The Importance of Inflammatory Markers In Prediction Of Mortality In COVID-19 Patients

Yıl 2024, Cilt: 19 Sayı: 1, 17 - 26, 28.03.2024

Hacer Kandilcik , Selçuk Nazik , Fatma Gümüşer , Selma Ateş

https://doi.org/10.17517/ksutfd.1174740

Öz

Objective: COVID-19, which emerged in China at the end of December 2019, spread all over the world in a short time and was accepted as a pandemic by the World Health Organization on March 11, 2020. The pandemic is still up-to-date with its changing variants and number of cases. In this study, we aimed to determine the importance of hematological, inflammatory, and biochemical markers measured on the 1st and 5th days in inpatients with a diagnosis of COVID-19 in predicting mortality.

Material And Methods: The research was designed as a retrospective and cross-sectional study. The study included 200 patients over the age of 18 who were admitted to Kahraman-maraş Sütçü İmam University Hospital between 1 November 2020 and 30 April 2021 with suspected symptoms of COVID-19, and the diagnosis was confirmed by the RT-PCR test. The patient's age, gender, comorbid diseases, 1st and 5th-day laboratory parameters, and out-come were recorded. The patients were divided into two groups discharged and deceased.

Results: Of the 200 patients included in the study, 75% (n=150) were discharged and 25% (n=50) died within 28 days. 63.5% (n=127) of the patients were male and 36.5% (n=73) were female. The mean age of the patients was 63±17.2 years. Of the patients, 50.5% had mild, 31% moderate, and 18.5% severe clinical. Logistic regression analysis was performed to determine the factors affecting the prognosis of COVID-19 patients. Factors associated with prognosis were found to be male gender, presence of DM, presence of chronic obstructive pulmonary disease, presence of hypertension, fever, shortness of breath, and cough. Lymphocyte (lymphopenia), CRP (C-Reactive Protein), PCT (Procalcitonin), NLR (Neutrophil lymphocyte ratio), PLR (Procalcitonin lymphocyte ratio), D-Dimer values measured on the 1st and 5th days of the patients were found to be a predictor of mortality at the time of diagnosis and during follow-ups (p<0.005).
Conclusion: In our study, it was determined that leukocyte, lymphocyte, NLR, PLR, CRP, PCT, ferritin, D-Dimer, and LDH values measured in COVID-19 patients were important parameters in predicting mortality at admission and during hospitalization. We think that these parameters will help the clinician in the follow-up of patients with COVID-19.

