We here present a retrospective study of 112 hospitalized patients with SARS-CoV-2 infection in Wuhan. Levels of lymphocytes and lymphocyte subsets are of great importance to keep the immune system functional. Usually viral infection, immunodeficiency diseases, and other infectious diseases lead to abnormal changes in the levels of lymphocyte subsets [18]. We confirmed in our cases that the clinical symptoms and the outcome of these patients with SARS-CoV-2 infection are closely related to the functions of immune system, as previously reported [19]. Notably, based on our findings in these 112 patients, total lymphocyte counts, absolute CD3+, CD4 + and CD8 + T lymphocyte counts were dramatically decreased as the pneumonia continues to progress. Among them, CD4 + and CD8 + T lymphocytes can be evaluated as a standard laboratory marker for disease progression and a dominant prognostic and predictive factor for SARS-CoV-2 infection.
The pneumonia associated with the fast-growing outbreak of 2019 novel coronavirus, therefore it is an immediate urgency to have medicines before a vaccine can be produced. However, no specific treatment is currently available for SARS-CoV-2 pneumonia to date. Several antiviral agents are being identified to further examine their potential use and development as therapeutic drugs based on sequencing data of SARS-CoV-2, coupled with molecular modelling according to the genomes of related virus proteins [14], such as antiviral agent remdesivir, virus inhibitor chloroquine analogs and the anti-HIV lopinavir plus ritonavir combination [20, 21]. Some Chinese medicine prescriptions have also been used to reduce viral entry into cells and minimize inflammatory storms in patients, yet the therapeutic effects of these medications are very limited. Currently one of the main treatments for SARS-CoV-2 pneumonia patients is immune support therapy, which might also cause excessive immune responses and consequently trigger inflammatory storms in patients [22]. Therefore, a further understanding on the pathogenesis of SARS-CoV-2 pneumonia and dynamic monitoring of clinical symptoms and pathological indicators in patients are urgent needs for more effective drug development and personalized treatment plans.
In general, SARS-CoV-2 pneumonia is an acute respiratory disease with a fatality rate of ~ 2% mainly due to dyspnea. A just published work have first characterized the pathological features of a patient who died from SARS-CoV-2 by obtaining biopsy samples at autopsy [23]. They observed the substantially reduced counts of peripheral CD4 + and CD8 + T lymphocytes with hyper-activated status, here we further confirmed in our 112 hospitalized cases that, total lymphocyte counts, absolute CD3+, CD4 + and CD8 + T lymphocyte count were gradually decreased as the pneumonia continues to progress by evaluating SARS-CoV-2 pneumonia patients at different stages including remission, deterioration and death. Meanwhile, we monitored and dynamically assessed the peripheral lymphocytes in 11 patients among 112. The counts of CD4 + and CD8 + T lymphocyte decreased during deterioration while increased in the process of remission. Particularly, total lymphocyte counts were maintained at a certain level among patients in remission, by contrast, the lymphocyte counts decreased dramatically when pneumonia advanced, especially at late stage. We further notice that the decrease of CD3 + T lymphocyte count was gradual in groups in line with the progression of pneumonia. In addition, CD4 + T lymphocyte count was significantly reduced in both deterioration and death groups comparing with remission patients, while the significant drop in CD8 + T lymphocyte count was observed in cases of the death compared to the other two groups. These data suggest that CD3 + T lymphocyte count is potentially used as a surrogate marker of SARS-CoV-2 pneumonia progression, CD4 + T lymphocyte count can be used as an early indicator of disease progression while CD8 + T lymphocyte count is an endpoint marker for critically advanced stage of SARS-CoV-2 pneumonia.
Moreover, the report has also revealed the pathological characteristics, pulmonary oedema with hyaline membrane formation, interstitial mononuclear inflammatory infltrates dominated by lymphocytes, desquamation of pneumocytes and multinucleated syncytial cells with atypical enlarged pneumocytes [23], which resembled those seen in SARS [24] and MERS [25]. Besides the pathological findings, the clinical and CT imaging features of SARS-CoV2 patients are similar to those observed in SARS and MERS [26], patients usually presented with fever, dry cough, ground-glass opacity in CT images, dyspnea and dense consolidation in lung can also be observed in patients with severe pneumonia, as suggested by our data as well as many other reports [27]. These evidence indicate that the pathological mechanisms could be similar among SARS-CoV2, SARS-CoV and MERS-CoV infections.
The pathophysiology of SARS is related to the dysfunction of immune system, including hyperinduction of chemokines and cytokines, abnormal cellular immune response and insufficient interferon reactions [28]. In the case study of 38 SARS patients, the researchers found that the absolute counts of lymphocyte subsets related to immune functions, such as CD4 + and CD8 + T cells, were significantly decreased in SARS patients, which can be monitored as a prognosis predictor for SARS [17]. In our present study, the decreased counts of T lymphocyte subsets including CD3, CD4 + and CD8 + T cells were also gradually reduced in patients of SARS-CoV-2 pneumonia as disease progressed, suggesting their potential role in predicting prognosis in SARS-CoV-2-infected pneumonia. Uniquely, we did not observe significant decreases in B lymphocytes and NK T cells in SARS-CoV-2 infected patients, indicating a relatively weak inflammation caused by SARS-CoV-2 compared with SARS-CoV and MERS-CoV. This could also explain the lower lethality in SARS-CoV2 than SARS-CoV and MERS-CoV, which needs to be confirmed by further investigations.
This study is limited by the small sample size and retrospective method. Several considerations should be taken into account when interpreting the findings. First, only 112 patients with confirmed SARS-CoV-2 pneumonia were included; hematological diseases and incomplete data cases were ruled out in the analyses. And patients in other cities in China, and even in other countries would be better to be included to get a more comprehensive understanding of SARS-CoV-2 pneumonia progression. Second, the present data are based on the clinical observations of nearly one-month period of these patients. Longer monitoring will give us a more comprehensive and accurate analysis on the pathological parameters and immune functions of the patients for further understanding on the pathological mechanisms of SARS-CoV-2 and therapeutic developments. However, the data in this study permit helpful assessment on clinical characteristics and early prediction for disease progression and mortality of SARS-CoV-2 pneumonia before the obvious symptoms appear in patients in Wuhan, China.