May be dysfunction of cellular immunity considered a sign of post-COVID syndrome?

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Abstract

Our aim was to study association between proliferative activity of peripheral blood lymphocytes after COVID, and developing post-COVID syndrome, and to determine whether the cell immunity dysfunction may be regarded as its marker.

The retrospective cohort study involved 242 patients (56 males, 186 females, 18 to 85 years old) who contracted new coronavirus infection. Of them, post-COVID syndrome was diagnosed in 180 cases (duration over 3 months). The patients were classified by severity of clinical course of COVID (i.e., presence of acute respiratory disease and pneumonias), and PHA-induced blast transformation of lymphocytes. Along with PHA-induced response, we studied cyclooxygenase (COG)-producing cells by morphological method. Control group consisted of 200 healthy people without any features of coronavirus infection. All patients were questioned and examined by multidisciplinary medical team, dependent on their complaints. We also registered incidence of comorbidities associated with cellular immune deficiency.

The patients with post-COVID syndrome exhibited a decrease of PHA-induced lymphocyte proliferation as compared with control group (significant at p < 0.01 in cases of acute respiratory infection, and p < 0.05 in patients with pneumonia). Activity of COG-producing cells was similar in all groups, independently on presence of post-COVID syndrome. Classification of patients by presence of cellular immune dysfunction (PHA-induced blast transformation ≤ 50%) allowed to detect higher activity of COG-producing cells. This enzyme is known to participate in development of inflammation promoting immune deficiency, thus, probably, manifesting in clinical activation of herpesvirus infection following COVID-19. Activity of COG-synthesizing cells was found to be higher in post-COVID syndrome which evolves after middle-severe and severe forms of new coronavirus infection complicated by pneumonias.

Chronic inflammation in post-COVID syndrome associated with high activity of COG-producing cells may promote dysfunction of cell immunity, thus being a cause of evolving syndrome, like as its biomarker. Absence of the immune cell dysfunction markers among other post-COVID features leads to decreased registration of post-COVID patients and misinterpretation of the results obtained.

About the authors

Nailya S. Asfandiyarova

I. Pavlov Ryazan State Medical University

Author for correspondence.
Email: n.asfandiyarova2010@yandex.ru
ORCID iD: 0000-0002-2025-8119

PhD, MD (Medicine), Senior Research Associate, Associate Professor, I. Pavlov Ryazan State Medical University, Ryazan, Russian Federation

Russian Federation, Ryazan

Mariya A. Rubtsova

City Clinical Hospital No. 10, Affiliation of Regional Clinical Hospital

Email: rubtsova.mariya@gmail.com

Head, Medical and Diagnostic Department, City Clinical Hospital No. 10, Affiliation of Regional Clinical Hospital, Ryazan, Russian Federation

