Using proxy markers from routine diagnostic PCR testing to assess the disease severity of new SARS-CoV-2 variants

Hussey, Hannah

Using proxy markers from routine diagnostic PCR testing to assess the disease severity of new SARS-CoV-2 variants

Thesis / Dissertation

2023

Abstract

Background With the emergence of new SARS-CoV-2 variants, understanding the clinical implications of these variants in our South African setting is critical. The Delta variant (B.1.617.2) has been associated with more severe disease, but most of this data is from high income countries. And while the Omicron variant (B.1.1.529, sub-lineages BA.1 and BA.2) has been associated with a reduced risk of severe disease, it is uncertain whether this is caused by a decrease in variant virulence or by higher levels of population immunity. Methods We used a novel proxy marker, RNA-dependent RNA polymerase (RdRp) target delay in the Seegene AllplexTM 2019-nCoV polymerase chain reaction assay, to identify suspected Delta variant infection in routine laboratory data. All cases diagnosed on this assay in the public sector in the Western Cape, South Africa, from 1 April to 31 July 2021 (for analysis of clinical severity of Delta vs previously circulating [mainly Beta] variant analysis) and from 1 November to 14 December 2021 (for analysis of clinical severity of Omicron vs Delta variant analysis), were included in the dataset provided by the Western Cape Provincial Health Data Centre (PHDC). We calculated odds/hazard ratios for the association between the proxy marker and death/hospitalization, adjusted for socio-demographic factors, comorbidities, prior diagnosed infection and vaccination status. Results For the analysis of the clinical severity of Delta vs previously circulating (mainly Beta) variants, we included 11,355 cases with 700 deaths. RdRp target delay (RTD - i.e., suspected Delta infection) was associated with higher mortality (adjusted odds ratio [aOR] 1.45; 95% confidence interval [CI]: 1.13-1.86), compared to presumptive Beta infection (absence of RTD). Prior diagnosed infection during the previous COVID-19 7 wave, which was driven by the Beta variant, was protective (aOR 0.32; 95%CI: 0.11-0.92) as was vaccination (aOR [95%CI] 0.15 [0.03-0.62] for complete vaccination [≥28 days post a single dose of Ad26.COV2.S or ≥14 days post second BNT162b2 dose]). For the Omicron (BA.1/BA.2) vs Delta variant analysis, we included 150 cases with RTD and 1486 cases without RTD. Cases without RTD (i.e., suspected Omicron cases) had a lower hazard of admission (adjusted hazard ratio [aHR], 0.56; 95% CI 0.34-0.91). Complete vaccination was protective against admission, with an aHR of 0.45 (95% CI, 0.26-0.77). Conclusion RdRp target delay, a proxy for infection with the Delta variant, is associated with an increased risk of mortality amongst those with laboratory-diagnosed COVID-19 in our setting. Omicron has resulted in a lower risk of hospital admission compared with contemporaneous Delta infection, when using the proxy marker of RTD. Under-ascertainment of reinfections with an immune escape variant remains a challenge to accurately assessing variant virulence. This study also resulted in two publications, that could be disseminated, initially on MedRxiv, and shared with policy makers in the Department of Health and other scientific colleagues in time to influence the pandemic response.

Keywords

Public Health Medicine

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