ACE2--Molecular speculations on abdominal symptoms after COVID-19 infection

Viral Infection ◽

Clinical Manifestations ◽

Gastrointestinal Symptoms ◽

Converting Enzyme ◽

Abdominal Symptoms ◽

The Difference ◽

Organ Infection

There is growing evidence that the clinical manifestations of COVID-19 are not just respiratory, but also gastrointestinal symptoms. The difference of organ infection should be considered. In addition, as a key molecule mediating viral infection of cells, angiotensin-converting enzyme 2 (ACE2) provides an important intervention means for the exploration of antivirus. This is particularly important as the pandemic intensifies.

Differential Virological and Immunological Outcome of Severe Acute Respiratory Syndrome Coronavirus Infection in Susceptible and Resistant Transgenic Mice Expressing Human Angiotensin-Converting Enzyme 2

Journal of Virology ◽

10.1128/jvi.02272-08 ◽

2009 ◽

Vol 83 (11) ◽

pp. 5451-5465 ◽

Cited By ~ 24

Author(s):

Naoko Yoshikawa ◽

Tomoki Yoshikawa ◽

Terence Hill ◽

Cheng Huang ◽

Douglas M. Watts ◽

...

Keyword(s):

T Cells ◽

Viral Infection ◽

Inflammatory Responses ◽

Fatal Outcome ◽

Converting Enzyme ◽

Inflammatory Infiltrates ◽

The Brain

ABSTRACT We previously reported that transgenic (Tg) mice expressing human angiotensin-converting enzyme 2 (hACE2), the receptor for severe acute respiratory syndrome coronavirus (SARS-CoV), were highly susceptible to SARS-CoV infection, which resulted in the development of disease of various severity and even death in some lineages. In this study, we further characterized and compared the pathogeneses of SARS-CoV infection in two of the most stable Tg lineages, AC70 and AC22, representing those susceptible and resistant to the lethal SARS-CoV infection, respectively. The kinetics of virus replication and the inflammatory responses within the lungs and brains, as well as the clinical and pathological outcomes, were assessed in each lineage. In addition, we generated information on lymphocyte subsets and mitogen-mediated proliferation of splenocytes. We found that while both lineages were permissive to SARS-CoV infection, causing elevated secretion of many inflammatory mediators within the lungs and brains, viral infection appeared to be more intense in AC70 than in AC22 mice, especially in the brain. Moreover, such infection was accompanied by a more profound immune suppression in the former, as evidenced by the extensive loss of T cells, compromised responses to concanavalin A stimulation, and absence of inflammatory infiltrates within the brain. We also found that CD8+ T cells were partially effective in attenuating the pathogenesis of SARS-CoV infection in lethality-resistant AC22 mice. Collectively, our data revealed a more intense viral infection and immunosuppression in AC70 mice than in AC22 mice, thereby providing us with an immunopathogenic basis for the fatal outcome of SARS-CoV infection in the AC70 mice.

Gastrointestinal and kidney manifestations in SARS-CoV and SARS-CoV-2 infections: role of angiotensin-converting enzyme 2

Physiology and Pharmacology ◽

10.32598/ppj.25.1.100 ◽

2020 ◽

Vol 25 (1) ◽

pp. 7-20

Author(s):

Fatemeh Maghool ◽

◽

Mohammad Hassan Emami ◽

Samaneh Mohammadzadeh ◽

Aida Heidari ◽

...

