Lymphopenia and neutrophilia at admission predicts severity and mortality in patients with COVID-19: a meta-analysis

Main Article Content

Brandon Henry
Isaac Cheruiyot
Jens Vikse
Victor Mutua
Vincent Kipkorir
Justin Benoit
Mario Plebani
Nicola Bragazzi
Giuseppe Lippi


lymphocytes; neutrophils; SARS-CoV-2; outcomes; laboratory medicine; prognosis


Background: There is a compelling need to identify clinical and laboratory predictors of unfavorable clinical course and death in patients with coronavirus disease (COVID-19). A trend towards low lymphocyte count and high neutrophil counts in patients with poor outcomes has been reported by earlier studies. We aim to synthesize existing data evaluating the relationship between clinical outcomes and abnormal neutrophil and lymphocyte counts at admission in COVID-19 patients.

Methods: An electronic search was carried out in PubMed, China National Knowledge Infrastructure (CNKI) and Cochrane Central Register of Controlled Trials (CENTRAL) to identify eligible studies reporting frequency data on neutrophilia and lymphopenia at admission in hospitalization in COVID-19 patients. Pooled odds ratios of clinical outcomes for each parameter were calculated using Comprehensive Meta-Analysis.

Results: A total of 22 studies (4,969 patients) were included in this meta-analysis. Lymphopenia at admission was found to be significantly associated with increased odd of progression to severe disease (odds ratio [OR], 4.20; 95% confidence interval [95CI%], 3.46-5.09) and death (OR, 3.71; 95%CI, 1.63-8.44). Neutrophilia at admission was also found to be significantly associated with increased odd of progression to severe disease (OR, 7.99; 95%CI, 1.77-36.14) and death (OR, 7.87; 95%CI, 1.75-35.35). Subgroup analysis revealed that COVID-19 patients with severe lymphopenia (<0.5 x10×9/L) had 12-fold increased odds of in-hospital mortality. 

Conclusion: Admission lymphopenia and neutrophilia are associated with poor outcomes in patients with COVID-19. Regular monitoring and early and even more aggressive intervention shall hence be advisable in patients with low lymphocyte and high neutrophil counts. These variables may be useful in risk stratification models.



Download data is not yet available.


