Risk of Vaccine Breakthrough SARS-CoV-2 Infection and Associated Factors in Healthcare Workers of Trieste Teaching Hospitals (North-Eastern Italy)

Background: Healthcare workers (HCWs) are particularly exposed to biological risk, including SARS-CoV-2 infection. In order to contrast the current pandemic and alleviate the burden of the disease on the healthcare system, a mass vaccination campaign against COVID-19 has been launched worldwide. Aim To evaluate the impact of COVID-19 vaccination in HCWs exposed to SARS-CoV-2, to describe the clinical presentation of COVID-19 in infected HCWs, and to investigate clinical and occupational risk factors for breakthrough infection. Design: Retrospective cohort study. Methods: The cohort of HCWs of Trieste Hospitals were followed up from 1 March 2020, to 30 November 2021 (21 months). All HCWs were periodically screened for SARS-CoV-2 infection by real-time PCR (RT–PCR) analysis. Clinical data were obtained through routine medical surveillance records. Risk factors for SARS-CoV-2 infection were investigated by univariable as well as multivariable logistic regression analysis. Results: Among 4394 HCWs routinely screened for SARS-CoV-2 by PCR on nasopharyngeal swab, a total of 800 incident cases were identified during the entire study period (1 March 2020 to 30 November 2021). Five hundred and sixty-four cases occurred before, and 236 after the start of the vaccination campaign against COVID-19, of whom 155 received a complete vaccination scheme before SARS-CoV-2 infection. Breakthrough infection was featured by mild or no symptoms and was significantly associated with the male sex, BMI > 25, and diabetes mellitus. Some categories of HCWs (physicians and nurse aids/auxiliary personnel) were at a higher risk of breakthrough infection. Conclusions: Fully vaccinated HCWs were less likely to acquire symptomatic as well as asymptomatic SARS-CoV-2 infection. Risk factors for SARS-CoV-2 infection after a full COVID-19 vaccination scheme included the male gender, diabetes mellitus, and overweight. HCWs with higher exposure to COVID-19 patients were at higher risk of breakthrough infection.     

Angiotensin converting enzyme-2 as therapeutic target in COVID-19

The pandemic of coronavirus disease 2019 (COVID-19) is a global health emergency that poses a significant threat to world people’s health. This outbreak causes major challenges to healthcare systems. Given the lack of effective treatments or vaccine for it, the identification of novel and safe drugs against COVID-19 infection is an urgent need. Angiotensin-converting enzyme 2 (ACE2) is not only an entry receptor of the SARS-CoV-2 virus, the virus that causes COVID-19, but also can protect from lung injury. In this view, we highlighted potential approaches to address ACE2-mediated SARS-CoV-2 virus, including 1) delivering an excessive soluble form of ACE2 (recombinant human ACE2: rhACE2) and 2) inhibition of the interaction between SARS-CoV-2 virus and ACE2 by some compounds with competitive effects (morphine and codeine). Further clinical trials in this regard can reveal a more definite conclusion against the COVID-19 disaster.     

Interferon-lambda: New role in intestinal symptoms of COVID-19

The tremendous public health and economic impact of coronavirus disease 2019(COVID-19), caused by severe acute respiratory syndrome coronavirus 2(SARSCoV-2), has become a huge challenge globally. There is increasing evidence that SARS-CoV-2 induces intestinal infections. Type Ⅲ interferon(IFN-λ) has an antiviral role in intestinal infection, with focused, long-lasting, and non-inflammatory characteristics. This review presents a summary of the structure of SARSCoV-2, including its invasion and i...     

Cardiovascular Tropism and Sequelae of SARS-CoV-2 Infection

The extrapulmonary manifestation of coronavirus disease-19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), became apparent early in the ongoing pandemic. It is now recognized that cells of the cardiovascular system are targets of SARS-CoV-2 infection and associated disease pathogenesis. While some details are emerging, much remains to be understood pertaining to the mechanistic basis by which SARS-CoV-2 contributes to acute and chronic manifestations of COVID-19. This knowledge has the potential to improve clinical management for the growing populations of patients impacted by COVID-19. Here, we review the epidemiology and pathophysiology of cardiovascular sequelae of COVID-19 and outline proposed disease mechanisms, including direct SARS-CoV-2 infection of major cardiovascular cell types and pathogenic effects of non-infectious viral particles and elicited inflammatory mediators. Finally, we identify the major outstanding questions in cardiovascular COVID-19 research.     

