RNAemia and Clinical Outcome in COVID-19 Patients

Yıl 2021, Cilt: 11 Sayı: 03, 116 - 123, 15.09.2021

Jyotsna Agarwal Vikramjeet Singh Jaya Garg Ritu Karoli2 Swasti Tiwari Shareh Naqvi Anupam Das Manodeep Sen

Öz

Objectives: Objectives: SARS-CoV-2 virus dynamics in the human body and its correlation with disease severity and biomarkers have not been elucidated. This study aims to evaluate the viral load in the blood sample of COVID-19 patients and viral load association with disease severity and progression.
Methods: Blood samples from COVID-19 positive inpatients were collected sequentially, at admission, and during hospitalization. Depending on the clinical presentation, the patients were classified into mild, moderate, and severe categories. The blood samples were subjected to SARS-CoV-2 Real-time polymerase chain reaction (RT-PCR); positive samples were then tested for viral load using digital drop RT-PCR. Patients were followed up until they were discharged.
Results: Of 83 enrolled patients, 15 (18.1%) were mild, 45 (54%) were moderate, and 23 (27.7%) had severe symptoms. The blood PCR in 21 patients was positive (rate was 25.3); one was mild, four moderate, and 16 severe on the day of admission. The mean cycle threshold (CT) of RNAemia in these 21 patients was 24.7+3.1. The viral load was significantly higher in patients with severe symptoms than others. Serum ferritin, D-dimer, and plasma fibrinogen were found raised along with lymphopenia in all patients. Viremia was found persistently detectable (or even rising) in patients in the severe category and associated with a fatal outcome.
Conclusion: A prolonged elevation of D-dimer, serum ferritin, and plasma fibrinogen together with lymphopenia lead to a greater risk of mortality and morbidity. Quantitative estimation of virus in blood has a clinical significance which may help in prognostication and management of patients of COVID-19. J Microbiol Infect Dis 2021; 11(3):116-123.

Anahtar Kelimeler

Viremia, Digital drop PCR, Serum ferritin, D-dimer, Lymphopenia, Plasma fibrinogen, Procalcitonin

Kaynakça

• 1. Peng L, Liu J, XuW, et al. SARS-CoV-2 can be detected in urine, blood, anal swabs, and oropharyngeal swabs specimens. J Med Virol 2020; 92 (9): 1676-1680. https://doi.org/10.1002/jmv.25936. 2. Chen JH-K, Yip CC-Y, Poon RW-S, et al. Evaluating the use of posterior oropharyngeal saliva in a point-of-care assay for the detection of SARS-CoV-2. Emerg Microbes Infect 2020;9(1):1–14. https://doi.org/10.1080/22221751.2020.1775133.
• 3. Pan Y, Zhang D, Yang P, Poon LLM, Wang Q. Viral load of SARS-CoV-2 in clinical samples. Lancet Infect Dis.2020;20(4):411–2. https://doi.org/10.1016/S1473-3099(20)30113-4 4. Wang W, XuY, Gao R, et al. Detection of SARS-CoV-2 in different types of clinical specimens. JAMA.2020; 323(18) :1843–4. https://doi.org/10.1001/jama.2020.3786 5. Graham TGW, Dugast-Darzacq C, Dailey GM, et al. Open-source RNA extraction and RTqPCR methods for SARS-CoV-2 detection. PLOS ONE. 2021 16(2): e0246647. https://doi.org/10.1371/journal.pone.0246647
• 6. Clinical management protocol for COVID-19. https://www.mohfw.gov.in/pdf/Updated ClinicalManagementProtocolforCOVID19dated03072020.pdf (accessed on December 29, 2020).
• 7. Bangash MN, Patel J, Parekh D. COVID-19 and the liver: little cause for concern. Lancet Gastroenterol Hepatol 2020; 5(6):529-530. https://doi.org/10.1016/S2468-1253(20)30084-4.
• 8. Mehta P, McAuley DF, Brown M, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020; 395(10229):1033-1034. https://doi.org/10.1016/S0140-6736(20)30628-0
• 9. Chen W, LanY, Yuan X, et al. Detectable 2019-nCoV viral RNA in blood is a strong indicator for the further clinical severity. Emerg Microbes Infect.2020;9:469–73. https://doi.org/10.1080/22221751.2020.1732837.
• 10. Huang C,Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020; 395(10223):497-506. https://doi.org/10.1016/S0140-6736(20)30183-5
• 11. Young, BE, Ong SWX, Kalimudiin S, et al. Epidemiologic features and clinical course of patients infected with SARS-CoV-2 in Singapore. JAMA 323, 1488–1494 (2020). https://doi.org/10.1001/jama.2020.3204
• 12. Chang L, Yan Y, Wang L. Coronavirus disease 2019: corona viruses and blood safety. Transfus Med Rev. 2020; 34(2):75–80. https://doi.org/10.1016/j.tmrv.2020.02.003.
• 13. Hagman K, Hedenstierna M, Gille-Johnson P, et al. SARS-CoV-2 RNA in serum as predictor of severe outcome in COVID-19: a retrospective cohort study. Clin Infect Dis. 2020; 2020:1285. https://doi.org/10.1093/cid/ciaa1285
• 14. 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. https://doi.org/10.1136/bmj.m1443
• 15. Dodd RY, Stramer SL. COVID-19 and blood safety: help with a dilemma.Transfus Med Rev. 2020; 34(2):73–4. https://doi.org/10.1016/j.tmrv.2020.02.004
• 16. Chen X, Zhao B, Qu Y, et al. Detectable serum SARS-CoV-2 viral load (RNAemia) is closely correlated with drastically elevated interleukin 6 (IL-6) level in critically ill COVID-19 patients. Clin Infect Dis. 2020; ciaa449. https://doi.org/10.1093/cid/ciaa449
• 17. Wölfel R, Corman VM, Guggemos W, et al. Virological assessment of hospitalized patients with COVID-2019. Nature. 2020; 581:465–9. https://doi.org/10.1038/s41586-020-2196-x
• 18. Xu H, Zhong L, Deng J, et al. High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa. Int J Oral Sci. 2020; 12(1):8. https://doi.org/10.1038/s41368-020-0074-x
• 19. Wang D, Hu B, Hu C, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020; 323(11):1061-1069. https://doi.org/10.1001/jama.2020.1585.
• 20. Fan BE, Chong VCL, Chan SSW, et al. Hematologic parameters in patients with COVID-19 infection. Am J Hematol. 2020; 95(6):E131-E134. https:// doi.org/10.1002/ajh.25774.
• 21. Yang X, Yu Y, Xu J, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med. 2020; 8 (5):475-481. https://doi.org/10.1016/S2213-2600(20)30079-5.
• 22. Deng Y, Liu W, Liu K, et al. Clinical characteristics of fatal and recovered cases of coronavirus disease 2019 (COVID-19) in Wuhan, China: a retrospective study. Chin Med J (Engl). 2020; 133 (11):1261-1267. https://doi.org/10.1097/CM9.0000000000000824
• 23. Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost JTH. 2020; 18(4):844–847. https://doi.org/10.1111/jth.14768
• 24. T. Liu, J. Zhang, Y. Yang, et al. The potential role of IL-6 in monitoring severe case of coronavirus disease 2019. Available: https://www.medrxiv.org/content/ 10.1101/2020.03.01.20029769v2 (accessed on December 29, 2020).