Associations between serum levels of C3, C4, and total classical complement activity in COVID-19 patients at the time of admission and clinical outcome

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Abstract

In the present study, we investigated the association between complement system status at the time of admission and clinical outcomes in COVID-19 patients. This single-center study was carried out with sixty-one adult patients with COVID-19 who were hospitalized at Imam Hassan Hospital of North Khorasan University of Medical Sciences (Bojnurd, Iran) with less than three days passage since onset of COVID-19 symptoms. Twenty-three healthy volunteers with demographic features similar to the patient group (matched by age and gender) were included in the study as a control group. Patient information including demographic information, demographic data, clinical characteristics, and clinical outcomes were obtained from electronic medical records. Of 61 hospitalized patients with COVID-19, 28 (47.54%) were female, and the average age was 48.7±8.8 years. The healthy control group included 23 cases (11 (47.8%) female, 12 (52.1%) males, mean age 46.4±4.4 years). Twenty-one of the 61 patients (34.4%) were admitted to the ICU, and sixteen of them (26.2%) died. Thirty-three (54.10%) patients with COVID-19 were hospitalized for less than 7 days, and 28 (45.90%) of them were hospitalized for ≥ 7 days. Our results show that length of hospital stay in the no-ICU group was significantly lower than the ICU admission or death groups (6.49±0.24 vs. 8.85±1.59 and 10.53±1.80, p = 0.0002). The levels of C3, C4, and CH50 were determined through the immunoturbidimetric method and single-radial-haemolysis plates, respectively, on serum samples obtained from patients at the time of admission or those in the control group. Our results indicate that C3, C4 and CH50 levels were markedly lower in COVID-19 patients than in the control group. We also found that complement parameter levels in COVID-19 patients who died or were admitted to ICU were significantly lower than in non-ICU COVID-19 patients. In general, it seems that serum level of C3, C4, and CH50 at admission may predict disease progression or adverse clinical outcome in COVID-19 patients.

About the authors

A. Razi

North Khorasan University of Medical Sciences

Email: raknv@mail.ru

PhD, MD (Medicine), Assistant Professor

Iran, Islamic Republic of, Bojnurd

A. Azimian

North Khorasan University of Medical Sciences

Email: raknv@mail.ru

PhD, MD (Medicine), Associate Professor, Faculty Member, Department of Pathobiology and Laboratory Sciences

Bojnurd

R. Arezumand

North Khorasan University of Medical Sciences

Email: raknv@mail.ru

PhD, MD (Medicine), Assistant Professor, Faculty Member, Department of Pathobiology and Laboratory Sciences

Iran, Islamic Republic of, Bojnurd

A. Solati

North Khorasan University of Medical Sciences

Email: raknv@mail.ru

PhD, MD (Philosophy), Associate Professor, Faculty Member, Department of English Language

Iran, Islamic Republic of, Bojnurd

H. N. Ahmadabad

North Khorasan University of Medical Sciences

Author for correspondence.
Email: namdar360@gmail.com

PhD, MD (Medicine), Associate Professor, Faculty Member, Department of Pathobiology and Laboratory Sciences

