MUC1-C influences cell survival in lung adenocarcinoma Calu-3 cells after SARS-CoV-2 infection

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces coronavirus disease 2019 (COVID-19) and may increase the risk of adverse outcomes in lung cancer patients. In this study, we investigated the expression and function of mucin 1 (MUC1) after SARS-CoV-2 infection in the lung epithelial cancer cell line Calu-3. MUC1 is a major constituent of the mucus layer in the respiratory tract and contributes to pathogen defense. SARS-CoV-2 infection induced MUC1 C-terminal subunit (MUC1-C) expression in a STAT3 activation-dependent manner. Inhibition of MUC1-C signaling increased apoptosis-related protein levels and reduced proliferation-related protein levels; however, SARS-CoV-2 replication was not affected. Together, these results suggest that increased MUC1-C expression in response to SARS-CoV-2 infection may trigger the growth of lung cancer cells, and COVID-19 may be a risk factor for lung cancer patients.     

SARS-CoV-2 infection in the Syrian hamster model causes inflammation as well as type I interferon dysregulation in both respiratory and non-respiratory tissues including the heart and kidney

COVID-19 (coronavirus disease 2019) caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection is a disease affecting several organ systems. A model that captures all clinical symptoms of COVID-19 as well as long-haulers disease is needed. We investigated the host responses associated with infection in several major organ systems including the respiratory tract, the heart, and the kidneys after SARS-CoV-2 infection in Syrian hamsters. We found significant increases in inflammatory cytokines (IL-6, IL-1beta, and TNF) and type II interferons whereas type I interferons were inhibited. Examination of extrapulmonary tissue indicated inflammation in the kidney, liver, and heart which also lacked type I interferon upregulation. Histologically, the heart had evidence of myocarditis and microthrombi while the kidney had tubular inflammation. These results give insight into the multiorgan disease experienced by people with COVID-19 and possibly the prolonged disease in people with post-acute sequelae of SARS-CoV-2 (PASC).     

Single-cell RNA analysis on ACE2 expression provides insights into SARS-CoV-2 potential entry into the bloodstream and heart injury

Coronavirus disease-2019 (COVID-19) is a global pandemic with high infectivity and pathogenicity, accounting for tens of thousands of deaths worldwide. Recent studies have found that the pathogen of COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), shares the same cell receptor angiotensin converting enzyme II (ACE2) as SARS-CoV. The pathological investigation of COVID-19 deaths showed that the lungs had characteristics of pulmonary fibrosis. However, how SARS-CoV-2 spreads from the lungs to other organs has not yet been determined. Here, we performed an unbiased evaluation of cell-type-specific expression of ACE2 in healthy and fibrotic lungs, as well as in normal and failed adult human hearts, using published single-cell RNA-seq data. We found that ACE2 expression in fibrotic lungs mainly locates in arterial vascular cells, which might provide a route for bloodstream spreading of SARS-CoV-2. Failed human hearts have a higher percentage of ACE2-expressing cardiomyocytes, and SARS-CoV-2 might attack cardiomyocytes through the bloodstream in patients with heart failure. Moreover, ACE2 was highly expressed in cells infected by respiratory syncytial virus or Middle East respiratory syndrome coronavirus and in mice treated by lipopolysaccharide. Our findings indicate that patients with pulmonary fibrosis, heart failure, and virus infection have a higher risk and are more susceptible to SARS-CoV-2 infection. The SARS-CoV-2 might attack other organs by getting into the bloodstream. This study provides new insights into SARS-CoV-2 blood entry and heart injury and might propose a therapeutic strategy to prevent patients from developing severe complications.     

SARS- CoV-2 infection and oxidative stress in early-onset preeclampsia

SARS-CoV-2 causes coronavirus disease 2019 (COVID-19) also in pregnant women. Infection in pregnancy leads to maternal and placental functional alterations. Pregnant women with vascular defects such as preeclampsia show high susceptibility to SARS-CoV-2 infection by undefined mechanisms. Pregnant women infected with SARS-CoV-2 show higher rates of preterm birth and caesarean delivery, and their placentas show signs of vasculopathy and inflammation. It is still unclear whether the foetus is affected by the maternal infection with this virus and whether maternal infection associates with postnatal affections. The SARS-CoV-2 infection causes oxidative stress and activation of the immune system leading to cytokine storm and next tissue damage as seen in the lung. The angiotensin-converting-enzyme 2 expression is determinant for these alterations in the lung. Since this enzyme is expressed in the human placenta, SARS-CoV-2 could infect the placenta tissue, although reported to be of low frequency compared with maternal lung tissue. Early-onset preeclampsia (eoPE) shows higher expression of ADAM17 (a disintegrin and metalloproteinase 17) causing an imbalanced renin-angiotensin system and endothelial dysfunction. A similar mechanism seems to potentially account for SARS-CoV-2 infection. This review highlights the potentially common characteristics of pregnant women with eoPE with those with COVID-19. A better understanding of the mechanisms of SARS-CoV-2 infection and its impact on the placenta function is determinant since eoPE/COVID-19 association may result in maternal metabolic alterations that might lead to a potential worsening of the foetal programming of diseases in the neonate, young, and adult.     

