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Biomarkers of Air-Blood Barrier Damage In COVID-19

https://doi.org/10.15360/1813-9779-2021-3-2-0

Abstract

The search for sensitive and specific markers enabling timely identification of patients with a life-threatening novel coronavirus infection (COVID-19) is important for a successful treatment.

The aim of the study was to examine the association of molecular biomarkers of air-blood barrier damage, surfactant proteins SP-A and SP-D and Club cell protein CC16, with the outcome of patients with COVID-19.

Materials and methods. A cohort of 109 patients diagnosed with COVID-19 was retrospectively divided into two groups. Group 1 comprised survivor patients discharged from the ICU (w=90). Group 2 included the patients who did not survive (w=19). Association of disease outcome and SP-A, SP-D, and CC16 levels in blood serum, clinical, and laboratory data were examined taking into account the day of illness at the time of biomaterial collection.

Results. The non-survivors had higher SP-A (from days 1 to 10 of symptoms onset) and lower CC16 (from days 11 to 20 of symptoms onset) levels vs survivors discharged from ICU. No significant differences in SP-D levels between the groups were found.

Conclusion. According to the study results, the surfactant protein SP-A and Club cell protein CC16 are associated with increased COVID-19 mortality.

About the Authors

M. B. Khadzhieva
V.A. Negovsky Research Institute of General Reanimatology, Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology; D. Rogachev Federal Scientific Clinical Centre of Pediatric Hematology, Oncology and Immunology, Ministry of Health of Russia; N.I. Vavilov Institute of General Genetics, Russian Academy of Sciences
Russian Federation

Maryam B. Khadzhieva

25 Petrovka Str., Bldg. 2, 107031 Moscow; 1 Samora Mashela Str., GSP-7, 117997 Moscow; 3    Gubkin Str., 119991 Moscow



A. S. Gracheva
V.A. Negovsky Research Institute of General Reanimatology, Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology; N.I. Vavilov Institute of General Genetics, Russian Academy of Sciences
Russian Federation

Alesya S. Gracheva

25 Petrovka Str., Bldg. 2, 107031 Moscow; 3 Gubkin Str., 119991 Moscow



A. V. Ershov
V.A. Negovsky Research Institute of General Reanimatology, Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology
Russian Federation

Anton V Ershov

25 Petrovka Str., Bldg. 2, 107031 Moscow



Yu. V. Chursinova
M.F. Vladimirsky Moscow Regional Research Clinical Institute
Russian Federation

Yulia V. Chursinova

61/2 Shchepkin Str., 129110 Moscow



V. A. Stepanov
M.F. Vladimirsky Moscow Regional Research Clinical Institute
Russian Federation

Vadim A. Stepanov

61/2 Shchepkin Str., 129110 Moscow



L. S. Avdeikina
Voronovskaya Hospital, Moscow City Health Department
Russian Federation

Lyudmila S. Avdeikina

LMS village Voronovskoe settlement, 142160 Moscow



O. A. Grebenchikov
V.A. Negovsky Research Institute of General Reanimatology, Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology
Russian Federation

Oleg A. Grebenchikov

25 Petrovka Str., Bldg. 2, 107031 Moscow



A. S. Babkina
V.A. Negovsky Research Institute of General Reanimatology, Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology
Russian Federation

Anastasia S. Babkina

25 Petrovka Str., Bldg. 2, 107031 Moscow



A. K. Shabanov
V.A. Negovsky Research Institute of General Reanimatology, Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology; N.V. Sklifosovsky Research Institute of Emergency Medicine
Russian Federation

Aslan K. Shabanov

25 Petrovka Str., Bldg. 2, 107031 Moscow; 3 Bolshaya Sukharevskaya Square, 129090 Moscow



A. V. Tutelyan
Central Research Institute of Epidemiology, Rospotrebnadzor
Russian Federation

Alexey V Tutelyan

3a Novogireevskaya Str., 111123 Moscow



S. S. Petrikov
N.V. Sklifosovsky Research Institute of Emergency Medicine
Russian Federation

Sergey S. Petrikov

3 Bolshaya Sukharevskaya Square, 129090 Moscow



A. N. Kuzovlev
V.A. Negovsky Research Institute of General Reanimatology, Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology
Russian Federation

