A comparison of the features of RT-PCR positive and negative COVID-19 pneumonia patients in the intensive care unit

Abstract

Background/Aim: COVID-19 is a serious disease, primarily affecting the respiratory system. The disease spreads from person to person and has become a global health problem of great concern worldwide. The aim of this study was to compare the clinical and laboratory characteristics and the mortality rates of suspected and confirmed COVID-19 cases admitted to the intensive care unit with severe pneumonia. Methods: A retrospective case-control study examination was made of 397 patients diagnosed with suspected or confirmed COVID-19 who were followed up in the intensive care unit (ICU) of Afyonkarahisar Health Sciences University Medical Faculty Hospital between 20 March 2020 and 31 December 2020. The cases were compared in respect of demographic, clinical and laboratory characteristics, prognosis, and mortality rates. Results: 397 patients comprised of 37 (9.3%) with suspected COVID-19 and 360 (90.7%) confirmed COVID-19. No difference was determined between the suspected and confirmed cases in respect of age, gender, and comorbidities (P<0.05). Malignancy was determined in 14 (37.8%) and in 33 (9.2%) of the suspected and confirmed COVID-19 cases, respectively. PaO2 and PaO2/FiO2 values of the confirmed COVID-19 patients were found to be significantly lower than those of suspected COVID-19 cases (P=0.027 and P=0.018, respectively). No statistically significant difference was determined between the mortality rates of suspected and confirmed COVID-19 patients (59.5% and 56.1%, respectively, P=0.731). Conclusion: When the blood analyses of 397 patients who were hospitalized in ICU with an initial diagnosis of severe COVID-19 pneumonia, regardless of COVID-19 RT-PCR test results, were compared, the LDH and CK values were determined to be significantly high, whereas PaO2 and PaO2/FiO2 values were significantly low. Since the sensitivity of RT-PCR test is low especially in cancer patients, it leads to false negative tests in a significant proportion of patients in acute phase of the disease. Therefore, the majority of patients with COVID-19 are not detected by this test, and clinical symptoms, as well as CT scans, are important to identify patients with COVID-19. Since COVID-19 infection has similar initial symptoms to other pneumonias, it is recommended to study other respiratory viral agents in patients with a negative RT-PCR test.

Keywords

• COVID-19 pneumonia
• Intensive care unit
• mortality
• RT-PCR

Kaynakça

1. 1. Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020;382:727–33. doi: 10.1056/NEJMoa2001017
2. 2. Organization WH. Coronavirus Disease (COVID-19) Situation reports. https:// www.who.int/emergencies/diseases/novel-coronavirus-2019/situation- reports.
3. 3. Lai CC, Shih TP, Ko WC, Tang HJ, Hsueh PR. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): The epidemic and the challenges. Int J Antimicrob Agents. 2020;55(3):10592. doi: 10.1016/j.ijantimicag.2020.105924
4. 4. 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;63:364–74. doi: 10.1007/s11427020-1643-8.
5. 5. Xu XW, Wu XX, Jiang XG, Xu KJ, Ying LJ, Ma CL, et al. Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series, BMJ. 2020;368. doi: 10.1136/bmj.m606
6. 6. Zou L, Ruan F, Huang M, Liang L, Huang H, Hong Z, et al. SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients. New England Journal of Medicine. 2020;1177–9. doi: 10.1056/nejmc2001737.
7. 7. Ai T, Yang Z, Hou H, Zhan C, Chen C, Lv W, et al. Correlation of Chest CT and RT-PCR Testing in Coronovirus Disease 2019 (COVID-19) in China: A Report of 1014 Cases. Radiology Radiology. 2020 Aug;296(2):E32-E40. doi: 10.1148/radiol.2020200642.
8. 8. Li Z, Yi Y, Luo X, et al. Development and clinical application of a rapid IgM-IgG combined antibody test for SARS-CoV-2 infection diagnosis. J Med Virol. 2020;92:1518–24. doi: 10.1002/jmv.25727.