A Comprehensive Review of Animal Models for Coronaviruses: SARS-CoV-2, SARS-CoV,and MERS-CoV

The recent outbreak of coronavirus disease(COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) has already affected a large population of the world. SARS-CoV-2 belongs to the same family of severe acute respiratory syndrome coronavirus(SARS-CoV) and Middle East respiratory syndrome coronavirus(MERSCoV). COVID-19 has a complex pathology involving severe acute respiratory infection, hyper-immune response, and coagulopathy. At present, there is no therapeutic drug or vaccine approved for the disease. There is an urgent need for an ideal animal model that can reflect clinical symptoms and underlying etiopathogenesis similar to COVID-19 patients which can be further used for evaluation of underlying mechanisms, potential vaccines, and therapeutic strategies. The current review provides a paramount insight into the available animal models of SARS-CoV-2, SARS-CoV, and MERS-CoV for the management of the diseases.     

SARS-CoV-2 mediated neuroinflammation and the impact of COVID-19 in neurological disorders

SARS-CoV-2 is a novel coronavirus that severely affects the respiratory system, is the cause of the COVID-19 pandemic, and is projected to result in the deaths of 2 million people worldwide. Recent reports suggest that SARS-CoV-2 also affects the central nervous system along with other organs. COVID-19-associated complications are observed in older people with underlying neurological conditions like stroke, Alzheimer's disease, and Parkinson’s disease. Hence, we discuss SARS-CoV-2 viral replication and its inflammation-mediated infection. This review also focuses on COVID-19 associated neurological complications in individuals with those complications as well as other groups of people. Finally, we also briefly discuss the current therapies available to treat patients, as well as ongoing available treatments and vaccines for effective cures with a special focus on the therapeutic potential of a small 5 amino acid peptide (PHSCN), ATN-161, that inhibits SARS-CoV-2 spike protein binding to both integrin α5β1 and α5β1/hACE2.     

Induced pluripotent stem cell-based disease modeling and prospective immune therapy for coronavirus disease 2019

The emergence of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic poses a never before seen challenge to human health and the economy. Considering its clinical impact, with no streamlined therapeutic strategies in sight, it is crucial to understand the infection process of SARS-CoV-2. Our limited knowledge of the mechanisms underlying SARS-CoV-2 infection impedes the development of alternative therapeutics to address the pandemic. This aspect can be addressed by modeling SARS-CoV-2 infection in the human context to facilitate drug screening and discovery. Human induced pluripotent stem cell (iPSC)-derived lung epithelial cells and organoids recapitulating the features and functionality of the alveolar cell types can serve as an in vitro human model and screening platform for SARS-CoV-2. Recent studies suggest an immune system asynchrony leading to compromised function and a decreased proportion of specific immune cell types in coronavirus disease 2019 (COVID-19) patients. Replenishing these specific immune cells may serve as useful treatment modality against SARS-CoV-2 infection. Here the authors review protocols for deriving lung epithelial cells, alveolar organoids and specific immune cell types, such as T lymphocytes and natural killer cells, from iPSCs with the aim to aid investigators in making relevant in vitro models of SARS-CoV-2 along with the possibility derive immune cell types to treat COVID-19.     

Antibodies at work in the time of severe acute respiratory syndrome coronavirus 2

In view of devastating effects of COVID-19 on human life, there is an urgent need for the licened vaccines or therapeutics for the SARS-CoV-2 infection. Age-old passive immunization with protective antibodies to neutralize the virus is one of the strategies for emergency prophylaxis and therapy for coronavirus disease 2019 (COVID-19). In this review, the authors discuss up-to-date advances in immune-based therapy for COVID-19. The use of convalescent plasma therapy as the first line of defense to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been established, with encouraging results. Monoclonal antibodies (mAbs) that bind to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein or block the interaction between SARS-CoV-2 RBD and the human angiotensin-converting enzyme 2 receptor have been found to be very promising as a countermeasure for tackling the SARS-CoV-2 infection, and clinical trials are underway. Considering the counterproductive antibody-dependent enhancement of the virus, mAbs therapy that is safe and efficacious, even in people with underlying conditions, will be a significant breakthrough. In addition, emerging immunotherapeutic interventions using nanobodies and cellular immunotherapy are promising avenues for tackling the COVID-19 pandemic. The authors also discuss the implication of mAbs as mediators of cytokine storm syndrome to modify the immune response of COVID-19 patients, thus reducing the fatality rate of COVID-19 infection.     

