Monocytosis in patients with coronavirus pneumonia after treatment with glucocorticoids

Abstract

Features of variation of peripheral blood leukocyte formula parameters in 86 patients with coronavirus pneumonia with leukocytosis with a background of glucocorticoid treatment were investigated. All patients were divided into 2 groups. Group 1 was 22 individuals who showed clinical signs of the bacterial infection (purulent sputum cough in combination with neutrophilic leukocytosis at hospital the admission). The 2^nd group was made up of 64 patients with the glucocorticoids developed against the background of treatment with glucocorticoids (dexamethasone 20 mg/day or prednisolone 150 mg/day, intravenously for 3 days) leukocytosis >10 ×10⁹/l without signs of a bacterial infection. It was found that in patients of the 1^st group compared to the 2^nd group, levels of the white blood cells and neutrophils significantly (p < 0.001) exceeded the reference values in the absence of a significant change in the number of monocytes. In patients of the 2^nd group after a three-day intravenous application of the glucocorticoids on the 4^th day of hospitalization, a statistically significant (p <0.001) increase in the number of neutrophils and monocytes was established. When comparing the quantitative parameters of the leukocyte formula between the 2^nd group on the 4^th day of the hospitalization and the 1^st group at admission, there were no differences in the level of leukocytes and neutrophils. Number of monocytes in group 2 (1.11 (0.90; 1.34) × 10⁹/l), on the contrary, statistically significantly (p < 0.001) exceeded their level in the 1^st group (0.59 (0.50; 0.77) × 10⁹/l). Thus, an indicator of the number of monocytes in the peripheral blood could be a promising differential diagnostic criterion for the genesis of the leukocytosis in patients with the COVID-19. This parameter may be one of the factors influencing the decision to prescribe the antibacterial therapy.

Keywords

specific viral pneumonia / virus-mediated tissue damage / viral replication / bacterial complications / glucocorticosteroids / induced leukocytosis / monocytosis / coronavirus disease

References

[1] Surveillances V The Epidemiological Characteristics of an Outbreak of 2019 Novel Coronavirus Diseases (COVID-19). Zhonghua Liu Xing Bing Xue Za Zhi. 2020;41(2):145–151. DOI: 10.3760/cma.j.issn.0254-6450.2020.02.003

[2] Surveillances V. The Epidemiological Characteristics of an Outbreak of 2019 Novel Coronavirus Diseases (COVID-19) // Zhonghua Liu Xing Bing Xue Za Zhi. 2020. Vol. 41, No. 2. P. 145–151. DOI: 10.3760/cma.j.issn.0254-6450.2020.02.003

[3] Zaytsev AA, Chernov SA, Kryukov EV, et al. Practical experience of managing patients with new coronavirus infection COVID-19 in hospital (preliminary results and guidelines). Lechaschi Vrach. 2020;(6):74–79. (In Russ.). DOI: 10.26295/OS.2020.41.94.014

[4] Зайцев А.А. Чернов С.А., Крюков Е.В., и др. Практический опыт ведения пациентов с новой коронавирусной инфекцией COVID-19 в стационаре (предварительные итоги и рекомендации) // Лечащий врач. 2020. № 6. С. 74–79. DOI: 10.26295/OS.2020.41.94.014

[5] Teuwen LA, Geldhof V, Pasut A, et al. COVID-19: the vasculature unleashed. Nat Rev Immunol. 2020;20(7):389–391. DOI: 10.1038/s41577-020-0343-0

[6] Teuwen L.A., Geldhof V., Pasut A., et al. COVID-19: the vasculature unleashed // Nat Rev Immunol. 2020. Vol. 20, No. 7. P. 389–391. DOI: 10.1038/s41577-020-0343-0

[7] Azkur AK, Akdis M, Azkur D, et al. Immune response to SARS-CoV-2 and mechanisms of immunopathological changes in COVID-19. Allergy. 2020;75(7):1564–1581. DOI: 10.1111/all.14364