Anahtar Kelimeler

COVID-19, prognosis, CRP, PCT, hematological parameters

COVID-19 Hastalarında Mortaliteyi Öngörmede İnflamatuvar Belirteçlerin Önemi

Öz

Amaç: Çin’de 2019 Aralık ayı sonunda ortaya çıkan COVID-19 kısa sürede tüm dünyaya yayılarak Dünya Sağlık Örgütü tarafından 11 Mart 2020’de pandemi olarak kabul edilmiştir. Pandemi hala değişen varyantlarıyla ve vaka sayılarıyla güncelliğini korumaktadır. Bu çalışmada COVID-19 tanılı yatan hastalarda 1. ve 5. gün bakılan hematolojik, inflamatuvar ve biyokimyasal belirteçlerin mortaliteyi öngörmede önemini belirlemeyi amaçladık.
Gereç ve Yöntemler: Araştırma retrospektif ve kesitsel çalışma olarak tasarlanmıştır. Çalışmaya 1 Kasım 2020-30 Nisan 2021 tarihleri arasında Kahramanmaraş Sütçü İmam Üniversitesi Hastanesi’ne COVID-19 şüpheli semptomları ile başvuran COVID-19 RT-PCR testi ile tanısı doğrulanarak yatışı yapılan 18 yaş üstü 200 hasta dahil edilmiştir. Hastaların yaş, cinsiyet, eşlik eden komorbid hastalıkları, 1. ve 5. gün laboratuvar parametreleri ve sonlanım durumları kaydedildi. Hastalar taburcu ve ölen şeklinde iki gruba ayrıldı.
Bulgular: Çalışmaya alınan 200 hastanın %75’i (n=150) taburcu olan, %25’i ise (n=50) 28 gün içinde ölen hastalardan oluşmaktaydı. Hastaların %63.5’i (n=127) erkek, %36.5’i (n=73) kadındı. Hastaların yaş ortalaması 63±17.2 yıldı. Hastaların %50.5’i hafif, %31’i orta, %18.5’i ise ağır klinik tabloya sahipti. COVID-19 hastalarının prognozunu etkileyen faktörleri belirlemek amacıyla lojistik regresyon analizi yapıldı. Prognoz ile ilişkili faktörler erkek cinsiyet, diyabetes mellitus, kronik obstrüktif akciğer hastalığı, hipertansiyon varlığı, ateş, nefes darlığı ve öksürük olarak bulundu. Hastaların 1. ve 5.gün bakılan lenfosit (lenfopeni), C-Reaktif Protein (CRP), Prokalsitonin (PCT), nötrofil/lenfosit oranı (NLO), platelet /lenfosit oranı (PLO), D-Dimer değerleri tanı anında ve takiplerde mortalite öngörücüsü olarak tespit edildi (p<0.05).
Sonuç: Çalışmamızda COVID-19 hastalarında bakılan lökosit, lenfosit, NLO, PLO, CRP, PCT, ferritin, D-Dimer ve LDH değerlerinin başvuru sırasında ve yatış takiplerinde mortaliteyi öngörmede önemli parametreler olduğu saptandı. Bu parametrelerin COVID-19 hasta takibinde klinisyene yardımcı olacağını düşünmekteyiz.

