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.     

COVID-19 Outcomes of Patients With Differentiated Thyroid Cancer: A Multicenter Los Angeles Cohort Study

ObjectiveCancer may be a risk factor for worse outcomes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infections. However, there is a significant variability across cancer types in the extent of disease burden and modalities of cancer treatment that may impact morbidity and mortality from coronavirus disease-19 (COVID-19). Therefore, we evaluated COVID-19 outcomes in patients with a differentiated thyroid cancer (DTC) history.MethodsThis is a retrospective cohort study of patients with a history of DTC and SARS-CoV2 infection from 2 academic Los Angeles healthcare systems. Demographic, thyroid cancer, and treatment data were analyzed for associations with COVID-19 outcomes.ResultsOf 21 patients with DTC and COVID-19, 8 (38.1%) were hospitalized and 2 (9.5%) died from COVID-19. Thyroid cancer initial disease burden and extent, treatment, or current response to therapy (eg, excellent vs incomplete) were not associated with COVID-19 severity in DTC patients. However, older age and the presence of a comorbidity other than DTC were significantly associated with COVID-19 hospitalization (P = .047 and P = .024, respectively). COVID-19–attributed hospitalization and mortality in DTC patients was lower than that previously reported in cancer patients, although similar to patients with nonthyroid malignancies in these centers.ConclusionThese data suggest that among patients with DTC, advanced age and comorbid conditions are significant contributors to the risk of hospitalization from SARS-CoV2 infection, rather than factors associated with thyroid cancer diagnosis, treatment, or disease burden. This multicenter report of clinical outcomes provides additional data to providers to inform DTC patients regarding their risk of COVID-19.     

Why the complications of COVID-19 patients differ in elderly and young cancer patients

Zhang et al. reported the impact of different risk factors and comorbidities in COVID-19 lethality. The authors observed that the odds of dying by COVID-19 in cancer patients decrease with age and cancer becomes a non-significant factor above 80 years. We speculate on the possible causes for the different COVID-19 severity between elderly and young patients. Several factors that can have a different impact on young and elderly have to be taken into account such as inflammation, microbiota and anti-cancer therapies. Inflammaging is a complex process that characterizes elderly people and it is believed to contribute to the severity of COVID-19 associated with old age. Cancer and related therapies may alter the process of inflammaging both quantitatively and qualitatively and could impact on COVID-19 severity. Moreover, therapies used in elderly cancer patients are usually different from that used for young people where the presence of comorbidities and the mechanisms of action of the different drugs both on the susceptibility genes and on other factors have to be considered. Sex hormones and anti-estrogen therapies affect significantly gene expression in target cells thereby modulating the susceptibility of the tissues to SARS-CoV-2 infection and as a consequence the extent of the symptoms. The concentration of sex hormones varies with aging and among sexes. Interestingly, recent evidences, further corroborate the hypothesis that also sex hormones or anti-estrogen therapies impact the susceptibility to COVID-19 and its severity.     

Is 2020 the year when primatologists should cancel fieldwork? A reply

The aim of this article is to explore the impact of coronavirus disease (COVID-19) pandemic on primate-related conservation work. The withdrawal of primatologists and conservation staff from field research can lead to a number of detrimental effects not just on conservation but also on local communities in low- and middle-income countries. Inequalities in access to health and financial insecurities may be drivers for the illegal wildlife trade and the lack of tourism and research activity may allow poachers to work with greater ease. The paper also looks at how conservation organizations and research bodies should modify their field protocols by developing robust occupational health policies that will not only make field work safer but also support local staff as they are likely to face the greatest threats to their physical health, psychological health, and economic loss from COVID-19. By adopting a One Health approach that considers the complex interactions between human and primate health, researchers will be able to find new ways of working not only to protect primates but understand how they adapt to the COVID-19 pandemic.     

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.     

COVID-19 disease and malignant cancers: The impact for the furin gene expression in susceptibility to SARS-CoV-2

