Determinants of clinical course and mortality in COVID-19 patients with hematological disorders: real life data from a single center

Abstract

Objectives: Patients with hematological disorders are often immunosuppressive due to underlying diseases, immunosuppressive therapies or cytotoxic chemotherapeutics. In the case of coronavirus disease 2019 (COVID-19), they are at high risk of poor prognosis. Therefore, the present study aimed to evaluate the determinants of clinical course and mortality in COVID-19 patients with hematological disorders.

Methods: Sixty-two hospitalized patients older than 18 years with documented COVID-19 and hematological disorders were included in the study. The clinical and laboratory data of the patients were recorded. Age, gender, overall follow-up time, duration of hospitalization, neutropenia, D-dimer levels, disease status, presence of underlying diseases, prior autologous and allogeneic stem cell transplant, immunosuppressive drug use, chemotherapy within 28 days, pneumonia, secondary bacterial infection, intubation, survival and mortality of the patients were evaluated.

Results: Twenty-eight (45.2%) of 62 patients died due to COVID-19 and its complications. It was observed that presence of pneumonia, secondary bacterial infection, intubation, neutropenia developed after the diagnosis of COVID-19, and elevated D-dimer levels were associated with significant mortality. A D-dimer level of >1.2 μg/dL was found to be associated with 5.02 fold increase in the risk of death, with 60.7% sensitivity and 76.5% specificity. Presence of rheumatologic diseases also affected survival negatively.

Conclusions: D-dimer levels have high predictive value for mortality. Considering the identified risk factors, it can be concluded that broad spectrum antibiotics can be administered earlier for prevention of high mortality rates in COVID-19 patients with underlying hematological disorders. These observations can give confidence to clinicians that delivery of effective anticancer regimens should continue during this difficult pandemic.

Keywords

• COVID-19
• hematological disorders
• mortality

References

1. 1. Yuen K-S, Ye Z-W, Fung S-Y, Chan C-P, Jin D-Y. SARS-CoV-2 and COVID-19: the most important research questions. Cell Biosci 2020;10:1-5.
2. 2. Organization WH. Coronavirus disease 2019 (COVID-19): situation report, 73. 2020.
3. 3. Lapostolle F, Schneider E, Vianu I, Dollet G, Roche B, Berdah J, et al. Clinical features of 1487 COVID-19 patients with outpatient management in the Greater Paris: the COVID-call study. Intern Emerg Med 2020;15:813-7.
4. 4. Barlow-Pay F, Htut TW, Khezrian M, Myint PK. Systematic review of immunosuppressant guidelines in the COVID-19 pandemic. Ther Adv Drug Safety 2021;12:2042098620985687.
5. 5. Girmenia C, Gentile G, Micozzi A, Petrucci L, Malaspina F, Di Prima A, et al. COVID-19 in patients with hematologic disorders undergoing therapy: perspective of a large referral hematology center in Rome. Acta Haematol 2020;143:574-82.
6. 6. Covid C, Team R, Covid C, Team R, COVID C, Team R, et al. Coronavirus disease 2019 in children-United States, February 12-April 2, 2020. MMWR Morb Mortal Wkly Rep 2020;69:422-6.
7. 7. Fung M, Babik JM. COVID-19 in immunocompromised hosts: what we know so far. Cli Infect Dis 2021;72:340-50.
8. 8. He W, Chen L, Chen L, Yuan G, Fang Y, Chen W, et al. COVID-19 in persons with haematological cancers. Leukemia 2020;34:1637-45.