Russian Federation, Ryazan

References

  1. Викулов Г.Х. Иммунологические аспекты герпес-вирусных инфекций // Клиническая дерматология и венерология, 2015. Т. 14, № 5. С. 104-114. [Vikulov G.Kh. Immunological aspects of herpesvirus infections. Klinicheskaya dermatologiya i venerologiya = Clinical Dermatology and Venereology, 2015, Vol. 14, no. 5, pp. 104-114. (In Russ.)]
  2. Глазанова Т.В., Шилова Е.Р. Нарушения в системе иммунитета после перенесенной новой коронавирусной инфекции COVID-19 // Журнал инфектологии, 2022. Т. 14, № 4. С. 26-37. [Glazanova T.V., Shilova E.R. Immune system disturbances after a new coronavirus infection COVID-19. Zhurnal infektologii = Journal of Infectology, 2022, Vol. 14, no. 4, pp. 26-37. (In Russ.)]
  3. Добин В.Л., Горбунов А.В., Муратов Е.Н. Клиническое наблюдение необычного течения коронавирусной инфекции у больного с хроническим диссеминированным туберкулезом легких и ВИЧ // Российский медико-биологический вестник им. акад. И.П. Павлова, 2021. Т. 29, № 4. С. 539-543. [Dobin V.L., Gorbunov A.V., Muratov E.N. Clinical case of an unusual course of coronavirus infection in patient with chronic disseminated pulmonary tuberculosis and human immunodeficiency virus infection. Rossiyskiy mediko-biologicheskiy vestnik im. akad. I.P. Pavlova = I. Pavlov Russian Medical Biological Herald, 2021, Vol. 29, no. 4, pp 539-543. (In Russ.)]
  4. Доценко Э.А., Доценко М.Л. Постковидный синдром // Рецепт, 2021. Т. 24, № 4, Ч. 2. С. 5-21. [Dotsenko E.A., Dotsenko M.L. Post-СOVID syndrome. Retsept = Recipe, 2021, Vol. 24, no. 4, pp. 5-21. (In Russ.)]
  5. Любавин А.В., Котляров С.Н. Особенности течения острого коронарного синдрома у пациентов с новой коронавирусной инфекцией COVID-19 // Наука молодых (Eruditio Juvenium), 2022. Т. 10, № 1. С.101-112. [Lyubavin A.V., Kotlyarov S.N. Peculiarities of the course of acute coronary syndrome in patients with new coronavirus infection. Nauka molodykh (Eruditio Juvenium) = Science of the Young (Eruditio Juvenium), 2022, Vol. 10, no. 1, pp. 101-112. (In Russ.)]
  6. A clinical case definition of post COVID-19 condition by a Delphi consensus, 6 October 2021”. www.who.int. Archived from the original on 2022-04-23. Retrieved 2022-01-07. Available at: https://www.who.int/publications/i/item/WHO-2019-nCoV-Post_COVID-19_condition-Clinical_case_definition-2021.1.
  7. Anaya J., Herrán M., Beltrán S., Rojas M. Is post-COVID syndrome an autoimmune disease? Expert Rev. Clin. Immunol., 2022, Vol. 18, no. 7, pp. 653-666.
  8. Ehrenfeld M., Tincani A., Andreoli L., Cattalini M., Greenbaum A., Kanduc D., Alijotas-Reig J., Zinserling V., Semenova N., Amital H., Shoenfeld Y. Covid-19 and autoimmunity. Autoimmun. Rev., 2020, Vol. 19, no. 8, 102597. doi: 10.1016/j.autrev.2020.102597.
  9. Guihot A., Litvinova E., Autran B., Debré P., Vieillard V. Cell-mediated immune responses to COVID-19 Infection. Front. Immunol., 2020, Vol. 11, 1662. doi: 10.3389/fimmu.2020.01662.
  10. Haunhorst S., Bloch W., Javelle F., Krüger K. Baumgart S., Drube S., Lemhöfer C., Reuken P., Stallmach A., Müller M., Zielinski C.E., Pletz M.W., Gabriel H.H.W., Puta C. A scoping review of regulatory T cell dynamics in convalescent COVID-19 patients – indications for their potential involvement in the development of Long COVID? Front. Immunol., 2022, Vol. 13, 1070994. doi: 10.3389/fimmu.2022.1070994.
  11. Huang C., Huang L., Wang Y., Li X., Ren L., Gu X., Kang L., Guo L., Liu M., Zhou X., Luo J., Huang Z., Tu S., Zhao Y., Chen L., Xu D., Li Y., Li C., Peng L., Li Y., Xie W., Cui D., Shang L., Fan G., Xu J., Wang G., Wang Y., Zhong J., Wang C., Wang J., Zhang D., Cao B. 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study. Lancet, 2021, Vol. 397, no. 10270, pp 220-232.