Furin is a proprotein convertase that activates different kinds of regulatory proteins, including SARS-CoV-2 spike protein which contains an additional furin-specific cleavage site. It is essential in predicting cancer patients'' susceptibility to SARS-CoV-2 and the disease outcomes due to varying furin expressions in tumor tissues. In this study, we analyzed furin''s expression, methylation, mutation rate, functional enrichment, survival rate and COVID-19 outcomes in normal and cancer tissues using online databases, and our IHC. As a result, furin presented with biased expression profiles in normal tissues, showing 12.25-fold higher than ACE2 in the lungs. The furin expression in tumors were significantly increased in ESCA and TGCT, and decreased in DLBC and THYM, indicating furin may play critical mechanistic functions in COVID-19 viral entry into cells in these cancer patients. Line with furin over/downexpression, furin promoter hypo-/hyper-methylation may be the regulatory cause of disease and lead to pathogenesis of ESCA and THYM. Furthermore, presence of FURIN-201 isoform with functional domains (P_proprotein, Peptidase_S8 and S8_pro-domain) is highest in all cancer types in comparison to other isoforms, demonstrating its use in tumorigenesis and SARS-Cov-2 entry into tumor tissues. Furin mutation frequency was highest in UCES, and its mutation might elevate ACE2 expression in LUAD and UCEC, reduce ACE2 expression in COAD, elevate HSPA5 expression in PAAD, and elevate TMPRSS2 expression in BRCA. These results showed that furin mutations mostly increased expression of ACE2, HSPA5, and TMPRSS2 in certain cancers, indicating furin mutations might facilitate COVID-19 cell entry in cancer patients. In addition, high expression of furin was significantly inversely correlated with long overall survival (OS) in LGG and correlated with long OS in COAD and KIRC, indicating that it could be used as a favorable prognostic marker for cancer patients'' survival. GO and KEGG demonstrated that furin was mostly enriched in genes for metabolic and biosynthetic processes, retinal dehydrogenase activity, tRNA methyltransferase activity, and genes involving COVID-19, further supporting its role in COVID-19 and cancer metabolism. Moreover, Cordycepin (CD) inhibited furin expression in a dosage dependent manner. Altogether, furin''s high expression might not only implies increased susceptibility to SARS-CoV-2 and higher severity of COVID-19 symptoms in cancer patients, but also it highlights the need for cancer treatment and therapy during the COVID-19 pandemic. CD might have a potential to develop an anti-SARS-CoV-2 drug through inhibiting furin expression.     

Family size and vaccination among older individuals: The case of COVID-19 vaccine

While vaccination is generally considered efficient in protecting against transmissible diseases, the compliance is not complete in many countries. In this study, we investigate how an individual-specific factor – family size – affects the probability of getting vaccinated against COVID-19. To answer this research question, we focus on individuals above 50 years of age, who are at a higher risk of developing severe symptoms. The analysis uses the Survey of Health, Ageing and Retirement in Europe Corona wave, conducted in the summer of 2021. To identify the effect of family size on vaccination, we exploit an exogenous variation in the probability of having more than two children, due to the sex composition of two firstborns. We document that a larger family size increases the probability of receiving the COVID-19 vaccine among older individuals. This impact is economically and statistically significant. We propose several potential mechanisms behind this result and document that family size can be related to the higher probability of being exposed to the disease. This effect can be by knowing someone who tested positive for COVID-19 or had symptoms similar to it, and by network size and frequency of contact with children, before the outbreak of COVID-19.     

Prognostic serum biomarkers in cancer patients with COVID-19: A systematic review

PurposeCancer patients with COVID-19 likely express biomarker changes in circulation. However, the biomarkers used in SARS-CoV-2 infected cancer patients for COVID-19 severity and prognosis are largely unclear. Therefore, this systematic review aims to determine what biomarkers were measured in cancer patients with COVID-19 and their prognostic utility.MethodsA systematic literature review in PubMed, Embase, and Scopus was performed on June 16th, 2021. The search keywords coronavirus, neoplasm, biomarkers, and disease progression were used to filter out 17 eligible studies, which were then carefully evaluated.ResultsA total of 4,168 patients, 16 types of cancer, and 60 biomarkers were included. Seven up-regulated markers, including CRP, d-dimer, ferritin, IL-2R, IL-6, LDH, and PCT, were identified in eligible studies. Albumin and hemoglobin were significantly down-regulated in cancer patients with COVID-19. Moreover, we observed that the SARS-CoV-2 infected cancer patients with lower CRP, ferritin, and LDH levels successfully survived from COVID-19 treatments.ConclusionSeveral important clinical biomarkers, such as CRP, ferritin, and LDH, may serve as the prognostic markers to predict the outcomes following COVID-19 treatment and monitor the deterioration of COVID-19 in cancer patients.     