Iran, Islamic Republic of, Bojnurd

References

  1. Agrawal P., Nawadkar R., Ojha H., Kumar J., Sahu A. Complement evasion strategies of viruses: an overview. Front. Microbiol., 2017, vol. 8, pp. 1117. doi: 10.3389/fmicb.2017.01117
  2. Baric R.S. Emergence of a highly fit SARS-CoV-2 variant. N. Engl. J. Med., 2020, vol. 383, no. 27, pp. 2684–2686. doi: 10.1056/NEJMcibr2032888
  3. Bjornson A.B., Mellencamp M.A., Schiff G.M. Complement is activated in the upper respiratory tract during influenza virus infection. Am. Rev. Respir. Dis., 1991, vol. 143, no. 5, pp. 1062–1066. doi: 10.1164/ajrccm/143.5_Pt_1.1062
  4. Bosmann M., Ward P.A. Role of C3, C5 and anaphylatoxin receptors in acute lung injury and in sepsis. In: Current Topics in Innate Immunity I.I. Advances in Experimental Medicine and Biology, vol. 946. Eds.: J. Lambris, G. Hajishengallis. New York: Springer, 2012, vol. 946, pp. 147–159. doi: 10.1007/978-1-4614-0106-3_9
  5. Dheir H., Sipahi S., Yaylaci S., Köroğlu M., Erdem A.F., Karabay O. Is there relationship between SARS-CoV-2 and the complement C3 and C4? Turk. J. Med. Sci., 2020, vol. 50, no. 4, pp. 687–688. doi: 10.3906/sag-2004-336
  6. Fang S., Wang H., Lu L., Jia Y., Xia Z. Decreased complement C3 levels are associated with poor prognosis in patients with COVID-19: a retrospective cohort study. Int. Immunopharmacol., 2020, vol. 89 (Pt A): 10707. doi: 10.1016/j.intimp.2020.107070
  7. Fletcher-Sandersjöö A., Bellander B.-M. Is COVID-19 associated thrombosis caused by overactivation of the complement cascade? A literature review. Thromb. Res., 2020, vol. 194, pp. 36–41. doi: 10.1016/j.thromres.2020.06.027
  8. Ghazavi A., Mosayebi G., Keshavarzian N., Rabiemajd S., Ganji A. Reduction of inflammatory C3 and C4 complement proteins in severe COVID-19 patients. Preprint (Version 1) available at Research Square. 2020. 13 p. doi: 10.21203/rs.3.rs-127493/v1
  9. Gibson P.G., Qin L., Puah S.H. COVID-19 acute respiratory distress syndrome (ARDS): clinical features and differences from typical pre-COVID-19 ARDS. Med. J. Aust., 2020, vol. 213, no. 2, pp. 54–56. doi: 10.5694/mja2.50674
  10. Gralinski L.E., Sheahan T.P., Morrison T.E., Menachery V.D., Jensen K., Leist S.R., Whitmore A., Heise M.T., Baric R.S. Complement activation contributes to severe acute respiratory syndrome coronavirus pathogenesis. mBio, 2018, vol. 9, no. 5: e01753-18 doi: 10.1128/mBio.01753-18
  11. Henry B.M., Szergyuk I., de Oliveira M.H.S., Lippi G., Benoit J.L., Vikse J., Benoit S.W. Complement levels at admission as a reflection of Coronavirus Disease 19 (COVID-19) severity state. J. Med. Virol., 2021, vol. 93, no. 9, pp. 5515–5522. doi: 10.1002/jmv.27077
  12. Java A., Apicelli A.J., Liszewski M.K., Coler-Reilly A., Atkinson J.P., Kim A.H., Kulkarni H.S. The complement system in COVID-19: friend and foe? JCI Insight, 2020, vol. 5, no. 15: e140711. doi: 10.1172/jci.insight.140711
  13. Jayarangaiah A., Kariyanna P.T., Chen X., Jayarangaiah A., Kumar A. COVID-19-associated coagulopathy: an exacerbated immunothrombosis response. Clin. Appl. Thromb. Hemost., 2020, vol. 26: 1076029620943293. doi: 10.1177/1076029620943293
  14. Jimenez-Cebrian A.M., Castro-Mendez A., García-Podadera B., Romero-Galisteo R., Medina-Alcántara M., Garcia-Paya I., Páez-Moguer J., Córdoba-Fernández A. Clinical manifestations of COVID-19 in the feet: a review of reviews. J. Clin. Med., 2021, vol. 10, no. 10: 2201. doi: 10.3390/jcm10102201
