Document Type : Original Research


1 Pathology and Stem Cells Research Centers, Pathology Department, Afzalipour Medical School, Kerman Medical Sciences University, Kerman, Iran

2 Department of Pathology, Shahid Beheshti University of Medical Sciences, Tehran, Iran

3 Department of Pathology, NYU Long Island School of Medicine, NYU Langone Hospital, New York, United States of America

4 Virology Research Center, National Research Institute of Tuberculosis and Lung Disease, Shahid Beheshti University of Medical Sciences, Tehran, Iran

5 Infectious Branch, Internal Medicine Department, Afzalipour Hospital, Kerman Medical Sciences University, Kerman, Iran


Background: To gain insight into the pathogenesis and clinical course of COVID-19 from a historical perspective, we reviewed paraclinical diagnostic tools of this disease and prioritized the patients with a more severe form of disease admitted to intensive care units (ICUs). The objective was to better predict the course and severity of the disease by collecting more paraclinical data, specifically by examining the relationship between hematological findings and cytological variation of blood neutrophils and monocytes.
Methods: This retrospective study was conducted on 112 patients with confirmed COVID-19 admitted to Imam Hossein Hospital (Tehran, Iran) from August to September 2020. Peripheral blood smears of these patients were differentiated according to several cytological variations of neutrophils and monocytes, and the correlation to the severity of the disease was specified.
Results: The mean percentages of degenerated monocytes, degenerated granulocytes, and spiky biky neutrophils were significantly different among critical and non-critical patients (P<0.05). Degenerated monocytes and granulocytes were higher in critical patients as opposed to spiky biky neutrophils, which were higher among non-critical ones. Comparing the peripheral blood smears of COVID-19 patients (regarding pulmonary involvement in chest computed tomography [CT] scans [subtle, mild, moderate, and severe groups]), the twisted form of neutrophils was significantly higher in the subtle group than in the mild and moderate groups (P=0.003).
Conclusion: Different cytological morphologies of neutrophils and monocytes, including degenerated monocytes, degenerated granulocytes, and spiky biky and twisted neutrophils, could help to predict the course and severity of the disease.


