Sürfaktan protein D düzeyleri ile COVID-19 klinik şiddeti arasindaki ilişkinin değerlendirilmesi: bir vaka kontrol çalışması

Year 2023, Volume: 16 Issue: 1, 137 - 147, 31.01.2023

Emre Karslı , Ramazan Sabırlı , Tarık Gören , Aykut Kemancı , Denizhan Karış , İbrahim Türkçüer , Özgür Kurt , Philippe Bertrand Aylin Koseler

https://doi.org/10.31362/patd.1159512

Abstract

Amaç: Serum surfaktan protein D (SP-D) vücutta viral enfeksiyona karşı koruma, bakteriyel ve fungal klirens,
apoptotik hücrelerin temizlenmesi ve inflamasyonun baskılanması gibi roller oynar. Bu çalışma, SP-D düzeyi ile
koronavirüs hastalığı (COVID-19) şiddeti arasındaki ilişkiyi incelemeyi amaçlamaktadır.
Gereç ve yöntem: Çalışmaya 80 hasta (30 hafif hastalığı ve 50 ağır/kritik COVID-19) ve 50 sağlıklı gönüllü dahil
edildi. Serum örneklerinde SP-D seviyeleri ELISA ile analiz edildi.
Bulgular: SP-D düzeyi ortanca değeri hafif hastalıkta 2,47 (1,67-7,79) ng/ml, ağır/kritik hastalık gruplarında
5,65 (3,09-16,55) ng/ml iken, sağlıklı control grubunda 2,89 (10,8-6,24) ng/ml olarak bulundu. Ağır/kritik hastalık
grubu hem hafif hastalık hem de kontrol grubu ile karşılaştırıldığında SP-D düzeylerindeki farklılıklar istatistiksel
olarak anlamlı bulundu (sırasıyla p=0,007 ve 0,001). ROC analizi, hafif COVID-19 hastalığı hastalarına kıyasla
şiddetli/kritik COVID-19 hastalarında serum SP-D seviyeleri için eğri altında kalan alan daha yüksek saptandı
(AUC=0.691, %95 CI=0,56-0.822; p=0,004). Ayrıca, ağır/kritik hastaları saptamak için SP-D düzeyleri 2,44 ng/
ml düzeyinde (p=0,004) %86 duyarlı ve %51,6 özgül saptandı.
Sonuç: SP-D seviyeleri, COVID-19 hastaları için klinik şiddeti ve prognozu tahmin etmede faydalıdır. SP-D,
klinik şiddeti ve prognozu tahmin etmek için değerli bir biyobelirteçtir.

Keywords

Sürfaktan protein D, COVID-19, pnömoni

Evaluation of the relationship between surfactant protein D levels and COVID-19 clinical severity: a case-control study

Abstract

Purpose: Serum surfactant protein D (SP-D) plays roles in the body such as protection against viral infection,
bacterial and fungal clearance, clearance of apoptotic cells and suppression of inflammation. This study aims to
examine the relationship between SP-D level and coronavirus disease (COVID-19) severity.
Methods: 80 patients (30 with mild disease and 50 with severe/critical COVID-19), and 50 healthy volunteers
were enrolled in the study. SP-D levels were analyzed by ELISA in serum samples.
Results: The median of SP-D was found to be 2.47 (1.67-7.79) ng/ml in mild disease and 5.65 (3.09-16.55) ng/
ml in severe/critical disease groups, while 2.89 (10.8-6.24) ng/ml in the healthy controls. The differences in SP-D
levels between the severe/critical disease group compared to both mild disease and control groups were found
statistically significant (p=0.007 and 0.001, respectively). ROC analysis showed greater AUC for the serum
SP-D levels of the severe/critical COVID-19 patients compared to mild COVID-19 disease patients (AUC=0,691,
95% CI=0.56-0,822; p=0.004). Furthermore, SP-D levels were 86% sensitive and 51.6% specific at 2.44 ng/ml
level (p=0.004) to detect severe/critical patients.
Conclusion: SP-D levels is useful for COVID-19 patients in the prediction of clinical severity and prognosis.
SP-D is a valuable biomarker for predicting the clinical severity and prognosis.