Attitudes toward COVID-19 vaccines in Chinese college students

Background: Vaccination is an important preventative measure against the coronavirus disease 19 (COVID-19) pandemic. To implement vaccination and immunization programs effectively, it is essential to investigate public attitudes toward COVID-19 vaccines. This study examined the attitudes of Chinese college students toward COVID-19 vaccines and their associated factors. Methods: A cross-sectional study was conducted in college students nationwide from December 27, 2020 to January 18, 2021. Attitudes toward COVID-19 vaccines and acceptance of future vaccination programs were assessed. Results: Totally, 2,881 college students participated in this survey; of them, 76.3% (95% CI: 74.8% - 77.9%) were willing to accept a COVID-19 vaccine in the future. Multiple logistic analysis revealed that students living in urban (OR=1.409, 95% CI: 1.152 - 1.724, p=0.001) and those studying health-related courses (OR=1.581, 95% CI: 1.291 - 1.935, p<0.001) were more likely to have a positive attitude toward COVID-19 vaccines. In addition, those who were worried about being infected with COVID-19 (very much vs no, OR=1.690, 95% CI: 1.212-2.356, p=0.002), heard previously about COVID-19 vaccines (OR=1.659, 95% CI: 1.268-2.170, p<0.001), believed that vaccines are safe (Yes vs No, OR=3.570, 95% CI: 1.825-6.980), thought that vaccines can protect people from being infected with COVID-19 (Yes vs No, OR=1.957, 95% CI: 1.286-2.979, p=0.002), and had encouraged their family and friends to have a vaccine (Yes vs No, OR=17.745, 95% CI: 12.271-25.660, p<0.001) had higher acceptance of COVID-19 vaccination. Conclusions: A high rate of acceptance of COVID-19 vaccines was found among Chinese college students. However, vaccine uptake may be reduced by concerns about vaccine safety and efficacy. Alleviating these concerns and enhancing public confidence in vaccines are crucial for future immunization programs against the COVID-19 pandemic.     

Endocrine Follow-up During Post-Acute COVID-19: Practical Recommendations Based on Available Clinical Evidence

ObjectiveCOVID-19 affects multiple endocrine organ systems during the disease course. However, follow-up data post-COVID-19 is scarce; hitherto available limited data suggest that most of the biochemical endocrine dysfunctions observed during acute phase of COVID-19 tend to improve after recovery. Hence, we aim to provide a rational approach toward endocrine follow-up of patients during post-acute COVID-19.MethodsWe performed a literature review across PubMed/MEDLINE database looking into the effects of COVID-19 on endocrine system and subsequent long-term endocrine sequelae. Accordingly, we have presented a practical set of recommendations regarding endocrine follow-up post-acute COVID-19.ResultsCOVID-19 can lead to new-onset hyperglycemia/diabetes mellitus or worsening of dysglycemia in patients with preexisting diabetes mellitus. Hence, those with preexisting diabetes mellitus should ensure optimum glycemic control in the post-COVID-19 period. New-onset diabetes mellitus has been described post-acute COVID-19; hence, a selected group of patients (aged <70 years and those requiring intensive care unit admission) may be screened for the same at 3 months. Thyroid dysfunction (euthyroid sick syndrome and atypical thyroiditis) and adrenal insufficiency have been described in COVID-19; however, thyroid/adrenal functions usually normalize on follow-up; hence, widespread screening post-acute COVID-19 should not be recommended. Pituitary apoplexy and male hypogonadism have rarely been documented in COVID-19; therefore, appropriate follow-up may be undertaken as per clinical context. Hypocalcemia during COVID-19 is not uncommon; however, routine estimation of serum calcium post-COVID-19 is not warranted.ConclusionThe recommendations herein provide a rational approach that would be expected to guide physicians to better delineate and manage the endocrine sequelae during post-acute COVID-19.     

COVID-19 pandemic and patients with cancer: The protocol of a Clinical Oncology center in Tehran,Iran

AimTo provide recommendations for the management of patients with cancer in the COVID-19 era.BackgroundThe current global pandemic of COVID-19 has severely impacted global healthcare systems. Several groups of people are considered high-risk for SARS-CoV-2 infection, including patients with cancer. Therefore, protocols for the better management of these patients during this viral pandemic are necessary. So far, several protocols have been presented regarding the management of patients with cancer during the COVID-19 pandemic. However, none of them points to a developing country with limited logistics and facilities.MethodsIn this review, we have provided a summary of recommendations on the management of patients with cancer during the COVID-19 pandemic based on our experience in Shohada-e Tajrish Hospital, Iran.ResultsWe recommend that patients with cancer should be managed in an individualized manner during the COVID-19 pandemic.ConclusionsOur recommendation provides a guide for oncology centers of developing countries for better management of cancer.     