[8] Azkur A.K., Akdis M., Azkur D., et al. Immune response to SARS-CoV-2 and mechanisms of immunopathological changes in COVID-19 // Allergy. 2020. Vol. 75, No. 7. P. 1564–1581. DOI: 10.1111/all.14364

[9] Minnullin TI, Stepanov AV, Chepur SV, et al. Immunological aspects of SARS-CoV-2 coronavirus damage. Bulletin of the Russian Military Medical Academy. 2021;23(2):187–198. (In Russ.). DOI: 10.17816/brmma72051

[10] Миннуллин Т.И., Степанов А.В., Чепур С.В., и др. Иммунологические аспекты поражения коронавирусом SARS-CoV-2 // Вестник Российской военно-медицинской академии. 2021. Т. 23, № 2. C. 187–198. DOI: 10.17816/brmma72051

[11] Wang J, Jiang M, Chen X, et al. Cytokine storm and leukocyte changes in mild versus severe SARS-CoV-2 infection: Review of 3939 COVID-19 patients in China and emerging pathogenesis and therapy concepts. J Leukoc Biol. 2020;108(1):17–41. DOI: 10.1002/JLB.3COVR0520-272R

[12] Wang J., Jiang M., Chen X., et al. Cytokine storm and leukocyte changes in mild versus severe SARS-CoV-2 infection: Review of 3939 COVID-19 patients in China and emerging pathogenesis and therapy concepts // J Leukoc Biol. 2020. Vol. 108, No. 1. P. 17–41. DOI: 10.1002/JLB.3COVR0520-272R

[13] Lansbury L, Lim B, Baskaran V, Lim WS. Co-infections in people with COVID-19: a systematic review and meta-analysis. J Infect. 2020;81(2):266–275. DOI: 10.1016/j.jinf.2020.05.046

[14] Lansbury L., Lim B., Baskaran V., Lim W.S. Co-infections in people with COVID-19: a systematic review and meta-analysis // J Infect. 2020. Vol. 81, No. 2. P. 266–275. DOI: 10.1016/j.jinf.2020.05.046

[15] Youngs J, Wyncoll D, Hopkins P, et al. Improving antibiotic stewardship in COVID-19: Bacterial co-infection is less common than with influenza. J Infect. 2020;81(3):e55–e57. DOI:10.1016/j.jinf.2020.06.056

[16] Youngs J., Wyncoll D., Hopkins P., et al. Improving antibiotic stewardship in COVID-19: Bacterial co-infection is less common than with influenza // J Infect. 2020. Vol. 81. No. 3. P. e55–e57. DOI:10.1016/j.jinf.2020.06.056

[17] Crotty MP, Akins R, Nguyen A, et al. Investigation of subsequent and co-infections associated with SARS-CoV-2 (COVID-19) in hospitalized patients. мedRxiv. 2020;2:1–19. DOI:10.1101/2020.05.29.20117176

[18] Crotty M.P., Akins R., Nguyen A., et al. Investigation of subsequent and co-infections associated with SARS-CoV-2 (COVID-19) in hospitalized patients // medRxiv. 2020. Vol. 2. P. 1–19. DOI:10.1101/2020.05.29.20117176

[19] Vazzana N, Dipaola F, Ognibene S. Procalcitonin and secondary bacterial infections in COVID-19: association with disease severity and outcomes. Acta Clin Belgica Int J Clin Lab Med. 2020:1–5. DOI: 10.1080/17843286.2020.1824749

[20] Vazzana N., Dipaola F., Ognibene S. Procalcitonin and secondary bacterial infections in COVID-19: association with disease severity and outcomes // Acta Clin Belgica Int J Clin Lab Med. 2020. P. 1–5. DOI: 10.1080/17843286.2020.1824749

[21] Zaitsev AA, Chernov SA, Stets VV, et al. Algorithms for the management of patients with a new coronavirus COVID-19 infection in a hospital. Guidelines. Consilium Medicum. 2020;22(11):91–97. (In Russ.). DOI: 10.26442/20751753.2020.11.200520

