Clinical Severity of COVID-19 Patients Admitted to Hospitals in Gauteng, South Africa During the Omicron-Dominant Fourth Wave

Jassat, Waasila; Karim, Salim Abdool; Mudara, Caroline; Welch, Richard; Ozougwu, Lovelyn; Groome, Michelle; Govender, Nevashan; Gottberg, Anne von; Wolter, Nicole; Group, DATCOV Author; Blumberg, Lucille

doi:10.2139/ssrn.3996320

Cited by 44 publications

(54 citation statements)

References 7 publications

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“…Our findings concur with current literature reporting less severe disease associated with Omicron vs. other variants of concern and previous waves (16)(17)(18)(19)(20)32). For example, cases with presumed Omicron infection (identified with S-gene target failure on PCR) were less likely to be admitted to hospital and experience severe outcomes compared to those with delta infections (18,19,21) and fewer admissions with less severe outcomes among those hospitalized have been reported in the fourth wave compared to previous waves in South Africa (16,17).…”

Section: Discussionsupporting

confidence: 93%

“…While there is emerging biological evidence of possible lower virulence of Omicron compared to previous variants due to modified cell entry mechanisms and preferential replication in bronchi rather than the lung parenchyma (6,7,14,15), even a virus resulting in is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) similar or lower clinical severity to earlier variants could overwhelm health services if protection conferred by prior COVID-19 infection and/or SARS-CoV-2 vaccination against severe disease is reduced. While there are now several reports from South Africa and other countries of reduced risk of severe disease in the fourth wave and in patients infected with Omicron compared to Delta (16)(17)(18)(19)(20)(21) in the context of a high seroprevalence setting such as South Africa, with moderate SARS-CoV-2 vaccination coverage (39% and 46% of adults fully vaccinated in South Africa and the Western Cape respectively by end December 2021) (22), it is important to establish whether protection against severe disease conferred by prior infection and/or vaccination is maintained against Omicron. Furthermore, to what extent does such protection account for milder clinical presentation of Omicron cases versus inherent differences in virulence of Omicron itself compared to previous variants?…”

Section: Introductionmentioning

confidence: 99%

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Outcomes of laboratory-confirmed SARS-CoV-2 infection in the Omicron-driven fourth wave compared with previous waves in the Western Cape Province, South Africa

Davies

Kassanjee

Rousseau³

et al. 2022

Preprint

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Objectives: We aimed to compare COVID-19 outcomes in the Omicron-driven fourth wave with prior waves in the Western Cape, the contribution of undiagnosed prior infection to differences in outcomes in a context of high seroprevalence due to prior infection, and whether protection against severe disease conferred by prior infection and/or vaccination was maintained. Methods: In this cohort study, we included public sector patients aged ≥20 years with a laboratory confirmed COVID-19 diagnosis between 14 November-11 December 2021 (wave four) and equivalent prior wave periods. We compared the risk between waves of the following outcomes using Cox regression: death, severe hospitalization or death and any hospitalization or death (all ≤14 days after diagnosis) adjusted for age, sex, comorbidities, geography, vaccination and prior infection. Results: We included 5,144 patients from wave four and 11,609 from prior waves. Risk of all outcomes was lower in wave four compared to the Delta-driven wave three (adjusted Hazard Ratio (aHR) [95% confidence interval (CI)] for death 0.27 [0.19; 0.38]. Risk reduction was lower when adjusting for vaccination and prior diagnosed infection (aHR:0.41, 95% CI: 0.29; 0.59) and reduced further when accounting for unascertained prior infections (aHR: 0.72). Vaccine protection was maintained in wave four (aHR for outcome of death: 0.24; 95% CI: 0.10; 0.58). Conclusions: In the Omicron-driven wave, severe COVID-19 outcomes were reduced mostly due to protection conferred by prior infection and/or vaccination, but intrinsically reduced virulence may account for an approximately 25% reduced risk of severe hospitalization or death compared to Delta.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Outcomes of laboratory-confirmed SARS-CoV-2 infection in the Omicron-driven fourth wave compared with previous waves in the Western Cape Province, South Africa

Davies

Kassanjee

Rousseau³

et al. 2022

Preprint

Self Cite

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“…It is becoming increasingly apparent that the evolutionary processes that yielded BA.1 involved balancing multiple fitness trade-offs: (1) between immune escape 6,9,26,49,50 and affinity for human and/or animal ACE2 proteins [7][8][9][10]30 ; (2) between efficient proteolytic priming with TMPRSS2 which expedites cellular entry via the cell surface [6][7][8] and increased resistance to endosomal restriction factors (such as IFITM proteins) which enable more efficient cellular entry via the endocytic route 7 ; (3) between preferred tropism for cells in the upper respiratory tract and preferred tropism for cells in the lower respiratory tract 7,8 , and (4) between increased propensity for Spike monomers to switch from the down to up configurations and overall Spike trimer stability 37,39 . Fortunately, the collection of mutations in BA.1 appear at present to have tilted the balance of these and other trade-offs towards the virus having decreased clinical severity in humans 51,52 .…”

