Research Article
BibTex RIS Cite

Role of Cycle Threshold of RT-PCR in the Prediction of COVID-19 Cases

Year 2021, Volume: 11 Issue: 03, 132 - 139, 15.09.2021
https://doi.org/10.5799/jmid.993878

Abstract

Objectives: It is currently unclear whether SARS-CoV-2 Cycle threshold (Ct) values could be leveraged to guide patients’ clinical manifestations and management decisions. The present study was undertaken to observe whether RT-PCR Ct values differ in COVID-19 symptomatic and asymptomatic individuals. This study also describes the clinical manifestations and epidemiological characteristics of both groups of patients.
Methods: Nasopharyngeal or oropharyngeal swabs of 35,391 clinically suspected COVID-19 patients were collected in VTM and tested in our dedicated COVID-19 diagnostic laboratory for SARS-CoV-2 RT-PCR test. Cycle threshold at day 1 of positive detection was correlated with the presence or absence of the patient’s symptoms. The Ct values were studied sequentially in the collected samples to understand the variation of Ct values with the patient’s first day of diagnosis up to the recovery day.
Results: Of 35,391 samples received for RT-PCR, data from 589 COVID-19 diagnosed patients (positivity 1.66%) was analyzed further. Among 589 patients, a total of 178 patients were symptomatic, while 411 were asymptomatic. Ct values obtained in symptomatic individuals (19.26±4.34) were significantly lower than in the asymptomatic (25.96±4.64) individuals (p<0.01). For 38 SARS-CoV-2 positive patients, data from sequential samples submitted to the laboratory was also analyzed. After adjusting for age, gender, co-morbidities, increased cycle threshold was associated with decreased odds of symptoms and in-hospital admission (0.91, CI 0.89– 0.94, p<0.001).
Conclusion: Clinical symptoms and laboratory results of RT-PCR (Ct Value) of symptomatic patients with COVID-19 are significantly lower than those without symptoms. Analyzing data from 38 SARS-CoV-2 positive patients’ sequential samples again demonstrated that symptoms correlate with lower Ct values; however, virus clearance took almost the same time in the two groups of individuals. J Microbiol Infect Dis 2021; 11(3):132-139.