9. 9. Wikramaratna PS, Paton RS, Ghafari M, Lourenço J. Estimating the false-negative test probablity of SARS-CoV-2 by RT-PCR. Euro Surveill. 2020;25(50):2000568. doi: 10.2807/1560-7917.ES.2020.25.50.2000568.
10. 10. https://COVID-19bilgi.saglik.gov.tr/depo/rehberler/COVID-19_Rehberi.pdf
11. 11. Woloshin S, Patel N, Kesselheim AS. False negative tests for SARS-CoV-2 infection– challenges and implications. N Engl J Med. 2020;383:e38
12. 12. Liu Q, Wang RS, Qu GQ, Wang YY, Liu P, Zhu YZ, et al. Gross examination report of a COVID-19 death autopsy. Fa Yi Xue Za Zhi. 2020;36:21–3. doi: 10.12116/j.issn.1004-5619.2020.01.005.
13. 13. Lei P, Fan B, Mao J, Wang P. Comprehensive analysis for diagnosis of novel coronavirus disease (COVID-19) infection. J Infect. 2020.80;6. doi: 10.1016/j.jinf.2020.03.016.
14. 14. Jin Y, Wang M, Zuo Z, Fan C, Ye F, Cai Z, et al. Diagnostic value and dynamic variance of serum antibody in coronavirus disease 2019. Int J Infect Dis. 2020;94:49–52. doi: 10.1016/j.ijid.2020.03.065
15. 15. Okba NMA, Muller MA, Li W, Wang C, GeurtsvanKessel CH, Corman VM, et al. Severe acute respiratory syndrome coronavirus 2specific antibody responses in coronavirus disease 2019 patients. Emerg Infect Dis. 2020;26:1478–88. doi: 10.3201/eid2607.200841
16. 16. Wölfel R, Corman VM, Guggemos W, Seilmaier M, Zange S, Müller MA, et al. Virological assessment of hospitalized patients with COVID-2019. Nature. 2020;581(7809):465–9. doi: 10.1038/s41586-020-2196-x.
17. 17. Xiang F, Wang X, He X, Peng Z, Yang B, Zhang J, et al. Antibody detection and dynamic characteristics in patients with coronavirus disease 2019. Clin Infect Dis. 2020;71(8):1930-34. doi: 10.1093/cid/ciaa461
18. 18. Song F, Shi N, Shan F, Zhang Z, Shen J, Lu H, et al. Emerging coronavirus 2019-nCoV pneumonia. Radiology. 2020;295:210–7. doi: 10.1148/radiol.2020200274
19. 19. Wang W, Xu Y, Gao R, Lu R, Han K, Wu G, et al. Detection of SARSCoV-2 in Different Types of Clinical Specimens. JAMA 2020;323:1843-4. doi: 10.1001/jama.2020.3786
20. 20. 20-Shah S J, Barish P N, Prasad P A, Kistler A, Neff N, Kamm J. Clinical features, diagnostics, and outcomes of patients presenting with acute respiratory illness: A retrospective cohort study of patients with and without COVID-19 E Clinical Medicine. 27 2020;100518. doi: 10.1016/j.eclinm.2020.100518
21. 21. Assaad S, Avrillon V, Fournier ML, Mastroianni B, Russias B, Swalduz A. et al. High mortality rate in cancer patients with symptoms of COVID-19 with or without detectable SARS-COV-2 on RT-PCR. European Journal of Cancer. 2020;135:251-9. doi: 10.1016/j.ejca.2020.05.028
22. 22. Solodky ML, Galvez C, Russias B, Detourbet P, N’GuyenBonin V, Herr AL, et al. Lower detection rates of SARS-COV2 antibodies in cancer patients vs healthcare workers after symptomatic COVID-19. Ann Oncol. 2020;31(8):1087-8. doi: 10.1016/j.annonc.2020.04.475
23. 23. Hui DS, Azhar EI, Madani TA, Ntoumi F, Kock R, Dar O, et al. The continuing 2019-nCoV epidemic threat of novel coronaviruses to global health - The latest 2019 novel coronavirus outbreak in Wuhan, China. Int J Infect Dis. 2020 Feb;91:264–6. doi: 10.1016/j.ijid.2020.01.009.
