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Volume 3, Issue 9

High SARS-CoV-2 viral load is associated with a worse clinical outcome of COVID-19 disease Open Access

Abstract

COVID-19 severity and progression are determined by several host and virological factors that may influence the final outcome of SARS-CoV-2-infected patients. The objective of this work was to determine a possible association between viral load, obtained from nasopharyngeal swabs, and the severity of the infection in a cohort of 448 SARS-CoV-2-infected patients from a hospital in Madrid during the first outbreak of the pandemic in Spain. To perform this, we clinically classified patients as mild, moderate and severe COVID-19 according to a number of clinical parameters such as hospitalization requirement, need of oxygen therapy, admission to intensive care units and/or death. Also, Ct values were determined using SARS-CoV-2-specific oligonucleotides directed to ORF1ab. Here we report a statistically significant association between viral load and disease severity, a high viral load being associated with worse clinical prognosis, independently of several previously identified risk factors such as age, sex, hypertension, cardiovascular disease, diabetes, obesity and lung disease (asthma and chronic obstructive pulmonary disease). The data presented here reinforce viral load as a potential biomarker for predicting disease severity in SARS-CoV-2-infected patients. It is also an important parameter in viral evolution since it relates to the numbers and types of variant genomes present in a viral population, a potential determinant of disease progression.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): COVID-19 , risk factors and viral load
Funding
This study was supported by the:
  • Comunidad de Madrid (Award PEJD-2019-PRE/BMD-16414)
    • Principle Award Recipient: RebecaLobo-Vega
  • Instituto de Salud Carlos III (Award PFIS FI19/00119)
    • Principle Award Recipient: BrendaMartínez-González
  • Instituto de Salud Carlos III (Award CP16/00116)
    • Principle Award Recipient: PabloMínguez
  • Instituto de Salud Carlos III (Award CPII17/00006)
    • Principle Award Recipient: MartaCortón
  • Instituto de Salud Carlos III (Award CPII19/00001)
    • Principle Award Recipient: CeliaPerales
  • Instituto de Salud Carlos III (Award PI18/00210)
    • Principle Award Recipient: CeliaPerales
  • Ministerio de Ciencia, Innovación y Universidades (Award BFU2017-91384-EXP)
    • Principle Award Recipient: CeliaPerales
  • Consejo Superior de Investigaciones Científicas (Award CSIC-COV19-014)
    • Principle Award Recipient: CeliaPerales
  • Instituto de Salud Carlos III (Award COV20/00181)
    • Principle Award Recipient: CarmenAyuso
© 2021 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.
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/content/journal/acmi/10.1099/acmi.0.000259
2021-09-21
2024-04-16
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References

  1. Huang C, Wang Y, Li X, Ren L, Zhao J et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395:497–506 [View Article] [PubMed]
     [Google Scholar]
  2. Domingo E, Sheldon J, Perales C. Viral quasispecies evolution. Microbiol Mol Biol Rev 2012; 76:159–216 [View Article] [PubMed]
     [Google Scholar]
  3. Domingo E, Perales C. Viral quasispecies. PLoS Genet 2019; 15:e1008271 [View Article]
     [Google Scholar]
  4. Domingo E. Virus as Populations, 2nd edn. Amsterdam: Academic Press, Elsevier; 2020
     [Google Scholar]
  5. Liu Y, Yang Y, Zhang C, Huang F, Wang F et al. Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury. Sci China Life Sci 2020; 63:364–374 [View Article] [PubMed]
     [Google Scholar]
  6. Liu Y, Yan L-M, Wan L, Xiang T-X, Le A et al. Viral dynamics in mild and severe cases of COVID-19. Lancet Infect Dis 2020; 20:656–657 [View Article] [PubMed]
