Role of inflammatory and liver function markers in assessing the prognosis of patients with COVID‑19

Moorthy,Swathy; Koshy,Teena; K,Mahesh Kumar; Silambanan,Santhi

doi:10.3892/wasj.2021.123

Role of inflammatory and liver function markers in assessing the prognosis of patients with COVID‑19

Authors:
- Swathy Moorthy
- Teena Koshy
- Mahesh Kumar K
- Santhi Silambanan
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Affiliations: Department of General Medicine, Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamil Nadu 600116, India, Department of Human Genetics, Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamil Nadu 600116, India, Department of Physiology and Biochemistry, Government Yoga and Naturopathy Medical College and Hospital, Chennai, Tamil Nadu 600106, India, Department of Biochemistry, Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamil Nadu 600116, India
Published online on: August 26, 2021 https://doi.org/10.3892/wasj.2021.123
Article Number: 52
Copyright: © Moorthy et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) caused Coronavirus disease 2019 (COVID‑19) in early December, 2019. The disease begins as a respiratory disease with varied outcomes, from complete recovery to long‑standing complications, such as respiratory distress, heart ailments and stroke. The present study was undertaken to identify the derangements in liver function and inflammatory status which may be used to diagnose the severity and thus assess the prognosis of patients with COVID‑19 infection. The present study was conducted at a tertiary care teaching hospital. The study population included 456 patients with COVID‑19, confirmed by the reverse transcription‑PCR of nasopharyngeal swabs for SARS‑CoV‑2. Data were collected from patient files. The study was approved by the institutional ethics committee. Data are expressed based on the normality of distribution. Variables were compared and correlation analyses were performed. Receiver operating characteristics and the Youden index were applied to obtain cut‑off values. The results revealed an increase in C‑reactive protein (CRP), ferritin, D‑dimer, lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and total bilirubin levels. In addition, there was evidence of leukocytosis, neutrophilia, lymphopenia and an increased neutrophil‑to‑lymphocyte ratio (NLR). The NLR exhibited an area under the curve of 0.77, with a cut‑off value of 2.23 mg/l. Collectively, the findings of the present study demonstrate that the CRP, LDH, neutrophil and eosinophil counts along with the total leucocyte counts and absolute lymphocyte counts, NLR, erythrocyte sedimentation rate, D‑dimer, ferritin and AST levels serve to predict the severity and prognosis of patients with COVID‑19. AST appears to be a more sensitive marker than alanine aminotransferase. However, the De Ritis ratio, although not as sensitive as AST, may provide insight towards morbidity.

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1	Kenneth Oh: Aberrant cytokine activity in the host immune response to COVID-19 leads to cytokine release syndrome; Bio-Rad Bulletin_7335; May, 2020. https://www.bio-rad.com/webroot/web/pdf/lsr/literature/Bulletin_7335.pdf.
2	Hanif M, Haider MA, Xi Q, Ali MJ and Ahmed MU: A review of the risk factors associated with poor outcomes in patients with coronavirus disease 2019. Cureus. 12(e10350)2020.PubMed/NCBI View Article : Google Scholar
3	Government of India Ministry of Health and Family Welfare: Clinical Management Protocol for COVID-19 (adults). https://www.mohfw.gov.in/pdf/UpdatedDetailedClinicalManagementProtocolforCOVID19adultsdated24052021.pdf. Accessed, July 27, 2021.
4	Bernheim A, Mei X, Huang M, Yang Y, Fayad ZA, Zhang N, Diao K, Lin B, Zhu X, Li K, et al: Chest CT findings in coronavirus disease-19 (COVID-19): Relationship to duration of infection. Radiology. 295(200463)2020.PubMed/NCBI View Article : Google Scholar
5	Falasca K, Ucciferri C, Brandimarte A, Auricchio A, Pontolillo M, Caiazzo L and Vecchiet J: Clinical characteristics and cardiovascular implications of the dead patients for COVID-19. Eur J Inflam. 19:2021.