24. 24. Zhang ZL, Hou YL, Li DT, Li FZ. Laboratory findings of COVID-19: a systematic review and meta-analysis. Scand J Clin Lab Invest. 2020;80(6):441-7. doi: 10.1080/00365513.2020.1768587
25. 25. Baskin CR, Bielefeldt-Ohmann H, Tumpey TM, Sabourin PJ, Long JP, García-Sastre A, et al. Early and sustained innate immune response defines pathology and death in nonhuman primates infected by highly pathogenic influenza virus. Proc Natl Acad Sci USA. 2009;106:3455–60.
26. 26. Liu B, Zhang X, Deng W, Liu J, Li H, Wen M, et al. Severe influenza A(H1N1)pdm09 infection induces thymic atrophy through activating innate CD8(+)CD44(hi) T cells by upregulating IFN-γ. Cell Death Dis. 2014;5:e1440
27. 27. Van den Brand JM, Haagmans BL, Van Riel D, Osterhaus AD, Kuiken T. The pathology and pathogenesis of experimental severe acute respiratory syndrome and influenza in animal models. J Comp Pathol. 2014;151:83–112.
28. 28. Gao R, Wang L, Bai T, Zhang Y, Bo H, Shu Y. C-reactive protein mediating immunopathological lesions: a potential treatment option for severe influenza A diseases. E Bio Medicine. 2017;22:133–42. doi: 10.1016/j.ebiom.2017.07.010
29. 29. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;10223:497-506. doi: 10.1016/S0140-6736(20)30183-5
30. 30. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395:507–13. doi: 10.1016/S0140-6736(20)30211-7.
31. 31. Zhao D, Yao F, Wang L, Zheng L, Gao Y, Ye J, et al. A Comparative Study on the Clinical Features of Coronavirus 2019 (COVID-19) Pneumonia With Other Pneumonias Clinical Infectious Diseases. 2020;28:71(15):756-61. doi: 10.1093/cid/ciaa247.
32. 32. Sepulveda J. Challenges in Routine Clinical Chemistry Analysis: Proteins and Enzymes. Editor(s): A. Dasgupta, J. L. Sepulveda, Chapter 9, Accurate Results in the Clinical Laboratory, Elsevier, 2013:131-48.
33. 33. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet (London, England). 2020;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5
34. 34. Shi J, Li Y, Zhou X, Zhang Q, Ye X, Wu Z, et al. Lactate dehydrogenase and susceptibility to deterioration of mild COVID-19 patients: a multicenter nested case-control study. BMC medicine. 2020;3;18(1):168. doi: 10.1186/s12916-020-01633-7
35. 35. Poggiali E, Zaino D, Immovilli P, Rovero L, Losi G, Dacrema A, et al. Lactate dehydrogenase and C-reactive protein as predictors of respiratory failure in CoVID-19 patients. Clinica chimica acta; international journal of clinical chemistry. 2020;509:135-8. doi: 10.1016/j.cca.2020.06.012
36. 36. Zheng S, Fan J, Yu F, Feng B, Lou B, Zou Q, 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: 10.1136/bmj.m1443
37. 37. Ke C, Yu C, Yue D, Zeng X, Hu Z, Yang C. Clinical characteristics of confirmed and clinically diagnosed patients with 2019 novel coronavirus pneumonia: a single-center, retrospective, case-control study Med Clin (Barc). 2020;155(8):327–34. doi: 10.1016/j.medcli.2020.06.055.