Table 1.
Changes in cytokine levels of severe cases when compared to mild cases or healthy controls of COVID-19 disease
| Sn. no | Authors | Location | Date of publication | Sample size | IL-1β | IL-2 | IL-2R | IL-4 | IL-6 | IL-7 | IL-8 | IL-10 | IL-17 | TNF-α | IFN-γ | Remarks |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | Huang et al. [23] | Wuhan, China | 24/01/2020 | 41 | ↑* | ↑* | – | ↑#* | ↑#** | ↑ | ↑#** | ↑* | ↑#* | ↑** | ↑#** | Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα |
| 2 | Chen et al. [56] | Wuhan, China | 29/01/2020 | 99 | – | – | – | – | ↑# | – | – | – | – | – | – | 52% of COVID-19 cases reported higher IL-6 levels than healthy controls. Older men with comorbidities and higher IL-6 levels are risk factors for developing ARDS |
| 3 | Wan et al. [26] | China | 12/02/2020 | 123 | – | – | – | ↑ | ↑*** | – | – | ↑*** | ↑ | ↓ | ↑ | IL-6, IL-10 and TNF-α can be used as to predict transition from mild to severe disease |
| 4 | Diao et al. (Pre-print) [25] | Wuhan, China | 20/02/2020 | 522 | – | – | – | – | ↑*** | – | – | ↑*** | – | ↑* | – | IL-6, IL10 and TNF-α significantly increased in severe cases and inversely correlated with Total T cell, CD4, CD8 cells |
| 5 | Zhang et al. (Pre-print) [57] | Wuhan, China | 27/02/2020 | 1334 | – | – | – | – | ↑# | – | – | – | – | – | – | Assessed IL-6 levels on admission and 24 h prior to death IL-6 were > 10 pg/ml in ICU cases 24 h prior to death |
| 6 | Sun et al. [65] | Wuhan, China | 02/03/2020 | 8 | – | – | – | – | ↑ (2/8) | - | - | ↑ (5/8) | – | – | ↑ (2/8) | Only some of the pediatric cases with severe disease had increased cytokine levels |
| 7 | Chen et al. (pre-print) [30] | Wuhan China | 03/03/2020 | 48 | – | – | – | – | ↑*** | – | – | – | – | – | – | tenfold increase of IL-6 in critically ill patients correlated with viral RNAaemia |
| 8 | Zhou et al. [34] | Beijing, China | 09/03/2020 | 191 | – | – | – | – | ↑**$ | – | – | – | – | – | – | Old age, higher SOFA score and D-dimer and IL-6 levels are risk factors for mortality in adult patients |
| 9 | Liu et al. [28] | Wuhan, China | 10/03/2020 | 69 | – | ND | – | ND | ↑* | – | – | ↑ | – | ND | ND | IL-6 levels can be a marker of disease progression and severity |
| 10 | Qin et al. [55] | Wuhan China | 12/03/2020 | 452 | ND | – | ↑** | – | ↑*** | – | ↑*** | ↑*** | – | ↑* | – | Significantly high levels of pro-inflammatory cytokines were observed in severe cases |
| 11 | Wu et al. [29] | Wuhan China | 13/03/2020 | 201 | – | – | – | – |
↑** ↑***$ |
– | – | – | – | – | – | IL-6 was more significantly high in non-survivors and survivors when compared to severe and non-s |
| 12 | Wang et al. [58] | Wuhan China | 16/03/2020 | 69 | – | ↑ | – | ↑ | ↑*** | – | – | ↑* | – | ↑ | – | increase of inflammatory cytokines, induced a mortality rate of 7.5% |
| 13 | Chen et al. [12] | Wuhan China | 27/03/2020 | 21 | ↑ | – | ↑*** | – | ↑* | – | ↑ | ↑*** | – | ↑** | – | Significant imbalance in cytokines in association with immune cell dysregulation is observed in severe cases |
| 14 | Herold et al. (pre-print) [33] | Germany | 10/04/2020 | 40 | – | – | – | – | ↑*** | – | – | – | – | – | – | 22-fold increased risk of respiratory failure with higher IL-6 levels |
| 15 | Liu et al. [31] | Wuhan China | 11/04/2020 | 140 | – | – | – | – | ↑*** | – | – | – | – | – | – | Serum levels of IL-6 and CRP can effectively assess disease severity and predict disease outcome |
| 16 | He et al. [37] | Wuhan China | 12/04/2020 | 204 | – | ↑ | – | ↑** | ↑ | – | – | ↑ | – | ↑** | ↑ | No significant difference was observed in IL-6, IL-10 |
| 17 | Zhu et al. (pre-print) [32] | China | 17/04/2020 | 127 | - | ↓ | - | ↑ | ↑*** | - | - | ↑*** | - | ↑ | ↑*** | IL-6 plays a key role in severity of diseases and can be used as potential marker for monitoring disease progression |
| 18 | Liu et al. [27] | Wuhan, China | 18/04/2020 | 40 | – | ↑* | – | ↑ | ↑* | – | – | ↑* | – | ↑ | ↑* | Kinetic difference in cytokine levels between severe and non-severe cases were observed |
| 19 | Ouyang et al. [38] | China | 20/04/2020 | 11 | – | ↑ | – | ↑ | ↑ | - | - | ↑* | ↑ | ↑ | ↑ | Difference in cytokine levels were compared between mild and severe cases in pre- and post-treatment groups |
| 20 | Evangelos et al. [53] | Greece | 21/04/2020 | 54 | ↓* | – | – | – | ↑** | – | – | – | ↓* | ↓ | – | Studied immune changes in severe COVID-19 cases in relation to H1N1 cases, bacterial pneumonia and healthy controls in addition to comparison with intermediate cases of COVID-19 |
| 21 | Wang et al. [64] | Wuhan China | 23/04/2020 | 65 | ND | – | ↑ | – | ↑** | – | ND | ↑** | – | ND | – | High IL-2R supports hyperfunction of Th cells and IL-10 supports degradation of Tregs |
#Indicates changes in severe cases when compared to healthy controls or reference range
$Indicated changes in non-survivors when compared with survivors, rest indicates in comparison to mild cases of COVID-19
ND indicates no difference observed when compared to mild cases or healthy controls; *p < 0.05; **p < 0.01; ***p < 0.001