References

  • 1. Cucinotta D, Vanelli M. WHO Declares COVID-19 a Pandemic. Acta Biomed. 2020 Mar 19;91(1):157-160. doi: 10.23750/abm.v91i1.9397. PMID: 32191675; PMCID: PMC7569573.
  • 2. National Centre for Infectious Diseases, Chapter of Infectious Disease Physicians, Academy of Medicine, Singapore. Position Statement from the National Centre for Infectious Diseases and the Chapter of Infectious Disease Physicians, Academy of Medicine, Singapore. 2020. May Available from: https://www.ams.edu.sg/view-pdf.aspx?file=media%5c5556_fi_331.pdf&ofile=Period+of+Infectivity+Position+Statement+(final)+23-5-20+(logos).pdf. Accessed June 12, 2020.
  • 3. Mizumoto K, Kagaya K, Zarebski A, et al. Estimating the asymptomatic proportion of coronavirus disease 2019 (COVID-19) cases on board the Diamond Princess cruise ship, Yokohama, Japan, 2020. Euro Surveill 2020; 25 (10):2000180. doi: 10.2807/1560-7917.ES.2020.25.10.2000180.
  • 4. Bai Y, Yao L, Wei T, et al. Presumed asymptomatic carrier transmission of COVID-19. JAMA 2020; 323 (14):1406–1407.
  • 5. Xu T, Chen C, Zhu Z, et al. Clinical features and dynamics of viral load in imported and non-imported patients with COVID-19. Int J Infect Dis 2020; 94 (5):68-71. doi: 10.1016/j.ijid.2020.03.022
  • 6. Walsh KA, Jordan K, Clyne B, et al., SARS-CoV-2 detection, viral load and infectivity over the course of an infection, Journal of Infection, 2020; 81 (3):357-371.
  • 7. Han A, Czajkowski LM, Donaldson A, et al. A Dose-Finding Study of a Wild-Type Influenza A(H3N2) Virus in a Healthy Volunteer Human Challenge Model. Clin. Infect. Dis. 2019; 69 (12):2082–2090.
  • 8. Chu CM, Poon LLM, Cheng VCC, et al. Initial Viral Load and the Outcomes of SARS. CMAJ 2004; 171 (11):1349–1352.
  • 9. Arons MM, Hatfield KM, Reddy SC, et al. Presymptomatic SARS-CoV-2 Infections and Transmission in a Skilled Nursing Facility. N Engl J Med 2020; 382(22):2081-2090. doi: 10.1056/NEJMoa2008457
  • 10. He X, Lau EHY, Wu P, et al. Temporal Dynamics in Viral Shedding and Transmissibility of COVID-19. Nat Med 2020; 26 (9): 672–675.
  • 11. To KK-W, Tsang OT-Y, Leung W-S, et al. Temporal Profiles of Viral Load in Posterior Oropharyngeal Saliva Samples and Serum Antibody Responses during Infection by SARS-CoV-2: An Observational Cohort Study. Lancet Infect. Dis. 2020;20(5):565–574.
  • 12. Zou L, Ruan F, Huang M, et al. SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients. N Engl J Med 2020; 382 (12): 1177–1179.
  • 13. Jacot D, Greub G, Jaton K, et al. Viral Load of SARS-CoV-2 across Patients and Compared to Other Respiratory Viruses. Microbes Infect 2020; 22(10):617-621.
  • 14. Karahasan AY, Sarinoglu RC, Bilgin H, et al. Relationship of the Cycle Threshold Values of SARS-CoV-2 Polymerase Chain Reaction and Total Severity Score of Computerized Tomography in Patients with COVID-19. Int. J Infect Dis 2020; 101: 160–166.
  • 15. Westblade LF, Brar G, Pinheiro LC, et al. SARS-CoV-2 Viral Load Predicts Mortality in Patients with and without Cancer Who Are Hospitalized with COVID-19. Cancer Cell 2020; 38 (5):661-671.
  • 16. Pujadas E, Chaudhry F, McBride R, et al. SARS-CoV-2 Viral Load Predicts COVID-19 Mortality. Lancet Respir Med 2020, 8(9), e70, doi: 10.1016/S2213-2600(20)30354-4.
  • 17. Faíco-Filho KS, Passarelli VC, Bellei N. Is Higher Viral Load in SARS-CoV-2 Associated with Death? Am J Trop Med Hyg 2020;103(5):2019-2021.
  • 18. Shlomai A, Ben-Zvi H, Glusman Bendersky A, et al. Nasopharyngeal Viral Load Predicts Hypoxemia and Disease Outcome in Admitted COVID-19 Patients. Crit Care 2020, 24 (1), 539.
  • 19. Lescure FX, Bouadma L, Nguyen D, et al. Clinical and virological data of the first cases of COVID-19 in Europe: a case series. Lancet Infect Dis 2020; 20(6):697-706.
  • 20. Liu Y, Yan LM, Wan L, et al. Viral dynamics in mild and severe cases of COVID-19. Lancet Infect Dis 2020; 20 (6):656-657.
  • 21. Pan Y, Zhang D, Yang P, et al. Viral load of SARS-CoV-2 in clinical samples. Lancet Infect Dis 2020; 20 (4):411-412.
  • 22. Yu F, Yan L, Wang N, Yang S, et al. Quantitative detection and viral load analysis of SARS-CoV-2 in infected patients. Clin Infect Dis 2020; 71 (15):793-798 doi: 10.1093/cid/ciaa345.
  • 23. Zhou R, Li F, Chen F, et al. Viral dynamics in asymptomatic patients with COVID-19. Int J Infect Dis 2020; 96: 288-290.
  • 24. Wolfel R, Corman VM, Guggemos W, et al. Virological assessment of hospitalized patients with COVID-2019. Nature 2020; 581 (7809):465-469. doi:10.1038/s41586-020-2196-x.
  • 25. Lee S, Kim T, Lee E, et al. Clinical course and molecular viral shedding among asymptomatic and symptomatic patients with SARS-CoV-2 infection in a community treatment center in the Republic of Korea. JAMA Intern Med 2020; 180 (11): 1447-1452. doi: 10.1001/jamainternmed.2020.3862.
Year 2021, Volume: 11 Issue: 03, 132 - 139, 15.09.2021
https://doi.org/10.5799/jmid.993878