Metrics Loading ...
Abstract 91 |


1. 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.
2. Lippi G, Sanchis-gomar F, Henry BM. Coronavirus disease 2019 (COVID-19): the portrait of a perfect storm. Ann Transl Med. 2020;8(7):497.
3. Henry BM. COVID-19, ECMO, and lymphopenia: a word of caution. Lancet Respir Med. 2020;8(4):e24.
4. Henry BM, Vikse J, Benoit S, Favaloro EJ, Lippi G. Hyperinflammation and derangement of renin-angiotensin-aldosterone system in COVID-19: A novel hypothesis for clinically suspected hypercoagulopathy and microvascular immunothrombosis. Clin Chim Acta. 2020;507:167-173.
5. Wang X, Xu W, Hu G, et al. SARS-CoV-2 infects T lymphocytes through its spike protein-mediated membrane fusion. Cell Mol Immunol. 2020;
6. 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: 32467125
7. Zuo Y, Yalavarthi S, Shi H, et al. Neutrophil extracellular traps in COVID-19. JCI Insight. 2020.
8. Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ. 2009;339:b2700.
9. 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;
10. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497-506.
11. Liu Y, Yang Y, Zhang C, Huang F, Wang F, Yuan J, Wang Z, Li J, Li J, Feng C, Zhang Z. Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury. Science China Life Sciences. 2020 Mar;63(3):364-74.
12. Wan S, Xiang Y, Fang W, Zheng Y, Li B, Hu Y, Lang C, Huang D, Sun Q, Xiong Y, Huang X. Clinical features and treatment of COVID‐19 patients in northeast Chongqing. Journal of medical virology. 2020 Mar 21.
13. Zhang JJ, Dong X, Cao YY, Yuan YD, Yang YB, Yan YQ, Akdis CA, Gao YD. Clinical characteristics of 140 patients infected with SARS‐CoV‐2 in Wuhan, China. Allergy. 2020 Feb 19.
14. Feng Y, Ling Y, Bai T, Xie Y, Huang J, Li J, Xiong W, Yang D, Chen R, Lu F, Lu Y. COVID-19 with different severities: a multicenter study of clinical features. American journal of respiratory and critical care medicine. 2020 Jun 1;201(11):1380-8.
15. Zheng F, Tang W, Li H, Huang YX, Xie YL, Zhou ZG. Clinical characteristics of 161 cases of corona virus disease 2019 (COVID-19) in Changsha. Eur Rev Med Pharmacol Sci. 2020 Mar 1;24(6):3404-10.
16. Zhang G, Hu C, Luo L, Fang F, Chen Y, Li J, Peng Z, Pan H. Clinical features and short-term outcomes of 221 patients with COVID-19 in Wuhan, China. Journal of Clinical Virology. 2020 Apr 9:104364.
17. Goyal P, Choi JJ, Pinheiro LC, Schenck EJ, Chen R, Jabri A, Satlin MJ, Campion Jr TR, Nahid M, Ringel JB, Hoffman KL. Clinical characteristics of Covid-19 in New York city. New England Journal of Medicine. 2020 Apr 17.
18. Cai Q, Huang D, Ou P, Yu H, Zhu Z, Xia Z, Su Y, Ma Z, Zhang Y, Li Z, He Q. COVID‐19 in a designated infectious diseases hospital outside Hubei Province, China. Allergy. 2020 Apr 2.
19. Wang Z, Yang B, Li Q, Wen L, Zhang R. Clinical features of 69 cases with coronavirus disease 2019 in Wuhan, China. Clinical infectious diseases. 2020 Mar 16.Ji D, Zhang D, Xu J, Chen Z, Yang T, Zhao P, Chen G, Cheng G, Wang Y, Bi J, Tan L. Prediction for progression risk in patients with COVID-19 pneumonia: the CALL Score. Clinical Infectious Diseases. 2020 Apr 9.
20. Ji D, Zhang D, Xu J, Chen Z, Yang T, Zhao P, Chen G, Cheng G, Wang Y, Bi J, Tan L. Prediction for progression risk in patients with COVID-19 pneumonia: the CALL Score. Clinical Infectious Diseases. 2020 Apr 9.
21. Colaneri M, Sacchi P, Zuccaro V, Biscarini S, Sachs M, Roda S, Pieri TC, Valsecchi P, Piralla A, Seminari E, Di Matteo A. Clinical characteristics of coronavirus disease (COVID-19) early findings from a teaching hospital in Pavia, North Italy, 21 to 28 February 2020. Eurosurveillance. 2020 Apr 23;25(16):2000460.
22. Yao Q, Wang P, Wang X, Qsie G, Meng M, Tong X, Bai X, Ding M, Liu W, Liu K, Chu Y. Retrospective study of risk factors for severe SARS-Cov-2 infections in hospitalized adult patients. Polish archives of internal medicine. 2020 Apr 24.