Artem N. Kuzovlev

25 Petrovka Str., Bldg. 2, 107031 Moscow



References

1. Mason R.J. Pathogenesis of COVID-19 from a cell biology perspective. Eur Respir J. 2020; 55 (4): 2000607. DOI: 10.1183/13993003.00607-2020. PMID: 32269085

2. Zhang G., Hu C., Luo L., Fang F., Chen Y., Li J., PengZ., Pan H. Clinical features and short-term outcomes of 221 patients with COVID-19 in Wuhan, China. J Clin Virol. 2020; 127: 104364. DOI: 10.1016/j.jcv.2020.104364. PMID: 32311650

3. Ciceri F., Castagna A., Rovere-Querini P, De Cobelli F., Ruggeri A., Galli L., Conte C., De Lorenzo R., Poli A., Ambrosio A., Signorelli C., Bossi E., Fazio M., Tresoldi C., Colombo S., Monti G., Fominskiy E., Franchini S., Spessot M., Martinenghi C., Carlucci M., Beretta L., Scandroglio A.M., Clementi M., Locatelli M., Tresoldi M., Scarpellini P, Martino G., Bosi E., Dagna L., Lazzarin A., Landoni G., Zangrillo A. Early predictors of clinical outcomes of COVID-19 outbreak in Milan, Italy. Clin Immunol. 2020; 217: 108509. DOI: 10.1016/j.clim.2020.108509. PMID: 32535188

4. Grasselli G., Zangrillo A., Zanella A., Antonelli M., Cabrini L., Castelli A., Cereda D., Coluccello A., Foti G., Fumagalli R., Iotti G., Latronico N., Lorini L. , Merler S., Natalini G., Piatti A., Ranieri M.V., Scandroglio A.M., Storti E., Cecconi M., Pesenti A; COVID-19 Lombardy ICU Network. Baseline Characteristics and Outcomes of1591 Patients Infected With SARS-CoV-2 Admitted to ICUs of the Lombardy Region, Italy. JAMA. 2020; 323 (16): 1574-1581. DOI: 10.1001/jama.2020.5394. PMID: 32250385

5. Rothan H.A., Byrareddy S.N. The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. J Autoimmun. 2020; 109: 102433. DOI: 10.1016/j.jaut.2020.102433. PMID: 32113704

6. Zabozlaev F.G., Kravchenko E.V., Gallyamova A.R., Letunovsky N.N. Pulmonary pathology of the new coronavirus disease (COVID-19). The preliminary analysis of post-mortem findings. Journal of Clinical Practice. 2020; 11 (2): 21-37 [In Russ.]. DOI: 10.17816/clinpract34849

7. Beloborodova N.V., Zuev E.V., Zamyatin M.N., Gusarov VG. Causal Therapy of COVID-19: Critical Review and Prospects. Obshchaya Rea-nimatologiya= GeneralReanimatology. 2020; 16 (6): 65-90 [In Russ.]. DOI: 10.15360/1813-9779-2020-4-0-1

8. Struyf T., Deeks J.J., Dinnes J., Takwoingi Y., Davenport C., Leeflang M. M., Spijker R., Hooft L., Emperador D., Dittrich S., Domen J., Horn S.R.A., Van den Bruel A; Cochrane COVID-19 Diagnostic Test Accuracy Group. Signs and symptoms to determine if a patient presenting in primary care or hospital outpatient settings has COVID-19 disease. Cochrane Database Syst Rev. 2020; 7 (7): CD013665. DOI: 10.1002/14651858.CD013665. Update in: Cochrane Database Syst Rev. 2021; 2: CD013665. PMID: 32633856

9. Li X., Xu S., Yu M., WangK., Tao Y., Zhou Y., Shi J., Zhou M., Wu B., Yang Z., Zhang C., Yue J., Zhang Z., Renz H., Liu X., Xie J., Xie M., Zhao J. Risk factors for severity and mortality in adult COVID-19 inpatients in Wuhan. J Allergy Clin Immunol. 2020; 146 (1): 110-118. DOI: 10.1016/j.jaci.2020.04.006. PMID: 32294485

10. Nardelli P, Landoni G. COVID-19-Related Thromboinflammatory Status: MicroCLOTS and Beyond. Obshchaya Reanimatologiya = Ob-shchaya Reanimatologiya= General Reanimatology. 2020; 16 (3): 1415. DOI: 10.15360/1813-9779-2020-3-0-2 [In Russ.]

