: Methodsmentioning

confidence: 85%

mentioning

confidence: 90%

mentioning

confidence: 92%

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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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“…These results indicate that, compared with the initial BA.1, BA.5 has increased viral fitness without increasing disease severity. Our results are in agreement with the clinical observations that (i) BA.1- and BA.5-infected patients develop similar disease severity and (ii) Omicron causes less severe disease than the previous Delta variant (Wolter et al, 2022). The reduced disease severity of Omicron infection may be caused by the lower cell-to-cell fusion activity mediated by the Omicron S protein (Du et al, 2022; Meng et al, 2022).…”

Section: Discussionsupporting

confidence: 92%

Cross-neutralization and viral fitness of SARS-CoV-2 Omicron sublineages

Xia

Yeung

Kalveram

et al. 2022

Preprint

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The rapid evolution of SARS-CoV-2 Omicron sublineages mandates a better un-derstanding of viral replication and cross-neutralization among these sublineages. Here we used K18-hACE2 mice and primary human airway cultures to examine the viral fit-ness and antigenic relationship among Omicron sublineages. In both K18-hACE2 mice and human airway cultures, Omicron sublineages exhibited a replication order of BA.5 ≥ BA.2 ≥ BA.2.12.1 > BA.1; no difference in body weight loss was observed among differ-ent sublineage-infected mice. The BA.1-, BA.2-, BA.2.12.1-, and BA.5-infected mice de-veloped distinguisable cross-neutralizations against Omicron sublineages, but exhibited little neutralization against the index virus (i.e., USA-WA1/2020) or the Delta variant. Surprisingly, the BA.5-infected mice developed higher neutralization activity against heterologous BA.2 and BA.2.12.1 than that against homologous BA.5; serum neutralizing titers did not always correlate with viral replication levels in infected animals. Our results reveal distinct antigenic cartography of Omicron sublineages and support the bivalent vaccine approach.

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Neurological diagnoses in hospitalized COVID‐19 patients during the B.1.1.529 surge

Kim

Sardar

Ayele

et al. 2023

Ann Clin Transl Neurol

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ObjectiveEmerging variants and sublineages of SARS‐CoV‐2 have differing disease severity, transmissibility, and immune evasion. The neurological conditions associated with the original strain of SARS‐CoV‐2 are well established. Our study assessed the neurological presentations specific to hospitalized patients during the B.1.1.529 (Omicron) variant surge in New York City.MethodsA total of 178 cases with positive RT‐PCR result within 6 weeks before admission, and subsequent development of select neurological conditions during the SARS‐CoV‐2 B.1.1.529 (Omicron) surge between December 1, 2021 and February 28, 2022, were included from 12,800 SARS‐CoV‐2‐positive hospital admissions. Clinical data from acute hospitalizations were compared to findings of inpatient neurological cases with COVID‐19 infections from the initial surge in NYC in the same hospital system.ResultsCompared to SARS‐CoV‐2 infections of the original strain, COVID‐19 cases hospitalized during the Omicron surge (B.1.1.529) were associated with incidental and/or asymptomatic COVID‐19 cases (96, 53.9%) and an increased incidence of pre‐existing neurological and immunocompromising conditions. Encephalopathy, seizures, and stroke remained the most prevalent neurological conditions identified in hospitalized COVID‐19 cases during the study period, reflecting a similar distribution of neurological presentations associated with the original strain.InterpretationIn our cohort of 178 admitted SARS‐CoV‐2‐positive patients with select neurological conditions during the Omicron B.1.1.529 surge, 54% of COVID‐19 cases were considered incidental and/or asymptomatic, and the identified neurological conditions resembled those associated with the original SARS‐CoV‐2 strain. Further studies characterizing neurological presentation in Omicron sublineages and other variants are warranted in an ongoing COVID‐19 pandemic.

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Clinical severity of SARS-CoV-2 Omicron BA.4 and BA.5 lineages compared to BA.1 and Delta in South Africa

Cited by 74 publications

References 18 publications

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

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

Cross-neutralization and viral fitness of SARS-CoV-2 Omicron sublineages

Neurological diagnoses in hospitalized COVID‐19 patients during the B.1.1.529 surge

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