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. 2020 Jun 13;108(1):17–41. doi: 10.1002/JLB.3COVR0520-272R

TABLE 1.

Summary of clinical cohort data on cytokines and aberrant leukocyte changes in mild-to-severe stages of COVID-19 infection

Leukocytes Cytokines
Hospital Cases Changes with Infection (n = cases whose leukocyte or cytokines changed/total cases) Severe cases vs mild cases,P < 0.05 Changes with Infection (n = cases whose leukocyte or cytokines changed/total cases) Severe cases vs mild cases, P < 0.05 References
Renmin Hospital, Wuhan University

N = 82

 

(Deaths)

Increase: Neutrophil count (55/74, but 74/74 in the last 24h); Neutrophil-to-lymphocyte ratio (NLR; 69/73)

 

Decrease: Lymphocyte count (66/74, but 74/74 in the last 24h); CD8+ T cell count (34/58); NK cell count (87/58)

No comparison Increase: IL-6 (11/11) No comparison 11
Jin Yintan Hospital

N = 41

 

(28 Non-ICU cases and 13 ICU cases)

Decrease: Lymphocyte count (26/41)

Increase: Neutrophil count

 

Decrease: WBC count; Lymphocyte count

Increase:IL-1B, IL-1RA, IL-7, IL-8, IL-9, IL-10, G-CSF, GM-CSF, IFN-γ, IP-10, MCP-1, MIP-1A, MIP-1B, and TNF

Increase: IL-2, IL-7, IL-10, G-CSF, IP-10, MCP-1, MIP-1A, and TNF

14
Xi’an No.8 Hospital and the First Affiliated Hospital of Xi’an Jiaotong University N = 28

Increase: Monocytes with CD11b+, CD14+, CD16+, CD68+, CD80+, CD163+, CD206+ (FSC-high monocytes) was consistent with inflammatory phenotype

No comparison

Increase: IL-6, IL-10, TNF (generated by FSC-high monocytes)

Increase: IL-6, IL-10, TNF (generated by FSC-high monocytes)

41

Tongji hospital

N = 452

 

(286 severe and 166 nonsevere cases)

Increase: B cells;

 

Decrease: Lymphocytes; NK cells (N = 44); Th cells (N = 44); Ts cells (N = 44); Treg cells (mainly naïve Treg) (N = 44)

Increase: Leukocyte count; neutrophils; NLR;

 

Decrease: Lymphocytes; Monocytes, Eosinophils, NK cells; Basophils; Th cells; Treg cells

Increase: TNF-α; IL-2R; IL-6

Increase: IL-6, IL-2R, TNF, IL-8, IL-10

68
Guangzhou Eighth People’s Hospital

N = 56

 

(31 mild and 25 severe cases)

Increase: Neutrophils; NLR; Treg cells

 

Decrease: Lymphocytes; CD45+ lymphocytes; CD4+ T cells; CD8+ T cells; B cells; NK cells

Increase: Neutrophils; WBC;

 

Decrease: Lymphocyte counts

Increase: IL-2, IL-4, IL-6, IL-10, TNF, IFN-γ

Increase: IL-2, IL-6, IL-10, TNF

86
Wuhan Tongji hospital

N = 21

 

(11 severe cases and 10 moderate cases)

Increase: Total B lymphocytes (7/14)

 

Decrease: Lymphocyte count (9/21); total T lymphocytes count (13/14); CD4+ T cells count (14/14); CD8+ T cells count (12/14); NK cells (8/14)

Increase: WBC count; Neutrophil count

 

Decrease: Lymphocyte count; total T lymphocytes; total T lymphocytes count; total B lymphocytes; CD4+T cells count; CD8 +T cells count

Increase: IL-6 (13/16); IL-2R (9/16), TNF (11/16), and IL-10 (9/16)

Increase: IL-6; IL-2R; IL-10; TNF

74
Chongqing Three Gorges Central Hospital

N = 123

 

(102 mild and 21 severe cases)

Decrease: CD4+ T cells (74/123); CD8+ T cells (42/123); B cells (32/123); NK cells (45/123)

Decrease: CD4+ (54/102 in mild cases, while 20/21 in severe cases) and CD8+ T cells (29/102 in mild cases, while 13/21 in severe cases)

Increase: IL-6 (47/123); IFN-γ (6/123)

Increase: IL-6, IL-10

76
The First Affiliated Hospital of Guangzhou Medical University

N = 11

 

(Patients with ARDS)

Increase: WBC count, Neutrophils; Tregs (2/11)

 

Decrease: Lymphocyte count (11/11); NK cells (11/11); CD4 and CD8 lymphocytes (11/11); B lymphocytes (3/11)

No comparison

Increase: IL-6 (11/11), IL-10 (5/11), IL-4 (3/11) and IFN-γ (2/11)

No comparison 77
Wuhan Union Hospital

N = 40

 

