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Cited by 45SARS-CoV-2 and COVID-19 ResearchCOVID-19 epidemiological studiesCOVID-19 Clinical Research Studies

Rapidly shifting immunologic landscape and severity of SARS-CoV-2 in the Omicron era in South Africa

Open access
Sun, Kaiyuan, Tempia, Stefano, Kleynhans, Jackie, von Gottberg, Anne, McMorrow, Meredith L., Wolter, Nicole, Bhiman, Jinal N., Moyes, Jocelyn +18 more·2023·Nature Communications
DOI 10.1038/s41467-022-35652-0PMC PMC9842214
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Abstract

South Africa was among the first countries to detect the SARS-CoV-2 Omicron variant. However, the size of its Omicron BA.1 and BA.2 subvariants (BA.1/2) wave remains poorly understood. We analyzed sequential serum samples collected through a prospective cohort study before, during, and after the Omicron BA.1/2 wave to infer infection rates and monitor changes in the immune histories of participants over time. We found that the Omicron BA.1/2 wave infected more than half of the cohort population, with reinfections and vaccine breakthroughs accounting for > 60% of all infections in both rural and urban sites. After the Omicron BA.1/2 wave, we found few (< 6%) remained naïve to SARS-CoV-2 and the population immunologic landscape is fragmented with diverse infection/immunization histories. Prior infection with the ancestral strain, Beta, and Delta variants provided 13%, 34%, and 51% protection against Omicron BA.1/2 infection, respectively. Hybrid immunity and repeated prior infections reduced the risks of Omicron BA.1/2 infection by 60% and 85% respectively. Our study sheds light on a rapidly shifting landscape of population immunity in the Omicron era and provides context for anticipating the long-term circulation of SARS-CoV-2 in populations no longer naïve to the virus.

AI snapshot

Written from the paper’s full text.

TL;DR

In South African PHIRST-C household cohorts, the Omicron BA.1/2 wave infected 64.6% of the rural cohort and 58.1% of the urban cohort, far exceeding prior variant waves and driven mainly by reinfections or breakthrough infections. Omicron BA.1/2 was more transmissible than Delta and had a much lower estimated infection fatality ratio, though severity estimates were shaped by prior immunity, age patterns, and under-ascertainment.

Key findings

  • Omicron BA.1/2 infection attack rates were 64.6% (95% CI 60.4–68.9%) in the rural site and 58.1% (95% CI 53.4–62.8%) in the urban site, compared with pre-Omicron rural attack rates of 8.2% for D614G, 20.7% for Beta, and 38.7% for Delta, and urban attack rates of 25.8%, 32.1%, and 23.2%, respectively.
  • Reinfections dominated the Omicron BA.1/2 wave: primary infections accounted for only 37.9% (95% CI 32.5–43.3%) of Omicron infections in the rural site and 28.6% (95% CI 23.0–34.3%) in the urban site; after the wave, only 5.7% and 5.4% remained SARS-CoV-2 naïve.
  • Omicron BA.1/2 was more than twice as likely to transmit as Delta (odds ratio 2.36, 95% CI 2.12–2.63), while vaccine breakthroughs and reinfections were 41% less likely to transmit than primary infections (OR 0.59, 95% CI 0.46–0.73); repeat infections provided the strongest protection against Omicron (OR 0.15, 95% CI 0.08–0.24).
  • The estimated infection fatality ratio during the Omicron BA.1/2 wave in the urban site was 0.043% (95% CI 0.040–0.047%), lower than 0.15% for D614G, 0.36% for Beta, and 0.41% for Delta; surveillance captured only 0.84% of rural-site district infections and 1.31% of urban-site district infections.

Methods

  • Prospective PHIRST-C household cohorts enrolled 1,200 individuals in 222 randomly selected households across a rural site in Agincourt, Mpumalanga Province, and an urban site in Jouberton township, North West Province; ten serum specimens were collected from July 2020 through April 2022, with twice-weekly nasal swabs during intense follow-up from July 2020 to August 2021.
  • Omicron BA.1/2 infections were inferred serologically using the Roche Elecsys Anti-SARS-CoV-2 nucleocapsid assay at blood draws 8, 9, and 10, with the approach calibrated against rRT-PCR-confirmed Delta infections; the optimized boosting threshold was γ = 1.4, yielding a Youden’s J of 0.820 and sensitivity of 0.804 for reinfections.
  • A chain-binomial household transmission model was fitted jointly to Delta and Omicron serology-inferred infections among 905 participants with complete serum specimens, estimating variant-specific transmissibility, prior-exposure protection, age, sex, household size, HIV status, and community versus household acquisition; a sensitivity model with exponential waning estimated a protection half-life of 229 days (95% CI 150–389 days).