SARS-CoV-2 infection and oxidative stress: Pathophysiological insight into thrombosis and therapeutic opportunities

The current coronavirus disease 2019 (COVID-19) pandemic has presented unprecedented challenges to global health. Although the majority of COVID-19 patients exhibit mild-to-no symptoms, many patients develop severe disease and need immediate hospitalization, with most severe infections associated with a dysregulated immune response attributed to a cytokine storm. Epidemiological studies suggest that overall COVID-19 severity and morbidity correlate with underlying comorbidities, including diabetes, obesity, cardiovascular diseases, and immunosuppressive conditions. Patients with such comorbidities exhibit elevated levels of reactive oxygen species (ROS) and oxidative stress caused by an increased accumulation of angiotensin II and by activation of the NADPH oxidase pathway. Moreover, accumulating evidence suggests that oxidative stress coupled with the cytokine storm contribute to COVID-19 pathogenesis and immunopathogenesis by causing endotheliitis and endothelial cell dysfunction and by activating the blood clotting cascade that results in blood coagulation and microvascular thrombosis. In this review, we survey the mechanisms of how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces oxidative stress and the consequences of this stress on patient health. We further shed light on aspects of the host immunity that are crucial to prevent the disease during the early phase of infection. A better understanding of the disease pathophysiology as well as preventive measures aimed at lowering ROS levels may pave the way to mitigate SARS-CoV-2-induced complications and decrease mortality.     

Phenotypes and Functions of SARS-CoV-2-Reactive T Cells

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), which is an ongoing pandemic disease. SARS-CoV-2-specific CD4⁺ and CD8⁺ T-cell responses have been detected and characterized not only in COVID-19 patients and convalescents, but also unexposed individuals. Here, we review the phenotypes and functions of SARS-CoV-2-specific T cells in COVID-19 patients and the relationships between SARS-CoV-2-specific T-cell responses and COVID-19 severity. In addition, we describe the phenotypes and functions of SARS-CoV-2-specific memory T cells after recovery from COVID-19 and discuss the presence of SARS-CoV-2-reactive T cells in unexposed individuals and SARS-CoV-2-specific T-cell responses elicited by COVID-19 vaccines. A better understanding of T-cell responses is important for effective control of the current COVID-19 pandemic.     

IL-15 immunotherapy is a viable strategy for COVID-19

Coronavirus disease 2019 (COVID-19) is a pulmonary inflammatory disease induced by a newly recognized coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 infection was detected for the first time in the city of Wuhan in China and spread all over the world at the beginning of 2020. Several millions of people have been infected with SARS-CoV-2, and almost 382,867 human deaths worldwide have been reported so far. Notably, there has been no specific, clinically approved vaccine or anti-viral treatment strategy for COVID-19. Herein, we review COVID-19, the viral replication, and its effect on promoting pulmonary fibro-inflammation via immune cell-mediated cytokine storms in humans. Several clinical trials are currently ongoing for anti-viral drugs, vaccines, and neutralizing antibodies against COVID-19. Viral clearance is the result of effective innate and adaptive immune responses. The pivotal role of interleukin (IL)-15 in viral clearance involves maintaining the balance of induced inflammatory cytokines and the homeostatic responses of natural killer and CD8⁺ T cells. This review presents supporting evidence of the impact of IL-15 immunotherapy on COVID-19.     

Assessment of global asymptomatic SARS-CoV-2 infection and management practices from China

With ongoing research, it was found that asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was widespread in coronavirus disease 2019 (COVID-19) populations. Studies have confirmed asymptomatic patients with COVID-19 have potential infectivity, and most of the transmission occurred before symptoms appear. Asymptomatic infection rates varied widely in different countries and regions. Identifying the asymptomatic infected persons and cutting off the infection source is an effective way to prevent the spread of this disease. However, asymptomatic patients have hidden clinical symptoms, and screening based only on the clinical symptoms of COVID-19 can easily lead to a missed diagnosis. Therefore, determining asymptomatic infection patients by SARS-CoV-2 nucleic acid testing is the gold standard. A series of prevention and control measures adopted by the Chinese government, especially the “Four Early” policy, have achieved outstanding achievements, which are worth learning from by other countries.     

