Effects of corticosteroid on T lymphocyte subsets in patients with coronavirus disease 2019_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

YANG Shuo ¹ , SU Bintao ² , CHEN Jin ¹ , LIU Xu ¹ , LU Dan ¹ ,  WEI Li ³ , LUO Guangwei ¹

1. Department of Pulmonary and Critical Care Medicine, Wuhan No. 1 Hospital, Wuhan, Hubei 430000, P. R. China;
2. Department of Clinical Laboratory, Wuhan No. 1 Hospital, Wuhan, Hubei 430000, P. R. China;
3. Department of Critical Care Medicine, Wuhan No. 1 Hospital, Wuhan, Hubei 430000, P. R. China;

Corresponding?author：

WEI Li, Email: y077088@sina.com

Keywords：

Coronavirus disease 2019; Corticosteroid; T lymphocyte subsets

DOI：

10.7507/1671-6205.202004070

Video：

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Objective To explore the effects of corticosteroid on peripheral blood T lymphocyte subsets in patients with coronavirus disease 2019 (COVID-19).Methods This was a retrospective study and 376 patients were included in the study. The patients were classified into three type: moderate type (118 patients), severe type (215 patients), critical type (43 patients). Six critical patients died. T lymphocyte subsets were analyzed and compared among these patients. In severe patients, T lymphocyte subsets were compared between no corticosteroid therapy patients (178 patients) and patients who were treated with corticosteroid for 3 to 5 days (37 patients).Results (1) In contrast with those in moderate patients, in severe patients total lymphocytes [(1359.2±597.9)×10⁶ vs. (1703.7±702.4)×10⁶/L, LSD-t=4.786, P<0.001], total T lymphocytes [(949.2±454.0)×10⁶ vs. (1235.5±555.7)×10⁶/L, LSD-t=5.175, P<0.001] and CD8⁺ T cells [(336.8±189.8)×10⁶ vs. (461.7±242.8)×10⁶/L, LSD-t=5.332, P<0.001] decreased significantly, and CD4⁺/CD8⁺ ratio (1.81±0.92 vs. 1.64±0.74, LSD-t=1.574, P=0.116) was increased. In contrast with those in severe patients, in critical patients CD4⁺/CD8⁺ ratio (2.23±1.24 vs. 1.81±0.92, LSD-t=2.627, P=0.009) increased and CD8⁺ T cells [(232.5±159.8)×10⁶/L vs. (336.8±189.8)×10⁶/L, LSD-t=2.867, P=0.004] decreased significantly, total lymphocytes [(1161.1±583.7)×10⁶/L vs. (1359.2±597.9)×10⁶/L, LSD-t=1.772, P=0.077], total T lymphocytes [(790.5±419.3)×10⁶/L vs. (949.2±454.0)×10⁶/L, LSD-t=1.846, P=0.066] also decreased but without significant difference. There was no significant difference between dead and survived critical patients. (2) In severe type, in contrast with no corticosteroid therapy patients, 37 patients were therapy with corticosteroid for 3 to 5 days, and their total T lymphocytes [(770.6±480.3)×10⁶ vs. (986.3±440.7)×10⁶/L, t=2.666, P=0.008] and CD4⁺/CD8⁺ ratio (1.30±0.73 vs. 1.91±0.92, t=3.771, P<0.001) were decreased significantly.Conclusions In COVID-19 patients, lymphocytes, T lymphocytes and CD8⁺ T cells are decreased, but CD4⁺/CD8⁺ ratio is increased, and these changes are positively related to the severity of the disease. After corticosteroid therapy, the increase of CD4⁺/CD8⁺ ratio is relieved, but T lymphocytes are decreased further.

Citation： YANG Shuo, SU Bintao, CHEN Jin, LIU Xu, LU Dan, WEI Li, LUO Guangwei. Effects of corticosteroid on T lymphocyte subsets in patients with coronavirus disease 2019. Chinese Journal of Respiratory and Critical Care Medicine, 2021, 20(3): 159-163. doi: 10.7507/1671-6205.202004070 Copy

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10.	Clark DR, Jonathan EM, J Kenneth B, et al. Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury. Lancet, 2020, 395(10223): 473-475.
11.	RECOVERY Collaborative Group, Horby P, Lim WS, Emberson JR, et al. Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med, 2021, 384(8): 693-704.
12.	Zhou YG, Fu BQ, Zheng XH, et al. Pathogenic T cells and inflammatory monocytes incite inflammatory storm in severe COVID-19 patients. Natl Sci Rev, 2020, 7(6): 998-1002.
13.	姚小紅, 李廷源, 何志承, 等. 新型冠狀病毒肺炎(COVID-19)三例遺體多部位穿刺組織病理學研究. 中華病理學雜志, 2020, 49(5): 411-417.
14.	Wan S, Yi Q, Fan S, et al. Relationships among lymphocyte subsets, cytokines and the pulmonary inflammation index in coronavirus (COVID-19) infected patients. Br J Haematol, 2020, 189(3): 428-437.
15.	Pallotto C, Suardi LR, Sperti S, et al. Increased CD4/CD8 ratio as a risk factor for critical illness in coronavirus disease 2019 (COVID-19): a retrospective multicentre study. Infect Dis (Lond), 2020, 52(9): 675-677.
16.	Mathew, D, Giles, JR, Baxter, AE, et al. Deep immune profiling of COVID‐19 patients reveals distinct immunotypes with therapeutic implications. Science, 2020, 369(6508): eabc8511.
17.	Meckiff BJ, Ramírez-Suástegui C, Fajardo V, et al. Imbalance of regulatory and cytotoxic SARS-CoV-2-reactive CD4⁺T cells in COVID-19. Cell, 2020, 183(5): 1340-1353.
18.	Xie MM, Fang S, Chen Q, et al. Follicular regulatory T cells inhibit the development of granzyme B-expressing follicular helper T cells. JCI Insight, 2019, 4(16): e128076.
19.	陳穎詩, 張旭, 彭治林, 等. 糖皮質激素對體外中央記憶性 CD8⁺ T 淋巴細胞的誘導分化作用. 中國病理生理雜志, 2018, 34(9): 1666-1671.