ARB might be superior to ACEI for treatment of hypertensive COVID-19 patients

The administration of ACEI/ARB (angiotensin-converting enzyme inhibitors/Angiotension II receptor blockers) in COVID-19 (coronavirus disease 2019) patients with hypertension exhibits a lower risk of mortality compared with ACEI/ARB non-users. In this context, an important question arises: is ACEI or ARB more suitable for the treatment of hypertensive COVID-19 patients? Taken into consideration the following four rationales, ARB may offer a more significant benefit than ACEI for the short-term treatment of hypertensive COVID-19 patients: 1. ACEI has no inhibition on non-ACE-mediated Ang II production under infection conditions, whereas ARB can function properly regardless of how Ang II is produced; 2. ACEI-induced bradykinin accumulation may instigate severe ARDS while ARB has no effects on kinin metabolism; 3. ARB alleviates viscous sputa production and inflammatory reaction significantly in contrast to ACEI; 4. ARB may attenuate the lung fibrosis induced by mechanical ventilation in severe patients and improve their prognosis significantly compared with ACEI. To examine the advantages of ARB over ACEI on hypertensive COVID-19 patients, retrospective case-control studies comparing the clinical outcomes for COVID-19 patients receiving ARB or ACEI treatment is strikingly needed in order to provide guidance for the clinical application.     

Political polarization of conservation issues in the era of COVID-19: An examination of partisan perspectives and priorities in the United States

As a zoonotic disease with unprecedented global impacts, COVID-19 may influence how people prioritize issues related to wildlife conservation. Using a nationally representative sample of US residents, we investigated: (1) how COVID-19 affected the relative importance of conservation issues among adults with different political ideologies, and (2) how the pandemic affected political polarization of conservation issues during the 2020 general election in the United States. Conservation issues such as endangered species and controlling zoonotic disease ranked low in importance among the 14 policy issues considered, even lower than environmental issues such as climate change and environmental protection; however, the importance of all conservation issues increased as a result of COVID-19. Political polarization surrounding the perceived importance of conservation issues also increased during the COVID-19 pandemic, with Democrats reporting larger increases in importance than Republicans. Polarization was driven by the most conservative Republicans and the most liberal Democrats. But this polarization was less extreme than it was for other issues such as climate change and healthcare. Findings highlight the need for communicating links between zoonotic disease and human interactions with wildlife and the environment. Acting quickly may be critical in areas where conservation issues are primed to succumb to political polarization.     

MicroRNA-425-5p modulates osteoporosis by targeting annexin A2

The disease (COVID-19) novel coronavirus pandemic has so far infected millions resulting in the death of over a million people as of Oct 2020. More than 90% of those infected with COVID-19 show mild or no symptoms but the rest of the infected cases show severe symptoms resulting in significant mortality. Age has emerged as a major factor to predict the severity of the disease and mortality rates are significantly higher in elderly patients. Besides, patients with underlying conditions like Type 2 diabetes, cardiovascular diseases, hypertension, and cancer have an increased risk of severe disease and death due to COVID-19 infection. Obesity has emerged as a novel risk factor for hospitalization and death due to COVID-19. Several independent studies have observed that people with obesity are at a greater risk of severe disease and death due to COVID-19. Here we review the published data related to obesity and overweight to assess the possible risk and outcome in Covid-19 patients based on their body weight. Besides, we explore how the obese host provides a unique microenvironment for disease pathogenesis, resulting in increased severity of the disease and poor outcome.

     

Advances and gaps in SARS-CoV-2 infection models

The global response to Coronavirus Disease 2019 (COVID-19) is now facing new challenges such as vaccine inequity and the emergence of SARS-CoV-2 variants of concern (VOCs). Preclinical models of disease, in particular animal models, are essential to investigate VOC pathogenesis, vaccine correlates of protection and postexposure therapies. Here, we provide an update from the World Health Organization (WHO) COVID-19 modeling expert group (WHO-COM) assembled by WHO, regarding advances in preclinical models. In particular, we discuss how animal model research is playing a key role to evaluate VOC virulence, transmission and immune escape, and how animal models are being refined to recapitulate COVID-19 demographic variables such as comorbidities and age.