  12. Lui D.T.W., Lee C.H., Chow W.S., Lee A.C.H., Tam A.R., Fong C.H.Y., Law C.Y., Leung E.K.H., To K.K.W., Tan K.C.B., Woo Y.C., Lam C.W., Hung I.F.N., Lam K.S.L. Thyroid dysfunction in relation to immune profile, disease status, and outcome in 191 Patients with COVID-19. J. Clin. Endocrinol. Metab., 2021, Vol. 106, no. 2, pp. e926-e935.
  13. Maamari K.A., Busaidi I.A., Kindi M.A., Zadjali F., BaAlawi F., Anesta W., Amri K.A., Albalushi W., Balushi H.A., Amri A.A., Aljufaili M., Al-Busaidi M., Muharrmi Z.A., Balkhair A., Riyami N.A., Ghanim Z., Alshekaili J. Short and long-term immune changes in different severity groups of COVID-19 disease. Int. J. Infect. Dis., 2022, Vol. 122, pp. 776-784.
  14. Mitsuyama Y., Yamakawa K., Fujimi S. Residual persistence of cytotoxicity lymphocytes and regulatory T cells in patients with severe coronavirus disease 2019 over a 1-year recovery process. Acute Med. Surg., 2022, Vol. 9, no. 1, e803. doi: 10.1002/ams2.803.
  15. Montes N., Domènech È., Guerrero S., Oliván-Blázquez B., Magallón-Botaya R. Analysis of cell-mediated immunity in people with long COVID. medRxiv, 202106.09.21258553. doi: 10.1101/2021.06.09.21258553.
  16. National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing the long-term effects of COVID-19. 2020. Available at: https://www.nice.org.uk/guidance/ng188.
  17. Ni L., Cheng M.-L., Feng Y., Zhao H., Liu J., Ye F., Ye Q., Zhu G., Li X., Wang P., Shao J., Deng Y.-Q., Wei P., Chen F., Qin C.-F., Wang G., Li F., Zeng H., Dong C. Impaired Cellular Immunity to SARS-CoV-2 in Severe COVID-19 Patients. Front. Immunol., 2021, Vol. 12, 603563. doi: 10.3389/fimmu.2021.603563.
  18. Pavli A., Theodoridou M., Maltezou HC. Post-COVID syndrome: Incidence, clinical spectrum, and challenges for primary healthcare professionals. Arch. Med. Res., 2021, Vol. 52, no. 6, pp. 575-581.
  19. Shuwa H.A., Shaw T.N., Knight S.B., Wemyss K., McClure F.A., Pearmain L., Prise I., Jagger C., Morgan D.J., Khan S., Brand O., Mann E.R., Ustianowski A., Bakerly N.D., Dark P., Brightling C.E., Brij S., CIRCO, Felton T., Simpson A., Grainger J.R., Hussel T., Konkel J.E., Menon M. Alterations in T and B cell function persist in convalescent COVID-19 patients. Med, 2021, Vol. 2, no 6, pp 720-735.
  20. Sudre C.H., Murray B., Varsavsky T., Graham M.S., Penfold R.S., Bowyer R.C., Pujol J.C., Klaser K., Antonelli M., Canas L.S., Molteni E., Modat M., Jorge Cardoso M., May A., Ganesh S., Davies R., Nguyen L.H., Drew D.A., Astley C.M., Joshi A.D., Merino J., Tsereteli N., Fall T., Gomez M.F., Duncan E.L., Menni C., Williams F.M.K., Franks P.W., Chan A.T., Wolf J., Ourselin S., Spector T., Steves C.J. Attributes and predictors of long COVID. Nat. Med., 2021, Vol. 27, no. 4, pp. 626-631.
  21. Vlachoyiannopoulos P.G., Magira E., Alexopoulos H., Jahaj E., Theophilopoulou K., Kotanidou A., Tzioufas A.G. Autoantibodies related to systemic autoimmune rheumatic diseases in severely ill patients with COVID-19. Ann. Rheum. Dis., 2020, Vol. 79, no. 12, pp. 1661-1663.
  22. Willi S., Lüthold R., Hunt A., Hänggi N.V., Sejdiu D., Scaff C., Bender N., Staub K., Schlagenhauf P. COVID-19 sequelae in adults aged less than 50 years: a systematic review. Travel Med. Infect. Dis., 2021, Vol. 40, 101995. doi: 10.1016/j.tmaid.2021.101995.
  23. Yong S.J. Long COVID or post-COVID-19 syndrome: putative pathophysiology, risk factors, and treatments. Infect. Dis. (Lond.), 2021, Vol. 53, no. 10, pp. 737-754.

Copyright (c) 2023 Asfandiyarova N.S., Rubtsova M.A.

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