Keyword(s):

Gastrointestinal Symptoms ◽

Renin Angiotensin System ◽

Structural Similarity ◽

Clinical Feature ◽

Converting Enzyme ◽

Kidney Impairment

The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in 2020, which has a substantial structural similarity to severe acute respiratory syndrome coronavirus (SARS-CoV) that caused the outbreak in 2003, is currently a threat to global health. Lung involvement is the principal clinical feature in infected patients but extra-pulmonary clinical presentations are also common. The reasons for the extensive involvement of other organs are not yet clear. Angiotensin-converting enzyme 2 (ACE2), the key peptide of renin–angiotensin system (RAS), has recently identified as a major receptor for the both SARS-CoV and SARS-CoV-2 that might be a main target of coronavirus infection. ACE2 is mainly expressed in the pulmonary pneumocytes, the small intestine enterocytes as well as the proximal tubule epithelial cells of the kidneys. In addition to the respiratory tract infection symptoms, the noticeable prevalence of gastrointestinal symptoms as well as kidney impairment in hospitalized infected patients highlights other routes of infection/transmission. In present review, we discussed the role of RAS with emphasis on ACE2 in the pathogenesis of SARS-CoV and SARS-CoV-2, particularly in gastrointestinal and kidney manifestations of the diseases.

Severe Acute Respiratory Syndrome Coronavirus Infection of Mice Transgenic for the Human Angiotensin-Converting Enzyme 2 Virus Receptor

Journal of Virology ◽

10.1128/jvi.01702-06 ◽

2006 ◽

Vol 81 (3) ◽

pp. 1162-1173 ◽

Cited By ~ 122

Author(s):

Chien-Te K. Tseng ◽

Cheng Huang ◽

Patrick Newman ◽

Nan Wang ◽

Krishna Narayanan ◽

...

Keyword(s):

Weight Loss ◽

Transgenic Mice ◽

Virus Replication ◽

Clinical Manifestations ◽

Converting Enzyme ◽

Sars Coronavirus ◽

Coronavirus Infection

ABSTRACT Animal models for severe acute respiratory syndrome (SARS) coronavirus infection of humans are needed to elucidate SARS pathogenesis and develop vaccines and antivirals. We developed transgenic mice expressing human angiotensin-converting enzyme 2, a functional receptor for the virus, under the regulation of a global promoter. A transgenic lineage, designated AC70, was among the best characterized against SARS coronavirus infection, showing weight loss and other clinical manifestations before reaching 100% mortality within 8 days after intranasal infection. High virus titers were detected in the lungs and brains of transgene-positive (Tg+) mice on days 1 and 3 after infection. Inflammatory mediators were also detected in these tissues, coinciding with high levels of virus replication. Lower virus titers were also detected in other tissues, including blood. In contrast, infected transgene-negative (Tg−) mice survived without showing any clinical illness. Pathologic examination suggests that the extensive involvement of the central nervous system likely contributed to the death of Tg+ mice, even though viral pneumonia was present. Preliminary studies with mice of a second lineage, AC63, in which the transgene expression was considerably less abundant than that in the AC70 line, revealed that virus replication was largely restricted to the lungs but not the brain. Importantly, despite significant weight loss, infected Tg+ AC63 mice eventually recovered from the illness without any mortality. The severity of the disease that developed in these transgenic mice—AC70 in particular—makes these mouse models valuable not only for evaluating the efficacy of antivirals and vaccines, but also for studying SARS coronavirus pathogenesis.

COVID-19 and Liver injury: hepatology perspectives

Clinical Medical Reviews and Reports ◽

10.31579/2690-8794/020 ◽

2020 ◽

Vol 2 (3) ◽

pp. 01-04

Author(s):

Irami Filho

Keyword(s):

Liver Disease ◽

Liver Injury ◽

Liver Damage ◽

Clinical Manifestations ◽

Protein S ◽

Clinical Syndrome ◽

Converting Enzyme ◽

Angiotensin Converting Enzyme 2

SARS-CoV-2, a severe acute respiratory syndrome caused by Coronavirus 2, discovered in 2019 in China, is responsible for the current pandemic declared by the WHO since March 2020. The clinical syndrome caused by Covid-19 has a broad spectrum of severity. The most common clinical manifestations are fever, dry cough, dyspnea, fatigue, and anosmia. The virus binds to receptors for angiotensin-converting enzyme 2 (ECA2) and serine protease TMPRSS2 for protein S initiation, which are expressed not only in the lungs but also in the liver, colonic, esophageal and biliary epithelial cells. In this context, the liver is a potential target for COVID-19 infection. Liver damage occurs during the course and treatment of viral infection in patients with or without previous liver disease. Therefore, the characteristics of liver injury associated with COVID-19 were reviewed based on research related, in the context of the pandemic.