Limitations

  • The paper states that Omicron BA.1/2 infections were ascertained by serology without rRT-PCR confirmation, risking misclassification; the serologic approach was less sensitive for reinfections, so Omicron reinfections may be underestimated.
  • The paper states that lack of virologic samples prevented differentiation between Omicron BA.1 and BA.2, vaccination rates were low with limited sample size and wide confidence intervals for vaccine effects, and the study was geographically confined, limiting broader representativeness.
  • Evident from the text: the fourth-wave variant assignment assumed all infections were Omicron BA.1/2 based on timing, and IFR estimates relied on district-level in-hospital deaths plus cohort infection rates assumed representative of the urban population.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1038/s41467-022-35652-0

Cites

Statistics

Nothing to recompute.

Claims the paper makes

0 of 29 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    In the rural site, the infection attack rate for Delta was 38.7% (95% CI 34.3-43.1%).

    “In the rural site, infection rates for pre-Omicron variants were 8.2% (95% CI 5.7-11.0%)for D614G, 20.7% (95% CI 17.1-24.3%)for Beta and 38.7% (95% CI 34.3-43.1%)for Delta, with higher attack rates in each successive wave (Fig. 2A, left panel).”
    Quote in the paperNot a substantial claim
  • Findingown data

    At the end of the third wave, only 30.1% of the population remained naïve to SARS-CoV-2 in the rural site.

    “At the end of the third wave, only 30.1% and 22.0% of the population remained naïve to SARS-CoV-2 in the rural and the urban site, respectively.”
    Quote in the paperNot a substantial claim
  • Findingown data

    60.4% of individuals in the urban site had experienced more than one exposure, whether prior infection or vaccination, after the fourth epidemic wave.

    “52.1% of individuals in rural site and 60.4% in the urban site had experienced more than one exposure, whether prior infection or vaccination, after the fourth epidemic wave.”
    Quote in the paperSubstantial claim
  • Findingown data

    Reinfections were predominant with Omicron BA.1/2.

    “In contrast, reinfections were predominant with Omicron BA.1/2, with primary infections representing only 37.9% (95% CI 32.5-43.3%)and 28.6% (95% CI 23.0-34.3%) of all Omicron BA.1/2 infections in the rural and urban site, respectively (Fig. S5, right panels).”
    Quote in the paperSubstantial claim
  • Findingown data

    In the rural site, infection attack rates were higher in each successive pre-Omicron wave.

    “In the rural site, infection rates for pre-Omicron variants were 8.2% (95% CI 5.7-11.0%)for D614G, 20.7% (95% CI 17.1-24.3%)for Beta and 38.7% (95% CI 34.3-43.1%)for Delta, with higher attack rates in each successive wave (Fig. 2A, left panel).”
    Quote in the paperNot a substantial claim
  • May combine two claims. 19
  • The quote only partly states this claim. 5
  • Classified as probably not a substantial claim. 7

  • May combine two claims.

    Findingown data

    The Omicron BA.1/2 wave left behind a heterogeneous immunological landscape, with population subgroups characterized by distinct exposure histories, and no exposure category accounting for more than 25% of the population.

    “As a result, the Omicron BA.1/2 wave left behind a heterogeneous immunological landscape, with population subgroups characterized by distinct exposure histories, and no exposure category accounting for more than 25% of the population (Fig. 2C, D).”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Findingown data

    In the rural cohort, the Omicron BA.1/2 infection attack rate among individuals with repeated infections was 21.1% (4/19).

    “Repeated infections | 4/19 (21.1) | 10/37 (27.0)”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    The infection ascertainment rate was estimated at 0.84% in the rural site district and 1.31% in the urban site district, considerably lower than the ascertainment rates of prior waves, indicating that the surveillance system captured only a very small fraction of all Omicron BA.1/2 infections.

    “The infection ascertainment rate was estimated at 0.84% in the rural site district and 1.31% in the urban site district, considerably lower than the ascertainment rates of prior waves 10,11 , indicating that the surveillance system captured only a very small fraction of all Omicron BA.1/2 infections.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [10] Sun, K. et al. SARS-CoV-2 transmission, persistence of immunity, and estimates of Omicron’s impact in South African population cohorts. Sci. Transl. Med. eabo7081 (2022). source

      Not checked in the free run.