6	Ali AHM, Mohamed SOO, Elkhidir IHE, Elbathani MEH, Ibrahim AAH, Elhassan ABE, Salman MST, Elhassan MAM, Elnil M and Abuzied AIH: The association of lymphocyte count, CRP, D-Dimer, and LDH with severe coronavirus disease 2019 (COVID-19): A meta-analysis. Sudan J Med Sci. 15:9–23. 2020.
7	Büyükaydın B: The relationship of hemogram and inflammatory biomarkers to lenght of stay in hospital and clinical course in patients with COVID-19. Bezm Sci. 8:7–14. 2020.
8	Moutchia J, Pokharel P, Kerri A, McGaw K, Uchai S, Nji M and Goodman M: Clinical laboratory parameters associated with severe or critical novel coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis. PLoS One. 15(e0239802)2020.PubMed/NCBI View Article : Google Scholar
9	Zhao Y, Nie HX, Hu K, Wu XJ, Zhang YT, Wang MM, Wang T, Zheng SC, Li XC and Zeng SL: Abnormal immunity of non-survivors with COVID-19: predictors for mortality. Infect Dis Poverty. 9(108)2020.PubMed/NCBI View Article : Google Scholar
10	Pourabdollah Toutkaboni M, Askari E and Khalili N, Tabarsi P, Jamaati H, Velayati AA, Dorudinia A, Rezaei M, Nadji SA, Mohamadnia A and Khalili N: Demographics, laboratory parameters and outcomes of 1061 patients with coronavirus disease 2019: A report from Tehran, Iran. New Microbe and New Infect. 38(100777)2020.PubMed/NCBI View Article : Google Scholar
11	Kordzadeh-Kermani E, Khalili H and Karimzadeh I: Pathogenesis, clinical manifestations and complications of COVID-19. Future Microbiol. 15:1287–1305. 2020.PubMed/NCBI View Article : Google Scholar
12	Thompson S, Bohn MK, Mancini N, Loh TP, Wang CB, Grimmler M, Yuen KY, Mueller R, Koch D, Sethi S, et al: Horvath and the IFCC taskforce on COVID-19. IFCC interim guidelines on biochemical/hematological monitoring of COVID-19 patients. Clin Chem Lab Med. 58:2009–2016. 2020.PubMed/NCBI View Article : Google Scholar
13	Danwang C, Endomba FT, Nkeck JR, Wouna DLA, Robert A and Noubiap JJ: A meta-analysis of potential biomarkers associated with severity of coronavirus disease 2019 (COVID-19). Biomark Res. 8(37)2020.PubMed/NCBI View Article : Google Scholar
14	Ucciferri C, Vecchiet J and Falasca K: Role of monoclonal antibody drugs in the treatment of COVID-19. World J Clin Cases. 8:4280–4285. 2020.PubMed/NCBI View Article : Google Scholar
15	Zenga F, Huangc Y, Guoa Y, Yina M, Chena X, Xiaod L and Deng G: Association of inflammatory markers with the severity of COVID-19: A meta-analysis. Int J Infect Dis. 96:467–474. 2020.PubMed/NCBI View Article : Google Scholar
16	Jurado A, Martín MC, Abad-Molina C, Orduña A, Martínez A, Ocaña E, Yarce O, Navas AM, Trujillo A, Fernández L, et al: COVID-19: Age, interleukin-6, C-reactive protein, and lymphocytes as key clues from a multicentre retrospective study. Immun Ageing. 17(22)2020.PubMed/NCBI View Article : Google Scholar
17	Khourssaji M, Chapelle V, Evenepoel A, Belkhir L, Yombi JC, van Dievoet MA, Saussoy P, Coche E, Fillée C, Constantinescu SN, et al: A biological profile for diagnosis and outcome of COVID-19 patients. Clin Chem Lab Med. 58:2141–2150. 2020.PubMed/NCBI View Article : Google Scholar
18	Marfia G, Navone S, Guarnaccia L, Campanella R, Mondoni M, Locatelli M, Barassi A, Fontana L, Palumbo F, Garzia E, et al: Decreased serum level of sphingosine-1-phosphate: A novel predictor of clinical severity in COVID-19. EMBO Mol Med. 13(e13424)2021.PubMed/NCBI View Article : Google Scholar
19	Hu H, Du H, Li J, Wang Y, Xu X, Wang C, Zhang Y, Zhang G, Zhao Y, Kang W and Lian J: Early prediction and identification for severe patients during the pandemic of COVID-19: A severe COVID-19 risk model constructed by multivariate logistic regression analysis. J Glob Health. 10(020510)2020.PubMed/NCBI View Article : Google Scholar
20	Mirmohammadi S, Kianmehr A, Arefi M and Mahrooz A: Biochemical parameters and pathogenesis of SARS-CoV-2 infection in vital organs: COVID-19 outbreak in Iran. New Microbes New Infect. 38(100792)2020.PubMed/NCBI View Article : Google Scholar
21	Alhenc-Gelas F and Drueke TB: Blockade of SARS-CoV-2 infection by recombinant soluble ACE2. Kidney Int. 97:1091–1093. 2020.PubMed/NCBI View Article : Google Scholar
22	Zhang L, Peng Y, Zheng Q, Jiang L, Tang S and Chen P: Retrospective analysis of clinical characteristics and laboratory results of COVID-19 patients. European Journal of Inflammation. January 2021. doi:10.1177/20587392211011919.