11. Han S., Mallampalli R.K. The Role of Surfactant in Lung Disease and Host Defense against Pulmonary Infections. Ann Am Thorac Soc. 2015; 12 (5): 765-774. DOI: 10.1513/AnnalsATS.201411-507FR. PMID: 25742123

12. Takano H. Pulmonary surfactant itself must be a strong defender against SARS-CoV-2. Med Hypotheses. 2020; 144: 110020. DOI: 10.1016/j.mehy.2020.110020. PMID: 32590326

13. Naha N., Muhamed J.C.J., Pagdhune A., Sarkar B., Sarkar K Club cell protein 16 as a biomarker for early detection of silicosis. Indian J Med Res. 2020; 151 (4): 319-325. DOI: 10.4103/ijmr.IJMR_1799_18. PMID: 32461395

14. Almuntashiri S., Zhu Y., Han Y., Wang X., Somanath P.R., Zhang D. Club Cell Secreted Protein CC16: Potential Applications in Prognosis and Therapy for Pulmonary Diseases. J Clin Med. 2020; 9 (12): 4039. DOI: 10.3390/jcm9124039. PMID: 33327505

15. Kuzovlev A.N., Moroz V.V. Nosocomial pneumonia — principles of early diagnosis and prevention. Alexander Saltanov Bulletin of Intensive Care. 2019; 2: 40-7 [In Russ.]. DOI: 10.21320/1818-474X-2019-2-40-47

16. Hasegawa Y., Takahashi M., Ariki S., Asakawa D., Tajiri M., Wada Y., Yamaguchi Y., Nishitani C., Takamiya R., Saito A., Uehara Y., Hashi-moto J., Kurimura Y., Takahashi H., Kuroki Y. Surfactant protein D suppresses lung cancer progression by downregulation of epidermal growth factor signaling. Oncogene. 2015; 34 (7): 838-45. DOI: 10.1038/onc.2014.20. PMID: 24608429

17. Yoshikawa T., Otsuka M., Chiba H., Ikeda K., Mori Y., Umeda Y., Nishi-kiori H., Kuronuma K., Takahashi H. Surfactant protein A as a biomarker of outcomes of anti-fibrotic drug therapy in patients with idiopathic pulmonary fibrosis. BMC Pulm Med. 2020 Jan 31; 20 (1): 27. DOI: 10.1186/s12890-020-1060-y. Erratum in: BMC Pulm Med. 2020 May 7; 20 (1): 131. PMID: 32005219

18. KuzovlevA.N., MorozV.V., GolubevA.M., PolovnikovS.G., Smelaya T.V. Diagnosis of Acute Respiratory Distress Syndrome in Nosocomial Pneumonia. Obshchaya Reanimatologiya= General Reanimatology. 2009; 5 (6): 5. [In Russ.] DOI: 10.15360/1813-9779-2009-6-5

19. Gallo Marin B., Aghagoli G., LavineK., YangL., Siff E.J., ChiangS.S., Sa-lazar-Mather T.P., Dumenco L., Savaria M.C., Aung S.N., Flanigan T., Michelow I.C. Predictors of COVID-19 severity: A literature review. Rev MedVirol. 2021; 31 (1): 1-10. DOI: 10.1002/rmv.2146. PMID: 32845042

20. Chen X., PengF, Zhou X., Zhu J., Chen X., Gong Y., Shupeng W., Niu W. Predicting severe or critical symptoms in hospitalized patients with COVID-19 from Yichang, China. Aging (Albany NY). 2020; 13 (2): 1608-1619. DOI: 10.18632/aging.202261. PMID: 33318316