Abstract

References

  • 1. Cucinotta D, Vanelli M. WHO Declares COVID-19 a Pandemic. Acta Biomed. 2020 Mar 19;91(1):157-160. doi: 10.23750/abm.v91i1.9397. PMID: 32191675; PMCID: PMC7569573.
  • 2. National Centre for Infectious Diseases, Chapter of Infectious Disease Physicians, Academy of Medicine, Singapore. Position Statement from the National Centre for Infectious Diseases and the Chapter of Infectious Disease Physicians, Academy of Medicine, Singapore. 2020. May Available from: https://www.ams.edu.sg/view-pdf.aspx?file=media%5c5556_fi_331.pdf&ofile=Period+of+Infectivity+Position+Statement+(final)+23-5-20+(logos).pdf. Accessed June 12, 2020.
  • 3. Mizumoto K, Kagaya K, Zarebski A, et al. Estimating the asymptomatic proportion of coronavirus disease 2019 (COVID-19) cases on board the Diamond Princess cruise ship, Yokohama, Japan, 2020. Euro Surveill 2020; 25 (10):2000180. doi: 10.2807/1560-7917.ES.2020.25.10.2000180.
  • 4. Bai Y, Yao L, Wei T, et al. Presumed asymptomatic carrier transmission of COVID-19. JAMA 2020; 323 (14):1406–1407.
  • 5. Xu T, Chen C, Zhu Z, et al. Clinical features and dynamics of viral load in imported and non-imported patients with COVID-19. Int J Infect Dis 2020; 94 (5):68-71. doi: 10.1016/j.ijid.2020.03.022
  • 6. Walsh KA, Jordan K, Clyne B, et al., SARS-CoV-2 detection, viral load and infectivity over the course of an infection, Journal of Infection, 2020; 81 (3):357-371.
  • 7. Han A, Czajkowski LM, Donaldson A, et al. A Dose-Finding Study of a Wild-Type Influenza A(H3N2) Virus in a Healthy Volunteer Human Challenge Model. Clin. Infect. Dis. 2019; 69 (12):2082–2090.
  • 8. Chu CM, Poon LLM, Cheng VCC, et al. Initial Viral Load and the Outcomes of SARS. CMAJ 2004; 171 (11):1349–1352.
  • 9. Arons MM, Hatfield KM, Reddy SC, et al. Presymptomatic SARS-CoV-2 Infections and Transmission in a Skilled Nursing Facility. N Engl J Med 2020; 382(22):2081-2090. doi: 10.1056/NEJMoa2008457
  • 10. He X, Lau EHY, Wu P, et al. Temporal Dynamics in Viral Shedding and Transmissibility of COVID-19. Nat Med 2020; 26 (9): 672–675.
  • 11. To KK-W, Tsang OT-Y, Leung W-S, et al. Temporal Profiles of Viral Load in Posterior Oropharyngeal Saliva Samples and Serum Antibody Responses during Infection by SARS-CoV-2: An Observational Cohort Study. Lancet Infect. Dis. 2020;20(5):565–574.
  • 12. Zou L, Ruan F, Huang M, et al. SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients. N Engl J Med 2020; 382 (12): 1177–1179.
  • 13. Jacot D, Greub G, Jaton K, et al. Viral Load of SARS-CoV-2 across Patients and Compared to Other Respiratory Viruses. Microbes Infect 2020; 22(10):617-621.
  • 14. Karahasan AY, Sarinoglu RC, Bilgin H, et al. Relationship of the Cycle Threshold Values of SARS-CoV-2 Polymerase Chain Reaction and Total Severity Score of Computerized Tomography in Patients with COVID-19. Int. J Infect Dis 2020; 101: 160–166.
  • 15. Westblade LF, Brar G, Pinheiro LC, et al. SARS-CoV-2 Viral Load Predicts Mortality in Patients with and without Cancer Who Are Hospitalized with COVID-19. Cancer Cell 2020; 38 (5):661-671.
  • 16. Pujadas E, Chaudhry F, McBride R, et al. SARS-CoV-2 Viral Load Predicts COVID-19 Mortality. Lancet Respir Med 2020, 8(9), e70, doi: 10.1016/S2213-2600(20)30354-4.
  • 17. Faíco-Filho KS, Passarelli VC, Bellei N. Is Higher Viral Load in SARS-CoV-2 Associated with Death? Am J Trop Med Hyg 2020;103(5):2019-2021.
  • 18. Shlomai A, Ben-Zvi H, Glusman Bendersky A, et al. Nasopharyngeal Viral Load Predicts Hypoxemia and Disease Outcome in Admitted COVID-19 Patients. Crit Care 2020, 24 (1), 539.
  • 19. Lescure FX, Bouadma L, Nguyen D, et al. Clinical and virological data of the first cases of COVID-19 in Europe: a case series. Lancet Infect Dis 2020; 20(6):697-706.
  • 20. Liu Y, Yan LM, Wan L, et al. Viral dynamics in mild and severe cases of COVID-19. Lancet Infect Dis 2020; 20 (6):656-657.
  • 21. Pan Y, Zhang D, Yang P, et al. Viral load of SARS-CoV-2 in clinical samples. Lancet Infect Dis 2020; 20 (4):411-412.
  • 22. Yu F, Yan L, Wang N, Yang S, et al. Quantitative detection and viral load analysis of SARS-CoV-2 in infected patients. Clin Infect Dis 2020; 71 (15):793-798 doi: 10.1093/cid/ciaa345.
  • 23. Zhou R, Li F, Chen F, et al. Viral dynamics in asymptomatic patients with COVID-19. Int J Infect Dis 2020; 96: 288-290.
  • 24. Wolfel R, Corman VM, Guggemos W, et al. Virological assessment of hospitalized patients with COVID-2019. Nature 2020; 581 (7809):465-469. doi:10.1038/s41586-020-2196-x.
  • 25. Lee S, Kim T, Lee E, et al. Clinical course and molecular viral shedding among asymptomatic and symptomatic patients with SARS-CoV-2 infection in a community treatment center in the Republic of Korea. JAMA Intern Med 2020; 180 (11): 1447-1452. doi: 10.1001/jamainternmed.2020.3862.
There are 25 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section Research Article
Authors