    • cites [11] Kleynhans, J. et al. SARS-CoV-2 Seroprevalence in a Rural and Urban Household Cohort during First and Second Waves of Infections, South Africa, July 2020-March 2021. Emerg. Infect. Dis. 27, 3020–3029 (2021). source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    After the third epidemic wave dominated by Delta, and prior to Omicron's emergence, more than 60% of the population at both sites had been infected by and/or vaccinated against SARS-CoV-2 at least once, with limited occurrence of reinfections.

    “After the third epidemic wave dominated by Delta, and prior to Omicron's emergence, more than 60% of the population at both sites had been infected by and/or vaccinated against SARS-CoV-2 at least once, with limited occurrence of reinfections (Fig. 2, Fig. S5).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingreasoning

    Mutations L452R and F486V have appeared in Omicron BA.4/5 lineages and these variants have now caused a fifth epidemic wave in South Africa.

    “Strikingly, mutations L452R and F486V have appeared in Omicron BA.4/5 lineages and these variants have now caused a fifth epidemic wave in South Africa.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Addition of a waning term decreased some of the variant-specific effects, but the trends remained the same, with the earlier variant generating less protection against Omicron than Delta.

    “While addition of a waning term decreased some of the variant-specific effects, the trends remained the same, with the earlier variant generating less protection against Omicron than Delta (Fig. S7).”
    Quote in the paperNot a substantial claim

  • May combine two claims. The quote only partly states this claim.

    Findingcitation

    The model with waning indicates a protection half-life of 229 days (95% CI 150-389 days), in line with the time scale of antibody waning described in other studies.

    “The model with waning also indicates a protection”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [18] Cohen, K. W. et al. Longitudinal analysis shows durable and broad immune memory after SARS-CoV-2 infection with persisting antibody responses and memory B and T cells. Cell Rep. Med 2, 100354 (2021). source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    Neither Janssen Ad26.COV2.S (1 dose) nor Pfizer-BioNTech BNT162b2 vaccination (1 or 2 doses) showed significant protection against Omicron.

    “Neither Janssen Ad26.COV2.S (1 dose) nor Pfizer-BioNTech BNT162b2 vaccination (1 or 2 doses) showed significant protection against Omicron (Fig. 3), despite > 90% being administered within 5 months of Omicron's emergence.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingreasoning

    Waning did not significantly improve model fit, likely because it conflated with the period when specific variants circulated.

    “Waning did not significantly improve model fit, likely because it conflated with the period when specific variants circulated.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    After the Omicron BA.1/2 epidemic wave in South Africa, only 5.7% and 5.4% of the cohort population remained naïve to SARS-CoV-2 in the rural and urban sites respectively, and past immune histories in the rest of the population were highly diverse.

    “After the Omicron BA.1/2 epidemic wave in South Africa, only 5.7% and 5.4% of the cohort population remained naïve to SARS-CoV-2 in the rural and urban sites respectively, and past immune histories in the rest of the population were highly diverse.”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Findingown data

    In the rural cohort, the Omicron BA.1/2 infection attack rate among individuals with hybrid immunity was 46.3% (19/41).

    “Hybrid immunity † | 19/41 (46.3) | 15/47 (31.9)”
    Quote in the paperNot a substantial claim

  • The quote only partly states this claim.

    Findingown data

    In the urban cohort, the Omicron BA.1/2 infection attack rate among individuals with repeated infections was 27.0% (10/37).

    “Repeated infections | 4/19 (21.1) | 10/37 (27.0)”
    Quote in the paperNot a substantial claim

  • The quote only partly states this claim.

    Findingown data

    In the urban cohort, the Omicron BA.1/2 infection attack rate among individuals with hybrid immunity was 31.9% (15/47).

    “Hybrid immunity † | 19/41 (46.3) | 15/47 (31.9)”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Of the 11 misclassified Delta primary infections, 2 had mis-classified trajectory.

    “Of the 11 misclassified Delta primary infections, 7 were non-responders measured by the Roche Elecsys Anti-SARS-CoV-2 nucleocapsid assay across all three blood draws, 2 were weak responders (highest readout < 10) and 2 had mis-classified trajectory.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    Prior work has demonstrated Omicron BA.1/2's significant immune escape properties.