9. 9. Wang C-C, Tseng K-C, Hsieh T-Y, Tseng T-C, Lin HH, Kao J-H. Assessing the durability of entecavir-treated hepatitis B using quantitative HBsAg. Am J Gastroenterol 2016;111:1286-94.
10. 10. Regalado-Artamendi I, Jiménez-Ubieto A, Hernández-Rivas JÁ, Navarro B, Núñez L, Alaez C, et al. Risk factors and mortality of COVID-19 in patients with lymphoma: a multicenter study. Hemasphere 2021;5:e538.
11. 11. Yang K, Sheng Y, Huang C, Jin Y, Xiong N, Jiang K, et al. Clinical characteristics, outcomes, and risk factors for mortality in patients with cancer and COVID-19 in Hubei, China: a multicentre, retrospective, cohort study. Lancet Oncol 2020;21:904-13.
12. 12. Sahu KK, Siddiqui AD, Cerny J. Managing sickle cell patients with COVID-19 infection: the need to pool our collective experience. Br J Haematol 2020;190:e86-9.
13. 13. Wu J, Liu J, Zhao X, Liu C, Wang W, Wang D, et al. Clinical characteristics of imported cases of COVID-19 in Jiangsu Province: a multicenter descriptive study. Clin Infect Dis. 2020;71:706-12.
14. 14. Debuc B, Smadja DM. Is COVID-19 a new hematologic disease? Stem Cell Rev Rep 2021;17:4-8.
15. 15. Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost 2020;18):844-7.
16. 16. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020;395:1054-62.
17. 17. Lee LY, Cazier JB, Starkey T, Turnbull C, Team UCCMP, Kerr R, et al. COVID-19 mortality in patients with cancer on chemotherapy or other anticancer treatments: a prospective cohort study. Lancet 2020;395:1919-26.
18. 18. Jain A, Singh C, Dhawan R, Jindal N, Mohindra R, Lad D, et al. How to use a prioritised approach for treating hematological disorders during the COVID-19 pandemic in India? Indian J Hematol Blood Transfus 2020;36:605-15.
19. 19. Wang H, Zhang L. Risk of COVID-19 for patients with cancer. Lancet Oncol 2020;21:e181.
20. 20. Yanez ND, Weiss NS, Romand J-A, Treggiari MM. COVID-19 mortality risk for older men and women. BMC Public Health 2020;20:1-7.
21. 21. Porcheddu R, Serra C, Kelvin D, Kelvin N, Rubino S. Similarity in case fatality rates (CFR) of COVID-19/SARS-COV-2 in Italy and China. J Infect Dev Ctries 2020;14:125-8.
22. 22. Piñana JL, Martino R, García-García I, Parody R, Morales MD, Benzo G, et al. Risk factors and outcome of COVID-19 in patients with hematological malignancies. Exp Hematol Oncol 2020;9:1-16.
23. 23. Lazarian G, Quinquenel A, Bellal M, Siavellis J, Jacquy C, Re D, et al. Autoimmune haemolytic anaemia associated with COVID-19 infection. Br J Haematol 2020;190:29-31.
24. 24. Zulfiqar A-A, Lorenzo-Villalba N, Hassler P, Andrès E. Immune thrombocytopenic purpura in a patient with Covid-19. N Eng J Med 2020;382:e43.
25. 25. Mozzini C, Girelli D. The role of neutrophil extracellular traps in Covid-19: only an hypothesis or a potential new field of research? Thromb Res 2020;191:26-7.
26. 26. López-Pereira P, Iturrate I, de La Cámara R, Cardeñoso L, Alegre A, Aguado B. Can COVID-19 cause severe neutropenia? Clin Case Rep 2020;8:3349-51.
27. 27. Shi X, Sims MD, Hanna MM, Xie M, Gulick PG, Zheng Y-H, et al. Neutropenia during HIV infection: adverse consequences and remedies. Int Rev Immunol 2014;33:511-36.
28. 28. Boxer LA. How to approach neutropenia. Hematology Am Soc Hematol Educ Program 2012;2012:174-82.
29. 29. Kumar A, Arora A, Sharma P, Anikhindi SA, Bansal N, Singla V, et al. Is diabetes mellitus associated with mortality and severity of COVID-19? A meta-analysis. Diabetes Metab Syndr 2020;14:535-45.
30. 30. Lippi G, Wong J, Henry BM. Hypertension and its severity or mortality in Coronavirus Disease 2019 (COVID-19): a pooled analysis. Pol Arch Intern Med 2020;130:304-9.
31. 31. Mehra MR, Desai SS, Kuy S, Henry TD, Patel AN. Cardiovascular disease, drug therapy, and mortality in Covid-19. N Eng J Med 2020;382:e102.
32. 32. Wang Y, Chen J, Chen W, Liu L, Dong M, Ji J, et al. Does asthma increase the mortality of patients with COVID-19?: a systematic review and meta-analysis. Int Arch Allergy Immunol 2021;182:76-82.
33. 33. Lieberman-Cribbin W, Rapp J, Alpert N, Tuminello S, Taioli E. The impact of asthma on mortality in patients with COVID-19. Chest 2020;158:2290.
34. 34. Du R-H, Liang L-R, Yang C-Q, Wang W, Cao T-Z, Li M, et al. Predictors of mortality for patients with COVID-19 pneumonia caused by SARS-CoV-2: a prospective cohort study. Eur Respir J 2020;55:2000524.
35. 35. Gattinoni L, Chiumello D, Rossi S. COVID-19 pneumonia: ARDS or not? Crit Care 2020;24:154.
36. 36. Rawson TM, Moore LS, Zhu N, Ranganathan N, Skolimowska K, Gilchrist M, et al. Bacterial and fungal coinfection in individuals with coronavirus: a rapid review to support COVID-19 antimicrobial prescribing. Clin Infect Dis 2020;71:2459-68.
37. 37. Dudoignon E, Caméléna F, Deniau B, Habay A, Coutrot M, Ressaire Q, et al. Bacterial Pneumonia in COVID-19 critically ill patients: a case series. Clin Infect Dis 2021;72:905-6.
38. 38. 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 Eng J Med 2020;382;727-33.
39. 39. Ji H-L, Zhao R, Matalon S, Matthay MA. Elevated plasmin (ogen) as a common risk factor for COVID-19 susceptibility. Physiol Rev 2020;100;1065-75.
40. 40. Li Y, Zhao K, Wei H, Chen W, Wang W, Jia L, et al. Dynamic relationship between D‐dimer and COVID-19 severity. Br J Haematol 2020;190:e24-7.
41. 41. Yao Y, Cao J, Wang Q, Shi Q, Liu K, Luo Z, et al. D-dimer as a biomarker for disease severity and mortality in COVID-19 patients: a case control study. J Intensive Care 2020;8:49.
42. 42. Zhang L, Yan X, Fan Q, Liu H, Liu X, Liu Z, et al. D-dimer levels on admission to predict in-hospital mortality in patients with Covid-19. J Thromb Haemost 2020;18(6):1324-9.
43. 43. Santos CS, Morales CM, Álvarez ED, Castro CÁ, Robles AL, Sandoval TP. Determinants of COVID-19 disease severity in patients with underlying rheumatic disease. Clin Rheumatol 2020;39:2789-96.