Join us   Log in  



Pages: 1-5

Hematological Alterations Associated with COVID-19 Severe

Gabriel Macedo Costa Guimarães* (BRAZIL)

Category: Virology

Download PDF


Since the onset of the COVID-19 pandemic in 2020, several studies have been relating the severity of the disease with hematological and coagulation changes besides a strong immune response. Understanding what these changes are, in addition to seeking predictive biomarkers of mortality, has become an essential task to help control and reduce the death rate during hospitalization of COVID-19 patients with a severe clinical conditions. The objective of this study was to evaluate the hematological alterations according to the clinical outcomes of COVID-19. Hematological alterations such as lymphopenia, leukocytosis, neutrophilia, and decrease in hemoglobin and red blood cells, in addition to a state of hypercoagulability and cytokine storm, have become the main alterations present in hospitalized patients with COVID-19. The initial identification of these abnormalities is useful for the early prognosis of individuals who may die during hospitalization and thus allow these patients to receive targeted support to improve their clinical condition.

Keywords: COVID-19, Hematological, Abnormalities, Lymphopenia, Neutrophilia


  1. Wang C, Horby PW, Hayden FG, Gao GF. A novel coronavirus outbreak of global health concern. Lancet. 2020;395(10223):470-473.
  2. Huang C, Wang Y, Li X, Ren L, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497-506.
  3. World Health Organization. Publications weekly epidemiological update on covid-19. WHO. Accessed February 1, 2022.
  4. Wiley Z, Kubes JN, Cobb J, et al. Age, comorbid conditions, and racial disparities in COVID-19 outcomes. J Racial Ethn Health Disparities. 2021;1(7):117-123.
  5. Lino K, Guimarães GM, Alves LS, et al. Serum ferritin at admission in hospitalized COVID-19 patients as a predictor of mortality. Braz J Infect Dis. 2021;25(2):101569.
  6. Asakura H, Ogawa H. COVID-19-associated coagulopathy and disseminated intravascular coagulation. Int J Hematol. 2021. 2021;113(1):45-57.
  7. Molaei S, Dadkhah M, Asghariazar V, Karami C, Safarzadeh E. The immune response and immune evasion characteristics in SARS-CoV, MERS-CoV, and SARS-CoV-2: Vaccine design strategies. Int Immunopharmacol. 2021;92:107051.
  8. Terpos E, Ntanasis-Stathopoulos I, Elalamy I, et al. Hematological findings and complications of COVID-19. Am J Hematol. 2020;95(7):834-847.
  9. Gonzalez-Mosquera LF, Gomez-Paz S, Lam E, et al. Hematologic Involvement as a Predictor of Mortality in COVID-19 Patients in a Safety Net Hospital. Kans J Med. 2022;15(1):8-16.
  10. Rahman A, Niloofa R, Jayarajah U, De Mel S, Abeysuriya V, Seneviratne SL. Hematological abnormalities in COVID-19: a narrative review. Am J Trop Med Hyg. 2021;104(4):1188.
  11. Al?Saadi EA, Abdulnabi MA. Hematological changes associated with COVID?19 infection. J Clin Lab Anal. 2022;36(1):e24064.
  12. Klok FA, Kruip MJ, Van der Meer NJ, et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res. 2020;191:145-147.
  13. Cui S, Chen S, Li X, Liu S, Wang F. Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia. J Thromb Haemost. 2020;18(6):1421-1424.
  14. Rovas A, Osiaevi I, Buscher K, et al. Microvascular dysfunction in COVID-19: the MYSTIC study. Angiogenesis. 2021;24(1):145-57.
  15. Varga Z, Flammer AJ, Steiger P, at el. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020;395(10234):1417-1418.
  16. Sabioni L, De Lorenzo A, Lamas C, Muccillo F, et al. Systemic microvascular endothelial dysfunction and disease severity in COVID-19 patients: Evaluation by laser Doppler perfusion monitoring and cytokine/chemokine analysis. Microvasc Res. 2021;134:104119.