Liver injury in COVID-19: A minireview

Coronavirus disease 2019 (COVID-19), caused by infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has escalated into a global tragedy afflicting human health, life, and social governance. Through the increasing depth of research and a better understanding of this disease, it has been ascertained that, in addition to the lungs, SARS-CoV-2 can also induce injuries to other organs including the liver. Liver injury is a common clinical manifestation of COVID-19, particularly in severe cases, and is often associated with a poorer prognosis and higher severity of COVID-19. This review focuses on the general existing information on liver injury caused by COVID-19, including risk factors and subpopulations of liver injury in COVID-19, the association between preexisting liver diseases and the severity of COVID-19, and the potential mechanisms by which SARS-CoV-2 affects the liver. This review may provide some useful information for the development of therapeutic and preventive strategies for COVID-19-associated liver injury.     

Impaired coagulation,liver dysfunction and COVID-19: Discovering an intriguing relationship

Coronavirus disease 2019 (COVID-19) is, at present, one of the most relevant global health problems. In the literature hepatic alterations have been described in COVID-19 patients, and they are mainly represented by worsening of underlying chronic liver disease leading to hepatic decompensation and liver failure with higher mortality. Several potential mechanisms used by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to cause liver damage have been hypothesized. COVID-19 primary liver injury is less common than secondary liver injury. Most of the available data demonstrate how liver damage in SARS-CoV-2 infection is likely due to systemic inflammation, and it is less likely mediated by a cytopathic effect directed on liver cells. Moreover, liver alterations could be caused by hypoxic injury and drugs (antibiotics and non-steroidal anti-inflammatory drugs, remdesivir, tocilizumab, tofacitinib and dexamethasone). SARS-CoV-2 infection can induce multiple vascular district atherothrombosis by affecting simultaneously cerebral, coronary and peripheral vascular beds. Data in the literature highlight how the virus triggers an exaggerated immune response, which added to the cytopathic effect of the virus can induce endothelial damage and a prothrombotic dysregulation of hemostasis. This leads to a higher incidence of symptomatic and confirmed venous thrombosis and of pulmonary embolisms, especially in central, lobar or segmental pulmonary arteries, in COVID-19. There are currently fewer data for arterial thrombosis, while myocardial injury was identified in 7%-17% of patients hospitalized with SARS-CoV-2 infection and 22%-31% in the intensive care unit setting. Available data also revealed a higher occurrence of stroke and more serious forms of peripheral arterial disease in COVID-19 patients. Hemostasis dysregulation is observed during the COVID-19 course. Lower platelet count, mildly increased prothrombin time and increased D-dimer are typical laboratory features of patients with severe SARS-CoV-2 infection, described as “COVID-19 associated coagulopathy.” These alterations are correlated to poor outcomes. Moreover, patients with severe SARS-CoV-2 infection are characterized by high levels of von Willebrand factor with subsequent ADAMTS13 deficiency and impaired fibrinolysis. Platelet hyperreactivity, hypercoagulability and hypofibrinolysis during SARS-CoV-2 infection induce a pathological state named as “immuno-thromboinflammation.” Finally, liver dysfunction and coagulopathy are often observed at the same time in patients with COVID-19. The hypothesis that liver dysfunction could be mediated by microvascular thrombosis has been supported by post-mortem findings and extensive vascular portal and sinusoidal thrombosis observation. Other evidence has shown a correlation between coagulation and liver damage in COVID-19, underlined by the transaminase association with coagulopathy, identified through laboratory markers such as prothrombin time, international normalized ratio, fibrinogen, D-dimer, fibrin/fibrinogen degradation products and platelet count. Other possible mechanisms like immunogenesis of COVID-19 damage or massive pericyte activation with consequent vessel wall fibrosis have been suggested.     