23. Li X, Xu S, Yu M, Wang K, Tao Y, Zhou Y, Shi J, Zhou M, Wu B, Yang Z, Zhang C. Risk factors for severity and mortality in adult COVID-19 inpatients in Wuhan. Journal of Allergy and Clinical Immunology. 2020 Apr 12.
24. Zheng Y, Zhang Y, Chi H, Chen S, Peng M, Luo L, Chen L, Li J, Shen B, Wang D. The hemocyte counts as a potential biomarker for predicting disease progression in COVID-19: a retrospective study. Clinical Chemistry and Laboratory Medicine (CCLM). 2020 Apr 29(0):20200377.
25. Aggarwal S, Garcia-Telles N, Aggarwal G, Lavie C, Lippi G, Henry BM. Clinical features, laboratory characteristics, and outcomes of patients hospitalized with coronavirus disease 2019 (COVID-19): Early report from the United States. Diagnosis. 2020 May 26;7(2):91-6.
26. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. The lancet. 2020 Mar 11.
27. Chen T, Wu D, Chen H, Yan W, Yang D, Chen G, Ma K, Xu D, Yu H, Wang H, Wang T. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study. Bmj. 2020 Mar 26;368.
28. Fan H, Zhang L, Huang B. Retrospective analysis of clinical features in 101 death cases with COVID-19. medRxiv 2020. DOI.;10(2020.03):09-20033068.
29. Bonetti G, Manelli F, Patroni A, Bettinardi A, Borrelli G, Fiordalisi G, Marino A, Menolfi A, Saggini S, Volpi R, Anesi A. Laboratory predictors of death from coronavirus disease 2019 (COVID-19) in the area of Valcamonica, Italy. Clinical Chemistry and Laboratory Medicine (CCLM). 2020 Apr 28;1(ahead-of-print).
30. Zhang G, Zhang J, Wang B, Zhu X, Wang Q, Qiu S. Analysis of clinical characteristics and laboratory findings of 95 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a retrospective analysis. Respiratory research. 2020 Dec;21(1):1-0.
31. Lippi G, Sanchis-Gomar F, Henry BM. Coronavirus disease 2019 (COVID-19): the portrait of a perfect storm. Ann Transl Med. 2020 Apr;8(7):497
32. Jiang S, Hillyer C, Du L. Neutralizing Antibodies against SARS-CoV-2 and Other Human Coronaviruses. Trends Immunol. 2020;41(5):355-359.
33. Channappanavar R, Zhao J, Perlman S. T cell-mediated immune response to respiratory coronaviruses. Immunol Res. 2014;59(1-3):118-28.
34. Chen J., Lau Y.F., Lamirande E.W., Paddock C.D., Bartlett J.H., Zaki S.R., Subbarao K. Cellular immune responses to severe acute respiratory syndrome coronavirus (SARS-CoV) infection in senescent BALB/c mice: CD4+ T cells are important in control of SARS-CoV infection. J. Virol. 2010;84:1289–1301. doi: 10.1128/JVI.01281-09
35. Wang X., Xu W., Hu G., Xia S., Sun Z., Liu Z., Xie Y., Zhang R., Jiang S., Lu L. SARS-CoV-2 infects T lymphocytes through its spike protein-mediated membrane fusion. Cell. Mol. Immunol. 2020:1–3. doi: 10.1038/s41423-020-0424-9
36. Tan L., Wang Q., Zhang D., Ding J., Huang Q., Tang Y.-Q., Wang Q., Miao H. Lymphopenia predicts disease severity of COVID-19: a descriptive and predictive study. Signal Transduct. Targeted Therapy. 2020;5:1–3. doi: 10.1038/s41392-020-0148-4.
37. Rosales C. Neutrophils at the crossroads of innate and adaptive immunity. J Leukoc Biol. 2020.
38. Lefrançais E, Mallavia B, Zhuo H, Calfee CS, Looney MR. Maladaptive role of neutrophil extracellular traps in pathogen-induced lung injury. JCI Insight. 2018;3(3)
39. Channappanavar R., Fehr A.R., Vijay R., Mack M., Zhao J., Meyerholz D.K., Perlman S. Dysregulated Type I Interferon and Inflammatory Monocyte-Macrophage Responses Cause Lethal Pneumonia in SARS-CoV-Infected Mice. Cell Host Microbe. 2016;19:181–193. doi: 10.1016/j.chom.2016.01.007.
40. Lippi G, Henry BM. Chronic obstructive pulmonary disease is associated with severe coronavirus disease 2019 (COVID-19). Respiratory Medicine. 2020 Jun;167:105941.
41. Aggarwal G, Cheruiyot I, Aggarwal S, Wong J, Lippi G, Lavie CJ, Henry BM, Sanchis-Gomar F. Association of cardiovascular disease with coronavirus disease 2019 (COVID-19) severity: a meta-analysis. Current Problems in Cardiology. 2020 Apr 28:100617.

DB Error: Unknown column 'Array' in 'where clause'