  17. American Society of Hematology. COVID-19 and VTE/Anticoagulation: Frequently Asked Questions, Accessed December 19, 2022.
  18. Henry BM, Cheruiyot I, Vikse J, et al. Lymphopenia and neutrophilia at admission predicts severity and mortality in patients with COVID-19: a meta-analysis. Acta Biomed. 2020;91(3):e2020008.
  19. Simadibrata DM, Calvin J, Wijaya AD, Ibrahim NA. Neutrophil-to-lymphocyte ratio on admission to predict the severity and mortality of COVID-19 patients: A meta-analysis. Am J Emerg Med. 2021;42(3):60-69.
  20. Urbano M, Costa E, Geraldes C. Hematological changes in SARS-COV-2 positive patients. Hematol Transfus Cell Ther. 2022;44(2):218-224.
  21. Huyut MT, Huyut Z, Ilkbahar F, Merto?lu C. What is the impact and efficacy of routine immunological, biochemical and hematological biomarkers as predictors of COVID-19 mortality?. Int Immunopharmacol. 2022;105:108542.
  22. Narasaraju T, Yang E, Samy RP, et al. Excessive neutrophils and neutrophil extracellular traps contribute to acute lung injury of influenza pneumonitis. Am J Pathol. 2011;179(1):199-210.
  23. Geerdink RJ, Pillay J, Meyaard L, Bont L. Neutrophils in respiratory syncytial virus infection: A target for asthma prevention. J Allergy Clin Immunol. 2015;136(4):838-847.
  24. Baseler LJ, Falzarano D, Scott DP, et al. An acute immune response to Middle East respiratory syndrome coronavirus replication contributes to viral pathogenicity. Am J Pathol. 2016;186(3):630-638.
  25. Bradley LM, Douglass MF, Chatterjee D, Akira S, Baaten BJ. Matrix metalloprotease 9 mediates neutrophil migration into the airways in response to influenza virus-induced toll-like receptor signaling. PLoS pathogens. 2012;8(4):e1002641.
  26. Galani IE, Andreakos E. Neutrophils in viral infections: current concepts and caveats. J Leukoc Biol. 2015;98(4):557-564.
  27. Pittman K, Kubes P. Damage-associated molecular patterns control neutrophil recruitment. J Innate Immun. 2013;5(4):315-323.
  28. Johansson C, Kirsebom FC. Neutrophils in respiratory viral infections. Mucosal Immunol. 2021;14(4):815-827.
  29. Caillon A, Trimaille A, Favre J, Jesel L, Morel O, Kauffenstein G. Role of neutrophils, platelets, and extracellular vesicles and their interactions in COVID?19?associated thrombopathy. J Thromb Haemost. 2022;20(1):17-31.
  30. Johnson JE, McGuone D, Xu ML, et al. Coronavirus disease 2019 (COVID-19) coronary vascular thrombosis: correlation with neutrophil but not endothelial activation. Am J Pathol. 2022;192(1):112-20.
  31. Youn YJ, Lee YB, Kim SH, Jin HK, Bae JS, Hong CW. Nucleocapsid and spike proteins of SARS-CoV-2 drive neutrophil extracellular trap formation. Immune Netw. 2021;21(2):e16.
  32. Nicolai L, Leunig A, Brambs S, et al. Immunothrombotic dysregulation in COVID-19 pneumonia is associated with respiratory failure and coagulopathy. Circulation. 2020;142(12):1176-1189.
  33. Iliadi V, Konstantinidou I, Aftzoglou K, Iliadis S, Konstantinidis TG, Tsigalou C. The emerging role of neutrophils in the pathogenesis of thrombosis in COVID-19. Int J Mol Sci. 2021;22(10):5368.
  34. Jafarzadeh A, Jafarzadeh S, Nozari P, Mokhtari P, Nemati M. Lymphopenia an important immunological abnormality in patients with COVID?19: possible mechanisms. Scand J Immunoly. 2021;93(2):e12967.
  35. Zhang S, Asquith B, Szydlo R, Tregoning JS, Pollock KM. Peripheral T cell lymphopenia in COVID-19: potential mechanisms and impact. Immunother Adv. 2021;1(1):ltab015.
  36. Chen LY, Hoiland RL, Stukas S, Wellington CL, Sekhon MS. Confronting the controversy: interleukin-6 and the COVID-19 cytokine storm syndrome. Eur Respir J. 2020;56(4):2003006.
