Association between SARS-CoV-2 gene specific Ct values and COVID-19 associated in-hospital mortality

Mpho L Sikhosana; Richard Welch; Alfred Musekiwa; Zinhle Makatini; Joy Ebonwu; Lucille Blumberg; Waasila Jassat

doi:10.3389/fepid.2024.1375975

Association between SARS-CoV-2 gene specific Ct values and COVID-19 associated in-hospital mortality

Front Epidemiol. 2024 Apr 26:4:1375975. doi: 10.3389/fepid.2024.1375975. eCollection 2024.

Authors

Mpho L Sikhosana^{1

2}, Richard Welch³, Alfred Musekiwa⁴, Zinhle Makatini^{1

2}, Joy Ebonwu³, Lucille Blumberg³, Waasila Jassat³

Affiliations

¹ Department of Virology, National Health Laboratory Service, Charlotte Maxeke Johannesburg Academic Hospital, Johannesburg, South Africa.
² Department of Virology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
³ Department of Public Health and Outbreak Response, National Institute for Communicable Diseases, Johannesburg, South Africa.
⁴ Faculty of Health Sciences, School of Health Systems and Public Health, University of Pretoria, Pretoria, South Africa.

Abstract

Background: Since there are currently no specific SARS-CoV-2 prognostic viral biomarkers for predicting disease severity, there has been interest in using SARS-CoV-2 polymerase chain reaction (PCR) cycle-threshold (Ct) values to predict disease progression.

Objective: This study assessed the association between in-hospital mortality of hospitalized COVID-19 cases and Ct-values of gene targets specific to SARS-CoV-2.

Methods: Clinical data of hospitalized COVID-19 cases from Gauteng Province from April 2020-July 2022 were obtained from a national surveillance system and linked to laboratory data. The study period was divided into pandemic waves: Asp614Gly/wave1 (7 June-22 Aug 2020); beta/wave2 (15 Nov 2020-6 Feb 2021); delta/wave3 (9 May-18 Sept 2021) and omicron/wave4 (21 Nov 2021-22 Jan 2022). Ct-value data of genes specific to SARS-CoV-2 according to testing platforms (Roche-ORF gene; GeneXpert-N2 gene; Abbott-RdRp gene) were categorized as low (Ct < 20), mid (Ct20-30) or high (Ct > 30).

Results: There were 1205 recorded cases: 836(69.4%; wave1), 122(10.1%;wave2) 21(1.7%; wave3) and 11(0.9%;in wave4). The cases' mean age(±SD) was 49 years(±18), and 662(54.9%) were female. There were 296(24.6%) deaths recorded: 241(81.4%;wave1), 27 (9.1%;wave2), 6 (2%;wave3), and 2 (0.7%;wave4) (p < 0.001). Sample distribution by testing platforms was: Roche 1,033 (85.7%), GeneXpert 169 (14%) and Abbott 3 (0.3%). The median (IQR) Ct-values according to testing platform were: Roche 26 (22-30), GeneXpert 38 (36-40) and Abbott 21 (16-24). After adjusting for sex, age and presence of a comorbidity, the odds of COVID-19 associated death were high amongst patients with Ct values 20-30[adjusted Odds Ratio (aOR) 2.25; 95% CI: 1.60-3.18] and highest amongst cases with Ct-values <20 (aOR 3.18; 95% CI: 1.92-5.27), compared to cases with Ct-values >30.

Conclusion: Although odds of COVID19-related death were high amongst cases with Ct-values <30, Ct values were not comparable across different testing platforms, thus precluding the comparison of SARS-CoV-2 Ct-value results.

Keywords: Ct values; PCR; SARS-CoV-2; South Africa; mortality.

Grants and funding

The author(s) declare no financial support was received for the research, authorship, and/or publication of this article.