21. Kermali M., Khalsa R.K., Pillai K., Ismail Z., Harky A. The role of biomarkers in diagnosis of COVID-19 — A systematic review. Life Sci. 2020; 254: 117788. DOI: 10.1016/j.lfs.2020.117788. PMID: 32475810

22. Henry B.M., de Oliveira M.H.S., 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; 58 (7): 10211028. DOI: 10.1515/cclm-2020-0369. PMID: 32286245

23. Zheng Z., Peng F, Xu B., Zhao J., Liu H., Peng J., Li Q., Jiang C., Zhou Y., Liu S., Ye C., ZhangP, Xing Y., Guo H., Tang W. Risk factors of critical & mortal COVID-19 cases: A systematic literature review and meta-analysis. J Infect. 2020; 81 (2): e16-e25. DOI: 10.1016/j.jinf.2020.04.021. PMID: 32335169

24. Williamson E.J., Walker A.J., Bhaskaran K., Bacon S., Bates C., Morton C.E., Curtis H.J., Mehrkar A., Evans D., Inglesby P, Cockburn J., McDonald H.I., MacKennaB., TomlinsonL., DouglasI.J., Rentsch C.T., Mat-hur R., Wong AKS., Grieve R., Harrison D., Forbes H., Schultze A., Cro-ker R., Parry J., Hester F., Harper S., Perera R., Evans S.J.W., Smeeth L., Goldacre B. Factors associated with COVID-19-related death using OpenSAFELY. Nature. 2020; 584 (7821): 430-436. DOI: 10.1038/s41586-020-2521-4. PMID: 32640463

25. Foy B.H., Carlson J.C.T., Reinertsen E., Padros I Valls R., Pallares Lopez R., Palanques-Tost E., Mow C., Westover M.B., Aguirre A.D., Higgins J.M. Association of Red Blood Cell Distribution Width With Mortality Risk in Hospitalized Adults With SARS-CoV-2 Infection. JAMA Netw Open. 2020; 3 (9): e2022058. DOI: 10.1001/jamanetworkopen.2020.22058. PMID: 32965501

26. Zhong Q., Peng J. Mean platelet volume/platelet count ratio predicts severe pneumonia of cOvID-19. JClin Lab Anal. 2021; 35 (1): e23607. DOI: 10.1002/jcla.23607. PMID: 33128497

27. Ozen M., Yilmaz A., Cakmak V, Beyoglu R., Oskay A., Seyit M., Senol H. D-Dimer as a potential biomarker for disease severity in COVID-19. Am J Emerg Med. 2021; 40: 55-59. DOI: 10.1016/j.ajem.2020.12.023. PMID: 33348224

28. Lin J., Yan H., Chen H., He C., Lin C., He H., Zhang S., Shi S., Lin K. COVID-19 and coagulation dysfunction in adults: A systematic review and meta-analysis. J Med Virol. 2021; 93 (2): 934-944. DOI: 10.1002/jmv.26346. PMID: 32706426

29. Liu Y., Du X., Chen J., Jin Y., Peng L., Wang H.H.X., Luo M., Chen L., Zhao Y. Neutrophil-to-lymphocyte ratio as an independent risk factor for mortality in hospitalized patients with COVID-19. J Infect. 2020; 81 (1): e6-e12. DOI: 10.1016/j.jinf.2020.04.002. PMID: 32283162

30. Kalemci S., Saryhan A., Zeybek A. Association between NLR and COVID-19. Int Immunopharmacol. 2020; 88: 106917. DOI: 10.1016/j.intimp.2020.106917. PMID: 32889243

31. Qin C., Zhou L., Hu Z., Zhang S., Yang S., Tao Y., Xie C., Ma K., Shang K., WangW., TianD.S. Dysregulation of Immune Response in Patients With Coronavirus 2019 (COVID-19) in Wuhan, China. Clin Infect Dis. 2020; 71 (15): 762-768. DOI: 10.1093/cid/ciaa248. PMID: 32161940