Doxycycline Inhibition of a Pseudotyped Virus Transduction Does Not Translate to Inhibition of SARS-CoV-2 Infectivity

The rapid spread of the pandemic caused by the SARS-CoV-2 virus has created an unusual situation, with rapid searches for compounds to interfere with the biological processes exploited by the virus. Doxycycline, with its pleiotropic effects, including anti-viral activity, has been proposed as a therapeutic candidate for COVID-19 and about twenty clinical trials have started since the beginning of the pandemic. To gain information on the activity of doxycycline against SARS-CoV-2 infection and clarify some of the conflicting clinical data published, we designed in vitro binding tests and infection studies with a pseudotyped virus expressing the spike protein, as well as a clinically isolated SARS-CoV-2 strain. Doxycycline inhibited the transduction of the pseudotyped virus in Vero E6 and HEK-293 T cells stably expressing human receptor angiotensin-converting enzyme 2 but did not affect the entry and replication of SARS-CoV-2. Although this conclusion is apparently disappointing, it is paradigmatic of an experimental approach aimed at developing an integrated multidisciplinary platform which can shed light on the mechanisms of action of potential anti-COVID-19 compounds. To avoid wasting precious time and resources, we believe very stringent experimental criteria are needed in the preclinical phase, including infectivity studies with clinically isolated SARS-CoV-2, before moving on to (futile) clinical trials.     

Human ACE2 Polymorphisms from Different Human Populations Modulate SARS-CoV-2 Infection

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in over 6 million deaths worldwide. The high variability in COVID-19 symptoms remains one of the most interesting mysteries of the pandemic. Genetic and environmental factors are likely to be key determinants of COVID-19 symptomatology. Here, we explored ACE2 as a genetic determinant for SARS-CoV-2 infection and COVID-19 symptomatology. Each human genome encodes two alleles of ACE2, which encodes the cell entry receptor for SARS-CoV-2. Here, we determined whether naturally occurring human ACE2 (hACE2) polymorphisms in the human population affect SARS-CoV-2 infection and the severity of COVID-19 symptoms. ACE2 variants S19P, I21V, E23K, K26R, K31R, N33I, H34R, E35K, and T92I showed increased virus infection compared to wild-type ACE2; thus, these variants could increase the risk for COVID-19. In contrast, variants D38V, Y83H, I468V, and N638S showed reduced infection, indicating a potential protective effect. hACE2 variants K26R and T92I increased infection by three-fold without changing the levels of ACE2 on the surface of the cells, suggesting that these variants may increase the risk of severe COVID-19. On the contrary, hACE2 variants D38V and Y83H decreased SARS-CoV-2 infection by four- and ten-fold, respectively, without changing surface expression, suggesting that these variants may protect against severe COVID-19. Remarkably, all protective hACE2 Polymorphisms were found almost exclusively in Asian populations, which may provide a partial explanation for the low COVID-19 mortality rates in Asian countries. Thus, hACE2 polymorphisms may modulate susceptibility to SARS-CoV-2 in the host and partially account for the differences in severity of COVID-19 among different ethnic groups.     

应高度关注新型冠状病毒肺炎合并的心血管系统损伤

新型冠状病毒感染引起的疫情已成为全球性重大突发公共卫生事件,其典型临床表现以呼吸系统症状为主,但对心血管系统造成的危害已有报道,不容忽视。该病毒感染可引起哪些心血管损伤?机制是什么?如何防治这种病毒感染所带来的心血管损伤?如何对心血管疾病合并新型冠状病毒感染患者规范心血管药物的使用?这些问题亟待深入研究。本刊从这一期开始连续两期开辟"新型冠状病毒感染及心血管损伤专栏",特邀相关领域专家对这些问题进行阐述和临床观察报告,旨在加深对新型冠状病毒病及其心血管损伤的认识,提高防治水平。     

COVID-19 and comorbidities of hepatic diseases in a global perspective

The worldwide outbreak of coronavirus disease 2019 (COVID-19) has challenged the priorities of healthcare system in terms of different clinical management and infection transmission, particularly those related to hepatic-disease comorbidities. Epidemiological data evidenced that COVID-19 patients with altered liver function because of hepatitis infection and cholestasis have an adverse prognosis and experience worse health outcomes. COVID-19-associated liver injury is correlated with various liver diseases following a severe acute respiratory syndrome-coronavirus type 2 (SARS-CoV-2) infection that can progress during the treatment of COVID-19 patients with or without pre-existing liver disease. SARS-CoV-2 can induce liver injury in a number of ways including direct cytopathic effect of the virus on cholangiocytes/hepatocytes, immune-mediated damage, hypoxia, and sepsis. Indeed, immediate cytopathogenic effects of SARS-CoV-2 via its potential target, the angiotensin-converting enzyme-2 receptor, which is highly expressed in hepatocytes and cholangiocytes, renders the liver as an extra-respiratory organ with increased susceptibility to pathological outcomes. But, underlying COVID-19-linked liver disease pathogenesis with abnormal liver function tests (LFTs) is incompletely understood. Hence, we collated COVID-19-associated liver injuries with increased LFTs at the nexus of pre-existing liver diseases and COVID-19, and defining a plausible pathophysiological triad of COVID-19, hepatocellular damage, and liver disease. This review summarizes recent findings of the exacerbating role of COVID-19 in pre-existing liver disease and vice versa as well as international guidelines of clinical care, management, and treatment recommendations for COVID-19 patients with liver disease.     

