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

Lewnard, Joseph A; Hong, Vennis; Tartof, Sara Y

doi:10.1101/2022.07.31.22278258

Cited by 15 publications

(21 citation statements)

References 38 publications

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“…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). In other settings such as the United States, a higher risk of breakthrough infection with Omicron BA.4 or BA.5 was observed among previously vaccinated or infected individuals, indicating greater immune escape, but these breakthrough infections were associated with low severity (17). Cell-mediated immunity likely contributed to the lower levels of hospitalisation and mortality in the Omicron BA.4/BA.5 wave (22).…”

Section: Discussionmentioning

confidence: 99%

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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: Discussionmentioning

confidence: 99%

“…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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“…First, whereas the EPIC-HR trial was conducted during the Delta (B.1.617.2) wave, our study confirms high effectiveness of nirmatrelvir-ritonavir in a period when most treated cases were likely infected with BA.4/BA.5 Omicron lineages. 15 Second, the EPIC-HR trial included only individuals who had no history of confirmed SARS-CoV-2 infection and who had never received a COVID-19 vaccine. Our study, however, showed a significant further benefit of treatment for preventing hospitalization in a cohort where 94% of recipients had received ≥1 COVID-19 vaccine dose, and 77% had received ≥3 doses.…”

Section: Discussionmentioning

confidence: 99%

“…Diagnosis codes used to define ARI-associated hospital admissions are listed in Table S1. (15,20) 42 (41, 43) 53.9 (-8.4, 81.0) Treatment effectiveness is measured as (1 − adjusted hazard ratio) × 100%, comparing outcomes among individuals who received treatment to those who did not. Time at risk is measured from treatment dispense date, for treatment recipients, and from an equivalent number of days following testing for non-recipients.…”

Section: Data Sharing Statementmentioning

confidence: 99%

“…[7][8][9][10][11][12] However, these studies have lacked sufficient statistical power to demonstrate effectiveness in other subpopulations that are at relatively low risk of severe illness; have been undertaken in contexts where access to treatment is relatively limited; and have lacked data describing patients' clinical status, including time from symptom onset, which may inform clinical decision-making around prescribing nirmatrelvir-ritonavir. 13 While data from the United States have identified that COVID-19 related emergency department (ED) presentations and hospital admissions are infrequent among patients receiving nirmatrelvir-ritonavir in ambulatory care settings, 14,15 systematic assessments of effectiveness are lacking. We therefore aimed to measure the effectiveness of nirmatrelvir-ritonavir in preventing severe outcomes of SARS-CoV-2 infection among cases ascertained via outpatient testing within a large, integrated US healthcare system.…”

Section: Introductionmentioning

confidence: 99%

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Effectiveness of nirmatrelvir-ritonavir against hospital admission or death: a cohort study in a large US healthcare system

Lewnard

Malden

Hong

et al. 2022

Preprint

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Background: In the United States, oral nirmatrelvir-ritonavir (PaxlovidTM) is authorized for use among patients aged ≥12 years with mild-to-moderate SARS-CoV-2 infection who are at risk for progression to severe COVID-19, including hospitalization. However, effectiveness under real-world conditions has not been well established. Methods: We undertook a matched, observational cohort study of non-hospitalized individuals with SARS-CoV-2 infection to compare outcomes between those who received or did not receive nirmatrelvir-ritonavir within the Kaiser Permanente Southern California healthcare system. Individuals were matched on testing date, age, sex, treatment/care setting, symptoms status (including presence or absence of acute COVID-19 symptoms at testing, and time from symptom onset to testing), history of vaccination and SARS-CoV-2 infection, Charlson comorbidity index, and prior-year healthcare utilization. Time to hospital admission was compared between matched COVID-19 cases who received or did not receive nirmatrelvir-ritonavir. Primary analyses evaluated treatment effectiveness against any hospital admission and acute respiratory infection (ARI)-associated hospital admission, with dispense occurring 0-5 days symptom onset. Secondary analyses evaluated effectiveness against the same endpoints for all treatment dispenses. We measured treatment effectiveness as (1-adjusted hazards ratio [aHR])*100%, estimating the aHR via Cox proportional hazards models accounting for match strata and additional patient characteristics. Results: Analyses included 4,329 nirmatrelvir-ritonavir recipients and 20,980 matched non-recipients who were followed ≥30 days after a positive SARS-CoV-2 outpatient test. Overall, 23,603 (93.3%) and 19,564 (78.1%) of 25,039 participants had received ≥2 and ≥3 COVID-19 vaccine doses, respectively. A total of 23,858 (94.2% of 25,039) patients were symptomatic at the point of testing, with a 2.1 day mean time from symptom onset to testing. For patients dispensed nirmatrelvir-ritonavir 0-5 days after symptom onset, effectiveness in preventing all hospital admissions was 88.1% (95% confidence interval: 49.0-97.5%) over 15 days and 71.9% (25.3-90.0%) over 30 days, respectively. Effectiveness in preventing ARI-associated hospital admissions was 88.3% (12.9-98.8%) and 87.3% (18.3-98.5%) over 15 and 30 days, respectively. In expanded analyses that included patients receiving treatment at any point during their clinical course, effectiveness was 86.6% (54.9-96.3%) and 78.0% (46.2-91.4%) in preventing all hospital admissions over 15 and 30 days, respectively, and 93.7% (52.5-99.4%) and 92.8% (53.9-99.1%) in preventing ARI-associated hospital admissions over 15 and 30 days. Subgroup analyses identified similar effectiveness estimates among patients who had received ≥2 COVID-19 vaccine doses. Implications: In a real-world setting with high levels of COVID-19 vaccine and booster uptake, receipt of nirmatrelvir-ritonavir 0-5 days after symptom onset was associated substantial reductions in risk of hospital admission among individuals testing positive for SARS-CoV-2 infection in outpatient settings.

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SARS‐CoV‐2 Omicron (BA.4, BA.5) variant: Lessons learned from a new variant during the COVID‐19 pandemic

Erabi,

Faridzadeh,

Parvin

et al. 2024

Health Science Reports

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Background and AimIn late 2021, the world faced the rapid spread of the SARS‐CoV‐2 Omicron variant, which quickly became the variant of concern. In April 2022, two new lineages of Omicron (BA.4/BA.5) emerged from Africa, where they caused the fifth wave of infection.MethodWe searched PubMed, Google Scholar, and Scopus online databases up to December 2023 for founding relevant studies.ResultsBA.4 and BA.5 subgroups, with changes in the spike protein, have a greater ability to escape from the immune system, which was possible with the help of L452R and F486V mutations. Epidemiologically, these evolving subtypes show similarities to seasonal influenza but with higher mortality rates. The symptoms of these subgroups are different from the previous types in the form of upper respiratory symptoms. Antiviral treatments, the use of antibodies such as bebtelovimab, and the development of vaccines are promising.ConclusionConsequently, we must continue to be vigilant in our joint surveillance efforts against COVID‐19 in diagnosis and treatment.

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

Cited by 15 publications

References 38 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

Effectiveness of nirmatrelvir-ritonavir against hospital admission or death: a cohort study in a large US healthcare system

SARS‐CoV‐2 Omicron (BA.4, BA.5) variant: Lessons learned from a new variant during the COVID‐19 pandemic

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