Vikramjeet Sıngh This is me

Jyotsna Agarwal This is me

Jaya Garg This is me

Mohammad Saquib This is me

Anupam Das This is me

Manodeep Sen This is me

Publication Date September 15, 2021
Published in Issue Year 2021 Volume: 11 Issue: 03

Cite

APA Sıngh, V., Agarwal, J., Garg, J., Saquib, M., et al. (2021). Role of Cycle Threshold of RT-PCR in the Prediction of COVID-19 Cases. Journal of Microbiology and Infectious Diseases, 11(03), 132-139. https://doi.org/10.5799/jmid.993878
AMA Sıngh V, Agarwal J, Garg J, Saquib M, Das A, Sen M. Role of Cycle Threshold of RT-PCR in the Prediction of COVID-19 Cases. J Microbil Infect Dis. September 2021;11(03):132-139. doi:10.5799/jmid.993878
Chicago Sıngh, Vikramjeet, Jyotsna Agarwal, Jaya Garg, Mohammad Saquib, Anupam Das, and Manodeep Sen. “Role of Cycle Threshold of RT-PCR in the Prediction of COVID-19 Cases”. Journal of Microbiology and Infectious Diseases 11, no. 03 (September 2021): 132-39. https://doi.org/10.5799/jmid.993878.
EndNote Sıngh V, Agarwal J, Garg J, Saquib M, Das A, Sen M (September 1, 2021) Role of Cycle Threshold of RT-PCR in the Prediction of COVID-19 Cases. Journal of Microbiology and Infectious Diseases 11 03 132–139.
IEEE V. Sıngh, J. Agarwal, J. Garg, M. Saquib, A. Das, and M. Sen, “Role of Cycle Threshold of RT-PCR in the Prediction of COVID-19 Cases”, J Microbil Infect Dis, vol. 11, no. 03, pp. 132–139, 2021, doi: 10.5799/jmid.993878.
ISNAD Sıngh, Vikramjeet et al. “Role of Cycle Threshold of RT-PCR in the Prediction of COVID-19 Cases”. Journal of Microbiology and Infectious Diseases 11/03 (September 2021), 132-139. https://doi.org/10.5799/jmid.993878.
JAMA Sıngh V, Agarwal J, Garg J, Saquib M, Das A, Sen M. Role of Cycle Threshold of RT-PCR in the Prediction of COVID-19 Cases. J Microbil Infect Dis. 2021;11:132–139.
MLA Sıngh, Vikramjeet et al. “Role of Cycle Threshold of RT-PCR in the Prediction of COVID-19 Cases”. Journal of Microbiology and Infectious Diseases, vol. 11, no. 03, 2021, pp. 132-9, doi:10.5799/jmid.993878.
Vancouver Sıngh V, Agarwal J, Garg J, Saquib M, Das A, Sen M. Role of Cycle Threshold of RT-PCR in the Prediction of COVID-19 Cases. J Microbil Infect Dis. 2021;11(03):132-9.