Resveratrol and Pterostilbene Inhibit SARS-CoV-2 Replication in Air–Liquid Interface Cultured Human Primary Bronchial Epithelial Cells

The current COVID-19 pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has an enormous impact on human health and economy. In search for therapeutic options, researchers have proposed resveratrol, a food supplement with known antiviral, anti-inflammatory, and antioxidant properties as an advantageous antiviral therapy for SARS-CoV-2 infection. Here, we provide evidence that both resveratrol and its metabolically more stable structural analog, pterostilbene, exhibit potent antiviral properties against SARS-CoV-2 in vitro. First, we show that resveratrol and pterostilbene antiviral activity in African green monkey kidney cells. Both compounds actively inhibit virus replication within infected cells as reduced virus progeny production was observed when the compound was added at post-inoculation conditions. Without replenishment of the compound, antiviral activity was observed up to roughly five rounds of replication, demonstrating the long-lasting effect of these compounds. Second, as the upper respiratory tract represents the initial site of SARS-CoV-2 replication, we also assessed antiviral activity in air–liquid interface (ALI) cultured human primary bronchial epithelial cells, isolated from healthy volunteers. Resveratrol and pterostilbene showed a strong antiviral effect in these cells up to 48 h post-infection. Collectively, our data indicate that resveratrol and pterostilbene are promising antiviral compounds to inhibit SARS-CoV-2 infection. Because these results represent laboratory findings in cells, we advocate evaluation of these compounds in clinical trials before statements are made whether these drugs are advantageous for COVID-19 treatment.     

Impact of chronic liver disease on SARS-CoV-2 infection outcomes: Roles of stage,etiology and vaccination

Since the first identification in December of 2019 and the fast spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, it has represented a dramatic global public health concern. Though affecting mainly the respiratory system, SARS-CoV-2 disease, defined as coronavirus disease 2019 (COVID-19), may have a systemic involvement leading to multiple organ dysfunction. Experimental evidence about the SARS-CoV-2 tropism for the liver and the increasing of hepatic cytolysis enzymes during infection support the presence of a pathophysiological relationship between liver and SARS-CoV-2. On the other side, patients with chronic liver disease have been demonstrated to have a poor prognosis with COVID-19. In particular, patients with liver cirrhosis appear extremely vulnerable to infection. Moreover, the etiology of liver disease and the vaccination status could affect the COVID-19 outcomes. This review analyzes the impact of the disease stage and the related causes on morbidity and mortality, clinical outcomes during SARS-CoV-2 infection, as well as the efficacy of vaccination in patients with chronic liver disease.     

COVID-19 cynomolgus macaque model reflecting human COVID-19 pathological conditions

The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global threat to human health and life. A useful pathological animal model accurately reflecting human pathology is needed to overcome the COVID-19 crisis. In the present study, COVID-19 cynomolgus monkey models including monkeys with underlying diseases causing severe pathogenicity such as metabolic disease and elderly monkeys were examined. Cynomolgus macaques with various clinical conditions were intranasally and/or intratracheally inoculated with SARS-CoV-2. Infection with SARS-CoV-2 was found in mucosal swab samples, and a higher level and longer period of viral RNA was detected in elderly monkeys than in young monkeys. Pneumonia was confirmed in all of the monkeys by computed tomography images. When monkeys were readministrated SARS-CoV-2 at 56 d or later after initial infection all of the animals showed inflammatory responses without virus detection in swab samples. Surprisingly, in elderly monkeys reinfection showed transient severe pneumonia with increased levels of various serum cytokines and chemokines compared with those in primary infection. The results of this study indicated that the COVID-19 cynomolgus monkey model reflects the pathophysiology of humans and would be useful for elucidating the pathophysiology and developing therapeutic agents and vaccines.

