Immune dysfunction following COVID-19, especially in severe patients

Abstract

The coronavirus disease 2019 (COVID-19) has been spreading worldwide. Severe cases quickly progressed with unfavorable outcomes. We aim to investigate the clinical features of COVID-19 and identify the risk factors associated with its progression. Data of confirmed SARS-CoV-2-infected patients and healthy participants were collected. Thirty-seven healthy people and 79 confirmed patients, which include 48 severe patients and 31 mild patients, were recruited. COVID-19 patients presented with dysregulated immune response (decreased T, B, and NK cells and increased inflammatory cytokines). Also, they were found to have increased levels of white blood cell, neutrophil count, and D-dimer in severe cases. Moreover, lymphocyte, CD4⁺ T cell, CD8⁺ T cell, NK cell, and B cell counts were lower in the severe group. Multivariate logistic regression analysis showed that CD4⁺ cell count, neutrophil-to-lymphocyte ratio (NLR) and D-dimer were risk factors for severe cases. Both CT score and clinical pulmonary infection score (CPIS) were associated with disease severity. The receiver operating characteristic (ROC) curve analysis has shown that all these parameters and scores had quite a high predictive value. Immune dysfunction plays critical roles in disease progression. Early and constant surveillance of complete blood cell count, T lymphocyte subsets, coagulation function, CT scan and CPIS was recommended for early screening of severe cases.

Figure 1

Flow chart of patients screening. Shown were the concrete procedures of patients screening. The whole screening process strictly followed the inclusion criteria and exclusion criteria.

Figure 2

Immune cell counts in healthy people and COVID-19 patients. Immune cell counts, including total T cell, CD4⁺ T cell, CD8⁺ T cell, NK cell, and B cell were compared between healthy people and COVID-19 patients. All these immune cell counts were lower in COVID-19 patients.

Figure 3

Immune cells count in mild and severe COVID-19 patients. Immune cell counts, including total T cell, CD4⁺ T cell, CD8⁺ T cell, NK cell, and B cell were compared between mild and severe COVID-19 patients. All these immune cell counts were lower in severe COVID-19 patients.

Figure 4

Inflammatory cytokines in healthy people and COVID-19 patients. Inflammatory cytokines, including IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ were compared between healthy people and COVID-19 patients. All these inflammatory cytokines were higher in COVID-19 patients.

Figure 5

Inflammatory cytokines in mild and severe COVID-19 patients. Inflammatory cytokines, including IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ were compared between mild and severe COVID-19 patients. There was no significant difference between two groups.

Figure 6

CT score and CPIS in mild and severe COVID-19 patients. CT score and CPIS were calculated and compared between mild and severe COVID-19 patients. CT score and CPIS were higher in severe patients and these two clinical scores were positively related to disease severity.

Figure 7

Receiver operating characteristic curves. ROC curve analysis showed CT score, CPIS, and combination of three clinical parameters (CD4⁺ T cell count, D-dimer, and NLR) had good predictive value, in which, CT score had the highest AUC. *Combination: combination of CD4⁺ T cell count, D-dimer, and NLR.