Hematological Abnormalities in Patients With COVID-19: An Emerging Approach to Differentiate Between Severe COVID-19; Compared With Non-Severe Forms of the Disease
Abstract
The 2019 novel coronavirus (2019-nCoV) or the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as a pandemic threat from December 2019. Coronavirus can cause varying degrees of illness that range from mild to severe or fatal disease. The exact mechanism on hematopoiesis induced by this coronavirus is not yet well understood, but scientific evidence indicates that COVID-19 can cause hematological changes in infected patients. The present study summarized pieces of literature regarding hematologic findings of COVID-19 and their correlation with disease severity. Finally, we offered some laboratory abnormalities which help to differentiate severe COVID-19 from non-severe forms of the disease. Among hematological parameters, decreased hemoglobin rather than anemia, leukocytosis, lymphopenia, neutrophilia, and thrombocytopenia have been observed in conducted studies in some patients with COVID-19. Furthermore, as the disease progresses to severe COVID-19, hemoglobin decline, leukocytosis, lymphopenia, neutrophilia, and thrombocytopenia continue to exacerbate. In addition, the neutrophil-to-lymphocyte ratio is also considered as an independent risk factor for severe infection in COVID-19 patients.
1. Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med 2020;382:727-33.
2. Li Q, Guan X, Wu P, Wang X, Zhou L, Tong Y, et al. Early transmission dynamics in Wuhan, China, of novelcoronavirus–infected pneumonia. N Engl J Med 2020;382:1199-207.
3. Petrosillo N, Viceconte G, Ergonul O, Ippolito G, Petersen E. COVID-19, SARS and MERS: are they closely related? Clin Microbiol Infect 2020;26:729-34.
4. Lauer SA, Grantz KH, Bi Q, Jones FK, Zheng Q, Meredith HR, et al. The incubation period of coronavirus disease 2019 (COVID-19) from publicly reported confirmed cases: estimation and application. Ann Intern Med 2020;172:577-82.
5. Backer JA, Klinkenberg D, Wallinga J. Incubation period of 2019 novel coronavirus (2019-nCoV) infections among travellers from Wuhan, China, 20–28 January 2020. Euro Surveill 2020;25:2000062.
6. Xu XW, Wu XX, Jiang XG, Xu KJ, Ying LJ, Ma CL, et al. Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series. BMJ 2020;368:m606.
7. Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 2020;382:1708-20.
8. Driggin E, Madhavan MV, Bikdeli B, Chuich T, Laracy J, Biondi-Zoccai G, et al. Cardiovascular considerations for patients, health care workers, and health systems during the COVID-19 pandemic. J Am Coll Cardiol 2020;75:2352-71.
9. Vincent JL, Taccone FS. Understanding pathways to death in patients with COVID-19. Lancet Respir Med 2020;8:430-2.
10. Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med 2020;46:846-8.
11. Zhao X, Wang K, Zuo P, Liu Y, Zhang M, Xie S, et al. Early decrease in blood platelet count is associated with poor prognosis in COVID-19 patients—indications for predictive, preventive, and personalized medical approach. EPMA J 2020;11:139-45.
12. Wu JT, Leung K, Leung GM. Nowcasting and forecasting the potential domestic and international spread of the 2019-nCoV outbreak originating in Wuhan, China: a modelling study. Lancet 2020;395:689-97.
13. Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus–infected pneumonia in Wuhan, China. JAMA 2020;323:1061-9.
14. Sun X, Wang T, Cai D, Hu Z, Liao H, Zhi L, et al. Cytokine storm intervention in the early stages of COVID-19 pneumonia. Cytokine Growth Factor Rev 2020;53:38-42.
15. Yang M, Li CK, Li K, Hon KLE, Ng MH, Chan PK, et al. Hematological findings in SARS patients and possible mechanisms. Int J Mol Med 2004;14:311-5.
16. Wong RS, Wu A, To K, Lee N, Lam CW, Wong C, et al. Haematological manifestations in patients with severe acute respiratory syndrome: retrospective analysis. BMJ 2003;326:1358-62.
17. Yang M, Ng MH, Li CK. Thrombocytopenia in patients with severe acute respiratory syndrome. Hematology 2005;10:101-5.
18. Poutanen SM, Low DE, Henry B, Finkelstein S, Rose D, Green K, et al. Identification of severe acute respiratory syndrome in Canada. N Engl J Med 2003;348:1995-2005.
19. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020;395:497-506.
20. Tsang KW, Ho PL, Ooi GC, Yee WK, Wang T, Chan-Yeung M, et al. A cluster of cases of severe acute respiratory syndrome in Hong Kong. N Engl J Med 2003;348:1977-85.
21. Liu X, Zhang R, He G. Hematological findings in coronavirus disease 2019: indications of progression of disease. Annals of Hematology. Ann Hematol 2020:1-8.
22. Nemeth E, Ganz T. Anemia of inflammation. Hematol Oncol Clin North Am 2014;28:671-81.
23. Coperchini F, Chiovato L, Croce L, Magri F, Rotondi M. The Cytokine storm in COVID-19: An overview of the involvement of the chemokine/chemokine-receptor system. Cytokine Growth Factor Rev 2020;53:25-32.
24. Soy M, Keser G, Atagündüz P, Tabak F, Atagündüz I, Kayhan S. Cytokine storm in COVID-19: pathogenesis and overview of anti-inflammatory agents used in treatment. Clin Rheumatol 2020;39:2085-94.
25. Fan BE, Ong KH, Chan SSW, Young BE, Chong VCL, Chen SPC, et al. Blood and blood product use during COVID‐19 infection. Am J Hematol 2020;95:E158-60.
26. Wenzhong L, Hualan L. COVID-19: Attacks the 1-beta chain of hemoglobin and captures the porphyrin to inhibit human heme metabolism. ChemRxiv 2020 (Preprint).
27. Lazarian G, Quinquenel A, Bellal M, Siavellis J, Jacquy C, Re D, et al. Autoimmune hemolytic anemia associated with Covid‐19 infection. Br J Haematol 2020;190:29-31.
28. Liebman HA, Weitz IC. Autoimmune hemolytic anemia. Med Clin North Am 2017;101:351-9.
29. Gehrs BC, Friedberg RC. Autoimmune hemolytic anemia. Am J Hematol 2002;69:258-71.
30. Coutelier JP, Detalle L, Musaji A, Meite M, Izui S. Two‐Step Mechanism of Virus‐induced Autoimmune Hemolytic Anemia. Ann N Y Acad Sci 2007;1109:151-7.
31. Lopez C, Kim J, Pandey A, Huang T, DeLoughery TG. Simultaneous Onset of COVID‐19 and Autoimmune Hemolytic Anemia. Br J Haematol 2020;190:31-2.
32. Wahlster L, Weichert‐Leahey N, Trissal M, Grace RF, Sankaran VG. COVID‐19 presenting with autoimmune hemolytic anemia in the setting of underlying immune dysregulation. Pediatr Blood Cancer 2020;67:e28382.
33. Henry BM, De Oliveira MHS, Benoit S, Plebani M, Lippi G. Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): a meta-analysis. Clin Chem Lab Med 2020;58:1021-8.
34. Fan BE, Chong VCL, Chan SSW, Lim GH, Lim KGE, Tan GB, et al. Hematologic parameters in patients with COVID‐19 infection. Am J Hematol 2020;95:E131-E4.
35. Lu G, Wang J. Dynamic changes in routine blood parameters of a severe COVID-19 case. Clin Chim Acta 2020;508:98-102.
36. Zhao XY, Xu XX, Yin HS, Hu QM, Xiong T, Tang YY, et al. Clinical characteristics of patients with 2019 coronavirus disease in a non-Wuhan area of Hubei Province, China: a retrospective study. BMC Infect Dis 2020;20:311.
37. Lippi G, Plebani M. The critical role of laboratory medicine during coronavirus disease 2019 (COVID-19) and other viral outbreaks. Clin Chem Lab Med 2020;58:1063-9.
38. Herbinger K-H, Hanus I, Beissner M, Berens-Riha N, Kroidl I, von Sonnenburg F, et al. Lymphocytosis and lymphopenia induced by imported infectious diseases: a controlled cross-sectional study of 17,229 diseased German travelers returning from the tropics and subtropics. Am J Trop Med Hyg 2016;94:1385-91.
39. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395:507-13.
40. Liu Y, Yang Y, Zhang C, Huang F, Wang F, Yuan J, et al. Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury. Sci China Life Sci 2020;63:364-74.
41. Zhang J-j, Dong X, Cao Y-y, Yuan Y-d, Yang Y-b, Yan Y-q, et al. Clinical characteristics of 140 patients infected with SARS‐CoV‐2 in Wuhan, China. Allergy 2020;75:1730-41.
