Concomitant diseases and their role in the development and course of a new coronavirus infection in patients with rheumatic diseases: оriginal research

OBJECTIVE. To study the features of the clinical course of rheumatic diseases affecting the risk of occurrence and course of a new coronavirus infection.

MATERIALS AND METHODS. An examination of 233 persons of both sexes with various immuno-inflammatory rheumatic diseases who were hospitalized in the clinic of faculty therapy of the Military Medical Academy named after S.M. Kirov, which included: rheumatoid arthritis (n=78, 33.5%), ankylosing spondylitis (n = 114; 48.9%), psoriatic arthritis (n=28.12%), systemic lupus erythematosus (n=13, 5.6%). An informed consent to participate in the study was signed with each of them. Patients who met the inclusion criteria were divided into 2 groups: the 1st group of patients, including immuno-inflammatory rheumatic diseases with a predominantly autoinflammatory mechanism; the 2nd group of patients, including IIRS with a predominantly autoimmune mechanism. The examination of patients with rheumatic diseases was carried out in accordance with the current clinical recommendations for each nosological form. Laboratory and instrumental studies were carried out in a certified laboratory and diagnostic departments of the Military Medical Academy named after S.M. Kirov.

RESULTS. Statistically significant differences were obtained as risk factors for the development of a new coronavirus infection in patients with spondyloarthritis with lower levels of low-density lipoprotein (2 mmol/l), DAPSA activity index (2 points), enalapril intake (p = 0.013; 95 % CI: 1.568 – 25.374) and secukinumab use (p = 0.024; 95% CI: 1,120 – 8,236). Risk factors for COVID-19 in patients with autoimmune diseases include: low levels of aspartate aminotransferase (16 IU/l), taking losartan (p = 0.024; 95% CI: 1,351 – 47.374) and using tocilizumab (p = 0.037; 95% CI: 1,128 – 117.238).

DISCUSSION. The relationship of these factors to the risk of developing a new coronavirus infection is associated not only with the manifestation of the activity of the underlying rheumatic disease (a lower AST level is characteristic, for example, of low SLE activity), but also with the effect on the inflammatory process itself — as a protective and adaptive reaction of the body to the invasion of a foreign agent. Inflammation and the severity of the inflammatory reaction not only affect the risk of new coronavirus infection, but also the course of this infection. Thus, lower activity in ankylosing spondylitis according to the ASDAS index (less than 2 points), rheumatoid arthritis according to the DAS28 index (less than 3 points) was associated with a more severe course of new coronavirus infection. The same pattern was observed with respect to the period from the date of administration of genetically engineered biological drugs to the date of the first symptoms of new coronavirus infection (the smaller it is, the more severe the infectious process was).

CONCLUSION. Our study demonstrated that the risk of developing a new coronavirus infection is associated with lower LDL, AST, DAPSA activity index, enalapril intake, losartan, using secukinum, tocilizumab. The activity of AS according to the ASDAS index (less than 2 points), RA according to the DAS28 index (less than 3 points), as well as the duration of the interval between the date of administration of immunosuppressive drugs and the appearance of the first symptoms of a new coronavirus infection (less than 6 days) were accompanied by a more severe course of a new coronavirus infection. Treatment of concomitant cardiovascular diseases is an additional factor contributing to a decrease in the activity of rheumatic disease. Taking drugs such as enalapril, lisinopril, bisoprolol and veroshpiron in patients with low IIRD activity in the first week of the disease may be associated with an increased risk of a more severe course of a new coronavirus infection.

marine medicine, COVID-19, autoimmune diseases, concomitant diseases

1. Velavan T. P., Meyer C. G. The COVID-19 epidemic. Trop Med Int Health, 2020, Vol. 25, No. 3, pp. 278–280. doi: 10.1111/tmi.13383. Epub 2020 Feb 16. PMID: 32052514; PMCID: PMC7169770.

2. Gianfrancesco M., Hyrich K. L., Al-Adely S., Carmona L., Danila M.I., Gossec L., Izadi Z., Jacobsohn L., Katz P., Lawson-Tovey S., Mateus E.F., Rush S., Schmajuk G., Simard J., Strangfeld A., Trupin L., Wysham K.D., Bhana S., Costello W., Grainger R., Hausmann J.S., Liew J.W., Sirotich E., Sufka P., Wallace Z.S., Yazdany J., Machado P.M., Robinson P.C. COVID-19 Global Rheumatology Alliance. Characteristics associated with hospitalisation for COVID-19 in people with rheumatic disease: data from the COVID-19 Global Rheumatology Alliance physician-reported registry. Ann Rheum Dis. 2020, Vol. 79, No. 7, pp 859–866. doi: 10.1136/annrheumdis-2020-217871. Epub 2020 May 29. PMID: 32471903; PMCID: PMC7299648.