Main Subjects

  1. Liu X, Zhang R, He G. Hematological findings in coronavirus disease 2019: indications of progression of disease. Ann Hematol. 2020;99(7):1421-8. [PMID] [PMCID] [DOI:10.1007/s00277-020-04103-5]
  2. Terpos E, Ntanasis-Stathopoulos I, Elalamy I, Kastritis E, Sergentanis TN, Politou M, et al. Hematological findings and complications of COVID-19. Am J Hematol. 2020 Jul;95(7):834-47. [DOI:10.1002/ajh.25829] [PMID] [PMCID]
  3. Yuan X, Huang W, Ye B, Chen C, Huang R, Wu F, et al. Changes of hematological and immunological parameters in COVID-19 patients. Int J Hematol. 2020;112(4):553-9. [DOI:10.1007/s12185-020-02930-w] [PMID] [PMCID]
  4. Pozdnyakova O, Connell NT, Battinelli EM, Connors JM, Fell G, Kim AS. Clinical Significance of CBC and WBC Morphology in the Diagnosis and Clinical Course of COVID-19 Infection. Am J Clin Pathol. 2021 Feb 11;155(3):364-375. [PMID] [PMCID] [DOI:10.1093/ajcp/aqaa231]
  5. Singh A, Sood N, Narang V, Goyal A. Morphology of COVID-19-affected cells in peripheral blood film. BMJ Case Rep. 2020 May 27;13(5):e236117. [DOI:10.1136/bcr-2020-236117] [PMID] [PMCID]
  6. Zhu L, Liu L, Zhang Y, Pu L, Liu J, Li X, et al. High Level of Neutrophil Extracellular Traps Correlates With Poor Prognosis of Severe Influenza A Infection. J Infect Dis. 2018;217(3):428-37. [DOI:10.1093/infdis/jix475] [PMID]
  7. Lakhdari N, Tabet B, Boudraham L, Laoussati M, Aissanou S, Beddou L et al. Red blood cells injuries and hypersegmented neutrophils in COVID-19 peripheral blood film. MedRxiv. 2020. [DOI:10.1101/2020.07.24.20160101.]
  8. Zhao Y, He J, Wang J, Li WM, Xu M, Yu X, et al. Development of pancytopenia in a patient with COVID-19. J Med Virol. 2021 Mar;93(3):1219-20. [DOI:10.1002/jmv.26566] [PMID] [PMCID]
  9. Bahadori M, Dabiri S, Javadi A, Shamsi Meymandi S, Movahedinia S, Shamsi Meymandi M, et al. Pathogenesis of COVID-19; Acute Auto-inflammatory Disease (Endotheliopathica & Leukocytoclastica COVIDicus). Arch Iran Med. 2021;24(5): 419-26. [DOI:10.34172/aim.2021.60] [PMID]
  10. World Health Organization. Laboratory testing of 2019 novel coronavirus (‎‎‎‎‎‎‎‎‎‎‎‎2019-nCoV)‎‎‎‎‎‎‎‎‎‎‎‎ in suspected human cases: interim guidance, 17 January 2020 [Internet]. 2022 [cited 19 August 2022]. Available from:
  11. Herbert V. Megaloblastic anemias. Laboratory Investigation; J Tech Methods Pathol. 1985;52(1):3-19.
  12. Pan F, Ye T, Sun P, Gui S, Liang B, Li L, et al. Time Course of Lung Changes at Chest CT during Recovery from Coronavirus Disease 2019 (COVID-19). Radiology. 2020;295(3):715-21. [PMID] [PMCID] [DOI:10.1148/radiol.2020200370]
  13. Kazancioglu S, Bastug A, Ozbay BO, Kemirtlek N, Bodur H. The role of haematological parameters in patients with COVID-19 and influenza virus infection. Epidemiol Infect. 2020 Nov 5;148:e272. [PMID] [PMCID] [DOI:10.1017/S095026882000271X]
  14. Sun DW, Zhang D, Tian RH, Li Y, Wang YS, Cao J, et al. The underlying changes and predicting role of peripheral blood inflammatory cells in severe COVID-19 patients: A sentinel? Clin Chim Acta. 2020;508:122-9. [PMID] [PMCID] [DOI:10.1016/j.cca.2020.05.027]
  15. Fan BE. Hematologic parameters in patients with COVID-19 infection: a reply. Am J Hematol. 2020;95(8):E215. [DOI:10.1002/ajh.25847]
  16. Lippi G, Plebani M. Laboratory abnormalities in patients with COVID-2019 infection. Clin Chem Lab Med. 2020;58(7):1131-4. [DOI:10.1515/cclm-2020-0198] [PMID]
  17. Chiang CC, Korinek M, Cheng WJ, Hwang TL. Targeting Neutrophils to Treat Acute Respiratory Distress Syndrome in Coronavirus Disease. Front Pharmacol. 2020;11:572009. [PMID] [PMCID] [DOI:10.3389/fphar.2020.572009]
  18. Yang S, Tsai Y, Pan Y, Hwang T. Understanding the role of neutrophils in acute respiratory distress syndrome. Biomed J. 2021;44(4):439-46. [PMID] [PMCID] [DOI:10.1016/]
  19. Zhu Y, Chen X, Liu X. NETosis and Neutrophil Extracellular Traps in COVID-19: Immunothrombosis and Beyond. Front Immunol. 2022 Mar 2;13:838011. [PMID] [PMCID] [DOI:10.3389/fimmu.2022.838011]
  20. Zini G, Bellesi S, Ramundo F, d'Onofrio G. Morphological anomalies of circulating blood cells in COVID-19. Am J Hematol. 2020;95(7): 870-2. [DOI:10.1002/ajh.25824] [PMID] [PMCID]
  21. Mitra A, Dwyre DM, Schivo M, Thompson GR 3rd, Cohen SH, Ku N, et al. Leukoerythroblastic reaction in a patient with COVID-19 infection. Am J Hematol. 2020;95(8):999-1000. [DOI:10.1002/ajh.25793] [PMID] [PMCID]
  22. Pezeshki, A., Vaezi, A. & Nematollahi, P. Blood cell morphology and COVID-19 clinical course, severity, and outcome. J Hematopathol 14, 221-8 (2021). [DOI:10.1007/s12308-021-00459-3.] [PMID] [PMCID]
  23. Nazarullah A, Liang C, Villarreal A, Higgins RA, Mais DD. Peripheral Blood Examination Findings in SARS-CoV-2 Infection. Am J Clin Pathol. 2020;154(3):319-29. [DOI:10.1093/ajcp/aqaa108] [PMID] [PMCID]
  24. Zhang D, Guo R, Lei L, Liu H, Wang Y, Wang Y, et al. Frontline Science: COVID-19 infection induces readily detectable morphologic and inflammation-related phenotypic changes in peripheral blood monocytes. J Leukoc Biol. 2021;109(1):13-22. [DOI:10.1002/JLB.4HI0720-470R] [PMID] [PMCID]
  25. Berber I, Cagasar O, Sarici A, Berber NK, Aydogdu I, Ulutas O, et al. Peripheral Blood Smear Findings of COVID-19 Patients Provide İnformation about the Severity of the Disease and the Duration of Hospital Stay. Mediterr J Hematol Infect Dis. 2021;13(1):e2021009. [PMID] [PMCID] [DOI:10.4084/mjhid.2021.009]
  26. Javadi A, Dabiri S, Meymandi MS, Hashemi Bahremani M, Soleimantabar H, Dabiri B, et al. Changes of Routine Hematological Parameters in COVID-19 Patients: Correlation with Imaging Findings, RT-PCR and Outcome. Iran J Pathol. 2022;17(1):37-47. [DOI:10.30699/ijp.2021.533645.2675] [PMID] [PMCID]
  27. Kannan G, Soni M. Leukocyte morphological changes in COVID-19, a peripheral smear study and analysis at a tertiary health care centre in India. Apollo Med [serial online] 2021 [cited 2022 Oct 22];18:158-61. Available from:
  28. Jafarzadeh A, Chauhan P, Saha B, Jafarzadeh S, Nemati M. Contribution of monocytes and macrophages to the local tissue inflammation and cytokine storm in COVID-19: Lessons from SARS and MERS, and potential therapeutic interventions. Life Sci. 2020;257:118102. [PMID] [PMCID] [DOI:10.1016/j.lfs.2020.118102]