Keywords

Serum surfactant protein D, COVID-19, pneumonia, pnömoni

References

• 1. CDC. 2019 Novel Coronavirus, Wuhan, China. CDC. Available at https://www.cdc.gov/coronavirus/2019-ncov/about/index.html. January 26, 2020; Accessed: January 27, 2020.
• 2. Cascella M, Rajnik M, Cuomo A, Dulebohn SC, Di Napoli R. Features, Evaluation, and Treatment of Coronavirus (COVID-.19) (Updated 2020 Aug 10). In: StatPearls (Internet). Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK554776/
• 3. Liu J, Li S, Liu J, et al. Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients. EBioMedicine 2020;55:102763. doi: 10.1016/j.ebiom.2020.102763.
• 4. Rothan HA, Byrareddy SN. The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. J Autoimmun 2020;109:102433. doi: 10.1016/j.jaut.2020.102433.
• 5. Mason RJ. Biology of alveolar type II cells. Respirology 2006 ;11 Suppl:S12-15. . doi: 10.1111/j.1440-1843.2006.00800.x.
• 6. Bernhard W. Lung surfactant: Function and composition in the context of development and respiratory physiology. Ann Anat 2016;208:146-150. doi: 10.1016/j.aanat.2016.08.003.
• 7. Kishore U, Greenhough TJ, Waters P, et al. Surfactant proteins SP-A and SP-D: structure, function and receptors. Mol Immunol 2006;43:1293-315. doi: 10.1016/j.molimm.2005.08.004.
• 8. Mori K, Kurihara N, Hayashida S, Tanaka M, Ikeda K. The intrauterine expression of surfactant protein D in the terminal airways of human fetuses compared with surfactant protein Eur J Pediatr 2002;161:431-4. doi: 10.1007/s00431-002-0917-9.
• 9. Knudsen L, Ochs M, Mackay R, et al. Truncated recombinant human SP-D attenuates emphysema and type II cell changes in SP-D deficient mice. Respir Res 2007;8:70. doi: 10.1186/1465-9921-8-70.
• 10. Ohnishi H, Yokoyama A, Kondo K, et al. Comparative study of KL-6, surfactant protein-A, surfactant protein-D, and monocyte chemoattractant protein-1 as serum markers for interstitial lung diseases. Am J Respir Crit Care Med 2002;165:378-81. doi: 10.1164/ajrccm.165.3.2107134.
• 11. Sims MW, Tal-Singer RM, Kierstein S, Musani AI, Beers MF, Panettieri RA, Haczku A. Chronic obstructive pulmonary disease and inhaled steroids alter surfactant protein D (SP-D) levels: a cross-sectional study. Respir Res 2008 Jan 28;9:13. doi: 10.1186/1465-9921-9-13.
• 12. Nakamura K, Kato M, Shukuya T, et al. Surfactant protein-D predicts prognosis of interstitial lung disease induced by anticancer agents in advanced lung cancer: a case control study. BMC Cancer 2017 ;17:302. doi: 10.1186/s12885-017-3285-6.
• 13. https://www.who.int/publications/i/item/clinical-management-of-COVID-19. Accessed: October 27, 2020.
• 14. M. Chung, A. Bernheim, X. Mei, et al. CT imaging features of 2019 novel coronavirus (2019-nCoV) Radiology. 2020;295:202-207. doi: 10.1148/radiol.2020200230.
• 15. Turkish Ministery of Health COVID-19 Diasnosis and Treatment Guideline Accessed at: https://covid19.saglik.gov.tr/Eklenti/39061/0/COVID19rehberieriskinhastatedavisipdf.pdf
• 16. Vieira F, Kung J, Bhatti F. Structure, genetics and function of the pulmonary associated surfactant proteins A and D: The extra-pulmonary role of these C type lectins. Ann Anat 2017;211:184-201. doi: 10.1016/j.aanat.2017.03.002.
• 17. Kong XN, Yan HX, Chen L, et al. LPS-induced down-regulation of signal regulatory protein {alpha} contributes to innate immune activation in macrophages. J Exp Med 2007;204:2719-31. doi: 10.1084/jem.20062611.