    “Prior work has demonstrated Omicron BA. 1/2's significant immune escape properties [13][14][15][16][17] .”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [13] Altarawneh, H. N. et al. Effects of previous infection and vaccination on symptomatic omicron infections. N. Engl. J. Med. 387, 21–34 (2022). source

      Not checked in the free run.

    • cites [14] Andrews, N., Stowe, J., Kirsebom, F., Toffa, S. & Rickeard, T. Covid-19 vaccine effectiveness against the Omicron (B.1.1.529) Variant. N. Engl. J. Med. 386, 1532–1546 (2022). source

      Not checked in the free run.

    • cites [15] Richardson, S. I. et al. SARS-CoV-2 Omicron triggers cross-reactive neutralization and Fc effector functions in previously vaccinated, but not unvaccinated, individuals. Cell Host Microbe 30, 880-886.e4–886.e4 (2022). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    This observation is in line with the finding of a durable immune protection conferred by prior infection and vaccination in the pre-Omicron era.

    “This observation is in line with the finding of a durable immune protection conferred by prior infection and vaccination in the pre-Omicron era 10 .”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [10] Sun, K. et al. SARS-CoV-2 transmission, persistence of immunity, and estimates of Omicron’s impact in South African population cohorts. Sci. Transl. Med. eabo7081 (2022). source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductown data

    The analysis was performed on a subset of 905 of 1200 cohort participants with complete serum specimens collected during the relevant Delta and Omicron periods.

    “The analysis was performed on a subset of 905 of 1200 cohort participants with complete serum specimens collected during the relevant Delta and Omicron periods.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    This suggests a transmission reduction effect of prior immunity, in line with other findings.

    “Vaccine breakthroughs and reinfections were 41% less likely to transmit than primary infections (odds ratio 0.59, 95% CI 0.46-0.73),suggesting a transmission reduction effect of prior immunity, in line with other findings 12 .”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [12] Prunas, O. et al. Vaccination with BNT162b2 reduces transmission of SARS-CoV-2 to household contacts in Israel. Science 375, 1151–1154 (2022). source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductown data

    <5% of participants (43/905) had received a complete vaccine schedule before Omicron, resulting in limited statistical power and wide confidence intervals on the effects of vaccination.

    “It is also worth noting that < 5% of participants (43/ 905, Table 1) had received a complete vaccine schedule before Omicron, resulting in limited statistical power and wide confidence intervals on the effects of vaccination.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    Reinfections and vaccine breakthrough infections accounted for the majority of Omicron BA.1/2 infections, likely attributable to a minority of population remaining naïve prior to the Omicron BA.1/2 wave and to Omicron BA.1/2's immune-escape properties.

    “Reinfections and vaccine breakthrough infections accounted for the majority of Omicron BA.1/2 infections, likely attributable to a minority of population remaining naïve prior to the Omicron BA.1/2 wave and to Omicron BA.1/2's immune-escape properties 16,21,22 .”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [16] Cele, S., Jackson, L., Khoury, D. S., Khan, K. & Moyo-Gwete, T. Omicron extensively but incompletely escapes Pfizer BNT162b2 neutralization. Nature https://doi.org/10.1038/s41586-021-04387-1 (2021). source

      Not checked in the free run.

    • cites [21] Cao, Y. et al. Omicron escapes the majority of existing SARS-CoV-2 neutralizing antibodies. Nature 602, 657–663 (2022). source

      Not checked in the free run.

    • cites [22] McCallum, M. et al. Structural basis of SARS-CoV-2 Omicron immune evasion and receptor engagement. Science 375, 864–868 (2022). source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Relaxing nonpharmaceutical interventions during the Omicron wave likely also contributed to the higher infection risk during the Omicron BA.1/2 wave (vs. Delta wave), as prior to the 4th epidemic wave (October 1, 2021), the national COVID-19 measures were tuned down to Alert Level 1, the lowest level in South Africa's COVID-19 alert system.

    “However, relaxing nonpharmaceutical interventions during the Omicron wave likely also contributed to the higher infection risk during the Omicron BA.1/2 wave (vs.Delta wave), as prior to the 4th epidemic wave (October 1, 2021), the national COVID-19 measures were tuned down to Alert Level 1, the lowest level in South Africa's COVID-19 alert system 24 .”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] About alert system. https://www.gov.za/covid-19/about/about-alert-system.

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    These findings support that the fitness advantage of Omicron BA.1/2 over Delta was not solely due to immune escape but also higher intrinsic transmissibility.