  15. Keshavarz F., Ghalamfarsa F., Javdansirat S., Hasanzadeh S., Azizi A., Sabz G., Salehi M., Ghalamfarsa G. Patients with COVID-19 have significantly reduced CH50 activity. Virusdisease, 2021, vol. 32, no. 4, pp. 681–689. doi: 10.1007/s13337-021-00710-6
  16. Kristensen M.K., Hansen M.B., Madsen M.B., Hansen C.B., Pilely K., Hyldegaard O., Garred P. Complement activation is associated with mortality in patients with necrotizing soft-tissue infections — a prospective observational study. Front. Immunol., 2020, vol. 11: 17. doi: 10.3389/fimmu.2020.00017
  17. Lippi G., Henry B.M., Hoehn J., Benoit S., Benoit J. Validation of the Corona-Score for rapid identification of SARS-CoV-2 infections in patients seeking emergency department care in the United States. Clin. Chem. Lab. Med., 2020, vol. 8, no. 12, pp. e311–e113. doi: 10.1515/cclm-2020-1121
  18. McPherson R.A., Pincus M.R. Henry’s clinical diagnosis and management by laboratory methods. Elsevier Health Sciences, 2021. 1618 p. URL: https://www.elsevier.com/books/henrys-clinical-diagnosis-and-management-by-laboratory-methods/mcpherson/ 978-0-323-67320-4 (10.02.2022)
  19. Melenotte C., Silvin A., Goubet A.G., Lahmar I., Dubuisson A., Zumla A., Raoult D., Merad M., Gachot B., Hénon C., Solary E., Fontenay M., André F., Maeurer M., Ippolito G., Piacentini M., Wang F.S., Ginhoux F., Marabelle A., Kroemer G., Derosa L., Zitvogel L. Immune responses during COVID-19 infection. Oncoimmunology, 2020, vol. 9, no. 1: 1807836. doi: 10.1080/2162402X.2020.1807836
  20. Qureshi A.I., Baskett W.I., Huang W., Shyu D., Myers D., Lobanova I., Naqvi S.H., Thompson V.S., Shyu C.R. Effect of race and ethnicity on in-hospital mortality in patients with COVID-2019. Ethn. Dis., 2021, vol. 31, no. 3, pp. 389–398. doi: 10.18865/ed.31.3.389
  21. Raghunandan S., Josephson C.D., Verkerke H., Linam W.M., Ingram T.C., Zerra P.E., Arthur C.M., Stowell S.R., Briones M., Chonat S. Complement inhibition in severe COVID-19 acute respiratory distress syndrome. Front. Pediatr., 2020, vol. 8: 616731. doi: 10.3389/fped.2020.616731
  22. Shakeri H., Azimian A., Ghasemzadeh-Moghaddam H., Safdari M., Haresabadi M., Daneshmand T., Namdar Ahmadabad H. Evaluation of the relationship between serum levels of zinc, vitamin B12, vitamin D, and clinical outcomes in patients with COVID-19. J. Med. Virol., 2022, vol. 94, no. 1, pp. 141–146. doi: 10.1002/jmv.27277
  23. Xu W., Sun N.N., Gao H.N., Chen Z.Y., Yang Y., Ju B., Tang L.L. Risk factors analysis of COVID-19 patients with ARDS and prediction based on machine learning. Sci. Rep., 2021, vol. 11, no. 1: 2933. doi: 10.1038/s41598-021-82492-x
  24. Zhang Z., Li X., Zhang W., Shi Z.-L., Zheng Z., Wang T. Clinical features and treatment of 2019-nCoV pneumonia patients in Wuhan: report of a couple cases. Virol. Sin., 2020, vol. 35, no. 3, pp. 330–336. doi: 10.1007/s12250-020-00203-8
  25. Zinellu A., Mangoni A.A. Serum complement C3 and C4 and COVID-19 severity and mortality: a systematic review and meta-analysis with meta-regression. Front. Immunol., 2021, vol. 12: 696085. doi: 10.3389/fimmu.2021.696085

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2. Figure. Comparison of hospital stay length in COVID-19 patients with serum levels of C3, C4 and CH50 at the time of admission

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Copyright (c) 2023 Razi A., Azimian A., Arezumand R., Solati A., Ahmadabad H.N.

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