A New Perspective of COVID-19 Infection: An Epigenetics Point of View

Global Medical Genetics ◽

10.1055/s-0041-1736565 ◽

2021 ◽

Author(s):

Ziya Ozturkler ◽

Rasime Kalkan

Keyword(s):

Virus Infection ◽

Viral Infection ◽

Epigenetic Modifications ◽

Point Of View ◽

Converting Enzyme ◽

Viral Response ◽

Coronavirus Infection ◽

New Perspective

AbstractCoronavirus disease 2019 (COVID-2019) started in Wuhan, China, in December 2019. Angiotensin-converting enzyme 2 (ACE2) receptor was one of the most important genes related to the entrance of the virus to the host. Until now, several variations have been identified in ACE2 and related transmembrane protease serine 2. Epigenetic modifications not only play an important role during the maintenance of genome and cellular homoeostasis but also for the etiopathophysiology of the virus infection. Studies showed methylation of ACE2 was changed to depend on host and age of the host during the viral infection.In this study, we provide an epigenetics point of view to the coronavirus infection. We highlight the importance of epigenetic modifications during viral replication and infection and their interaction with COVID-19 susceptibility and host viral response.

Gejala Gastrointestinal pada Pasien COVID-19

e-CliniC ◽

10.35790/ecl.v9i2.32851 ◽

2021 ◽

Vol 9 (2) ◽

pp. 279

Author(s):

Kristianty T Silangen ◽

Bradley J Waleleng ◽

Frans E. N. Wantania

Keyword(s):

