Association of cycle threshold values of CBNAAT with severity and outcome in COVID-19

Submitted: January 3, 2021
Accepted: June 8, 2021
Published: July 21, 2021
Abstract Views: 1772
PDF: 798
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Authors

Determination of viral load through cycle threshold (Ct) values may act as a predictor of severity and outcomes in patients with corona virus disease 2019 (COVID-19). However, variable literature is available regarding this relationship. Our study attempted to explore this association and the effect of various socio-demographic and clinical parameters on severity and outcome of COVID-19. Retrospective analysis of records of 731 patients whose nasopharyngeal/oropharyngeal swabs were subjected to cartridge based nucleic acid amplification (CBNAAT) on Cepheid Xpert Xpress SARS-CoV-2 was done. Ct values of N2 and E genes were studied in relation to severity and outcome of COVID-19. The viral load as determined by Ct values was classified as high (<25), medium (25.1-32) and low (>32). Association of socio-demographic and clinical parameters with respect to severity and outcome was also studied. Severity and mortality were significantly more in elder individuals, those belonging to the rural background, those with symptoms >7 days in duration before presentation and those with increasing number of co-morbidities (severity: p<0.001; mortality: p<0.001, 0.005, 0.006 and <0.001, respectively). The Ct values of gene N2 and E inversely correlated with severity and mortality from the disease (N2 gene: p=0.001 for both severity and mortality, E gene: severity: p<0.001, mortality: p=0.016, respectively). The severity of the illness and chances of mortality were significantly lesser when the CT value of N2 gene was >32, in comparison when it was upto 25, and when between 25.1 and 32 (severity: p=0.032 and 0.003, respectively; mortality: p=0.018 and <0.001, respectively). Almost similar trends were seen with respect to E gene (severity: p<0.001 and 0.067, respectively; mortality p=0.175 and 0.005, respectively). Viral load as determined by Ct values of N2 and E genes can act as surrogate markers for prediction of severity and disease outcomes in COVID-19.

Dimensions

Altmetric

PlumX Metrics

Downloads

Download data is not yet available.

Citations

World Health Organization. Coronavirus disease (COVID-19). Accessed: 16 December 2020. Available from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019
World Health Organization. Laboratory testing for 2019 novel coronavirus (2019-nCoV) in suspected human cases. WHO - Interim guidance 2020. Available from: https://www.who.int/publications/i/item/10665-331501
Zheng S, Fan J, Yu F, et al. Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January-March 2020: Retrospective cohort study. BMJ 2020;369:m1443. DOI: https://doi.org/10.1136/bmj.m1443
Magleby R, Westblade LF, Trzebucki A, et al. Impact of SARS-CoV-2 viral load on risk of intubation and mortality among hospitalized patients with coronavirus disease 2019. Clin Infect Dis 2020;ciaa851. Online ahead of print. DOI: https://doi.org/10.1093/cid/ciaa851
Liu Y, Yan LM, Wan L, et al. Viral dynamics in mild and severe cases of COVID-19. Lancet Infect Dis 2020;20:656–7. DOI: https://doi.org/10.1016/S1473-3099(20)30232-2
Eberhardt KA, Meyer-Schwickerath C, Heger E, et al. RNAemia corresponds to disease severity and antibody response in hospitalized COVID-19 patients. Viruses 2020;12:1045. DOI: https://doi.org/10.3390/v12091045
Chu CM, Poon LLM, Cheng VCC, et al. Initial viral load and the outcomes of SARS. CMAJ 2004;171:1349–52. DOI: https://doi.org/10.1503/cmaj.1040398
Lui G, Ling L, Lai CK, et al. Viral dynamics of SARS-CoV-2 across a spectrum of disease severity in COVID-19. J Infect 2020;81:324–7. DOI: https://doi.org/10.1016/j.jinf.2020.04.014
Shi F, Wu T, Zhu X, et al. Association of viral load with serum biomarkers among COVID-19 cases. Virology 2020;546:122–6. DOI: https://doi.org/10.1016/j.virol.2020.04.011
He X, Lau EHY, Wu P, et al. Temporal dynamics in viral shedding and transmissibility of COVID-19. Nat Med 2020;26 672–5. DOI: https://doi.org/10.1038/s41591-020-0869-5
US Food and Drug Administration. Coronavirus (COVID-19) Update: FDA Issues first Emergency Use Authorization for Point of Care Diagnostic. Accessed: 16 December 2020. Available from: https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-issues-first-emergency-use-authorization-point-care-diagnostic
Indian Council of Medical Research. Advisory Newer Additional Strategies for COVID-19 Testing. Accessed: 16 December 2020. Available from: https://www.icmr.gov.in/pdf/covid/strategy/Advisory_for_rapid_antigen_test_14062020.pdf
Cepheid. Xpert ® Xpress SARS-CoV-2 - Instructions for Use. Accessed: 16 December 2020. Available from: https://www.fda.gov/media/136314/download
Public Helath Ontario. An overview of cycle threshold values and their role in SARS-CoV-2 real-time PCR test interpretation. 2020. Available from: https://www.publichealthontario.ca/-/media/documents/ncov/main/2020/09/cycle-threshold-values-sars-cov2-pcr.pdf?la=en
Indian Council of Medical Research. ICMR Specimen Referral Form for COVID-19 (SARS-CoV2). Available from: https://www.icmr.gov.in/pdf/covid/labs/SRF_v12.pdf
Ministry of Health and Family Welfare. Clinical management protocol: COVID-19. Version 3. 2020.
Guan WJ, Liang WH, He JX, et al. Cardiovascular comorbidity and its impact on patients with COVID-19. Eur Respir J 2020;55:2001227. DOI: https://doi.org/10.1183/13993003.01227-2020
Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020;395:1054-62. DOI: https://doi.org/10.1016/S0140-6736(20)30566-3
World Health Organization. Clinical Management of COVID-19 - Interim guidance. Available from: https://apps.who.int/iris/bitstream/handle/10665/332196/WHO-2019-nCoV-clinical-2020.5-eng.pdf?sequence=1&isAllowed=y
Geddes L. Puzzle over viral load. New Sci 2020;245:8. DOI: https://doi.org/10.1016/S0262-4079(20)30658-8
Ng EKO, Hui DS, Chan KCA, et al. Quantitative analysis and prognostic implication of SARS coronavirus RNA in the plasma and serum of patients with severe acute respiratory syndrome. Clin Chem 2003;49:1976–80. DOI: https://doi.org/10.1373/clinchem.2003.024125
Rao S, Manissero D, Steele VR, Pareja J. A narrative systematic review of the clinical utility of cycle threshold values in the context of COVID-19. Infect Dis Ther 2020;9:573-86. DOI: https://doi.org/10.1007/s40121-020-00324-3
Peiris JSM, Chu CM, Cheng VCC, et al. Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: A prospective study. Lancet 2003;361:1767–72. DOI: https://doi.org/10.1016/S0140-6736(03)13412-5

How to Cite

Garg, Kranti, Karan Sharma, Aditi Gupta, and Vishal Chopra. 2021. “Association of Cycle Threshold Values of CBNAAT With Severity and Outcome in COVID-19”. Monaldi Archives for Chest Disease 91 (4). https://doi.org/10.4081/monaldi.2021.1759.