1. Wang F, Nie JY, Wang HL, et al. Characteristics of peripheral lymphocyte subset alteration in 2019-nCoV pneumonia. J Infect Dis, 2020, 221(11): 1762-1769.
2. 向天新, 劉家明, 許飛, 等. 江西地區 49 例新型冠狀病毒肺炎患者臨床特征分析. 中國呼吸與危重監護雜志, 2020, 19(2): 154-160.
3. 國家衛生健康委辦公廳, 國家中醫藥管理局辦公室. 《新型冠狀病毒肺炎診療方案 (試行第八版)》[EB/OL]. http://www.gov.cn/zhengce/zhengceku/2020-08/19/5535757/files/da89edf7cc9244fbb34ecf6c61df40bf.pdf.
4. 趙建平, 胡軼, 杜榮輝, 等. 新型冠狀病毒肺炎糖皮質激素使用的建議. 中華結核和呼吸雜志, 2020, 43(3): 183-184.
5. 國家衛生健康委辦公廳, 國家中醫藥管理局辦公室. 《新型冠狀病毒感染的肺炎診療方案(試行第五版)》[EB/OL]. http://www.nhc.gov.cn/yzygj/s7653p/202002/3b09b894ac9b4204a79db5b8912d4440.shtml.
6. Malik YS, Sircar S, Bhat S, et al. Emerging novel Coronavirus (2019-nCoV) – Current scenario, evolutionary perspective based on genome analysis and recent developments. Vet Q, 2020, 40(1): 68-76.
7. Moore JB, June CH. Cytokine release syndrome in severe COVID-19. Science, 2020, 368(6490): 473-474.
8. Wu ZY, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72314 cases from the Chinese Center for Disease Control and Prevention. JAMA, 2020, 323(13): 1239-1242.
9. Wu JF, Huang JQ, Zhu GC, et al. Systemic corticosteroids show no benefit in severe and critical COVID-19 patients in Wuhan, China: a retrospective cohort study[J/OL]. medRxiv preprint. https://www.researchgate.net/publication/341392226_Systemic_corticosteroids_show_no_benefit_in_severe_and_critical_COVID-19_patients_in_Wuhan_China_A_retrospective_cohort_study.
10. Clark DR, Jonathan EM, J Kenneth B, et al. Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury. Lancet, 2020, 395(10223): 473-475.
11. RECOVERY Collaborative Group, Horby P, Lim WS, Emberson JR, et al. Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med, 2021, 384(8): 693-704.
12. Zhou YG, Fu BQ, Zheng XH, et al. Pathogenic T cells and inflammatory monocytes incite inflammatory storm in severe COVID-19 patients. Natl Sci Rev, 2020, 7(6): 998-1002.
13. 姚小紅, 李廷源, 何志承, 等. 新型冠狀病毒肺炎(COVID-19)三例遺體多部位穿刺組織病理學研究. 中華病理學雜志, 2020, 49(5): 411-417.
14. Wan S, Yi Q, Fan S, et al. Relationships among lymphocyte subsets, cytokines and the pulmonary inflammation index in coronavirus (COVID-19) infected patients. Br J Haematol, 2020, 189(3): 428-437.
15. Pallotto C, Suardi LR, Sperti S, et al. Increased CD4/CD8 ratio as a risk factor for critical illness in coronavirus disease 2019 (COVID-19): a retrospective multicentre study. Infect Dis (Lond), 2020, 52(9): 675-677.
16. Mathew, D, Giles, JR, Baxter, AE, et al. Deep immune profiling of COVID‐19 patients reveals distinct immunotypes with therapeutic implications. Science, 2020, 369(6508): eabc8511.
17. Meckiff BJ, Ramírez-Suástegui C, Fajardo V, et al. Imbalance of regulatory and cytotoxic SARS-CoV-2-reactive CD4⁺T cells in COVID-19. Cell, 2020, 183(5): 1340-1353.
18. Xie MM, Fang S, Chen Q, et al. Follicular regulatory T cells inhibit the development of granzyme B-expressing follicular helper T cells. JCI Insight, 2019, 4(16): e128076.
19. 陳穎詩, 張旭, 彭治林, 等. 糖皮質激素對體外中央記憶性 CD8⁺ T 淋巴細胞的誘導分化作用. 中國病理生理雜志, 2018, 34(9): 1666-1671.

Chinese Journal of Respiratory and Critical Care Medicine

Effects of corticosteroid on T lymphocyte subsets in patients with coronavirus disease 2019

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