(13 severe and 27 mild cases)

Decrease: Lymphocytes

Increase: WBC; Neutrophils

 

Decrease: Lymphocyte; CD3+ T cells; CD8+ T cells

Increase: IL-6

Increase: IL-6 (0–16 d); IL-10 (0–13 d); IL-2 and IFN-γ (4–6 d)

78

Yunnan Provincial

 

Hospital of Infectious Diseases

N = 16

 

(10 mild and 6 severe cases)

Decrease: T cells

Increase: HLA-DR+TIGIT+CD8+ T cells increased

 

Decrease: Granulocytes; Multifunction CD4+ T cells

Increase: IL-6, TNF-α

 

Decrease: IFN-γ and IL-2 (from CD4+ T cells)

Decrease: IFN-γ (from CD4+ T cells)

81

General hospital of central theatre command and Hanyang Hospital

N = 262

 

(151 mild cases, 40 severe cases, 13 critical cases, 8 perished cases and 40 healthy control)

Increase: PD1+ CD4+ T cells; PD1+ CD8+ T cells

 

Decrease: Total T cells (166/222); CD4+ T cells (166/222); CD8+ T cells (156/222)

Increase: PD1+ CD4+ T cells; PD1+ CD8+ T cells; CD8+ T cell (high expression of PD-1 and Tim-3)

 

Decrease: Total T cells; CD4+ T cells; CD8+ T cells

Increase: TNF, IL-10, IL-6, and IFN-γ

Increase: TNF, IL-10, and IL-6

83
Shenzhen Third People’s Hospital

N = 53

 

(34 severe cases and 19 mild cases)

Decrease: CD4 and CD8 counts

Increase: Neutrophil

 

Decrease: CD4 and CD8 counts

Increase: IL-6, IL-2Ra, IFN-γ, IL-18, IL-10, IL-1ra, HGF, MIG, M-CSF, G-CSF, MIG-1a, CTACK, and IP-10

Increase: IL-1ra, IP-10, and MIG

93
Union Hospital, Tongji Medical College

N = 80

 

(69 severe and 11 nonsevere cases)

Decrease: Lymphocytes (60/80)

Increase: Neutrophils and NK cells

 

Decrease: Lymphocytes

Increase: IL-6, IL-10

Increase: IL-6

95
Fifth Hospital of Wuhan

N = 36

 

(Nonsurvivors)

Increase: Leukocytes (11/36); Neutrophils (17/36)

 

Decrease: Lymphocytes (25/36)

No comparison

Increase: IL-6 (11/36)

No comparison 102
From 552 hospitals

N = 1099

 

(173 severe and 926 nonsevere cases)

Decrease: Leukocyte count (731/890); Lymphocyte count (330/978)

Decrease: Leukocyte count (106/173 in severe cases and 228/811 of mild cases); Lymphocyte count

No test No test 162
(147/154 in severe cases and 584/736 in mild cases)
The First Affiliated Hospital of University of Science and Technology

N = 43

 

(10 healthy control, 21 No-ICU cases, and 12 ICU cases)

Increase: Tim+PD-1+ CD4+ T cells; Tim+PD-1+ CD8+ T cells; GM-CSF CD4+ T cells; IL-6+CD4+ T cells; CD14+CD16+ monocytes; GM-CSF+CD14+ monocytes

 

Decrease: T cells number; Monocytes; CD4+ T cells; CD8+ T cells

Increase: Tim+PD-1+ CD4+ T cells; IFN-γ+GM-CSF+CD4+ T cells; GM-CSF CD4+ T cells; IL-6+CD4+ T cells; D14+CD16+ monocytes; GM-CSF+CD14+ monocytes IL-6+CD14+ monocytes

 

Decrease: CD8+ T cells

Increase: IL-6; IFN-γ Increase: IL-6; IFN-γ 39

Tongji hospital affiliated to Hua Zhong University of Science and Technology

N = 29

 

(15 mild cases, 9 severe cases, and 5 critical cases)

Decrease: Lymphocyte count (20/29)

No significant difference

Increase: IL-2R; IL-6; IL-8; IL-10; TNF

Increase: IL-2R; IL-6

163
Tongji Hospital

N = 100

 

(34 mild cases, 34 severe cases and 32 critical cases)

Decrease: Eosinophils

Increase: Neutrophils

 

Decrease: Eosinophils; lymphocytes

Increase: IL-6, IL-2R, IL-8, IL-10, TNF, and IL-1β

Increase: IL-6, IL-2R, IL-8, IL-10, and TNF

164
Union hospital in Wuhan

N = 69

 

(the SpO2 ≥ 90% group (n = 55) and the SpO2 < 90% group [n = 14])

Increase: Neutrophils (41/67)

 

Decrease: WBC count (36/67); Lymphocyte count (29/69); Eosinophil count (49/69)

Increase: Neutrophil count; WBC count

 