    “These findings support that the fitness advantage of Omicron BA.1/2 over Delta was not solely due to immune escape but also higher intrinsic transmissibility 23 .”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [23] Pearson, C. A. B. et al. Bounding the levels of transmissibility & immune evasion of the Omicron variant in South Africa. bioRxiv https://doi.org/10.1101/2021.12.19.21268038 (2021). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    Several studies have demonstrated that the antibody response after Omicron BA.1 breakthrough infection is dominated by recall memory B-cells against conserved epitopes shared between pre-Omicron strains and Omicron BA.1/2.

    “Several studies have demonstrated that the antibody response after Omicron BA.1 breakthrough infection is dominated by recall memory B-cells against conserved epitopes shared between pre-Omicron strains and Omicron BA.1/2.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationcitation

    Among individuals that were primed by different types of pre-Omicron variants or vaccines, differences in antibody responses are also expected, though they would be less prominent than the differences between individuals primed by the Omicron vs. pre-Omicron variants.

    “Among individuals that were primed by different types of pre-Omicron variants or vaccines, differences in antibody responses are also expected, though they would be less prominent than the differences between individuals primed by the Omicron vs. pre-Omicron variants 28 .”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [28] Allison J.Greaney, Tyler N. Starr, Jesse Bloom, Escape calculator for SARS-CoV-2 RBD. Escape calculator for SARS-CoV-2 RBD. https://jbloomlab.github.io/SARS2_RBD_Ab_escape_maps/escape-calc/.

      Not checked in the free run.

  • May combine two claims.

    Study design and conductcitation

    A unique feature of the cohort populations includes intense monitoring since the first SARS-CoV-2 epidemic wave, with nasal swab collection at a twice weekly frequency, combined with frequent serum specimen collection.

    “A unique feature of our cohort populations includes intense monitoring since the first SARS-CoV-2 epidemic wave, with nasal swab collection at a twice weekly frequency, combined with frequent serum specimen collection 10 .”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [10] Sun, K. et al. SARS-CoV-2 transmission, persistence of immunity, and estimates of Omicron’s impact in South African population cohorts. Sci. Transl. Med. eabo7081 (2022). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    Variations in the intrinsic severity of each variant would also impact the observed variations in IFRs across different epidemic waves.

    “Finally, each epidemic wave was dominated by a different variant (Fig. 4F), and variations in the intrinsic severity of each variant would also impact the observed variations in IFRs across different epidemic waves.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    Prior immunity has an important role in shaping IFR, with the fraction of primary infections decreasing with each new epidemic wave, from 100% during the 1st wave to 93%, and 73% and 28% during the Beta (2nd) and Delta (3rd) and Omicron BA.1/2 (4th) waves.

    “Prior immunity has an important role in shaping IFR, with the fraction of primary infections decreasing with each new epidemic wave, from 100% during the 1st wave to 93%, and 73% and 28% during the Beta (2nd) and Delta (3rd) and Omicron BA.1/2 (4th) waves (Fig. 4D).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    These two population groups primed by different antigens will likely have different antibody responses as the sera of individuals primed by pre-Omicron variants or vaccines poorly neutralize the Omicron BA.1/2 variant and vice versa.

    “These two population groups primed by different antigens will likely have different antibody responses as the sera of individuals primed by pre-Omicron variants or vaccines poorly neutralize the Omicron BA.1/2 variant and vice versa 26,27 .”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [26] Rössler, A., Knabl, L., von Laer, D. & Kimpel, J. Neutralization Profile after Recovery from SARS-CoV-2 Omicron Infection. N. Engl. J. Med. 386, 1764–1766 (2022). source

      Not checked in the free run.

    • cites [27] Mykytyn, A.Z. et al. Antigenic cartography of SARS-CoV-2 reveals that Omicron BA.1 and BA.2 are antigenically distinct. Sci. Immunol. eabq4450 (2022). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

    Interpretationreasoning

    With each new variant wave, and vaccine reformulation anticipated for later in 2022, imprinting could play a role in shaping future disease trajectories.

    “With each new variant wave, and vaccine reformulation anticipated for later in 2022, imprinting could play a role in shaping future disease trajectories.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    As SARS-CoV-2 moves into the endemic phase, multiple antigen exposures will become the norm, and these complex exposure histories will define population immune pressure to select new variants.

    “As SARS-CoV-2 moves into the endemic phase, multiple antigen exposures will become the norm, and these complex exposure histories will define population immune pressure to select new variants.”
    Quote in the paperSubstantial claim
30 of 30

  • The authors state this as an assumption.