Anahtar Kelimeler

COVID-19, prognoz, CRP, PCT, hematolojik parametreler

Kaynakça

• Cao, Y., Liu, X., Xiong, L., & Cai, K. Imaging and clinical features of patients with 2019 novel coronavirus SARS‐CoV‐2: a systematic review and meta‐analysis. Journal of medical virology, 2020; 92(9), 1449-1459.
• Fan, Yi; Zhao, Kai; Shi, Zheng-Li; Zhou, Peng. "Bat Coronaviruses in China." Viruses 2019; 11, no. 3: 210 PMC 6466186. PMID 30832341.
• Ciotti, Marco, et al. "COVID-19 outbreak: an overview." Chemotherapy 64.5-6 2019: 215-223.
• Tan W, Zhao W, Ma X, et al. A Novel Coronavirus Genome Identified in a Cluster of Pneumonia Cases Wuhan, China 2019−2020, Notes from the Field, China CDC Weekly.
• World Health Organization. Coronavirus disease (COVID-19) situation dashboard. 2020. Accessed April, 2.
• Doruk ÖG, Örmen M, Tuncel P. COVID-19’da biyokimyasal ve hematolojik parametreler. DEU Tıp Derg 2021;35(Özel Sayı 1): 71-80.
• DO W, Ni Z, Hu Y, et al. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020;382(18): 1708-1720. Doi: 10.1056/nejmoa2002032.
• Temgoua MN, Endomba FT, Nkeck JR, Kenfack GU, Tochie JN, Essouma M. Coronavirus Disease 2019 (COVID-19) as a Multi-Systemic Disease and its Impact in Low and Middle-Income Countries (LMICs). SN Compr Clin Med. Published online July 2020: 1-11. doi: 10.1007/s42399-020-00417-7.
• Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. www.covid19treatmentguidelines.nih.gov
• Wu C, Chen X, Cai Y, et al. Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Intern Med.2020;180(7): 934-943.
• Arslan B, Dinçel AS. Biyokimya laboratuvarında COVID-19: Klinik araştırmadan rutine inflamatuvar belirteçler. Yücel D, editör. COVID-19 Pandemisinde Tıbbi Biyokimyanın Artan Rolü. 1. Baskı. Ankara: Türkiye Klinikleri; 2021. p.13-8.
• WHO. Clinical management of COVID-19. https://www.who.int/publications/i/item/clinical-management-of-covid-19.
• Li, J., Huang, D. Q., Zou, B., Yang, H., Hui, W. Z., Rui, F., & Nguyen, M. H. (2021). Epidemiology of COVID‐19: a systematic review and meta‐analysis of clinical characteristics, risk factors, and outcomes. Journal of medical virology, 93(3), 1449-1458.
• Albitar, O., Ballouze, R., Ooi, J. P., & Ghadzi, S. M. S. (2020). Risk factors for mortality among COVID-19 patients. Diabetes research and clinical practice, 166, 108293.
• Jaillon, S., Berthenet, K., & Garlanda, C. (2019). Sexual dimorphism in innate immunity. Clinical reviews in allergy & immunology, 56(3), 308-321.
• Acar, E., Demir, A., Yıldırım, B., Kaya, M. G., & Gökçek, K. (2021). The role of hemogram parameters and Creactive protein in predicting mortality in COVID‐19 infection. International journal of clinical practice, 75(7), e14256.
• Du Y, Zhou N, Zha W, Lv Y. Hypertension is a clinically important risk factor for critical illness and mortality in COVID-19: A meta-analysis. Nutr Metab Cardiovasc Dis. 2021;31(3):745-755. Doi: 10.1016/j.numecd.2020.12.009.
• Semenzato L, Botton J, Drouin J, Cuenot F, Dray-Spira R, Weill A, Zureik M. Chronic diseases, health conditions and risk of COVID-19-related hospitalization and in-hospital mortality during the first wave of the epidemic in France: a cohort study of 66 million people. Lancet Reg Health Eur. 2021 Sep; 8:100158. Doi: 10.1016/j.lanepe.2021.100158. Epub 2021 Jul 16. PMID: 34308411; PMCID: PMC8282330.
• The Novel Coronavirus Pneumonia Emergency Response Epidemiology Team (2020). The Epidemiological Characteristics of an Outbreak of 2019 Novel Coronavirus Diseases (COVID-19) China, 2020. China CDC weekly, 2(8), 113–122.
• Della Salute, M. (2020). Covid-19-Situazione in Italia. Roma, I: Governo-Repubblica Italiana. Retrieved, 3(11), 2020.
• Al Mutair A, Al Mutairi A, Alhumaid S, Maaz Abdullah S, Zia Zaidi AR, Rabaan AA, Al-Omari A. Examining and investigating the impact of demographic characteristics and chronic diseases on mortality of COVID-19: Retrospective study. PLoS One. 2021 Sep 10;16(9): e0257131. Doi: 10.1371/journal.pone.0257131. PMID: 34506551; PMCID: PMC843275