42. Lippi G, Plebani M. Laboratory abnormalities in patients with COVID-2019 infection. Clin Chem Lab Med 2020;58:1131-4.
43. Kaul D. An overview of coronaviruses including the SARS-2 coronavirus–Molecular biology, epidemiology and clinical implications. Curr Med Res Pract 2020;10:54-64.
44. Chauhan S. Comprehensive review of coronavirus disease 2019 (COVID-19). Biomed J 2020;43: 334-40.
45. Barnes BJ, Adrover JM, Baxter-Stoltzfus A, Borczuk A, Cools-Lartigue J, Crawford JM, et al. Targeting potential drivers of COVID-19: Neutrophil extracellular traps. J Exp Med 2020;217:e20200652.
46. Chen L, Liu H, Liu W, Liu J, Liu K, Shang J, et al. Analysis of clinical features of 29 patients with 2019 novel coronavirus pneumonia. Zhonghua Jie He He Hu Xi Za Zhi 2020;43:E005.
47. Wang D, Yin Y, Hu C, Liu X, Zhang X, Zhou S, et al. Clinical course and outcome of 107 patients infected with the novel coronavirus, SARS-CoV-2, discharged from two hospitals in Wuhan, China. 2020;24:188.
48. Liu Y, Sun W, Guo Y, Chen L, Zhang L, Zhao S, et al. Association between platelet parameters and mortality in coronavirus disease 2019: Retrospective cohort study. Platelets 2020;31:490-6.
49. Liu J, Liu Y, Xiang P, Pu L, Xiong H, Li C, et al. Neutrophil-to-lymphocyte ratio predicts severe illness patients with 2019 novel coronavirus in the early stage. J Transl Med 2020;2020;18:206.
50. Vanderschueren S, De Weerdt A, Malbrain M, Vankersschaever D, Frans E, Wilmer A, et al. Thrombocytopenia and prognosis in intensive care. Crit Care Med 2000;28:1871-6.
51. Lippi G, Plebani M, Henry BM. Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: a meta-analysis. Clin Chim Acta 2020;506:145-8.
52. Lefrançais E, Ortiz-Muñoz G, Caudrillier A, Mallavia B, Liu F, Sayah DM, et al. The lung is a site of platelet biogenesis and a reservoir for haematopoietic progenitors. Nature 2017;544:105-9.
53. Xu P, Zhou Q, Xu J. Mechanism of thrombocytopenia in COVID-19 patients. Ann Hematol 2020;99:1205-8.
2. Li Q, Guan X, Wu P, Wang X, Zhou L, Tong Y, et al. Early transmission dynamics in Wuhan, China, of novelcoronavirus–infected pneumonia. N Engl J Med 2020;382:1199-207.
3. Petrosillo N, Viceconte G, Ergonul O, Ippolito G, Petersen E. COVID-19, SARS and MERS: are they closely related? Clin Microbiol Infect 2020;26:729-34.
4. Lauer SA, Grantz KH, Bi Q, Jones FK, Zheng Q, Meredith HR, et al. The incubation period of coronavirus disease 2019 (COVID-19) from publicly reported confirmed cases: estimation and application. Ann Intern Med 2020;172:577-82.
5. Backer JA, Klinkenberg D, Wallinga J. Incubation period of 2019 novel coronavirus (2019-nCoV) infections among travellers from Wuhan, China, 20–28 January 2020. Euro Surveill 2020;25:2000062.
6. Xu XW, Wu XX, Jiang XG, Xu KJ, Ying LJ, Ma CL, et al. Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series. BMJ 2020;368:m606.
7. Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 2020;382:1708-20.
8. Driggin E, Madhavan MV, Bikdeli B, Chuich T, Laracy J, Biondi-Zoccai G, et al. Cardiovascular considerations for patients, health care workers, and health systems during the COVID-19 pandemic. J Am Coll Cardiol 2020;75:2352-71.
9. Vincent JL, Taccone FS. Understanding pathways to death in patients with COVID-19. Lancet Respir Med 2020;8:430-2.
10. Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med 2020;46:846-8.
11. Zhao X, Wang K, Zuo P, Liu Y, Zhang M, Xie S, et al. Early decrease in blood platelet count is associated with poor prognosis in COVID-19 patients—indications for predictive, preventive, and personalized medical approach. EPMA J 2020;11:139-45.