3. Akiyama S., Hamdeh S., Micic D., Sakuraba A. Response to ‘Correspondence on ‘Prevalence and clinical outcomes of COVID-19 in patients with autoimmune diseases: a systematic review and meta-analysis’’ by Shi et al. Ann Rheum Dis, 2023, Vol. 82, No. 2, e29 P. doi: 10.1136/annrheumdis-2020-219394. Epub 2020 Nov 10. PMID: 33172858.

4. Akiyama S., Hamdeh S., Micic D., Sakuraba A. Prevalence and clinical outcomes of COVID-19 in patients with autoimmune diseases: a systematic review and meta-analysis. Ann Rheum Dis, 2021, Vol. 80, No. 3, pp. 384–391. doi: 10.1136/annrheumdis-2020-218946. Epub 2020 13. PMID: 33051220.

5. D’Silva K. M., Serling-Boyd N., Wallwork R., Hsu T., Fu X., Gravallese E. M., Choi H. K., Sparks J. A., Wallace Z. S. Clinical characteristics and outcomes of patients with coronavirus disease 2019 (COVID-19) and rheumatic disease: a comparative cohort study from a US ‘hot spot’. Ann Rheum Dis, 2020, Vol. 79, No. 9, 1156–1162. doi: 10.1136/ annrheumdis-2020-217888. Epub 2020 May 26. PMID: 32457048; PMCID: PMC7456555.

6. Murtas R., Andreano A., Gervasi F., Guido D., Consolazio D., Tunesi S., Andreoni L., Greco M.T., Gattoni M.E., Sandrini M., Riussi A., Russo A.G. Association between autoimmune diseases and COVID-19 as assessed in both a test-negative case-control and population case-control design. Auto Immun Highlights. 2020, Vol. 11, No. 1, 15 P. doi: 10.1186/s13317-020-00141-1. PMID: 33023649; PMCID: PMC7537783.

7. Sparks J. A., Wallace Z. S., Seet A. M., Gianfrancesco M. A., Izadi Z., Hyrich K. L., Strangfeld A., Gossec L., Carmona L., Mateus E.F., Lawson-Tovey S., Trupin L., Rush S., Katz P., Schmajuk G., Jacobsohn L., Wise L., Gilbert E. L., Duarte-García A., Valenzuela-Almada M. O., Pons-Estel G. J, Isnardi C. A., Berbotto G. A., Hsu T. Y, D’Silva K. M., Patel N. J., Kearsley-Fleet L., Schäfer M., Ribeiro S. L. E., Al Emadi S., Tidblad L., Scirè C. A., Raffeiner B., Thomas T., Flipo R. M., Avouac J., Seror R., Bernardes M., Cunha M. M., Hasseli R., Schulze-Koops H., Müller-Ladner U., Specker C., Souza V. A., Mota L. M. H. D., Gomides A. P. M., Dieudé P., Nikiphorou E., Kronzer V. L., Singh N., Ugarte-Gil M. F., Wallace B., Akpabio A., Thomas R., Bhana S., Costello W., Grainger R., Hausmann J. S., Liew J. W., Sirotich E., Sufka P., Robinson P. C., Machado P. M, Yazdany J. COVID-19 Global Rheumatology Alliance. Associations of baseline use of biologic or targeted synthetic DMARDs with COVID-19 severity in rheumatoid arthritis: Results from the COVID-19 Global Rheumatology Alliance physician registry. Ann Rheum Dis. 2021; Vol. 80, No. 9, pp. 1137–1146. doi: 10.1136/annrheumdis-2021-220418. Epub 2021 May 28. PMID: 34049860; PMCID: PMC8172266.

