INFLAMMATORY BIOMARKERS IN PATIENTS WITH COVID-19
Keywords:
COVID-19, inflammatory biomarkers, CRP, ferritin, IL-6Abstract
The new coronavirus, termed severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2), is causing the coronavirus disease 2019 (COVID-19), which is a complex multisystem disease that in its severe form is manifested by severe pneumonia and damage to the blood vessels, heart, liver, and kidneys. Clinical data suggest that a high percentage of the patients with COVID-19 develop an abnormal inflammatory response, which can progress to multiorgan failure and death. This study aims to analyze the values of inflammatory biomarkers C-reactive protein (CRP) and interleukin 6 (IL-6), together with white blood cell (WBC) count, erythrocyte sedimentation rate (Se), ferritin (FER), and serum iron (IRN) in patients with COVID-19 who develop clinical presentations that differ in severity, and to assess the clinical significance of these parameters for diagnosis and prognosis of the course of the disease. This study was designed as a retrospective observational study. The study included a total of 115 patients divided in two groups: Group A- asymptomatic and mild cases of COVID-19, N=55 (36 men and 19 women; mean age 53.3 ± 1.4 y.) and Group B- moderate and severe cases of COVID-19 patients in need of hospitalization, N=60 (38 men and 22 women; mean age 56.1 ± 1.3 y.). All patients had a positive PCR test for SARS‑CoV‑2. The study was conducted in the period September – December 2020. Statistical analysis of the data showed that the two groups of patients did not differ in age. Mean values of Se, WBC, CRP, IL-6, and FER were higher in Group B patients than in Group A. Very high statistical significance was observed for CRP and IL-6 (p<0.001), while high statistical significance was observed for Se and FER (p<0.01). The mean value of WBC was higher in Group B patients, but with borderline statistical significance (р=0.051). The mean value of IRN was significantly lower in Group B patients compared with Group A (p<0.05). We observed a statistically significant positive correlation between CRP and IL-6 in both groups of patients [0.525, р<0.01 in Group A vs. 0.259, р<0.05 in Group B]. Serum iron shows a significant inverse correlation with CRP and IL-6, but only in Group A patients [CRP (-0.380), IL-6 (-0.424); р<0.01 for both parameters]. The results of this study show that the evaluation of inflammatory biomarkers is an available and practical tool for assessing the severity of the disease, and further for assessing the response to therapy and the outcome of COVID-19. Imbalance of iron homeostasis is associated with tissue damage and impaired host immune system function, and in this respect serum iron and ferritin are parameters that play an important role in diagnosis and monitoring of patients with COVID-19.
References
Colafrancesco, S., Alessandri, C., Conti, F., & Priori, R. (2020). COVID-19 gone bad: A new character in the spectrum of the hyperferritinemic syndrome? Autoimmun Rev, 19(7), 102573. https://doi.org/10.1016/j.autrev.2020.102573
Dienz, O., Rud, J. G., Eaton, S. M., Lanthier, P. A., Burg, E., Drew, A., Bunn, J., Suratt, B. T., Haynes, L., & Rincon, M. (2012). Essential role of IL-6 in protection against H1N1 influenza virus by promoting neutrophil survival in the lung. Mucosal Immunol, 5(3), 258-266. https://doi.org/10.1038/mi.2012.2
Hadjadj, J., Yatim, N., Barnabei, L., Corneau, A., Boussier, J., Smith, N., Péré, H., Charbit, B., Bondet, V., Chenevier-Gobeaux, C., Breillat, P., Carlier, N., Gauzit, R., Morbieu, C., Pène, F., Marin, N., Roche, N., Szwebel, T. A., Merkling, S. H., Treluyer, J. M., Veyer, D., Mouthon, L., Blanc, C., Tharaux, P. L., Rozenberg, F., Fischer, A., Duffy, D., Rieux-Laucat, F., Kernéis, S., & Terrier, B. (2020). Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients. Science, 369(6504), 718-724. https://doi.org/10.1126/science.abc6027
Kernan, K. F., & Carcillo, J. A. (2017). Hyperferritinemia and inflammation. Int Immunol, 29(9), 401-409. https://doi.org/10.1093/intimm/dxx031
Lepanto, M. S., Rosa, L., Paesano, R., Valenti, P., & Cutone, A. (2019). Lactoferrin in Aseptic and Septic Inflammation. Molecules, 24(7). https://doi.org/10.3390/molecules24071323
Pop-Kostova, A., & Ruskovska, T. (2021). Clinical significance of circulating enzymes in patients with COVID-19. KNOWLEDGE - International journal, 47(4), 611-616.
Romagnoli, S., Peris, A., De Gaudio, A. R., & Geppetti, P. (2020). SARS-CoV-2 and COVID-19: From the Bench to the Bedside. Physiol Rev, 100(4), 1455-1466. https://doi.org/10.1152/physrev.00020.2020
Siddiqi, H. K., & Mehra, M. R. (2020). COVID-19 illness in native and immunosuppressed states: A clinical-therapeutic staging proposal. J Heart Lung Transplant, 39(5), 405-407. https://doi.org/10.1016/j.healun.2020.03.012
Tan, C., Huang, Y., Shi, F., Tan, K., Ma, Q., Chen, Y., Jiang, X., & Li, X. (2020). C-reactive protein correlates with computed tomographic findings and predicts severe COVID-19 early. J Med Virol, 92(7), 856-862. https://doi.org/10.1002/jmv.25871
Tanaka, T., Narazaki, M., & Kishimoto, T. (2016). Immunotherapeutic implications of IL-6 blockade for cytokine storm. Immunotherapy, 8(8), 959-970. https://doi.org/10.2217/imt-2016-0020
Vargas-Vargas, M., & Cortés-Rojo, C. (2020). Ferritin levels and COVID-19. Rev Panam Salud Publica, 44, e72. https://doi.org/10.26633/rpsp.2020.72
Velazquez-Salinas, L., Verdugo-Rodriguez, A., Rodriguez, L. L., & Borca, M. V. (2019). The Role of Interleukin 6 During Viral Infections. Front Microbiol, 10, 1057. https://doi.org/10.3389/fmicb.2019.01057
Ye, Q., Wang, B., & Mao, J. (2020). The pathogenesis and treatment of the `Cytokine Storm' in COVID-19. J Infect, 80(6), 607-613. https://doi.org/10.1016/j.jinf.2020.03.037
Young, B., Gleeson, M., & Cripps, A. W. (1991). C-reactive protein: a critical review. Pathology, 23(2), 118-124. https://doi.org/10.3109/00313029109060809
Zhang, Z. L., Hou, Y. L., Li, D. T., & Li, F. Z. (2020). Laboratory findings of COVID-19: a systematic review and meta-analysis. Scand J Clin Lab Invest, 80(6), 441-447. https://doi.org/10.1080/00365513.2020.1768587
Zhao, K., Huang, J., Dai, D., Feng, Y., Liu, L., & Nie, S. (2020). Serum Iron Level as a Potential Predictor of Coronavirus Disease 2019 Severity and Mortality: A Retrospective Study. Open Forum Infect Dis, 7(7), ofaa250. https://doi.org/10.1093/ofid/ofaa250