Abdominal Pain ◽

Literature Review ◽

Gastrointestinal Symptoms ◽

Hepatic Function ◽

Converting Enzyme ◽

Impaired Liver Function ◽

Stomach Pain ◽

Using Data

Abstract: Patients suffering from corona virus desease of 2019 (COVID-19) could have gastro-intestinal symptoms such as diarrhea, vomiting, and stomach pain. Studies show that human receptor for COVID-19 namely the angiotensin-converting enzyme 2 (ACE2) receptors are also expressed in small intestinal epithelial cells. This study was aimed to determine the gastrointestinal symptoms often found in patients with COVID-19. This was a literature review study using data-bases of Google Scholar, the keywords were (“Covid” AND “gastrointestinal symptoms”), and filtering data by time 2019-2020. The results obtained 10 literatures that fulfilled the inclusion and exclusion criteria. The review obtained that viral infection causes changes in intestinal permeability. SARS-CoV was also identified in ileal and terminal colon biopsy. Gastrointestinal symptoms are accompanied by inflammation of the intestines. The highest percentage of gastrointestinal symptoms were anorexia, followed by diarrhea, nausea/vomiting, abdominal pain. Gastrointestinal symptoms could be the first symptoms or even the only symptoms that appeared in Covid-19 patients. Gastrointestinal symptoms were also associated by impaired hepatic function. In conclusion, gastrointestinal symptoms in Covid-19 patients had a relatively high prevalence, and often appeared as anorexia, diarrhea, nausea/vomiting, and abdominal pain. Some of these symptoms were related to the severe course of Covid-19. Impaired liver function also exacerbated these symptoms as well as a marker of a poor clinical course of Covid-19. Keywords: COVID-19, gastrointestinal symptoms Abstrak: Penderita COVID-19 dapat disertai gejala gastrointestinal seperti diare, muntah, dan sakit perut. Studi menunjukkan bahwa reseptor manusia untuk COVID-19 yaitu reseptor angiotensin-converting enzyme 2 (ACE2) diekspresikan juga dalam sel epitel usus kecil. Penelitian ini bertujuan untuk mengetahui gejala gastrointestinal yang sering ditemukan pada pasien dengan COVID-19. Jenis penelitian ialah literature review yang menggunakan database Google Cendekia, dan kata kunci (“Covid” DAN “gejala gastrointestinal”) dengan filter rentang waktu tahun 2019-2020 Hasil penelitian mendapatkan 10 literatur yang memenuhi kriteria inklusi dan eksklusi penelitian. Kajian mendapatkan infeksi virus menyebabkan perubahan permeabilitas usus. SARS-CoV juga diidentifikasi pada biopsi ileum dan kolon terminal. Masalah usus dikaitkan dengan tingkat keparahan infeksi. Gejala gastrointestinal disertai dengan peradangan atau kerusakan usus. Beberapa penelitian menunjukkan persentase gejala gastrointestinal tertinggi ialah anoreksia, diikuti diare, mual/muntah, dan terakhir nyeri perut. Juga disebutkan bahwa gejala gastrointestinal dapat merupakan yang pertama muncul atau bahkan satu-satunya gejala pada pasien Covid-19. Gejala gastrointestinal juga dikaitkan dengan gangguan fungsi hati. Simpulan penelitian ini ialah gejala gastrointestinal pada pasien Covid-19 memiliki prevalensi yang relatif tinggi dan sering berupa anoreksia, diare, mual/muntah, dan nyeri perut. Beberapa gejala tersebut berhubungan dengan perjalanan Covid-19 yang berat. Gangguan fungsi hati juga turut memper-berat gejala tersebut sekaligus menjadi penanda perjalanan klinis yang buruk dari Covid-19.Kata kunci: COVID-19, gejala gastrointestinal

Combination of Angiotensin (1-7) Agonists and Convalescent Plasma as a New Strategy to Overcome Angiotensin Converting Enzyme 2 (ACE2) Inhibition for the Treatment of COVID-19

Frontiers in Medicine ◽

10.3389/fmed.2021.620990 ◽

2021 ◽

Vol 8 ◽

Author(s):

Hawraa Issa ◽

Ali H. Eid ◽

Bassam Berry ◽

Vahideh Takhviji ◽

Abbas Khosravi ◽

...

Keyword(s):

Viral Infection ◽

Viral Entry ◽

The Body ◽

Protective Effects ◽

Ang Ii ◽

Converting Enzyme ◽

Neutralizing Capacity ◽

New Strategy

Coronavirus disease-2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently the most concerning health problem worldwide. SARS-CoV-2 infects cells by binding to angiotensin-converting enzyme 2 (ACE2). It is believed that the differential response to SARS-CoV-2 is correlated with the differential expression of ACE2. Several reports proposed the use of ACE2 pharmacological inhibitors and ACE2 antibodies to block viral entry. However, ACE2 inhibition is associated with lung and cardiovascular pathology and would probably increase the pathogenesis of COVID-19. Therefore, utilizing ACE2 soluble analogs to block viral entry while rescuing ACE2 activity has been proposed. Despite their protective effects, such analogs can form a circulating reservoir of the virus, thus accelerating its spread in the body. Levels of ACE2 are reduced following viral infection, possibly due to increased viral entry and lysis of ACE2 positive cells. Downregulation of ACE2/Ang (1-7) axis is associated with Ang II upregulation. Of note, while Ang (1-7) exerts protective effects on the lung and cardiovasculature, Ang II elicits pro-inflammatory and pro-fibrotic detrimental effects by binding to the angiotensin type 1 receptor (AT1R). Indeed, AT1R blockers (ARBs) can alleviate the harmful effects associated with Ang II upregulation while increasing ACE2 expression and thus the risk of viral infection. Therefore, Ang (1-7) agonists seem to be a better treatment option. Another approach is the transfusion of convalescent plasma from recovered patients with deteriorated symptoms. Indeed, this appears to be promising due to the neutralizing capacity of anti-COVID-19 antibodies. In light of these considerations, we encourage the adoption of Ang (1-7) agonists and convalescent plasma conjugated therapy for the treatment of COVID-19 patients. This therapeutic regimen is expected to be a safer choice since it possesses the proven ability to neutralize the virus while ensuring lung and cardiovascular protection through modulation of the inflammatory response.