Section: Discussionmentioning

confidence: 99%

Selection analysis identifies unusual clustered mutational changes in Omicron lineage BA.1 that likely impact Spike function

Martin

Lytras

Lucaci

et al. 2022

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Among the 30 non-synonymous nucleotide substitutions in the Omicron S-gene are 13 that have only rarely been seen in other SARS-CoV-2 sequences. These mutations cluster within three functionally important regions of the S-gene at sites that will likely impact (i) interactions between subunits of the Spike trimer and the predisposition of subunits to shift from down to up configurations, (ii) interactions of Spike with ACE2 receptors, and (iii) the priming of Spike for membrane fusion. We show here that, based on both the rarity of these 13 mutations in intrapatient sequencing reads and patterns of selection at the codon sites where the mutations occur in SARS-CoV-2 and related sarbecoviruses, prior to the emergence of Omicron the mutations would have been predicted to decrease the fitness of any virus within which they occurred. We further propose that the mutations in each of the three clusters therefore cooperatively interact to both mitigate their individual fitness costs, and, in combination with other mutations, adaptively alter the function of Spike. Given the evident epidemic growth advantages of Omicron over all previously known SARS-CoV-2 lineages, it is crucial to determine both how such complex and highly adaptive mutation constellations were assembled within the Omicron S-gene, and why, despite unprecedented global genomic surveillance efforts, the early stages of this assembly process went completely undetected.

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“…During November 2021, a new variant of concern, Omicron was reported to WHO (first reported from South Africa on 24 November 2021) 9 . Unlike previous VOC, Omicron shows a relatively lower case-fatality rate although the variant has a high transmissibility 10,11 .…”

Section: Introductionmentioning

confidence: 88%

The Global case-fatality rate of COVID-19 has been declining disproportionately between top vaccinated countries and the rest of the world

Haider

Hasan

Khan

et al. 2022

Preprint

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Globally 58.83% human population received at least one dose of the COVID-19 vaccines as of 5 January 2021. COVID-19 vaccination rollout is progressing at varied rates globally and data on the impact of mass vaccination on infection and case-fatality rates require definition. We compared the global reported cumulative case-fatality rate (rCFR) between top-20 countries with COVID-19 vaccination rates (>125 doses/100 people) and the rest of the world, before and after commencement of vaccination programmes. We considered the 28th day of receiving the first vaccine in the world as a cut-off to compare the pre-vaccine period (Jan 1, 2020 - Jan 5, 2021) and the post-vaccine period (Jan 6, 2021 - Jan 5, 2022). We used a Generalized linear mixed model (GLMM) with a beta distribution to investigate the association between the CFR and potential predictors of each country and reported the relative risk (RR) of each variable. The mean rCFR of COVID-19 in the top-20 countries with vaccination rates was 1.83 (95% CI: 1.24-2.43) on 5 Jan 2021 and 1.18 (95% CI: 0.73-1.62) on 5 Jan 2022. The CFR for the rest of the world on 5 Jan 2021 was 2.32 (95% CI: 1.86-2.79) and 2.20 (95% CI: 1.86-2.55) on 5 January 2022. In Sub-Saharan Africa, the CFR remained roughly unchanged at 1.97 (95% CI: 1.59-2.35) on 5 Jan 2021 and 1.98 (95% CI:1.58-2.37) on 5 Jan 2022. The GLMM showed vaccination (/100 population) (RR:0.37) and Stringency Index (RR:0.88) were strong protective factors for the country's COVID-19 CFR indicating that both vaccination and lockdown measures help in the reduction of COVID-19 CFR. The rCFR of COVID-19 continues to decline, although at a disproportionate rate between top vaccinated countries and the rest of the world. Vaccine equity and faster roll-out across the world is critically important in reducing COVID-19 transmission and CFR.

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Clinical Severity of COVID-19 Patients Admitted to Hospitals in Gauteng, South Africa During the Omicron-Dominant Fourth Wave

Cited by 44 publications

References 7 publications

Outcomes of laboratory-confirmed SARS-CoV-2 infection in the Omicron-driven fourth wave compared with previous waves in the Western Cape Province, South Africa

Outcomes of laboratory-confirmed SARS-CoV-2 infection in the Omicron-driven fourth wave compared with previous waves in the Western Cape Province, South Africa

Selection analysis identifies unusual clustered mutational changes in Omicron lineage BA.1 that likely impact Spike function

The Global case-fatality rate of COVID-19 has been declining disproportionately between top vaccinated countries and the rest of the world

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