23	Kho J, Ioannou A, Van den Abbeele K, Mandal AKJ and Missouris CG: Pulmonary embolism in COVID-19: Clinical characteristics and cardiac implications. Am J Emerg Med. 38:2142–2146. 2020.PubMed/NCBI View Article : Google Scholar
24	Farooqi F, Dhawan N, Morgan R, Dinh J, Nedd K and Yatzkan G: Treatment of severe COVID-19 with Tocilizumab mitigates cytokine storm and averts mechanical ventilation during acute respiratory distress: A case report and literature review. Trop Med Infect Dis. 5(112)2020.PubMed/NCBI View Article : Google Scholar
25	Guillén L, Padilla S, Fernández M, Agulló V, García JA, Telenti G, García-Abellán J, Botella Á, Gutiérrez F and Masiá M: Preemptive interleukin-6 blockade in patients with COVID-19. Sci Rep. 10(16826)2020.PubMed/NCBI View Article : Google Scholar
26	Cavalli G, Farina N, Campochiaro C, De Luca G, Della-Torre E, Tomelleri A and Dagna L: Repurposing of biologic and targeted synthetic Anti-Rheumatic drugs in COVID-19 and Hyper-Inflammation: A comprehensive review of available and emerging evidence at the Peak of the Pandemic. Front Pharmacol. 11(598308)2020.PubMed/NCBI View Article : Google Scholar
27	Li H, Liu L, Zhang D, Xu J, Dai H, Tang N, Su X and Cao B: SARS-CoV-2 and viral sepsis: Observations and hypotheses. Lancet. 395:1517–1520. 2020.PubMed/NCBI View Article : Google Scholar
28	Ponti G, Maccaferri M, Ruini C, Tomasi A and Ozben T: Biomarkers associated with COVID-19 disease progression. Crit Rev Clin Lab Sci. 57:389–399. 2020.PubMed/NCBI View Article : Google Scholar
29	Huang I, Pranata R, Lim MA, Oehadian A and Alisjahbana B: C-reactive protein, procalcitonin, D-dimer, and ferritin in severe coronavirus disease-2019: A meta-analysis. Ther Adv Respir Dis. 14(1753466620937175)2020.PubMed/NCBI View Article : Google Scholar
30	Weidmann MD, Ofori K and Rai AJ: Laboratory Biomarkers in the management of patients with COVID-19. Am J Clin Pathol. 155:333–342. 2021.PubMed/NCBI View Article : Google Scholar
31	Gris JC, Perez-Martin A, Quéré I and Sotto A: COVID-19 associated coagulopathy: The crowning glory of thrombo-inflammation concept. Anaesth Crit Care Pain Med. 39:381–382. 2020.PubMed/NCBI View Article : Google Scholar
32	Yazdanpanah F, Hamblin MR and Rezaei N: The immune system and COVID-19: Friend or foe? Life Sci. 256(117900)2020.PubMed/NCBI View Article : Google Scholar
33	Zhang L and Guo H: Biomarkers of COVID-19 and technologies to combat SARS-CoV-2. Adv Biomark Sci Technol. 2:1–23. 2020.PubMed/NCBI View Article : Google Scholar
34	South AM, Brady TM and Flynn JT: ACE2 (Angiotensin-Converting Enzyme 2), COVID-19, and ACE Inhibitor and Ang II (Angiotensin II) Receptor blocker use during the Pandemic: The Pediatric perspective. Hypertension. 76:16–22. 2020.PubMed/NCBI View Article : Google Scholar