Decrease: Lymphocytes count

Increase: IL-6 (11/43); IL-10 (16/43)

Increase: IL-6, IL-10

165

Three designed-hospitals in Chongqing municipality

N = 267

 

(217 Nonsevere cases and 50 severe cases)

Decrease: Blood leukocyte count (118/267); Lymphocyte count (231/267); CD3 T cells (51/96); CD4 T cells (74/96)

Increase: Neutrophils count

 

Decrease: Blood leukocyte count (87/217 in nonsevere cases, 31/50 in severe cases); CD3 T cells (20/51 in nonsevere cases, 31/45 in severe cases); CD4 T cells (29/51 in nonsevere cases, 45/45 in severe cases)

Increase: IL-6 (47/67); IL-17A (35/67); TNF (22/67); IL-10 (12/67); IFN-γ (11/67); IL-2 (5/67); IL-4 (4/67)

Increase: IL-6; TNF; IL-17A

166
Zhongnan Hospital of Wuhan University

N = 138

 

(36 ICU patients and 102 non-ICU patients)

Decrease: Lymphocyte count

Increase: WBC; Neutrophils (continued in 5 cases);

 

Decrease: Lymphocyte count (continued in 5 cases)

No test No test 167
General Hospital of Central Theater Command

N = 48

 

(21 mild cases, 10 severe cases, and 17 critical cases)

Decrease: Lymphocytes

Increase: WBC; neutrophil;

 

Decrease: Lymphocytes

Increase: IL-6

Increase: IL-6

96
Wuhan Children’s Hospital

N = 8

 

(severe or critical pediatric patients)

Decrease: CD16+CD56+ lymphocytes (5/8); CD3+ lymphocytes (2/8), CD4+ lymphocytes (4/8) and CD8+ (1/8);

 

One patient co-infected with influenza A virus showed significant decrease of leukocytes, neutrophils, and lymphocytes, while other patients did not show significant change

No comparison

Increase: IL-6 (2/8); IFN-γ (2/8); IL-10 (5/8)

No comparison 168
Beijing Youan Hospital

N = 11

 

(5 mild cases and 6 severe cases)

Increase: Leukocytes; neutrophils

 

Decrease: Lymphocytes

Increase: Neutrophils

Increase: IL-2; IL-4; IL-6; IL-10; IL-17; TNF; IFN-γ

Increase: IL-10

169

Second People’s Hospital of Fuyang City

N = 155

 

(30 severe cases and 125 moderate cases)

Decrease: CD4+ T cells; CD8+ T cells

Decrease: CD4+ T cells; CD8+ T cells

Increase: IL-6

Increase: IL-6

170
Central Theater General Hospital

N = 13

 

(Death)

Decrease: CD3+ T cells;CD4+ T cells; CD8+ T cells; (decreased more substantially during the disease course)

No comparison

Increase: IL-6; (Gradually increased and peaked before death)

No comparison 37
Hubei Provincial Hospital of Integrated Chinese and Western Medicine

N = 110

 

(57 moderate cases, 39 severe cases and 14 critical cases)

Decrease: CD4+ T cells; CD8+ T cells

Decrease: CD4+ T cells; CD8+ T cells

Increase: IL-6; IL-10; IL-8

Increase: IL-6; IL-10

171
Sino-French New City Branch of Tongji Hospital

N = 548

 

(279 nonsevere cases and 269 severe cases)

Increase: WBC (63/542); Neutrophils (118/542)

 

Decrease: Lymphocytes (118/542)

Increase: WBC (8/275 in nonsevere cases and 55/267 in severe cases); Neutrophils (22/275 in nonsevere cases and 96/267 in severe cases)

 

Decrease: Lymphocytes (234/275 in nonsevere cases and 255/267 in severe cases)

Increase: IL-1β (51/306); IL-2R (164/309); IL-6 (221/312); IL-10 (93/307); IL-8 (24/309); TNF (182/309)

Increase: IL-2R (73/171 in nonsevere cases and 91/138 in severe cases); IL-6 (107/175 in nonsevere cases and 114/137 in severe cases); IL-10 (34/170 in nonsevere cases and 49/170 in severe cases); TNF (89/171 in nonsevere cases and 93/138 in severe cases)

172
*

Abbrevations: COVID-19, coronavirus disease 2019; CTACK, cutaneous T cell-attracting chemokine; HFG, hepatocyte growth factor; ICU, intensive care unit; IP-10, IFN-induced protein 10; M-CSF, macrophage CSF; MIG, monokine induced by gamma IFN; MIP-1A, macrophage inflammatory protein-1 alpha; NK, natural killer; Treg, regulatory T cells; SpO2: blood oxygen saturation; and WBC, white blood cells.

**

Note: In column 3, N is the number of cases with available data. In addition, in columns 3 and 5, “n” is the number of cases in which leukocyte or cytokines changed overall, according to the corresponding report.