• 18. Schurch D, Ospina OL, Cruz A, Perez-Gil J. Combined and Independent Action of Proteins SP-B and SP-C in the Surface Behavior and Mechanical Stability of Pulmonary Surfactant Films. Biophys J 2010;99(10):3290-9. doi: 10.1016/j.bpj.2010.09.039.
• 19. LeVine AM, Hartshorn K, Elliott J, Whitsett J, Korfhagen T. Absence of sp-a modulates innate and adaptive defense responses to pulmonary influenza infection. Am J Physiol Lung Cell Mol Physiol 2002;282:L563-72. doi: 10.1152/ajplung.00280.2001.
• 20. Botas C, Poulain F, Akiyama J, et al.Altered surfactant homeostasis and alveolar type II cell morphology in mice lacking surfactant protein D. Proc Natl Acad Sci U S A. 1998;95:11869-74. doi: 10.1073/pnas.95.20.11869.
• 21. Ikegami M, Grant S, Korfhagen T, Scheule RK, Whitsett JA.Surfactant protein-D regulates the postnatal maturation of pulmonary surfactant lipid pool sizes. J Appl Physiol (1985) 2009;106:1545-52. doi: 10.1152/japplphysiol.91567.2008.
• 22. Guillot L, Epaud R, Thouvenin G, et al. New surfactant protein C gene mutations associated with diffuse lung disease. J Med Genet 2009;46:490-4. doi: 10.1136/jmg.2009.066829.
• 23. Chroneos ZC, Sever-Chroneos Z, Shepherd VL. Pulmonary surfactant: an immunological perspective. Cell Physiol Biochem 2010;25:13-26. doi: 10.1159/000272047.
• 24. Matthay MA, Ware LB, Zimmerman GA: The acute respiratory distress syndrome. J Clin Invest 2012;122:2731-40. doi: 10.1172/JCI60331.
• 25. El-Deek SE, Makhlouf HA, Saleem TH, Mandour MA, Mohamed NA. Surfactant protein D, soluble intercellular adhesion molecule-1 and high-sensitivity C-reactive protein as biomarkers of chronic obstructive pulmonary disease. Med Princ Pract 2013;22:469-74. doi: 10.1159/000349934.
• 26. Takahashi H, Kuroki Y, Tanaka H, et al.Serum levels of surfactant proteins A and D are useful biomarkers for interstitial lung disease in patients with progressive systemic sclerosis. Am J Respir Crit Care Med 2000;162:258-63. doi: 10.1164/ajrccm.162.1.9903014.
• 27. Nishikiori H, Chiba H, Ariki S, et al. Distinct compartmentalization of SP-A and SP-D in the vasculature and lungs of patients with idiopathic pulmonary fibrosis. BMC Pulm Med 2014;14:196. doi: 10.1186/1471-2466-14-196.
• 28. Gong MN, Wei Z, Xu LL, Miller DP, Thompson BT, Christiani DC. Polymorphism in the surfactant protein-B gene, gender, and the risk of direct pulmonary injury and ARDS. Chest 2004;125:203-11. doi: 10.1378/chest.125.1.203.
• 29. Leth-Larsen R, Nordenbaek C, Tornoe I, Moeller V, Schlosser A, Koch C, et al. Surfactant protein D (SP-D) serum levels in patients with community-acquired pneumonia. Clin Immunol 2003;108:29-37. doi: 10.1016/s1521-6616(03)00042-1.
• 30. Francone M, Iafrate F, Masci GM , et al. Chest CT score in COVID-19 patients: correlation with disease severity and short-term prognosis. Eur Radiol 2020;30:6808-6817. doi: 10.1007/s00330-020-07033-y.
• 31. Saito A, Kuronuma K, Moniwa K, Kodama K, Takahashi S, Takahashi H, Chiba H. Serum surfactant protein A and D may be novel biomarkers of COVID-19 pneumonia severity. Preprint from Research Square. https://doi.org/10.21203/rs.3.rs-29567/v1
• 32. Kerget B, Kerget F, Koçak AO, Kızıltunç A, Araz Ö, Uçar EY, Akgün M. Are Serum Interleukin 6 and Surfactant Protein D Levels Associated with the Clinical Course of COVID-19? Lung 2020;198:777-784. doi: 10.1007/s00408-020-00393-8.
• 33. Choreño-Parra JA, Jiménez-Álvarez LA, Ramírez-Martínez G, et al. Expression of Surfactant protein D (SP-D) distinguishes severe pandemic influenza A(H1N1) from COVID-19. J Infect Dis 2021;224:21-30. doi: 10.1093/infdis/jiab113.