BACKGROUND Since December 2019, an outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, and is now becoming a global threat. We aimed to delineate and compare the immunological features of severe and moderate COVID-19.METHODS In this retrospective study, the clinical and immunological characteristics of 21 patients (17 male and 4 female) with COVID-19 were analyzed. These patients were classified as severe (11 cases) and moderate (10 cases) according to the guidelines released by the National Health Commission of China.RESULTS The median age of severe and moderate cases was 61.0 and 52.0 years, respectively. Common clinical manifestations included fever, cough, and fatigue. Compared with moderate cases, severe cases more frequently had dyspnea, lymphopenia, and hypoalbuminemia, with higher levels of alanine aminotransferase, lactate dehydrogenase, C-reactive protein, ferritin, and D-dimer as well as markedly higher levels of IL-2R, IL-6, IL-10, and TNF-α. Absolute numbers of T lymphocytes, CD4+ T cells, and CD8+ T cells decreased in nearly all the patients, and were markedly lower in severe cases (294.0, 177.5, and 89.0 × 106/L, respectively) than moderate cases (640.5, 381.5, and 254.0 × 106/L, respectively). The expression of IFN-γ by CD4+ T cells tended to be lower in severe cases (14.1%) than in moderate cases (22.8%).CONCLUSION The SARS-CoV-2 infection may affect primarily T lymphocytes, particularly CD4+ and CD8+ T cells, resulting in a decrease in numbers as well as IFN-γ production by CD4+ T cells. These potential immunological markers may be of importance because of their correlation with disease severity in COVID-19.TRIAL REGISTRATION This is a retrospective observational study without a trial registration number.FUNDING This work is funded by grants from Tongji Hospital for the Pilot Scheme Project, and partly supported by the Chinese National Thirteenth Five Years Project in Science and Technology for Infectious Disease (2017ZX10202201).
Guang Chen, Di Wu, Wei Guo, Yong Cao, Da Huang, Hongwu Wang, Tao Wang, Xiaoyun Zhang, Huilong Chen, Haijing Yu, Xiaoping Zhang, Minxia Zhang, Shiji Wu, Jianxin Song, Tao Chen, Meifang Han, Shusheng Li, Xiaoping Luo, Jianping Zhao, Qin Ning
Submitter: Nicholas Bennett | firstname.lastname@example.org
Currently unaffiliated but I am a speaker/consultant to Horizon Pharma.
Published May 26, 2020
I read with interest the findings in patients with COVID-19 described by Chen et al (1) including the profound CD4+ and CD8+ T cell lymphopenia and reduced interferon-gamma (IFN-γ) response. Coronaviruses encode several genes that directly reduce IFN-γ response to viral infection, and many coronaviruses, including SARS-CoV2, are thought to originate in bats, a host with higher endogenous type I IFN and greater antiviral responses (2). Although studies on bat IFN-γ are limited, these responses apparently lead to increased production of promotors of IFN-γ (3). It is reasonable to hypothesize that a zoonotic infection would result in more severe disease in a relatively immune-deficient host. Coronavirus pathology is worse among older humans and in aged murine models of disease, and recovery and long-term protection from SARS-CoV is associated with vigorous and lasting T cell memory responses (enhanced by IFN-γ) (4, 5). Interestingly, whereas SARS-related inflammation is associated with high levels of IFN-γ, severe MERS virus infection is associated with an attenuated IFN-γ response similar to SARS-CoV2 (6).
IFN-γ enhances macrophage activity, antigen presentation, and the development of effector CD8+ cytotoxic T cells. Furthermore, IFN-γ downregulates the ACE2 receptor that is the binding site of SARS-COV2 (7). IFN-γ may also avoid the pro-inflammatory concerns of the type I interferons on treating COVID-19 (8). While promising results are being reported from early studies of antiviral therapies and blockade of IL-6, neither of these approaches necessarily improves the adaptive immune response, with subsequent development of lasting immunity.
IFN-γ is available as a commercial product with a known biosafety profile. It seems reasonable to systematically investigate the possibility of modifying the course of the disease process in high-risk individuals with COVID-19 disease through the administration of systemic or inhaled IFN-γ.
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