8. Ference B. A., Ginsberg H. N., Graham I., Ray K. K., Packard C. J., Bruckert E., Hegele R. A., Krauss R. M., Raal F. J., Schunkert H., Watts G. F., Borén J., Fazio S., Horton J. D., Masana L., Nicholls S. J., Nordestgaard B. G., van de Sluis B., Taskinen M. R., Tokgözoglu L., Landmesser U., Laufs U., Wiklund O., Stock J. K., Chapman M. J., Catapano A. L. Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J. 2017, Vol. 38, No. 32, pp. 2459–2472. doi: 10.1093/eurheartj/ehx144. PMID: 28444290; PMCID: PMC5837225.

9. Galkina E., Ley K. Immune and inflammatory mechanisms of atherosclerosis (*). Annu Rev Immunol, 2009, 27, 165–197. doi: 10.1146/annurev.immunol.021908.132620. PMID: 19302038; PMCID: PMC2734407.

10. Cassel S. L., Joly S., Sutterwala F. S. The NLRP3 inflammasome: a sensor of immune danger signals. Semin Immunol. 2009, Vol. 21, No. 4, pp. 194–198. doi: 10.1016/j.smim.2009.05.002. Epub 2009 Jun 5. PMID: 19501527; PMCID: PMC2758520.

11. Xu X. H., Shah P. K., Faure E., Equils O., Thomas L., Fishbein M. C., Luthringer D., Xu X. P., Rajavashisth T. B., Yano J., Kaul S., Arditi M. Toll-like receptor-4 is expressed by macrophages in murine and human lipid-rich atherosclerotic plaques and upregulated by oxidized LDL. Circulation. 2001, Vol. 104, No. 25, pp. 3103–3108. doi: 10.1161/hc5001.100631. PMID: 11748108.

12. Bernstein K. E., Khan Z., Giani J. F., Cao D. Y., Bernstein E. A., Shen X. Z. Angiotensin-converting enzyme in innate and adaptive immunity. Nat Rev Nephrol, 2018, Vol. 14, No. 5, pp. 325–336. doi: 10.1038/nrneph.2018.15. Epub 2018 Mar 26. PMID: 29578208; PMCID: PMC6192041.

13. Bernstein K. E., Ong F. S., Blackwell W. L., Shah K. H, Giani J. F., Gonzalez-Villalobos R. A., Shen X. Z., Fuchs S., Touyz R. M. A modern understanding of the traditional and nontraditional biological functions of angiotensin-converting enzyme. Pharmacol Rev. 2012; 65(1): 1–46. doi: 10.1124/pr.112.006809. Erratum in: Pharmacol Rev, 2013, Vol. 65, No. 1, 544 P. PMID: 23257181; PMCID: PMC3565918.

14. Suzuki Y., Ruiz-Ortega M., Lorenzo O., Ruperez M., Esteban V., Egido J. Inflammation and angiotensin II. Int J Biochem Cell Biol. 2003, Vol. 35, No. 6, pp. 881–900. doi: 10.1016/s1357-2725(02)00271-6. PMID: 12676174.

15. Benigni A., Cassis P., Remuzzi G. Angiotensin II revisited: new roles in inflammation, immunology and aging. EMBO Mol Med, 2010, Vol. 7, No. 2, pp. 247–257. doi: 10.1002/emmm.201000080. PMID: 20597104; PMCID: PMC3377325.

16. Chang Y., Wei W. Angiotensin II in inflammation, immunity and rheumatoid arthritis. Clin Exp Immunol, 2015, Vol. 179, No. 2, pp. 137–145. doi: 10.1111/cei.12467. PMID: 25302847; PMCID: PMC4298392.

17. Xu Z., Shi L., Wang Y., Zhang J., Huang L., Zhang C., Liu S., Zhao P., Liu H., Zhu L., Tai Y., Bai C., Gao T., Song J., Xia P., Dong J., Zhao J., Wang F.S. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med, 2020, Vol. 8, No. 4, pp. 420–422. doi: 10.1016/S2213-2600(20)30076-X. Epub 2020 Feb 18. Erratum in: Lancet Respir Med. 2020; PMID: 32085846; PMCID: PMC7164771.

18. Вахлевский В. В., Тыренко В. В., Свинцицкая И. С. Гиперинтерферонемия при ревматических заболеваниях как фактор защиты против вирусных инфекций. Русский медицинский журнал. 2022. № 6. С. 36–41 [Vahlevsky V. V., Tyrenko V. V., Sventsitskaya I. S. Hyperinterferonemia in rheumatic diseases as a factor of protection against viral infections. Russian Medical Journal, 2022, No. 6, pp. 36–41 (In Russ.)].