At the end of 2019, cases of infection with a novel coronavirus, later named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), that causes various respiratory symptoms expanded globally from China. On 11 March 2020, the World Health Organization declared a pandemic status based on the spread of infection worldwide and increase in the number of deaths. The outbreak of SARS-CoV-2 has resulted in a miserable reality for global health and life, and infection cases are continuing to increase worldwide. A detailed understanding of pathological conditions and development of effective therapeutic agents are needed to overcome the pandemic of diseases caused by SARS-CoV-2 infection, which has been named COVID-19. A new strategy including the development of pharmaceutical products and the use of appropriate animal models reflecting the human pathogenesis of COVID-19 is required.The common clinical features of COVID-19 are respiratory symptoms associated with pneumonia including fever, cough, myalgia, fatigue, dyspnea, and lymphopenia (1). COVID-19 symptoms range from no symptoms to severe symptoms. COVID-19 has shown severe pathogenicity in people with underlying diseases and in elderly people (2, 3). The period from onset of COVID-19 symptoms to death varies depending on the age of the patient and underlying disease status of the patient (4). Therefore, in addition to elucidating the pathological features in healthy individuals, it is necessary to elucidate the pathological conditions in patients with underlying diseases and in elderly patients.Cynomolgus monkeys (CMs), which are common laboratory animals among nonhuman primates (NHPs), show various human-like characteristics, including higher brain functions, long life span, single pregnancy, and regular menstrual periods, which are not found in other experimental animals. In the present study, COVID-19 model CMs, including healthy young CMs, elderly CMs (23 to 30 y of age, equivalent to 69 to 90 y of age in humans), and CMs with underlying diseases including diabetes and hyperlipidemia were experimentally infected with SARS-CoV-2 as animal models reflecting human pathology.     

Interaction between hepatitis B virus and SARS-CoV-2 infections

Coronavirus disease 2019(COVID-19)has become a global pandemic and garnered international attention.The causative pathogen of COVID-19 is severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),a novel,highly contagious coronavirus.Numerous studies have reported that liver injury is quite common in patients with COVID-19.Hepatitis B has a worldwide distribution as well as in China.At present,hepatitis B virus(HBV)remains a leading cause of cirrhosis,liver failure,and hepatocellular carcinoma.Because both viruses challenge liver physiology,it raises questions as to how coinfection with HBV and SARS-CoV-2 affect disease progression and mortality.Is there an increased risk of COVID-19 in patients with HBV infection?In this review,we summarize the current reports of SARS-CoV-2 and HBV coinfection and elaborate the interaction of the two diseases.The emphasis was placed on evaluating the impact of HBV infection on disease severity and clinical outcomes in patients with COVID-19 and discussing the potential mechanism behind this effect.     

Implications of the Immune Polymorphisms of the Host and the Genetic Variability of SARS-CoV-2 in the Development of COVID-19

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for the current pandemic affecting almost all countries in the world. SARS-CoV-2 is the agent responsible for coronavirus disease 19 (COVID-19), which has claimed millions of lives around the world. In most patients, SARS-CoV-2 infection does not cause clinical signs. However, some infected people develop symptoms, which include loss of smell or taste, fever, dry cough, headache, severe pneumonia, as well as coagulation disorders. The aim of this work is to report genetic factors of SARS-CoV-2 and host-associated to severe COVID-19, placing special emphasis on the viral entry and molecules of the immune system involved with viral infection. Besides this, we analyze SARS-CoV-2 variants and their structural characteristics related to the binding to polymorphic angiotensin-converting enzyme type 2 (ACE2). Additionally, we also review other polymorphisms as well as some epigenetic factors involved in the immunopathogenesis of COVID-19. These factors and viral variability could explain the increment of infection rate and/or in the development of severe COVID-19.     

Mechanisms of gastrointestinal barrier dysfunction in COVID-19 patients

Coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a major global public health event, resulting in a significant social and economic burden. Although COVID-19 was initially characterized as an upper respiratory and pulmonary infection, recent evidence suggests that it is a complex disease including gastrointestinal symptoms, such as diarrhea, nausea, and vomiting. Moreover, it remains unclear whether the gastrointestinal symptoms are caused by direct infection of the gastrointestinal tract by SARS-CoV-2 or are the result of systemic immune activation and subsequent dysregulation of homeostatic mechanisms. This review provides a brief overview of the mechanisms by which SARS-CoV-2 disrupts the integrity of the gastrointestinal barrier including the mechanical barrier, chemical barrier, microbial barrier, and immune barrier.     