[22] Зайцев А.А., Чернов С.А., Стец В.В., и др. Алгоритмы ведения пациентов с новой коронавирусной инфекцией COVID-19 в стационаре. Методические рекомендации // Consilium Medicum. 2020. Т. 22, № 11. С. 91–97. DOI: 10.26442/20751753.2020.11.200520

[23] Lee H. Procalcitonin as a biomarker of infectious diseases. Korean J Intern Med. 2013;28(3):285–291. DOI:10.3904/kjim.2013.28.3.285

[24] Lee H. Procalcitonin as a biomarker of infectious diseases // Korean J Intern Med. 2013. Vol. 28, No. 3. P. 285–291. DOI:10.3904/kjim.2013.28.3.285

[25] Shoenfeld Y, Gurewich Y, Gallant LA, et al. Prednisone-induced leukocytosis. Am J Med. 1981;71(5):773–778. DOI: 10.1016/0002-9343(81)90363-6

[26] Shoenfeld Y., Gurewich Y., Gallant L.A., et al. Prednisone-induced leukocytosis // Am J Med. 1981. Vol. 71, No. 5. P. 773–778. DOI: 10.1016/0002-9343(81)90363-6

[27] Martinez FO, Combes TW, Orsenigo F, et al. Monocyte activation in systemic Covid-19 infection: Assay and rationale. EBioMedicine. 2020;59:(102964):1–7. DOI: 10.1016/j.ebiom.2020.102964

[28] Martinez F.O., Combes T.W., Orsenigo F., et al. Monocyte activation in systemic Covid-19 infection: Assay and rationale // EBioMedicine. 2020. Vol. 59, No. 102964. P. 1–7. DOI: 10.1016/j.ebiom.2020.102964

[29] Zaitsev AA, Golukhova EZ, Mamalyga ML, et al. Efficacy of methylprednisolone pulse therapy in patients with COVID-19. Clinical Microbiology and Antimicrobial Chemotherapy. 2020;22(2):88–91. (In Russ.). DOI: 10.36488/cmac.2020.2.88-91

[30] Зайцев А.А., Голухова Е.З., Мамалыга М.Л., и др. Эффективность пульс-терапии метилпреднизолоном у пациентов с COVID-19 // Клиническая микробиология и антимикробная химиотерапия. 2020. Т. 22, № 2. С. 88–91. DOI: 10.36488/cmac.2020.2.88-91

[31] Dubinski D, Won SY, Gessler F, et al. Dexamethasone-induced leukocytosis is associated with poor survival in newly diagnosed glioblastoma. J Neurooncol. 2018;137(3):503–510. DOI: 10.1007/s11060-018-2761-4

[32] Dubinski D., Won S.Y., Gessler F., et al. Dexamethasone-induced leukocytosis is associated with poor survival in newly diagnosed glioblastoma // J Neurooncol. 2018. Vol. 137, No. 3. P. 503–510. DOI: 10.1007/s11060-018-2761-4

[33] Liles WC, Dale DC, Klebanoff SJ Glucocorticoids inhibit apoptosis of human neutrophils. Blood. 1995;86(8):3181–3188.

[34] Liles W.C., Dale D.C., Klebanoff S.J. Glucocorticoids inhibit apoptosis of human neutrophils // Blood. 1995. Vol. 86, No. 8. P. 3181–3188.

[35] Burton JL, Kehrli ME, Kapil S, et al. Regulation of l-selectin and CD18 on bovine neutrophils by glucocorticoids: effects of cortisol and dexamethasone. J Leukoc Biol. 1995;57(2):317–325. DOI: 10.1002/jlb.57.2.317

[36] Burton J.L., Kehrli M.E., Kapil S., et al. Regulation of l-selectin and CD18 on bovine neutrophils by glucocorticoids: effects of cortisol and dexamethasone // J Leukoc Biol. 1995. Vol. 57, No. 2. P. 317–325. DOI: 10.1002/jlb.57.2.317

[37] Ehrchen JM, Roth J, Barczyk-Kahlert K. More Than Suppression: Glucocorticoid Action on Monocytes and Macrophages. Front Immunol. 2019;10:2028. DOI: 10.3389/fimmu.2019.02028

