Evaluation of endothelial dysfunction and inflammation in recovered COVID-19 patients

Abstract

Aim: In our study, we aimed to evaluate the endothelial functions and hemogram parameters, which are considered as inflammation markers, in young people with a history of COVID-19 infection. Methods: This prospective study included 109 recovered COVID-19 patients and 50 healthy controls. Demographic characteristics, laboratory values and flow-mediated vasodilation test (FMD) results of the groups were compared. Results: Demographic and biochemistry parameters of the groups were similar. The calculated FMD values were significantly lower in the recovered COVID-19 patient group compared to the control group (8.66±3.31 vs 11.69±3.01; p= 0.001). While there was no difference between the groups in terms of neutrophil/lymphocyte ratio (NLR) and Platelet/Lymphocyte ratio (PLR), systemic immune-inflammation index (SII) was found to be higher in the patient group with recovered COVID-19 patients (p = 0.02). In correlation analysis, there was a low moderate negative correlation between FMD and SII (r = -0.35, p=0.002). Conclusion: FMD measurement and SII are simple, easily accessible parameters that can be useful in the early period to evaluate cardiovascular risks in the long term after COVID-19. There is a need for larger and multicenter studies on this subject.

Keywords

• endothelial dysfunction
• Covid-19
• inflammation

İyileşmiş COVID-19 hastalarının endotel disfonksiyonu ve inflamasyonun değerlendirilmesi

Abstract

Amaç: Çalışmamızda COVİD-19 enfeksiyonu geçirme hikayesi olan genç kişilerde endoteyal fonksiyonunu ve inflamasyon belirteci olarak kabul edilen hemogram parametrelerini değerlendirmeyi amaçladık. Yöntemler: Bu prospektif çalışmaya 109 iyileşen COVID-19 hastası ve 50 sağlıklı kontrol olgusu alındı. Grupların demografik özellikleri, laboratuvar değerleri ve akım aracılı vazodilatasyon testi (FMD) sonuçları karşılaştırılmıştır. Bulgular: Grupların demografik verileri ve biyokimya parametreleri benzerdi. Hesaplanan FMD değerleri COVID-19 geçiren hasta grubunda kontrol grubuna kıyasla anlamlı derecede daha düşüktü (8,66±3,31 ve 11,69±3,01; p= 0,001). Nötrofil/lenfosit oranı (NLR) ve Platelet/Lenfosit oranı (PLR) arasında gruplar arasında fark yokken, sistemik immün-inflamasyon indeksi (Sİİ) COVID-19 enfeksiyonu geçirmiş hasta grubunda daha yüksek saptandı (p = 0.02). Spearman korelasyon analizinde FMD ve SII arasında düşük orta derecede korelasyon saptandı (r=0.35, p=0.002). Sonuç: COVID-19 sonrası uzun vadede kardiyovasküler riskleri değerlendirmek amaçlı erken dönemde FMD ölçümü ve SII faydalı olabilecek basit, kolay ulaşılabilir parametrelerdir. Bu konu hakkında daha geniş çaplı ve çok merkezli çalışmalara ihtiyaç vardır.

Keywords

• endotel disfonksiyonu
• Covid-19
• inflamasyon

References

1. Xue G, Gan X, Wu Z, et al. Novel serological biomarkers for inflammation in predicting disease severity in patients with COVID-19. Int Immunopharmacol. 2020;89(PtA):107065. doi: 10.1016/j.intimp.2020.107065
2. Fois AG, Paliogiannis P, Scano V, et al. The systemic ınflammation ındex on admission predicts ın-hospital mortality in COVID-19 patients. Molecules. 2020;25(23):5725. doi:10.3390/molecules25235725
3. Salman E, Çelikbilek N, Aydoğan S, et al. Investigation of the relationship of systemic ımmune-ınflammation ındex, C-reactive protein and ınterleukin-6 with viral dynamics in patients with COVID-19]. Mikrobiyol Bul. 2021;55(4):539-552. doi:10.5578/mb.20219706
4. Magadum A, Kishore R. Cardiovascular manifestations of COVID-19 infection. Cells. 2020;9(11):2508. doi:10.3390/cells9112508
5. Yeboah J, Folsom AR, Burke GL, et al. Predictive value of brachial flow-mediated dilation for incident cardiovascular events in a population-based study: the multi-ethnic study of atherosclerosis. Circulation. 2009;120(6):502-509. doi:10.1161/CIRCULATIONAHA.109.864801
6. Yang R, Chang Q, Meng X, Gao N, Wang W. Prognostic value of systemic immune-inflammation index in cancer: A meta-analysis. J Cancer. 2018;9(18):3295-3302
7. Zhong JH, Huang DH, Chen ZY. Prognostic role of systemic immune-inflammation index in solid tumors: a systematic review and meta-analysis. Oncotarget. 2017;8(43):75381-75388.
8. Shi S, Qin M, Shen B, et al. Association of cardiac ınjury with mortality in hospitalized patients with COVID-19 in Wuhan, China. JAMA Cardiol. 2020;5(7):802-810. doi:10.1001/ jamacardio.2020.0950