• Li L. Q., Huang T., Wang Y. Q., Wang Z. P., Liang Y., Huang T. B., et al. (2020). COVID-19 patients’ clinical characteristics, discharge rate, and fatality rate of meta-analysis. Journal of medical virology, 92(6), 577–583. pmid:32162702.
• Goodman KE, Magder LS, Baghdadi JD, Pineles L, Levine AR, Perencevich EN, Harris AD. Impact of Sex and Metabolic Comorbidities on Coronavirus Disease 2019 (COVID-19) Mortality Risk Across Age Groups: 66 646 Inpatients Across 613 U.S. Hospitals. Clin Infect Dis. 2021 Dec 6;73(11): 4113-4123. Doi: 10.1093/cid/ciaa1787. PMID: 33337474; PMCID: PMC7799326.
• Atalla E, Zhang R, Shehadeh F, Mylona EK, Tsikala-Vafea M, Kalagara S, Henseler L, Chan PA, Mylonakis E. Clinical Presentation, Course, and Risk Factors Associated with Mortality in a Severe Outbreak of COVID-19 in Rhode Island, USA, April-June 2020. Pathogens. 2020 Dec 24;10(1):8. doi: 10.3390/pathogens10010008. PMID: 33374131; PMCID: PMC7824344.
• Struyf, T., Deeks, J. J., Dinnes, J., Takwoingi, Y., Davenport, C., Leeflang, M. M., & COVID, C. (2021). Signs and symptoms to determine if a patient presenting in primary care or hospital outpatient settings has COVID‐19. Cochrane Database of Systematic Reviews, (2).
• Nasserie, T., Hittle, M., & Goodman, S. N. (2021). Assessment of the frequency and variety of persistent symptoms among patients with COVID-19: a systematic review. JAMA network open, 4(5), e2111417-e2111417.
• Yang, M. (2020). Cell pyroptosis, a potential pathogenic mechanism of 2019-nCoV infection. Available at SSRN 3527420.
• Qu R, Ling Y, Zhang YH, Wei LY, Chen X, Li XM, Liu XY, Liu HM, Guo Z, Ren H, Wang Q. Platelet-to-lymphocyte ratio is associated with prognosis in patients with coronavirus disease-19. J Med Virol. 2020 Sep;92(9):1533-1541. Doi: 10.1002/jmv.25767. Epub 2020 Mar 26. PMID: 32181903; PMCID: PMC7228291.
• Simadibrata DM, Calvin J, Wijaya AD, Ibrahim NAA. Neutrophil-to-lymphocyte ratio on admission to predict the severity and mortality of COVID-19 patients: A meta-analysis. Am J Emerg Med. 2021 Apr; 42:60-69. doi: 10.1016/j.ajem.2021.01.006. Epub 2021 Jan 9. PMID: 33453617; PMCID: PMC7832118.
• Wu L, Zou S, Wang C, Tan X, Yu M. Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio in Chinese Han population from Chaoshan region in South China. BMC Cardiovasc Disord. 2019 May 27;19(1):125. doi: 10.1186/s12872-019-1110-7. PMID: 31132989; PMCID: PMC6537433.
• Sarkar S, Kannan S, Khanna P, Singh AK. Role of platelet-to-lymphocyte count ratio (PLR), as a prognostic indicator in COVID-19: A systematic review and meta-analysis. J Med Virol. 2022 Jan;94(1):211-221. doi: 10.1002/jmv.27297. Epub 2021 Aug 31. PMID: 34436785; PMCID: PMC8661888.
• Fois, A. G., Paliogiannis, P., Scano, V., Cau, S., Babudieri, S., Perra, R., ... & Zinellu, A. (2020). The systemic inflammation index on admission predicts in-hospital mortality in COVID-19 patients. Molecules, 25(23), 5725.
• Wang, R., He, M., Yin, W., Liao, X., Wang, B., Jin, X., & Kang, Y. (2020). The Prognostic Nutritional Index is associated with mortality of COVID‐19 patients in Wuhan, China. Journal of clinical laboratory analysis, 34(10), e23566.
• Kazancioglu, S., Bastug, A., Ozbay, B. O., Kemirtlek, N., & Bodur, H. (2020). The role of haematological parameters in patients with COVID-19 and influenza virus infection. Epidemiology & Infection, 148.
• Korkmaz, C., Demirbaş, S., Vatansev, H., Yosunkaya, S., Turgut, T. E. K. E., Zamani, A., & Mehmet, U.Y.A.R. (2021). The Association of Neutrophil/Lymphocyte Ratio, Lymphocyte/Monocyte Ratio, Platelet/Lymphocyte Ratio and Hematological Parameters with Severity and Prognosis in Hospitalized Patients with COVID-19. Online Türk Sağlık Bilimleri Dergisi, 6(2), 251-261.