12. Wu JT, Leung K, Leung GM. Nowcasting and forecasting the potential domestic and international spread of the 2019-nCoV outbreak originating in Wuhan, China: a modelling study. Lancet 2020;395:689-97.
13. Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus–infected pneumonia in Wuhan, China. JAMA 2020;323:1061-9.
14. Sun X, Wang T, Cai D, Hu Z, Liao H, Zhi L, et al. Cytokine storm intervention in the early stages of COVID-19 pneumonia. Cytokine Growth Factor Rev 2020;53:38-42.
15. Yang M, Li CK, Li K, Hon KLE, Ng MH, Chan PK, et al. Hematological findings in SARS patients and possible mechanisms. Int J Mol Med 2004;14:311-5.
16. Wong RS, Wu A, To K, Lee N, Lam CW, Wong C, et al. Haematological manifestations in patients with severe acute respiratory syndrome: retrospective analysis. BMJ 2003;326:1358-62.
17. Yang M, Ng MH, Li CK. Thrombocytopenia in patients with severe acute respiratory syndrome. Hematology 2005;10:101-5.
18. Poutanen SM, Low DE, Henry B, Finkelstein S, Rose D, Green K, et al. Identification of severe acute respiratory syndrome in Canada. N Engl J Med 2003;348:1995-2005.
19. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020;395:497-506.
20. Tsang KW, Ho PL, Ooi GC, Yee WK, Wang T, Chan-Yeung M, et al. A cluster of cases of severe acute respiratory syndrome in Hong Kong. N Engl J Med 2003;348:1977-85.
21. Liu X, Zhang R, He G. Hematological findings in coronavirus disease 2019: indications of progression of disease. Annals of Hematology. Ann Hematol 2020:1-8.
22. Nemeth E, Ganz T. Anemia of inflammation. Hematol Oncol Clin North Am 2014;28:671-81.
23. Coperchini F, Chiovato L, Croce L, Magri F, Rotondi M. The Cytokine storm in COVID-19: An overview of the involvement of the chemokine/chemokine-receptor system. Cytokine Growth Factor Rev 2020;53:25-32.
24. Soy M, Keser G, Atagündüz P, Tabak F, Atagündüz I, Kayhan S. Cytokine storm in COVID-19: pathogenesis and overview of anti-inflammatory agents used in treatment. Clin Rheumatol 2020;39:2085-94.
25. Fan BE, Ong KH, Chan SSW, Young BE, Chong VCL, Chen SPC, et al. Blood and blood product use during COVID‐19 infection. Am J Hematol 2020;95:E158-60.
26. Wenzhong L, Hualan L. COVID-19: Attacks the 1-beta chain of hemoglobin and captures the porphyrin to inhibit human heme metabolism. ChemRxiv 2020 (Preprint).
27. Lazarian G, Quinquenel A, Bellal M, Siavellis J, Jacquy C, Re D, et al. Autoimmune hemolytic anemia associated with Covid‐19 infection. Br J Haematol 2020;190:29-31.
28. Liebman HA, Weitz IC. Autoimmune hemolytic anemia. Med Clin North Am 2017;101:351-9.
29. Gehrs BC, Friedberg RC. Autoimmune hemolytic anemia. Am J Hematol 2002;69:258-71.
30. Coutelier JP, Detalle L, Musaji A, Meite M, Izui S. Two‐Step Mechanism of Virus‐induced Autoimmune Hemolytic Anemia. Ann N Y Acad Sci 2007;1109:151-7.
31. Lopez C, Kim J, Pandey A, Huang T, DeLoughery TG. Simultaneous Onset of COVID‐19 and Autoimmune Hemolytic Anemia. Br J Haematol 2020;190:31-2.
32. Wahlster L, Weichert‐Leahey N, Trissal M, Grace RF, Sankaran VG. COVID‐19 presenting with autoimmune hemolytic anemia in the setting of underlying immune dysregulation. Pediatr Blood Cancer 2020;67:e28382.
33. Henry BM, De Oliveira MHS, Benoit S, Plebani M, Lippi G. Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): a meta-analysis. Clin Chem Lab Med 2020;58:1021-8.
34. Fan BE, Chong VCL, Chan SSW, Lim GH, Lim KGE, Tan GB, et al. Hematologic parameters in patients with COVID‐19 infection. Am J Hematol 2020;95:E131-E4.