  37. Halim C, Mirza AF, Sari MI. The Association between TNF-α, IL-6, and Vitamin D Levels and COVID-19 Severity and Mortality: A Systematic Review and Meta-Analysis. Pathogens. 2022;11(2):195.
  38. Gómez-Pastora J, Weigand M, Kim J, et al. Hyperferritinemia in critically ill COVID-19 patients-is ferritin the product of inflammation or a pathogenic mediator?. Clin Chim Acta. 2020; 509:249-251.
  39. Bojan A, Parvu A, Zsoldos IA, Torok T, Farcas AD. Macrophage activation syndrome: A diagnostic challenge. Exp Ther Med. 2021;22(2):1-9.
  40. Colafrancesco S, Alessandri C, Conti F, Priori R. COVID-19 gone bad: A new character in the spectrum of the hyperferritinemic syndrome?. Autoimmun Rev. 2020;19(7):102573.
  41. Mahroum N, Alghory A, Kiyak Z, et al. Ferritin–from iron, through inflammation and autoimmunity, to COVID-19. J Autoimmun. 2022;126:102778.
  42. Lippi G, Plebani M. Laboratory abnormalities in patients with COVID-2019 infection. Clin Chem Lab Med. 2020;58(7):1131-1134.
  43. Algassim AA, Elghazaly AA, Alnahdi AS, et al. Prognostic significance of hemoglobin level and autoimmune hemolytic anemia in SARS-CoV-2 infection. Ann Hematol. 2021;100(1):37-43.
  44. Moghadam S, Azari B, Azhang A, Hasanzadeh S. Alterations in immune-inflammatory indices and hematological parameters in COVID-19 patients: with positive RT-PCR. New Microbes New Infect. 2022;45:100963.
  45. Bellmann-Weiler R, Lanser L, Barket R, et al. Prevalence and predictive value of anemia and dysregulated iron homeostasis in patients with COVID-19 infection. J Clin Med. 2020;9(8):2429.
  46. Faghih Dinevari M, Somi MH, Sadeghi Majd E, Abbasalizad Farhangi M, Nikniaz Z. Anemia predicts poor outcomes of COVID-19 in hospitalized patients: a prospective study in Iran. BMC Infect Dis. 2021;21:1-7.
  47. Lippi G, Mattiuzzi C. Hemoglobin value may be decreased in patients with severe coronavirus disease 2019. Hematol Transfus Cell Ther. 2020;42(2):116-117.
  48. Sayad B, Afshar ZM, Mansouri F, Rahimi Z. Leukocytosis and alteration of hemoglobin level in patients with severe COVID?19: Association of leukocytosis with mortality. Health Sci Rep. 2020;3(4):e194
  49. Kuno T, Miyamoto Y, Iwagami M, et al. The association of hemoglobin drop with in-hospital outcomes in COVID-19 patients. QJM. 2022;114(11):789-794
  50. Barbosa LC, Goncalves TL, de Araujo LP, de Oliveira Rosario LV, Ferrer VP. Endothelial cells and SARS-CoV-2: An intimate relationship. Vascul Pharmacol. 2021;137:106829
  51. Rauti R, Shahoha M, Leichtmann-Bardoogo Y, et al. Effect of SARS-CoV-2 proteins on vascular permeability. Elife. 2021;10:e69314.
  52. Siddiqi HK, Libby P, Ridker PM. COVID-19 - A vascular disease. Trends Cardiovasc Med. 2021;31(1):1-5.
  53. Willems LH, Nagy M, Ten Cate H, et al. Sustained inflammation, coagulation activation and elevated endothelin-1 levels without macrovascular dysfunction at 3 months after COVID-19. Thrombosis Res. 2022;209:106-114.
  54. Jiang SQ, Huang QF, Xie WM, Lv C, Quan XQ. The association between severe COVID?19 and low platelet count: evidence from 31 observational studies involving 7613 participants. Br J Haematol. 2020;190(1):e29-e33.
  55. Connors JM, Levy JH. COVID-19 and its implications for thrombosis and anticoagulation. Blood. 2020;135(23):2033-2040.
  56. Zaid Y, Puhm F, Allaeys I, et al. Platelets can associate with SARS-Cov-2 RNA and are hyperactivated in COVID-19. Circ Res. 2020;127(11):1404-18.
  57. Bonaventura A, Vecchié A, Dagna L, et al. Endothelial dysfunction and immunothrombosis as key pathogenic mechanisms in COVID-19. Nat Rev Immunol. 2021;21(5):319-329.

DOI: 10.55828/ijcicr-21-01