In February of 2020, the World Health Organization (WHO) R&D Blueprint convened a group of experts to develop preclinical models of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Since its inception, the goal of this WHO COVID Modeling group (WHO-COM) has been to accelerate the development of Coronavirus Disease 2019 (COVID-19) vaccines and therapeutics by rapidly sharing data among member scientists worldwide. In addition, concerns were raised at that time about the possibility of vaccine-associated enhanced respiratory disease (VAERD) or antibody-dependent enhancement (ADE) after vaccination or infection. In September of 2020, the WHO-COM published a review on COVID-19 animal models [1], which reflected the state-of-the art at that time, with the vast majority of publications authored by members of the group.Preclinical studies in nonhuman primates (NHPs) of COVID-19 vaccines that are currently being deployed [2–5] proved remarkably predictive of the outcome of clinical efficacy studies. In particular, NHP studies not only predicted high clinical efficacy of these vaccines but also suggested immune correlates of protection. Moreover, preclinical studies accurately predicted that protection against severe pneumonia would be easier to achieve than protection against viral replication in nasal mucosa. These observations confirm the value and importance of the use of animal models for COVID-19.In 2021, with several vaccines rolling out worldwide and the detection of variants of concern (VOCs), the development of preclinical models of SARS-CoV-2 infection and their role in COVID-19 research has entered into a new phase. This paper provides an update from the WHO-COM regarding advances in preclinical models. In particular, we discuss how animal model research has provided insight into VOC pathogenesis and correlates of protection and has helped therapeutic development. Finally, we discuss the current status of VAERD research and the race to develop models that recapitulate COVID-19 demographic variables such as comorbidities and age.     

间充质干细胞在2019新型冠状病毒肺炎(COVID-19)中的治疗潜能、临床研究与应用前景*

当前因SARS-CoV-2感染而引起的2019新型冠状病毒肺炎(COVID-19)肆虐全球,严重危害人类健康。SARS-CoV-2感染性强,危重症患者死亡率高,尽管各种各样的治疗正在进行临床试验,但目前尚无有效的治疗方法。间充质干细胞(mesenchymal stem cell,MSC)在临床前试验中对多种疾病有良好的治疗效果,因而受到了广泛地关注。MSC可能利用分化潜能诱导分化成功能性肺样细胞、免疫调节与免疫细胞互作、抑制炎症来降低促炎细胞因子分泌、迁移和归巢靶向损伤肺部、抗病毒作用来减少肺上皮细胞中的病毒复制、产生细胞外囊泡来修复受损的组织,进而使COVID-19患者肺功能逐渐恢复正常,缓解并达到治疗COVID-19的目的。综合讨论了COVID-19的基本特征和当前主要治疗手段,同时总结了MSC在COVID-19中的临床研究和当前面临的挑战,探讨了MSC治疗COVID-19的应用前景,为MSC在COVID-19中的治疗提供了理论基础和现实依据。     

A Potential Role of the CD47/SIRPalpha Axis in COVID-19 Pathogenesis

The coronavirus SARS-CoV-2 is the cause of the ongoing COVID-19 pandemic. Most SARS-CoV-2 infections are mild or even asymptomatic. However, a small fraction of infected individuals develops severe, life-threatening disease, which is caused by an uncontrolled immune response resulting in hyperinflammation. However, the factors predisposing individuals to severe disease remain poorly understood. Here, we show that levels of CD47, which is known to mediate immune escape in cancer and virus-infected cells, are elevated in SARS-CoV-2-infected Caco-2 cells, Calu-3 cells, and air−liquid interface cultures of primary human bronchial epithelial cells. Moreover, SARS-CoV-2 infection increases SIRPalpha levels, the binding partner of CD47, on primary human monocytes. Systematic literature searches further indicated that known risk factors such as older age and diabetes are associated with increased CD47 levels. High CD47 levels contribute to vascular disease, vasoconstriction, and hypertension, conditions that may predispose SARS-CoV-2-infected individuals to COVID-19-related complications such as pulmonary hypertension, lung fibrosis, myocardial injury, stroke, and acute kidney injury. Hence, age-related and virus-induced CD47 expression is a candidate mechanism potentially contributing to severe COVID-19, as well as a therapeutic target, which may be addressed by antibodies and small molecules. Further research will be needed to investigate the potential involvement of CD47 and SIRPalpha in COVID-19 pathology. Our data should encourage other research groups to consider the potential relevance of the CD47/ SIRPalpha axis in their COVID-19 research.     

Host genetic variability and determinants of severe COVID-19

Since the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak, convergent studies have provided evidence that host genetic background may contribute to the development of severe coronavirus disease (COVID-19). Here, we summarize how some genetic variations, such as in SARS-CoV-2 receptor angiotensin-converting enzyme 2 or interferon signaling pathway, may help to understand why some individuals can develop severe COVID-19.