35	Gong J, Ou J, Qiu X, Jie Y, Chen Y, Yuan L, Cao J, Tan M, Xu W, Zheng F, et al: A tool for early prediction of severe Coronavirus disease 2019 (COVID-19): A multicenter study using the risk Nomogram in Wuhan and Guangdong, China. Clin Infect Dis. 71:833–840. 2020.PubMed/NCBI View Article : Google Scholar
36	Adhikari IP, Tiwari R and Bala R: Estimation of the De Ritis ratio in the cases of chronic alcoholic liver disease attending OPD of a tertiary health care level institute of Kanpur, UP. PARIPEX-Indian J Res. 7:219–221. 2018.
37	Ghahramani S, Tabrizi R, Lankarani KB, Kashani SMA, Rezaei S, Zeidi N, Akbari M, Heydari ST, Akbari H, Nowrouzi-Sohrabi P and Ahmadizar F: Laboratory features of severe vs. non-severe COVID-19 patients in Asian populations: A systematic review and meta-analysis. Eur J Med Res. 25(30)2020.PubMed/NCBI View Article : Google Scholar
38	Yazar H, Kayacan Y and Ozdin M: De Ritis ratio and biochemical parameters in COVID-19 patients. Arch Physiol Biochem. 1–5. 2020.PubMed/NCBI View Article : Google Scholar : (Epub ahead of print).
39	Zinellu A, Arru F, De Vito A, Sassu A, Valdes G, Scano V, Zinellu E, Perra R, Madeddu G, Carru C, et al: The De Ritis ratio as prognostic biomarker of in-hospital mortality in COVID-19 patients. Eur J Clin Invest. 51(e13427)2021.PubMed/NCBI View Article : Google Scholar
40	Parmar KS, Singh GK, Gupta GP, Pathak T and Nayak S: Evaluation of De Ritis ratio in liver-associated diseases. Int J Med Sci Public Health. 5:1783–1788. 2016.
41	Qin C, Wei Y, Lyu X, Zhao B, Feng Y, Li T, Cao H, Yang X, Zhou X, Wang W, et al: High aspartate aminotransferase to alanine aminotransferase ratio on admission as risk factor for poor prognosis in COVID-19 patients. Sci Rep. 10(16496)2020.PubMed/NCBI View Article : Google Scholar
42	Botros M and Sikaris KA: The de ritis ratio: The test of time. Clin Biochem Rev. 34:117–130. 2013.PubMed/NCBI
43	Varim C, Yaylaci S, Demirci T, Kaya T, Nalbant A, Dheir H, Senocak D, Kurt R, Cengiz H and Karacaer C: Neutrophil count to albumin ratio as a new predictor of mortality in patients with COVID-19 infection. Rev Assoc Med Bras (1992). 66 (Suppl 2):S77–S81. 2020.PubMed/NCBI View Article : Google Scholar
44	Ucciferri C, Caiazzo L, Di Nicola M, Borrelli P, Pontolillo M, Auricchio A, Vecchiet J and Falasca K: Parameters associated with diagnosis of COVID-19 in emergency department. Immun Inflamm Dis. 9:851–861. 2021.PubMed/NCBI View Article : Google Scholar
45	Kabak M, Çil B and Hocanlı I: Relationship between leukocyte, neutrophil, lymphocyte, platelet counts, and neutrophil to lymphocyte ratio and polymerase chain reaction positivity. Int Immunopharmacol. 93(107390)2021.PubMed/NCBI View Article : Google Scholar