Potent NKT cell ligands overcome SARS-CoV-2 immune evasion to mitigate viral pathogenesis in mouse models.

One of the major pathogenesis mechanisms of SARS-CoV-2 is its potent suppression of innate immunity, including blocking the production of type I interferons. However, it is unknown whether and how the virus interacts with different innate-like T cells, including NKT, MAIT and γδ T cells. Here we reported that upon SARS-CoV-2 infection, invariant NKT (iNKT) cells rapidly trafficked to infected lung tissues from the periphery. We discovered that the envelope (E) protein of SARS-CoV-2 efficiently down-regulated the cell surface expression of the antigen-presenting molecule, CD1d, to suppress the function of iNKT cells. E protein is a small membrane protein and a viroporin that plays important roles in virion packaging and envelopment during viral morphogenesis. We showed that the transmembrane domain of E protein was responsible for suppressing CD1d expression by specifically reducing the level of mature, post-ER forms of CD1d, suggesting that it suppressed the trafficking of CD1d proteins and led to their degradation. Point mutations demonstrated that the putative ion channel function was required for suppression of CD1d expression and inhibition of the ion channel function using small chemicals rescued the CD1d expression. Importantly, we discovered that among seven human coronaviruses, only E proteins from highly pathogenic coronaviruses including SARS-CoV-2, SARS-CoV and MERS suppressed CD1d expression, whereas the E proteins of human common cold coronaviruses, HCoV-OC43, HCoV-229E, HCoV-NL63 and HCoV-HKU1, did not. These results suggested that E protein-mediated evasion of NKT cell function was likely an important pathogenesis factor, enhancing the virulence of these highly pathogenic coronaviruses. Remarkably, activation of iNKT cells with their glycolipid ligands, both prophylactically and therapeutically, overcame the putative viral immune evasion, significantly mitigated viral pathogenesis and improved host survival in mice. Our results suggested a novel NKT cell-based anti-SARS-CoV-2 therapeutic approach.

Abnormal myocardial enzymes are important indicators of poor prognosis in COVID-19 patients

Objective: Researching the prognostic value of myocardial enzymes in COVID-19 patients. Materials &methods: We collected 113 confirmed COVID-19 patients. The dynamic changes of CK, LDH and α-HBDH in patients were studied retrospectively, the correlation between myocardial enzyme index, clinical classification and outcome of patients and its significance to prognosis. Results: There are significant statistical differences between LDH, α-HBDH, CK and the clinical classification, and patient’s outcome. In the receiver operating characteristic curve analysis, LDH, α-HBDH and CK have a good diagnostic value for the death outcome of patients. Conclusion: LDH, α-HBDH and CK were the components of myocardial enzyme profiles, and our results found that they were significantly positively correlated with clinical classification and prognosis of COVID-19 patients. The values of LDH, α-HBDH and CK increased with the increase of the severity of admission clinical classification and the deterioration of outcome. Therefore, we propose that continuous monitoring of LDH, α-HBDH and CK indicators can warn the deterioration of COVID-19 to a certain extent, regardless of whether patients with cardiovascular diseases are combined or not, and prompt early intervention.

Effects of SARS-CoV-2 and its functional receptor ACE2 on the cardiovascular system.

The clinical manifestations of COVID-19 are mainly respiratory symptoms, but some patients present with cardiovascular system disease such as palpitations and shortness of breath as the first or secondary symptoms. In this paper, we describe the characteristics of SARS-CoV­2 and its functional receptor angiotensin-converting enzyme 2 (ACE2). Furthermore, we explore the impact of virus-induced myocardial damage, decreased ACE2 activity, immune imbalance, hypoxemia, and heart damage caused by antiviral drugs.