35. Lu G, Wang J. Dynamic changes in routine blood parameters of a severe COVID-19 case. Clin Chim Acta 2020;508:98-102.
36. Zhao XY, Xu XX, Yin HS, Hu QM, Xiong T, Tang YY, et al. Clinical characteristics of patients with 2019 coronavirus disease in a non-Wuhan area of Hubei Province, China: a retrospective study. BMC Infect Dis 2020;20:311.
37. Lippi G, Plebani M. The critical role of laboratory medicine during coronavirus disease 2019 (COVID-19) and other viral outbreaks. Clin Chem Lab Med 2020;58:1063-9.
38. Herbinger K-H, Hanus I, Beissner M, Berens-Riha N, Kroidl I, von Sonnenburg F, et al. Lymphocytosis and lymphopenia induced by imported infectious diseases: a controlled cross-sectional study of 17,229 diseased German travelers returning from the tropics and subtropics. Am J Trop Med Hyg 2016;94:1385-91.
39. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395:507-13.
40. Liu Y, Yang Y, Zhang C, Huang F, Wang F, Yuan J, et al. Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury. Sci China Life Sci 2020;63:364-74.
41. Zhang J-j, Dong X, Cao Y-y, Yuan Y-d, Yang Y-b, Yan Y-q, et al. Clinical characteristics of 140 patients infected with SARS‐CoV‐2 in Wuhan, China. Allergy 2020;75:1730-41.
42. Lippi G, Plebani M. Laboratory abnormalities in patients with COVID-2019 infection. Clin Chem Lab Med 2020;58:1131-4.
43. Kaul D. An overview of coronaviruses including the SARS-2 coronavirus–Molecular biology, epidemiology and clinical implications. Curr Med Res Pract 2020;10:54-64.
44. Chauhan S. Comprehensive review of coronavirus disease 2019 (COVID-19). Biomed J 2020;43: 334-40.
45. Barnes BJ, Adrover JM, Baxter-Stoltzfus A, Borczuk A, Cools-Lartigue J, Crawford JM, et al. Targeting potential drivers of COVID-19: Neutrophil extracellular traps. J Exp Med 2020;217:e20200652.
46. Chen L, Liu H, Liu W, Liu J, Liu K, Shang J, et al. Analysis of clinical features of 29 patients with 2019 novel coronavirus pneumonia. Zhonghua Jie He He Hu Xi Za Zhi 2020;43:E005.
47. Wang D, Yin Y, Hu C, Liu X, Zhang X, Zhou S, et al. Clinical course and outcome of 107 patients infected with the novel coronavirus, SARS-CoV-2, discharged from two hospitals in Wuhan, China. 2020;24:188.
48. Liu Y, Sun W, Guo Y, Chen L, Zhang L, Zhao S, et al. Association between platelet parameters and mortality in coronavirus disease 2019: Retrospective cohort study. Platelets 2020;31:490-6.
49. Liu J, Liu Y, Xiang P, Pu L, Xiong H, Li C, et al. Neutrophil-to-lymphocyte ratio predicts severe illness patients with 2019 novel coronavirus in the early stage. J Transl Med 2020;2020;18:206.
50. Vanderschueren S, De Weerdt A, Malbrain M, Vankersschaever D, Frans E, Wilmer A, et al. Thrombocytopenia and prognosis in intensive care. Crit Care Med 2000;28:1871-6.
51. Lippi G, Plebani M, Henry BM. Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: a meta-analysis. Clin Chim Acta 2020;506:145-8.
52. Lefrançais E, Ortiz-Muñoz G, Caudrillier A, Mallavia B, Liu F, Sayah DM, et al. The lung is a site of platelet biogenesis and a reservoir for haematopoietic progenitors. Nature 2017;544:105-9.
53. Xu P, Zhou Q, Xu J. Mechanism of thrombocytopenia in COVID-19 patients. Ann Hematol 2020;99:1205-8.
| Files | ||
| Issue | Vol 59, No 3 (2021) | |
| Section | Review Article(s) | |
| DOI | https://doi.org/10.18502/acta.v59i3.5781 | |
| Keywords | ||
| Coronavirus disease (COVID-19) Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Hemoglobin Lymphopenia Neutrophilia Thrombocytopenia | ||
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Mehrpouri M. Hematological Abnormalities in Patients With COVID-19: An Emerging Approach to Differentiate Between Severe COVID-19; Compared With Non-Severe Forms of the Disease. Acta Med Iran. 2021;59(3):126-132.