[38] Ehrchen J.M., RothJ., Barczyk-Kahlert K. More Than Suppression: Glucocorticoid Action on Monocytes and Macrophages // Front Immunol. 2019. Vol. 10. P. 2028. DOI: 10.3389/fimmu.2019.02028

[39] Gómez-Rial J, Rivero-Calle I, Salas A. Role of Monocytes/Macrophages in COVID-19 Pathogenesis: Implications for Therapy. Infect Drug Resist. 2020;13:2485–2493. DOI: 10.2147/IDR.S258639

[40] Gómez-Rial J., Rivero-Calle I., Salas A. Role of Monocytes/Macrophages in COVID-19 Pathogenesis: Implications for Therapy // Infect Drug Resist. 2020. No. 13. P. 2485–2493. DOI: 10.2147/IDR.S258639

[41] Qin C, Zhou L, Hu Z, et al. 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

[42] Qin C., Zhou L., Hu Z., et al. Dysregulation of Immune Response in Patients With Coronavirus 2019 (COVID-19) in Wuhan, China // Clin Infect Dis. 2020. Vol. 71. No. 15. P. 762–768. DOI: 10.1093/cid/ciaa248

[43] Solinas C, Perra L, Aiello M, et al. A critical evaluation of glucocorticoids in the management of severe COVID-19. Cytokine Growth Factor Rev. 2020;54:8–23. DOI: 10.1016/j.cytogfr.2020.06.012

[44] Solinas C., Perra L., Aiello M., et al. A critical evaluation of glucocorticoids in the management of severe COVID-19 // Cytokine Growth Factor Rev. 2020. No. 54. P. 8–23. DOI: 10.1016/j.cytogfr.2020.06.012

[45] Liu B, Dhanda A, Hirani S, et al. CD14++CD16+ Monocytes Are Enriched by Glucocorticoid Treatment and Are Functionally Attenuated in Driving Effector T Cell Responses. J Immunol. 2015;194(11):5150–5160. DOI: 10.4049/jimmunol.1402409

[46] Liu B., Dhanda A., Hirani S., et al. CD14++CD16+ Monocytes Are Enriched by Glucocorticoid Treatment and Are Functionally Attenuated in Driving Effector T Cell Responses // J Immunol. 2015. Vol. 194, No. 11. P. 5150–5160. DOI: 10.4049/jimmunol.1402409

[47] Solomay TV, Semenenko TA, Filatov NN, et al. Reactivation of Epstein – Barr virus (Herpesviridae: Lymphocryptovirus, HHV-4) infection during COVID-19: epidemiological features. Problems of Virology. 2021;66(2):152–161 (In Russ.). DOI:10.36233/0507-4088-40

[48] Соломай Т.В., Семененко Т.А., Филатов Н.Н., и др. Реактивация инфекции, вызванной вирусом Эпштейна–Барр (Herpesviridae: Lymphocryptovirus, HHV-4) на фоне COVID-19: эпидемиологические особенности // Вопросы вирусологии. 2021. Т. 66, № 2. С. 152–161. DOI:10.36233/0507-4088-40

[49] Blinov DV, Akarachkova ES, Orlova AS, et al. New framework for the development of clinical guidelines in Russia. Farmakoekonomika. Modern Pharmacoeconomics and Pharmacoepidemiology. 2019;12(2):125–144. (In Russ.). DOI: 10.17749/2070-4909.2019.12.2.125-144

[50] Блинов Д.В., Акарачкова Е.С., Орлова А.С., и др. Новая концепция разработки клинических рекомендаций в России // Фармакоэкономика. Современная фармакоэкономика и фармакоэпидемиология. 2019. Т. 12, № 2. С. 125–144. DOI: 10.17749/2070-4909.2019.12.2.125-144

RIGHTS & PERMISSIONS

Shperling M.I., Kovalev A.V., Sukachev V.S., Vlasov A.A., Polyakov A.S., Noskov Y.A., Morozov A.D., Merzlyakov V.S., Zvyagintsev D.P., Kozlov K.V., Zhdanov K.V.