SARS-CoV-2 cell receptor gene ACE2 -mediated immunomodulation in breast cancer subtypes

The recent outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has impacted the world severely. The binding of the SARS-CoV-2 virus to the angiotensin-converting enzyme 2 (ACE2) and its intake by the host cell is a necessary step for infection. ACE2 has garnered widespread therapeutic possibility as it is entry/interactive point for SARS-CoV-2, responsible for coronavirus disease 2019 (COVID-19) pandemic and providing a critical regulator for immune modulation in various disease. Patients with suffering from cancer always being on the verge of being immune compromised therefore gaining knowledge about how SARS-CoV-2 viruses affecting immune cells in human cancers will provides us new opportunities for preventing or treating virus-associated cancers. Despite COVID-19 pandemic got center stage at present time, however very little research being explores, which increase our knowledge in context with how SARS-CoV-2 infection affect cancer a cellular level. Therefore, in light of the ACE-2 as an important contributor of COVID-19 global, we analyzed correlation between ACE2 and tumor immune infiltration (TIL) level and the type markers of immune cells were investigated in breast cancer subtypes by using TIMER database. Our findings shed light on the immunomodulatory role of ACE2 in the luminal A subtype which may play crucial role in imparting therapeutic resistance in this cancer subtype.     

An Impaired Inflammatory and Innate Immune Response in COVID-19

The recent appearance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected millions of people around the world and caused a global pandemic of coronavirus disease 2019 (COVID-19). It has been suggested that uncontrolled, exaggerated inflammation contributes to the adverse outcomes of COVID-19. In this review, we summarize our current understanding of the innate immune response elicited by SARS-CoV-2 infection and the hyperinflammation that contributes to disease severity and death. We also discuss the immunological determinants behind COVID-19 severity and propose a rationale for the underlying mechanisms.     

新型冠状病毒的相关研究进展

2019年12月出现于湖北武汉的一种新型冠状病毒(SARS-CoV-2)感染所致肺炎疫情,给人类生命安全造成威胁。迄今为止,对2019年出现的SARS-CoV-2的研究仍处于起步阶段,本文就其相关研究进展进行综述,重点阐述了目前关于SARS-CoV-2的病原学与致病机制方面的研究成果,同时对其流行病学以及该病毒引发的肺炎临床特点加以总结,有助于读者及时了解SARS-CoV-2最新的研究动态,并为今后开展治疗药物及疫苗研发提供方向。     

Low level of plasminogen increases risk for mortality in COVID-19 patients

The pathophysiology of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and especially of its complications is still not fully understood. In fact, a very high number of patients with COVID-19 die because of thromboembolic causes. A role of plasminogen, as precursor of fibrinolysis, has been hypothesized. In this study, we aimed to investigate the association between plasminogen levels and COVID-19-related outcomes in a population of 55 infected Caucasian patients (mean age: 69.8 ± 14.3, 41.8% female). Low levels of plasminogen were significantly associated with inflammatory markers (CRP, PCT, and IL-6), markers of coagulation (D-dimer, INR, and APTT), and markers of organ dysfunctions (high fasting blood glucose and decrease in the glomerular filtration rate). A multidimensional analysis model, including the correlation of the expression of coagulation with inflammatory parameters, indicated that plasminogen tended to cluster together with IL-6, hence suggesting a common pathway of activation during disease’s complication. Moreover, low levels of plasminogen strongly correlated with mortality in COVID-19 patients even after multiple adjustments for presence of confounding. These data suggest that plasminogen may play a pivotal role in controlling the complex mechanisms beyond the COVID-19 complications, and may be useful both as biomarker for prognosis and for therapeutic target against this extremely aggressive infection.Subject terms: Viral infection, Diagnostic markers     

Prolonged humoral and cellular immunity in COVID-19-recovered patients

By the beginning of 2021, the battle against coronavirus disease 2019 (COVID-19) remains ongoing. Investigating the adaptive immune response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19, in patients who have recovered from this disease could contribute to our understanding of the natural host immune response. We enrolled 38 participants in this study. 7 healthy participants and 31 COVID-19 patients who had recovered from COVID-19 and categorized them into 3 groups according to their previous clinical presentations: 10 moderate, 9 mild, and 12 asymptomatic. Flow cytometry analysis of peripheral lymphocyte counts in recovered patients showed significantly increased levels of CD4⁺ T cells in patients with a history of mild and moderate COVID-19 symptoms compared with those healthy individuals (p < 0.05 and p < 0.0001 respectively). whereas no significant difference was observed in the CD8⁺ T cell percentage in COVID-19-recovered patients compared with healthy individuals. Our study demonstrated that antibodies against the SARS-CoV-2 spike protein (anti-S) IgG antibody production could be observed in all recovered COVID-19 patients, regardless of whether they were asymptomatic (p < 0.05)or presented with mild (p < 0.0001) or moderate symptoms (p < 0.01). Anti-S IgG antibodies could be detected in participants up to 90 days post-infection. In conclusion, the lymphocyte levels in recovered patients were associated with the clinical presentation of the disease, and further analysis is required to investigate relationships between different clinical presentations and lymphocyte activation and function.