32. Yang A.P., Liu J.P., Tao W.Q., Li H.M. The diagnostic and predictive role of NLR, d-NLR and PLR in COVID-19 patients. Int Immunopharma-col. 2020; 84: 106504. DOI: 10.1016/j.intimp.2020.106504. PMID: 32304994

33. Popov D.A., Borovkova U.L., Rybka M.M., Ramnenok T.V., Golukhova E.Z. Predictive value of proadrenomedullin in patients with COVID-19. Anesteziol. iReanimatol.2020; (6-2): 6-12 [In Russ.]. DOI: 10.17116/anaesthesiology20200626

34. Bertsimas D., Lukin G., Mingardi L., Nohadani O., Orfanoudaki A., Stel-lato B., WibergH., Gonzalez-Garcia S., Parra-Calderon C.L., Robinson K., Schneider M., Stein B., Estirado A., Beccara L., Canino R., Dal Bello M., Pezzetti F., Pan A.; Hellenic COVID-19 Study Group. COVID-19 mortality risk assessment: An international multi-center study. PLoS One. 2020; 15 (12): e0243262. DOI: 10.1371/journal.pone.0243262. PMID: 33296405

35. Ghayda R.A., Lee J., Lee J.Y., Kim D.K., Lee K.H., Hong S.H., Han Y.J., Kim J.S., Yang J.W., Kronbichler A., Smith L., Koyanagi A., Jacob L., Shin J.I. Correlations of Clinical and Laboratory Characteristics of COVID-19: A Systematic Review and Meta-Analysis. Int J Environ Res Public Health. 2020; 17 (14): 5026. DOI: 10.3390/ijerph17145026. PMID: 32668763

36. Vieira F., KungJ.W., 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

37. KharlamovaO.S.,NikolayevK.Y.,RaginoY.I.,VoyevodaM.I.Association of SP-A and SP-D Surfactant Proteins with the Severity of Communi-tyAcquired Pneumonia. Russian Sklifosovsky Journal«Emergency Medical Care». 2020; 9 (3): 348-355 [In Russ.]. DOI: 10.23934/2223-9022-2020-9-3-348-355

38. Moroz V.V., GolubevA.M., KuzovlevA.N., Pisarev V.M., ShabanovA.K., Golubev MA. Surfactant Protein D Is a Biomarker of Acute Respiratory Distress Syndrome. Obshchaya Reanimatologiya= General Reanima-tology. 2013; 9 (4): 11 [In Russ.]. DOI: 10.15360/1813-9779-2013-4-11

39. Moroz W, Golubev A.M., Kuzo vlev A.N., Pisarev V.M., Polovnikov S.G., ShabanovA.K., Golubev M.A. Surfactant Protein A (SP-A) is a Prognostic Molecular Biomarker in Acute Respiratory Distress Syndrome. Obshchaya Reanimatologiya= General Reanimatology. 2013; 9 (3): 5 [In Russ.]. DOI: 10.15360/1813-9779-2013-3-5779-2013-3-5

40. Dahmer M.K., Flori H., Sapru A., Kohne J., Weeks H.M., Curley M.A.Q., Matthay M.A., Quasney M.W.; BALI and RESTORE Study Investigators and Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network. Surfactant Protein D Is Associated With Severe Pediatric ARDS, Prolonged Ventilation, and Death in Children With Acute Respiratory Failure. Chest. 2020; 158 (3): 1027-1035. DOI: 10.1016/j.chest.2020.03.041. PMID: 32275979

41. Jensen J.S., Itenov T.S., Thormar K.M., Hein L., Mohr T.T., Andersen M.H., Loken J., Tousi H., Lundgren B., Boesen H.C., Johansen M.E., Ost-rowski S.R., Johansson PI., Grarup J., Vestbo J., Lundgren J.D.; Procalcitonin And Survival Study (PASS) Group. Prediction of non-recovery from ventilator-demanding acute respiratory failure, ARDS and death using lung damage biomarkers: data from a 1200-patient critical care randomized trial. Ann Intensive Care. 2016; 6 (1): 114. DOI: 10.1186/s13613-016-0212-y. PMID: 27873291

