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. 2020 Nov 26:2020:7570981.
doi: 10.1155/2020/7570981. eCollection 2020.

Circulating Cytokines and Lymphocyte Subsets in Patients Who Have Recovered from COVID-19

Hasichaolu  1 , Xinri Zhang  2 , Xin Li  3 , Xin Li  1 , Dongyan Li  2
Affiliations

Circulating Cytokines and Lymphocyte Subsets in Patients Who Have Recovered from COVID-19

Hasichaolu et al. Biomed Res Int. .

Abstract

To investigate the immune status of people who previously had COVID-19 infections, we recruited two-week postrecovery patients and analyzed circulating cytokine and lymphocyte subsets. We measured levels of total lymphocytes, CD3+ T cells, CD4+ T cells, CD8+ T cells, CD19+ B cells, and CD56+ NK cells and the serum concentrations of interleukin- (IL-) 1, IL-4, IL-6, IL-8, IL-10, transforming growth factor beta (TGF-β), tumor necrosis factor alpha (TNF-α), and interferon gamma (IFN-γ) by flow cytometry. We found that in most postrecovery patients, levels of total lymphocytes (66.67%), CD3+ T cells (54.55%), CD4+ T cells (54.55%), CD8+ T cells (81.82%), CD19+ B cells (69.70%), and CD56+ NK cells (51.52%) remained lower than normal, whereas most patients showed normal levels of IL-2 (100%), IL-4 (80.88%), IL-6 (79.41%), IL-10 (98.53%), TNF-α (89.71%), IFN-γ (100%), and IL-17 (97.06%). Compared to healthy controls, two-week postrecovery patients had significantly lower absolute numbers of total lymphocytes, CD3+ T cells, CD4+ T cells, CD8+ T cells, CD19+ B cells, and CD56+ NK cells, along with significantly higher levels of IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ, and IL-17. Among postrecovery patients, T cells, particularly CD4+ T cells, were positively correlated with CD19+ B cell counts. Additionally, CD8+ T cells were positively correlated with CD4+ T cells and IL-2 levels, and IL-6 positively correlated with TNF-α and IFN-γ. These correlations were not observed in healthy controls. By ROC curve analysis, postrecovery decreases in lymphocyte subsets and increases in cytokines were identified as independent predictors of rehabilitation efficacy. These findings indicate that the immune system gradually recovers following COVID-19 infection; however, the sustained hyperinflammatory response for more than 14 days suggests a need to continue medical observation following discharge from the hospital. Longitudinal studies of a larger cohort of recovered patients are needed to fully understand the consequences of the infection.

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Conflict of interest statement

The authors declare that there are no conflicts of interest regarding the publication of this paper.

Figures

Figure 1
Figure 1
Comparison of lymphocyte subsets and cytokines between two-week postrecovery patients and HCs. Individual data are presented as dots. The absolute numbers of (a) total lymphocyte, (b) CD3+ T cell, (c) CD3+CD4+ T cell, (d) CD3+CD8+ T cell, (e) CD19+ B cell, (f) CD56+ NK cell, and (g) CD4+/CD8+ in the peripheral blood of recovered patients (red dot) and HCs (blue dot) were analyzed. The concentrations of (h) IL-2, (i) IL-4, (j) IL-6, (k) IL-10, (l) TNF-α, (m) IFN-γ, and (n) IL-17 in the serum of recovered patients (red dot) and healthy controls (blue dot) were analyzed. ∗∗∗P ≤ 0.001; ns: not significant.
Figure 2
Figure 2
Correlation analysis was performed by R package to identify correlated variables among two-week postrecovery patients and described by correlation heat map. The red color represents positive correlation, the blue represents negative correlation, and the number in each grid represents correlation coefficient.
Figure 3
Figure 3
Correlation analysis was performed by R package to identify correlated variables among HCs and described by correlation heat map. The red color represents positive correlation, the blue represents negative correlation, and the number in each grid represents correlation coefficient.
Figure 4
Figure 4
Receiver operating characteristic (ROC) curve analysis of postrecovery alteration of each lymphocyte subset in predicting rehabilitation efficacy.
Figure 5
Figure 5
Receiver operating characteristic (ROC) curve analysis of postrecovery alteration of each cytokine in predicting rehabilitation efficacy.
Figure 6
Figure 6
Receiver operating characteristic (ROC) curve analysis of post- recovery alteration of overall lymphocyte subsets and cytokines in predicting rehabilitation efficacy.
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References

    1. Lu H., Stratton C. W., Tang Y. W. Outbreak of pneumonia of unknown etiology in Wuhan, China: the mystery and the miracle. Journal Of Medical Virology. 2020;92(4):401–402. doi: 10.1002/jmv.25678. - DOI - PMC - PubMed
    1. Huang C. L., Wang Y. M., Li X. W., et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet. 2020;395(10223):497–506. doi: 10.1016/S0140-6736(20)30183-5. - DOI - PMC - PubMed
    1. Tang P. F., Hou Z. Y., Wu X. B., et al. Expert consensus on management principles of orthopedic emergency in the epidemic of coronavirus disease 2019. Chinese Medical Journal. 2020;133(9):1096–1098. doi: 10.1097/CM9.0000000000000810. - DOI - PMC - PubMed
    1. Balachandar V., Mahalaxmi I., Subramaniam M., et al. Follow-up studies in COVID-19 recovered patients - is it mandatory? Science of The Total Environment. 2020;729(139021, aritcle 32360909) doi: 10.1016/j.scitotenv.2020.139021. - DOI - PMC - PubMed
    1. Liu J., Li S., Liu J., et al. Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients. EBioMedicine. 2020;55(102763, article 32361250) doi: 10.1016/j.ebiom.2020.102763. - DOI - PMC - PubMed
-