9. Guo T, Fan Y, Chen M, et al. Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 (COVID-19). JAMA Cardiol. 2020;5(7):811-818. doi:10.1001/jamacardio.2020.1017.
10. Mao L, Jin H, Wang M, et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol. 2020;77(6):683-690. doi:10.1001/ jamaneurol.2020.1127
11. Puntmann VO, Carerj ML, Wieters I, et al. Outcomes of cardiovascular magnetic resonance ımaging in patients recently recovered from coronavirus disease 2019 (COVID-19). JAMA Cardiol. 2020;5(11): 1265-1273. doi:10.1001/jamacardio.2020.3557
12. Fayol A, Livrozet M, Boutouyrie P, et al. Cardiac performance in patients hospitalized with COVID-19: a 6 month follow-up study. ESC Heart Fail. 2021;8(3):2232-2239. doi:10. 1002/ehf2.13315
13. Xie Y, Xu E, Bowe B, et al. Long-term cardiovascular outcomes of COVID-19. Nat Med. 2022;28(3):583-590
14. Peluso MJ, Lu S, Tang AF, et al. Markers of immüne activation and inflammation in individuals with postacute sequelae of severe acute respiratory syndrome coronavirus 2 infection. J Infect Dis. 2021;224(11):1839-1848.
15. Visvabharathy L, Hanson B, Orban Z, et al. NeuroCOVID long-haulers exhibit broad dysfunction in T cell memory generation and responses to vaccination. MedRxiv. 2021. doi: 10.1101/2021.08.08.21261763
16. Gold JE, Okyay RA, Licht WE, Hurley DJ. Investigation of long COVID prevalence and ıts relationship to epstein-barr virus reactivation. Pathogens. 2021;10(6):763. doi:10.3390/pathogens10060763
17. Wang EY, Mao T, Klein J, et al. Diverse functional autoantibodies in patients with COVID-19. Nature. 2021;595(7866):283-288.
18. Rinaldo RF, Mondoni M, Parazzini EM, et al. Deconditioning as main mechanism of impaired exercise response in COVID-19 survivors. Eur Respir J. 2021;58(2):2100870.
19. Patell R, Bogue T, Koshy A, et al. Postdischarge thrombosis and hemorrhage in patients with COVID-19. Blood. 2020;136(11):1342-1346. doi:10.1182/blood.2020007938
20. Matsuzawa Y, Kwon TG, Lennon RJ, Lerman LO, Lerman A. Prognostic value of flow-mediated vasodilation in brachial artery and fingertip artery for cardiovascular events: a systematic review and meta-analysis. J Am Heart Assoc. 2015;4(11):e002270. doi:10. 1161/JAHA.115.002270
21. Inaba Y, Chen JA, Bergmann SR. Prediction of future cardiovascular outcomes by flow-mediated vasodilatation of brachial artery: a meta-analysis. Int J Cardiovasc Imaging. 2010;26(6):631-640. doi:10.1007/s10554-010-9616-1
22. Celermajer DS, Sorensen KE, Gooch VM, et al. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet. 1992; 340:1111-1115.
23. Kitta Y, Obata JE, Nakamura T, et al. Persistent impairment of endothelial vasomotor function has a negative impact on outcome in patients with coronary artery disease. J Am Coll Cardiol. 2009;53:323-330.
24. Oliveira MR, Back GD, da Luz GC, Domingos BC, Arena R, Borghi-Silva A. Endothelial function provides early prognostic information in patients with COVID-19: a cohort study. Respir Med. 2021;185:106469.
25. Çiftel M, Ateş N, Yılmaz O. Investigation of endothelial dysfunction and arterial stiffness in multisystem inflammatory syndrome in children. Eur J Pediatr. 2021;181:91-97.
26. Ambrosino P, Molino A, Calcaterra I, et al. Clinical assessment of endothelial function in convalescent COVID-19 patients undergoing multidisciplinary pulmonary rehabilitation. Biomedicines. 2021;9(6):614. doi:10.3390/biomedicines9060614
27. Yilmaz Y, Kelesoglu S, Elcik D, Ozmen R, Kalay N. Predictive values of systemic ımmune-ınflammation ındex in new-onset atrial fibrillation following coronary artery bypass grafting. Braz J Cardiovasc Surg. 2023;38(1):96-103. doi:10.21470/1678-9741-2021-0278
28. Evans PC, Rainger GE, Mason JC, et al. Endothelial dysfunction in COVID-19: a position paper of the ESC Working Group for Atherosclerosis and Vascular Biology, and the ESC Council of Basic Cardiovascular Science. Cardiovasc Res. 2020;116:2177- 2184.