• Seyit M, Avci E, Nar R, et al. Neutrophil to lymphocyte ratio, lymphocyte to monocyte ratio and platelet to lymphocyte ratio to predict the severity of COVID‐19. Am J Emerg Med. 2021; 40:110‐114. 10.1016/j.ajem.2020.11.058.
• Mousavi, S. A., Rad, S., Rostami, T., Rostami, M., Mousavi, S. A., Mirhoseini, S. A., & Kiumarsi, A. (2020). Hematologic predictors of mortality in hospitalized patients with COVID-19: a comparative study. Hematology, 25(1), 383-388.
• Henry BM, de Oliveira MHS, Benoit S, Plebani M, Lippi G. Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): a meta-analysis. Clin Chem Lab Med. 2020 Jun 25;58(7):1021-1028. Doi: 10.1515/cclm-2020-0369. PMID: 32286245.
• Zeng F, Li L, Zeng J, Deng Y, Huang H, Chen B, Deng G. Can we predict the severity of coronavirus disease 2019 with a routine blood test? Pol Arch Intern Med. 2020 May 29;130(5):400-406. doi: 10.20452/pamw.15331. Epub 2020 May 1. PMID: 32356642.
• Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, Qiu Y, Wang J, Liu Y, Wei Y, Xia J, Yu T, Zhang X, Zhang L. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020 Feb 15;395(10223):507-513. doi: 10.1016/S0140-6736(20)30211-7. Epub 2020 Jan 30. PMID: 32007143; PMCID: PMC7135076.
• Beyan, C., & Beyan, E. (2021). Mean platelet volume may not be a mortality marker in patients with COVID-19 pneumonia. The American journal of emergency medicine, S0735-6757(21)01032-9. Advance online publication. https://doi.org/10.1016/j.ajem.2021.12.061
• Asan, A., Üstündağ, Y., Koca, N., Şimşek, A., Sayan, H. E., Parildar, H., ... & Huysal, K. (2021). Do initial hematologic indices predict the severity of COVID-19 patients? Turkish Journal of Medical Sciences, 51(1), 39-44.
• Işler Y, Kaya H. The author responds: MPV, cardiovascular risk, and COVID prognosis. The American Journal of Emergency Medicine. 2021 Dec. DOI: 10.1016/j.ajem.2021.12.060. PMID: 34996649; PMCID: PMC8718869.
• Kotula JJ 3rd, Moore WS 2nd, Chopra A, Cies JJ. Association of Procalcitonin Value and Bacterial Coinfections in Pediatric Patients With Viral Lower Respiratory Tract Infections Admitted to the Pediatric Intensive Care Unit. J Pediatr Pharmacol Ther. 2018 Nov-Dec;23(6):466-472. doi: 10.5863/1551-6776-23.6.466. PMID: 30697132; PMCID: PMC6336174.
• Ke C, Wang Y, Zeng X, Yang C, Hu Z. 2019 Novel coronavirus disease (COVID-19) in hemodialysis patients: A report of two cases. Clin Biochem. 2020 Jul; 81:9-12. doi: 10.1016/j.clinbiochem.2020.04.008. Epub 2020 Apr 30. PMID: 32360479; PMCID: PMC719127.
• Lippi G, Plebani M. Procalcitonin in patients with severe coronavirus disease 2019 (COVID-19): A meta-analysis. Clin Chim Acta. 2020 Jun; 505: 190-191. doi: 10.1016/j.cca.2020.03.004. Epub 2020 Mar 4. PMID: 32145275; PMCID: PMC7094472.
• Chaudhary R, Garg J, Houghton DE, Murad MH, Kondur A, Chaudhary R, Wysokinski WE, McBane RD 2nd. Thromboinflammatory Biomarkers in COVID-19: Systematic Review and Meta-analysis of 17,052 Patients. Mayo Clin Proc Innov Qual Outcomes. 2021 Apr;5(2):388-402. doi: 10.1016/j.mayocpiqo.2021.01.009. Epub 2021 Feb 8. PMID: 33585800; PMCID: PMC7869679.
• Zhou, F., Yu, T., Du, R., Fan, G., Liu, Y., Liu, Z., & Cao, B. (2020). Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. The lancet, 395(10229), 1054-1062.
• Zhang, Z. L., Hou, Y. L., Li, D. T., & Li, F. Z. (2020). Laboratory findings of COVID-19: a systematic review and meta-analysis. Scandinavian journal of clinical and laboratory investigation, 80(6), 441-447.
• Orioli, L., Servais, T., Belkhir, L., Laterre, P. F., Thissen, J. P., Vandeleene, B., & Hermans, M. P. (2021). Clinical characteristics and short-term prognosis of in-patients with diabetes and COVID-19: a retrospective study from an academic center in Belgium. Diabetes & Metabolic Syndrome: Clinical Research & Reviews, 15(1), 149-15