     [Google Scholar]
  7. Pujadas E, Chaudhry F, McBride R, Richter F, Zhao S et al. SARS-CoV-2 viral load predicts COVID-19 mortality. Lancet Respir Med 2020; 8:e70 [View Article] [PubMed]
     [Google Scholar]
  8. Magleby R, Westblade LF, Trzebucki A, Simon MS, Rajan M 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 [View Article] [PubMed]
     [Google Scholar]
  9. Westblade LF, Brar G, Pinheiro LC, Paidoussis D, Rajan M et al. SARS-COV-2 viral load predicts mortality in patients with and without cancer who are hospitalized with covid-19. Cancer Cell 2020; 38:661–671 [View Article] [PubMed]
     [Google Scholar]
  10. Faico-Filho KS, Passarelli VC, Bellei N. Is higher viral load in SARS-CoV-2 associated with death?. Am J Trop Med Hyg 2020; 103:2019–2021 [View Article] [PubMed]
     [Google Scholar]
  11. Shlomai A, Ben-Zvi H, Glusman Bendersky A, Shafran N, Goldberg E et al. Nasopharyngeal viral load predicts hypoxemia and disease outcome in admitted COVID-19 patients. Crit Care 2020; 24:539 [View Article] [PubMed]
     [Google Scholar]
  12. de la Calle C, Lalueza A, Mancheno-Losa M, Maestro-de la Calle G, Lora-Tamayo J et al. Impact of viral load at admission on the development of respiratory failure in hospitalized patients with SARS-CoV-2 infection. Eur J Clin Microbiol Infect Dis 2021; 40:1209–1216 [View Article] [PubMed]
     [Google Scholar]
  13. Zacharioudakis IM, Prasad PJ, Zervou FN, Basu A, Inglima K et al. Association of SARS-CoV-2 genomic load with COVID-19 patient outcomes. Ann Am Thorac Soc 2020
     [Google Scholar]
  14. Zacharioudakis IM, Zervou FN, Prasad PJ, Shao Y, Basu A et al. Association of SARS-COV-2 genomic load trends with clinical status in COVID-19: A retrospective analysis from an academic hospital center in New York City. PLoS One 2020; 15:e0242399 [View Article]
     [Google Scholar]
  15. Trunfio M, Venuti F, Alladio F, Longo BM, Burdino E et al. Diagnostic SARS-COV-2 cycle threshold value predicts disease severity, survival, and six-month sequelae in COVID-19 symptomatic patients. Viruses 2021; 13: [View Article] [PubMed]
     [Google Scholar]
  16. Rao SN, Manissero D, Steele VR, Pareja J. A systematic review of the clinical utility of cycle threshold values in the context of COVID-19. Infect Dis Ther 2020; 9:573–586 [View Article] [PubMed]
     [Google Scholar]
  17. Lesho E, Reno L, Newhart D, Clifford R, Vasylyeva O et al. Temporal, spatial, and epidemiologic relationships of severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2) gene cycle thresholds: A pragmatic ambi-directional observation. Clin Infect Dis 2020 [View Article] [PubMed]
     [Google Scholar]
  18. Ra SH, Lim JS, Kim G-U, Kim MJ, Jung J et al. Upper respiratory viral load in asymptomatic individuals and mildly symptomatic patients with SARS-COV-2 infection. Thorax 2021; 76:61–63 [View Article] [PubMed]
     [Google Scholar]
  19. Jacot D, Greub G, Jaton K, Opota O. Viral load of SARS-CoV-2 across patients and compared to other respiratory viruses. Microbes Infect 2020; 22:617–621 [View Article] [PubMed]
     [Google Scholar]
  20. Karahasan Yagci A, Sarinoglu RC, Bilgin H, Yanılmaz Ö, Sayın E 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 [View Article]
     [Google Scholar]
  21. Shah S, Singhal T, Davar N, Thakkar P. No correlation between Ct values and severity of disease or mortality in patients with COVID 19 disease. Indian J Med Microbiol 2021; 39:116–117 [View Article] [PubMed]
     [Google Scholar]
  22. Argyropoulos KV, Serrano A, Hu J, Black M, Feng X et al. Association of initial viral load in SARS-CoV-2 patients with outcome and symtoms. Am J Pathol 2020; 190:1881–1887
     [Google Scholar]
