Depletion and Dysfunction of Dendritic Cells: Understanding SARS-CoV-2 Infection.

Uncontrolled severe acute respiratory syndrome-coronavirus (SARS-CoV)-2 infection is closely related to disorders of the innate immune and delayed adaptive immune systems. Dendritic cells (DCs) "bridge" innate immunity and adaptive immunity. DCs have important roles in defending against SARS-CoV-2 infection. In this review, we summarize the latest research concerning the role of DCs in SARS-CoV-2 infection. We focus on the complex interplay between DCs and SARS-CoV-2: pyroptosis-induced activation; activation of the renin-angiotensin-aldosterone system; and activation of dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin. We also discuss the decline in DC number, the impaired antigen-presentation capability, and the reduced production of type-I interferon of DCs in severe SARS-CoV-2 infection. In addition, we discuss the potential mechanisms for pathological activation of DCs to understand the pattern of SARS-CoV-2 infection. Lastly, we provide a brief overview of novel vaccination and immunotherapy strategies based on DC targeting to overcome SARS-CoV-2 infection.

Increased Expression of Tim-3 Is Associated With Depletion of NKT Cells In SARS-CoV-2 Infection.

In the ongoing coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), natural killer T (NKT) cells act as primary initiators of immune responses. However, a decrease of circulating NKT cells has been observed in COVID-19 different stages, of which the underlying mechanism remains to be elucidated. Here, by performing single-cell RNA sequencing analysis in three large cohorts of COVID-19 patients, we found that increased expression of Tim-3 promotes depletion of NKT cells during the progression stage of COVID-19, which is associated with disease severity and outcome of patients with COVID-19. Tim-3+ NKT cells also expressed high levels of CD147 and CD26, which are potential SARS-CoV-2 spike binding receptors. In the study, Tim-3+ NKT cells showed high enrichment of apoptosis, higher expression levels of mitochondrial genes and caspase genes, with a larger pseudo time value. In addition, Tim-3+ NKT cells in COVID-19 presented a stronger capacity to secrete IFN-γ, IL-4 and IL-10 compared with healthy individuals, they also demonstrated high expression of co-inhibitory receptors such as PD-1, CTLA-4, and LAG-3. Moreover, we found that IL-12 secreted by dendritic cells (DCs) was positively correlated with up-regulated expression of Tim-3 in NKT cells in COVID-19 patients. Overall, this study describes a novel mechanism by which up-regulated Tim-3 expression induced the depletion and dysfunction of NKT cells in COVID-19 patients. These findings not only have possible implications for the prediction of severity and prognosis in COVID-19 but also provide a link between NKT cells and future new therapeutic strategies in SARS-CoV-2 infection.

Prognosis of COVID-19 in patients with breast cancer: A protocol for systematic review and meta-analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has become a pandemic in the world and posed a great threat to people's health. Several meta-analyses have indicated that many comorbidities were associated with increased risk of COVID-19 severity or mortality. The original report also showed that the mortality rate of COVID-19 in breast cancer patients is more dependent on comorbidities than previous radiation therapy or current anti-cancer therapy. However, no meta-analysis has focused on this aspect. This systematic review aims to assess whether breast cancer will increase the severity and mortality of patients infected with COVID-19 and to explore which factors that may affect the severity or mortality rate of breast cancer patients with COVID-19. METHODS: We will search the PubMed, Embase, Web of Science, the Cochrane Central Register of Controlled Trials (CENTRAL), China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), and Wanfang database from December 1, 2019 to June 30, 2020. Cohort studies comparing the disease severity and mortality of COVID-19 patients with and without breast cancer will be included. Two independent reviewers will assess the risk of bias of the included cohort studies using the modified Newcastle-Ottawa Scale. We will conduct meta-analyses to calculate the risk ratio (RR) and 95% confidence interval (95% CI) using the random-effects model with the Mantel-Haenszel method. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach will be used to rate the quality of the evidence. RESULTS: The results of this study will be published in a peer-reviewed journal. CONCLUSION: This study will provide comprehensive evidence for medical staff to adopt effective treatment strategies for breast cancer patients during the COVID-19 pandemic. PROSPERO REGISTRATION NUMBER: CRD42020188208.