COVID-19 is a novel infectious disease that is seriously threatening human health and global public health security. According to the report from the Chinese Center for Disease Control and Prevention, the mortality was 2.3%. However, this figure increased to 49.0% among critical cases [14]. Thus, it is of great significance to study the laboratory data and the clinical development of the disease in order to guide management.
In this study, the clinical manifestations and laboratory data of severe and mild patients with COVID-19 were compared. In addition, the characteristics of lymphocyte subsets and cytokine profiles of peripheral blood in the enrolled patients were analyzed. It was found that most of severe patients were older than mild patients. In addition, the severe group had more patients with basic diseases than the mild group, which means that older patients, in particular those with basic diseases, such as hypertension and diabetes, may be more likely to develop severe COVID-19. These findings are consistent with several previous studies [13, 15]. Fever, cough, and expectoration were found to be the most common symptoms. However, the above symptoms did not appear in some patients. In addition, some patients had symptoms in the digestive system or nervous system only.
In terms of laboratory findings, a majority of COVID-19 patients suffered from lymphocytopenia. This study showed that lymphocytopenia occurred in 97.9% of severe patients and 80% of mild patients. Specifically, lymphocyte counts, absolute number of total T lymphocytes, CD4+T cells, CD8+T cells, and total B lymphocytes were significantly lower in severe patients than mild patients. The decrease in lymphocyte and lymphocyte subsets was related to the severity of the disease. Cellular immunity is an important part of the human immune system in a viral infection. It has been confirmed that cell-mediated specific cellular immunity plays a crucial role in the process of virus elimination and killing [16].
Increasing evidence suggests that lymphocytes play a crucial role in airway diseases [17, 18]. Previous studies have shown that a marked lymphocytopenia also occurred in a majority of the patients during the acute phase of severe acute respiratory syndrome (SARS) and middle east respiratory syndrome (MERS), with CD4+ and CD8+T cell subsets particularly affected. In addition, the degree of decrease in the T lymphocytes was found to be associated with disease severity [19-23]. However, the mechanisms by which they cause lymphocyte changes were different. Previous data and the results of this study found that there was a remarkable decrease in lymphocyte subsets in COVID-19 patients, especially in severe patients. Currently, the pathophysiological mechanism of lymphocyte decline in COVID-19 patients remains unclear and further investigations are required. Although there is insufficient knowledge to understand the mechanism, cellular immunodeficiency may be one of the primary immunopathologic changes in COVID-19 patients.
Early studies have documented that cytokine storms, also known as inflammatory storms, have occurred in a large number of patients with COVID-19. In SARS patients, increased amounts of proinflammatory cytokines in the serum, such as IL1B, IL6, IL12, IFN-γ, IP10, and MCP1, were observed and were considered to be related to the pulmonary inflammation and extensive lung damage, and even multiple organ failure [24]. Study showed that MERS patients also had increased concentrations of proinflammatory cytokines (IFN-γ, TNF-α, IL15, and IL17) [25]. Recent data have indicated that patients with COVID-19 also had high concentrations of serum cytokine profiles, such as TNF-α, IL-1, IL-6, and IFN-γ [13, 15]. In clinical work, it was found that the course of disease and lung lesions progressed rapidly, and even multiple organ failure developed in a short time in some patients with a high concentration of cytokines. In this study, it was noted that patients typically had increased concentrations of serum IL-6. Moreover, concentrations of serum IL-6 was significantly higher in severe patients than in mild patients, and this agreed with the concept of a cytokine storm [26]. However, IL-4, IL-10, IL-17, TNF-α, and IFN-γ were all nearly in the normal range. Although the exact mechanism of changes in the cytokines remains to be elucidated, a higher concentration of serum cytokine seems to be associated with poor outcomes. Therefore, monitoring the changes in cytokines is of certain significance for the early detection and management of critically ill patients.
Early screening of critically ill patients may improve clinical outcomes. In the current study, the clinical and laboratory features of patients with COVID-19 were explored. The enrolled patients were divided into two cohorts based on disease severity. Baseline characteristics, clinical presentation, and laboratory data were compared between severe and mild patients. A multivariate logistic regression analysis and a ROC curve analysis were further performed. In addition, AUC and cutoff values were calculated. It was found that patients with CRP > 32.9 mg/L, NLR > 2.9, and age > 53.5 years tended to develop into a severe condition. CRP is an acute-phase reactant that increases in the circulation in response to a variety of inflammatory stimuli. CRP has traditionally been considered a biomarker of bacterial infection. However, evidence is needed to distinguish bacterial and viral infections with CRP. A study indicated that COPD patients with lower plasma CRP and IL-6 levels had lower grade systemic inflammation and better physical activity [23]. A systematic review suggested that the average CRP levels upon diagnosis were significantly higher in patients who developed severe H1N1 influenza compared to their counterparts with a no severe disease. Furthermore, levels of CRP have been associated with the degree of H1N1 severity [27]. It was noted in this study that a majority of patients with COVID-19 had increased levels of CRP. In this study, CRP was significantly higher in severe patients than mild patients, which indicated that CRP may be associated with disease severity. The results of this study showed that CRP was the most significant factor that affected the incidence of severe illness, and it had a significant predictive value. The AUC of CRP was 0.90, and the cutoff value was 32.9 (Specificity: 83.1%, Sensitivity: 85.4%). A recent study showed that the NLR was the most useful prognostic factor that affected the prognosis for severe patients with COVID-19. In this study, NLR was significantly higher in severe group than mild group. NRP can also be considered as one of the warning indexes for critically ill patients. Our study revealed that patients with a CRP > 32.9 mg/L, NLR > 2.9, and age > 53.5 years tended to develop into the severe condition.
In summary, the characteristics of lymphocyte subsets and cytokine profiles between severe and mild patients with COVID-19 were compared in this study. On the basis of the results, risk factors for patients developing a severe condition were identified. This is helpful to identify high-risk patients as early as possible and to provide intensive monitoring and treatment, ultimately to reduce the mortality rate of COVID-19 patients.
This study has several potential limitations. First, the retrospective single-center design leads to missing data and unavoidable biases. However, researchers responsible for data collection were trained before the study began so that they could correctly fill out the case report form and reduce errors. In addition, two researchers collected data independently and checked each other's forms for mistakes so as to minimize the bias as much as possible. Second, data were not collected continuously during the patients’ hospitalization, and as a consequence, the trend of these clinical and laboratory indicators could not be described. Fortunately, all of the data was recorded in our electronic medical record system, and we will extract and collect parameters needed for further study in the future.