42. Nayak A., Dodagatta-Marri E., Tsolaki A.G., Kishore U. An Insight into the Diverse Roles of Surfactant Proteins, SP-A and SP-D in Innate and Adaptive Immunity. Front Immunol. 2012; 3: 131. DOI: 10.3389/fimmu.2012.00131. PMID: 22701116

43. Al-Qahtani A.A., Murugaiah V., Bashir H.A., Pathan A.A., Abozaid S.M., Makarov E., Nal-Rogier B., Kishore U., Al-Ahdal M.N. Full-length human surfactant protein A inhibits influenza A virus infection of A549 lung epithelial cells: A recombinant form containing neck and lectin domains promotes infectivity. Immunobiology. 2019; 224 (3): 408-418. DOI: 10.1016/j.imbio.2019.02.006. PMID: 30954271

44. HarrodK.S., TrapnellB.C., Otake K., Korfhagen T.R., WhitsettJ.A. SPA enhances viral clearance and inhibits inflammation after pulmonary adenoviral infection. Am J Physiol. 1999; 277 (3): L580-8. DOI: 10.1152/ajplung.1999.277.3.L580. PMID: 10484466

45. van Iwaarden J.F., van Strijp J.A., Visser H., Haagsman H.P., Verhoef J., van Golde L.M. Binding of surfactant protein A (SP-A) to herpes simplex virus type 1-infected cells is mediated by the carbohydrate moiety of SP-A. J Biol Chem. 1992; 267 (35): 25039-43. PMID: 1334078

46. Broeckaert F., Bernard A. Clara cell secretory protein (CC16): characteristics and perspectives as lung peripheral biomarker. Clin Exp Allergy. 2000; 30 (4): 469-75. DOI: 10.1046/j.1365-2222.2000.00760.x. PMID: 107188430

47. Determann R.M., Millo J.L., Waddy S., Lutter R., Garrard C.S., Schultz M.J. Plasma CC16 levels are associated with development of ALI/ARDS in patients with ventilator-associated pneumonia: a retrospective observational study. BMC Pulm Med. 2009; 9: 49. DOI: 10.1186/1471-2466-9-49

48. Lin J., Zhang W., Wang L., Tian F. Diagnostic and prognostic values of Club cell protein 16 (CC16) in critical care patients with acute respiratory distress syndrome. J Clin Lab Anal. 2018; 32 (2): e22262. DOI: 10.1002/jcla.22262. PMID: 28548310

49. Johansson S., Kristjansson S., Bjarnarson S.P., Wennergren G., Rudin A. Clara cell protein 16 (CC16) serum levels in infants during respiratory syncytial virus infection. Acta Paediatr. 2009; 98 (3): 579-81. DOI: 10.1111/j.1651-2227.2008.01083.x. PMID: 18976364

50. Leth-Larsen R., Zhong F., Chow V.T., Holmskov U., Lu J. The SARS co-ronavirus spike glycoprotein is selectively recognized by lung surfactant protein D and activates macrophages. Immunobiology. 2007; 212 (3): 201-11. DOI: 10.1016/j.imbio.2006.12.001. PMID: 17412287

51. Kerget B., Kerget F., Kogak A.O., Kyzyltung A., Araz O., Ugar E.Y., Akgun M. Are Serum Interleukin 6 and Surfactant Protein D Levels Associated with the Clinical Course of COVID-19? Lung. 2020; 198 (5): 777784. DOI: 10.1007/s00408-020-00393-8. PMID: 32918573


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Khadzhieva M.B., Gracheva A.S., Ershov A.V., Chursinova Yu.V., Stepanov V.A., Avdeikina L.S., Grebenchikov O.A., Babkina A.S., Shabanov A.K., Tutelyan A.V., Petrikov S.S., Kuzovlev A.N. Biomarkers of Air-Blood Barrier Damage In COVID-19. General Reanimatology. 2021;17(3):16-31. https://doi.org/10.15360/1813-9779-2021-3-2-0

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