    The Omicron wave prior to blood draw 10 consisted of BA.1 and BA.2 subvariants.

    “Since in South Africa, Omicron BA.4 and BA.5 only started to rise at April, 2022 8 , we assume the Omicron wave prior to BD 10 were BA.1 and BA.2 subvariants.”

  • The paper relies on this without support.

    The urban site of the study is more representative of South Africa's urbanized population than the rural site.

    “In Fig. 4A, we estimate the infection fatality ratio (IFR) of each epidemic wave in the urban site of the study, which is more representative of South Africa's urbanized population.”

  • The authors state this as an assumption.

    The waning rate is constant for all types of prior exposures.

    “We assume a constant waning rate for all types of prior exposures; thus”

  • The authors state this as an assumption.

    All infections during the 4th wave were due to Omicron BA.1/2 variants.

    “*For the 4th wave, we could not confirm variant type by variant-specific rRT-PCR or sequencing, however, judging from the timing of emergence and dominance of Omicron in South Africa in late November 2021, we assumed here that all infections during the 4th wave were due to Omicron BA.1/2 variants.”

  • The authors state this as an assumption.

    The urban cohort population is representative of the population of the North West Province.

    “C The infection attack rate of each epidemic wave in the North West based on the PHIRST-C urban cohort, assuming that the urban cohort population is representative of the population of the North West Province.”
5 of 5

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Rural cohort size differs between sections

    Minor

    The Results report 643 individuals enrolled at the rural site, while the Methods describe the same 114-household rural cohort as having 638 participants. The Methods site counts also total 1,195, rather than the reported enrollment of 1,200.

  • Incorrect attack rate for the urban unknown-HIV-status group

    Minor

    Six infections among 11 participants give an attack rate of 54.5%, not 58.2%.

    Reported 58.2 · recomputed 54.545455

  • Less-than-1% surveillance claim conflicts with the urban estimate

    Minor

    The Discussion says routine surveillance captured less than 1% of infections, but the Results estimate ascertainment at 1.31% in the urban site district.

  • Conflicting blood-draw matching descriptions

    Minor

    One Methods passage pairs Omicron blood draws 8, 9 and 10 with Delta blood draws 5, 6 and 8, respectively. A later passage instead says blood draw 8 matches both blood draws 5 and 10.

4 of 4

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References 45 · Cited by 45

Research works printed but not linked: 1

  1. Nocedal, J., Wright, S. J. Numerical Optimization (Springer New York).

Authors
Sun, K., Tempia, S., Kleynhans, J., von Gottberg, A., McMorrow, M. L., Wolter, N., Bhiman, J. N., Moyes, J., Carrim, M., Martinson, N. A., Kahn, K., Lebina, L., du Toit, J. D., Mkhencele, T., Viboud, C., Cohen, C., the PHIRST-C group, Buys, A., de Gouveia, L., du Plessis, M., Gómez-Olivé, F. X., Kgasago, K. P., Kotane, R., Moloantoa, T., Tollman, S., & Wafawanaka, F.
Affiliations
  • National Institutes of Health (US)
  • National Health Laboratory Service (ZA)
  • Centers for Disease Control and Prevention (US)
  • Johns Hopkins University (US)
  • University of the Witwatersrand (ZA)
Corresponding author
  • Sun, Kaiyuan
  • Cohen, Cheryl
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2023-01-16
Volume
14
Issue
1
Pages
246-246
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-022-35652-0
PMC
PMC9842214
OpenAlex
W4316506872
Cited by
45
References
45
Citations by year
2026: 4 · 2025: 11 · 2024: 16 · 2023: 13 · 2022: 1
FWCI
9.11
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • medRxiv (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by-nc-nd)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Wellcome Trust (221003/Z/20/Z)
  • National Health Laboratory Service (221003/Z/20/Z)
  • Foreign, Commonwealth and Development Office
  • National Institutes of Health
  • Centers for Disease Control and Prevention (6 U01IP001048, U01IP001048)
Topics
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
  • Physical Sciences › Mathematics › Modeling and Simulation › COVID-19 epidemiological studies
  • Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
Keywords
Omicron variant, herd immunity, reinfection, vaccine breakthrough infection, hybrid immunity, prior SARS-CoV-2 infection, COVID-19 severity, South Africa, seroprevalence, Delta variant, Beta variant

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-06.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-06.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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