  23. Laguna-Goya R, Utrero-Rico A, Talayero P, Lasa-Lazaro M, Ramirez-Fernandez A et al. IL-6-based mortality risk model for hospitalized patients with COVID-19. J Allergy Clin Immunol 2020; 146:799–807 [View Article] [PubMed]
     [Google Scholar]
  24. Ortiz-Prado E, Simbana-Rivera K, Gomez-Barreno L, Rubio-Neira M, Guaman LP et al. Clinical, molecular, and epidemiological characterization of the SARS-CoV-2 virus and the Coronavirus Disease 2019 (COVID-19), a comprehensive literature review. Diagn Microbiol Infect Dis 2020; 98:115094 [View Article] [PubMed]
     [Google Scholar]
  25. Guo G, Ye L, Pan K, Chen Y, Xing D et al. New insights of emerging SARS-COV-2: Epidemiology, etiology, clinical features, clinical treatment, and prevention. Front Cell Dev Biol 2020; 8:410 [View Article] [PubMed]
     [Google Scholar]
  26. Chen N, Zhou M, Dong X, Qu J, Gong F et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 2020; 395:507–513 [View Article] [PubMed]
     [Google Scholar]
  27. Xu J, Yang X, Yang L, Zou X, Wang Y et al. Clinical course and predictors of 60-day mortality in 239 critically ill patients with COVID-19: a multicenter retrospective study from Wuhan, China. Crit Care 2020; 24:394 [View Article] [PubMed]
     [Google Scholar]
  28. Fukushima T, Kabata H, Yamamoto R, Suhara T, Uwamino Y et al. The real-time reverse transcription-polymerase chain reaction threshold cycle values for severe acute respiratory syndrome coronavirus 2 predict the prognosis of coronavirus disease 2019 pneumonia. Respir Investig 2021; 59:360–363 [View Article] [PubMed]
     [Google Scholar]
  29. Miller EH, Zucker J, Castor D, Annavajhala MK, Sepulveda JL et al. Pretest symptom duration and cycle threshold values for severe Acute Respiratory syndrome coronavirus 2 reverse-transcription polymerase chain reaction predict coronavirus disease 2019 mortality. Open Forum Infect Dis 2021; 8:ofab003 [View Article] [PubMed]
     [Google Scholar]
  30. Zheng S, Fan J, Yu F, Feng B, Lou B 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 [View Article] [PubMed]
     [Google Scholar]
  31. Lucas C, Wong P, Klein J, Castro TBR, Silva J et al. Longitudinal analyses reveal immunological misfiring in severe COVID-19. Nature 2020; 584:463–469 [View Article] [PubMed]
     [Google Scholar]
  32. He X, Lau EHY, Wu P, Deng X, Wang J et al. Temporal dynamics in viral shedding and transmissibility of COVID-19. Nat Med 2020; 26:672–675 [View Article] [PubMed]
     [Google Scholar]
  33. Pan Y, Zhang D, Yang P, Poon LLM, Wang Q. Viral load of SARS-CoV-2 in clinical samples. Lancet Infect Dis 2020; 20:411–412 [View Article] [PubMed]
     [Google Scholar]
  34. El Saleeby CM, Bush AJ, Harrison LM, Aitken JA, Devincenzo JP. Respiratory syncytial virus load, viral dynamics, and disease severity in previously healthy naturally infected children. J Infect Dis 2011; 204:996–1002 [View Article] [PubMed]
     [Google Scholar]
  35. Fujiwara K, Kojima H, Yasui S, Okitsu K, Yonemitsu Y et al. Hepatitis A viral load in relation to severity of the infection. J Med Virol 2011; 83:201–207 [View Article] [PubMed]
     [Google Scholar]
  36. Granados A, Peci A, McGeer A, Gubbay JB. Influenza and rhinovirus viral load and disease severity in upper respiratory tract infections. J Clin Virol 2017; 86:14–19 [View Article] [PubMed]
     [Google Scholar]
  37. Li C-C, Wang L, Eng H-L, You H-L, Chang L-S et al. Correlation of pandemic (H1N1) 2009 viral load with disease severity and prolonged viral shedding in children. Emerg Infect Dis 2010; 16:1265–1272 [View Article] [PubMed]
     [Google Scholar]
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High SARS-CoV-2 viral load is associated with a worse clinical outcome of COVID-19 disease
Access Microbiology 3, 000259 (2021); https://doi.org/10.1099/acmi.0.000259
/content/journal/acmi/10.1099/acmi.0.000259
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