Pandémie COVID-19 : impact sur le systeme cardiovasculaire. Données disponibles au 1er avril 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells with angiotensin receptors, leading to pneumonia linked to COVID-19. The virus has a double impact on the cardiovascular system, the infection will be more intense if the host has cardiovascular co-morbidities and the virus can cause life-threatening cardiovascular lesions. Therapies associated with COVID-19 may have adverse cardiovascular effects. Therefore, special attention should be given to cardiovascular protection during COVID-19 infection.     

Anakinra,una alternativa potencial en el tratamiento de la infección respiratoria grave por SARS-CoV-2 refractaria a tocilizumab

SARS-CoV-2 is a new RNA virus which causes coronavirus disease 2019 (COVID-19), declared a pandemic by the World Health Organization (WHO). It triggers an atypical pneumonia that can progress to multiorgan failure. COVID-19 can cause dysregulation of the immune system, triggering an inflammatory response, and simulate haemophagocytic lymphohistiocytosis. Several studies have proposed that anti-IL-6 receptor antibodies, such as tocilizumab, play an important role in the treatment of severe acute respiratory infection associated with SARS-CoV-2. However, the role of anti-IL-1 receptor antibodies, such as anakinra, in the treatment of COVID-19 has not been established.We present a case report of a 51-year-old man diagnosed with severe respiratory infection associated with SARS-CoV-2 that was refractory to antiviral and anti-IL-6 treatment, with a favourable clinical outcome and analytical improvement after treatment with anti-IL-1 (anakinra).     

Ferristatin II Efficiently Inhibits SARS-CoV-2 Replication in Vero Cells

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to have a significant impact on global public health. Multiple mechanisms for SARS-CoV-2 cell entry have been described; however, the role of transferrin receptor 1 (TfR1) in SARS-CoV-2 infection has received little attention. We used ferristatin II to induce the degradation of TfR1 on the surface of Vero cells and to study the consequences of such treatment on the viability of the cells and the replication of SARS-CoV-2. We demonstrated that ferristatin II is non-toxic for Vero cells in concentrations up to 400 µM. According to confocal microscopy data, the distribution of the labeled transferrin and receptor-binding domain (RBD) of Spike protein is significantly affected by the 18h pretreatment with 100 µM ferristatin II in culture medium. The uptake of RBD protein is nearly fully inhibited by ferristatin II treatment, although this protein remains bound on the cell surface. The findings were well confirmed by the significant inhibition of the SARS-CoV-2 infection of Vero cells by ferristatin II with IC₅₀ values of 27 µM (for Wuhan D614G virus) and 40 µM (for Delta virus). A significant reduction in the infectious titer of the Omicron SARS-CoV-2 variant was noted at a ferristatin II concentration as low as 6.25 µM. We hypothesize that ferristatin II blocks the TfR1-mediated SARS-CoV-2 host cell entry; however, further studies are needed to elucidate the full mechanisms of this virus inhibition, including the effect of ferristatin II on other SARS-CoV-2 receptors, such as ACE2, Neuropilin-1 and CD147. The inhibition of viral entry by targeting the receptor on the host cells, rather than the viral mutation-prone protein, is a promising COVID-19 therapeutic strategy.     

Current understanding of the impact of COVID-19 on gastrointestinal disease: Challenges and openings

The novel coronavirus disease-2019(COVID-19)is caused by a positive-sense single-stranded RNA virus which belongs to the Coronaviridae family.In March 2019 the World Health Organization declared that COVID-19 was a pandemic.COVID-19 patients typically have a fever,dry cough,dyspnea,fatigue,and anosmia.Some patients also report gastrointestinal(GI)symptoms,including diarrhea,nausea,vomiting,and abdominal pain,as well as liver enzyme abnormalities.Surprisingly,many studies have found severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)viral RNA in rectal swabs and stool specimens of asymptomatic COVID-19 patients.In addition,viral receptor angiotensin-converting enzyme 2 and transmembrane protease serine-type 2,were also found to be highly expressed in gastrointestinal epithelial cells of the intestinal mucosa.Furthermore,SARS-CoV-2 can dynamically infect and replicate in both GI and liver cells.Taken together these results indicate that the GI tract is a potential target of SARS-CoV-2.Therefore,the present review summarizes the vital information available to date on COVID-19 and its impact on GI aspects.