Genetic Variability of Human Angiotensin-Converting Enzyme 2 (hACE2) Among Various Ethnic Populations

10.1101/2020.04.14.041434 ◽

2020 ◽

Cited By ~ 4

Author(s):

Quan Li ◽

Zanxia Cao ◽

Proton Rahman

Keyword(s):

Missense Mutations ◽

Converting Enzyme ◽

East Asians ◽

Binding Characteristics ◽

Functional Studies ◽

Ethnic Populations ◽

The Difference

AbstractThere appears to be large regional variations for susceptibility, severity and mortality for Covid-19 infections. We set out to examine genetic differences in the human angiotensin-converting enzyme 2 (hACE2) gene, as its receptor serves as a cellular entry for SARS- CoV-2. By comparing 56,885 Non-Finnish European and 9,197 East Asians (including 1,909 Koreans) four missense mutations were noted in the hACE2 gene. Molecular dynamic demonstrated that two of these variants (K26R and I468V) may affect binding characteristics between S protein of the virus and hACE2 receptor. We also examined hACE2 gene expression in eight global populations from the HapMap3 and noted marginal differences in expression for some populations as compared to the Chinese population. However, for both of our studies, the magnitude of the difference was small and the significance is not clear in the absence of further in vitro and functional studies.

Dampak Coronavirus Disease 2019 terhadap Sistem Kardiovaskular

e-CliniC ◽

10.35790/ecl.v8i2.30540 ◽

2020 ◽

Vol 8 (2) ◽

Author(s):

Herick A. Willim ◽

Infan Ketaren ◽

Alice I. Supit

Keyword(s):

Myocardial Injury ◽

Clinical Manifestations ◽

Cardiovascular Complications ◽

Converting Enzyme ◽

Cardiovascular Comorbidity ◽

Cardiovascular Comorbidities ◽

Severe Manifestation

Abstract: Coronavirus disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection has become a pandemic. Patient with cardiovascular comorbidity has a higher risk of suffering more severe manifestation of COVID-19 associated with a higher mortality. Although dominated by respiratory clinical manifestation, COVID-19 may also cause severe cardiovascular disorders. Angiotensin converting enzyme 2 (ACE2) acts as a receptor of SARS-CoV-2. Patients of COVID-19 with cardiovascular comorbidities may experience more severe clinical manifestations, presumably due to higher ACE2 expression in this population. Cardiovascular complications in COVID-19 may include myocardial injury, myocarditis, acute myocardial infarction, acute heart failure, thromboembolism, and arrhythmias. Therefore, optimization of conservative medical therapy needs to be prioritized in patients with cardiovascular comorbidities. Emergency intervention can be considered in certain cases with hemodynamic instability.Keywords: cardiovascular system, COVID-19, SARS-CoV-2, ACE2 Abstrak: Coronavirus disease 2019 (COVID-19) telah merupakan pandemi yang disebabkan oleh infeksi Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Pasien dengan komorbid kardiovaskular berisiko lebih tinggi untuk mengalami manifestasi yang lebih berat jika terinfeksi COVID-19 dan berhubungan dengan mortalitas yang lebih tinggi. Meskipun didominasi oleh manifestasi klinis respiratorik, COVID-19 juga dapat menyebabkan gangguan kardiovaskular yang berat. Angiotensin converting enzyme 2 (ACE2) berperan sebagai reseptor SARS-CoV-2. Diduga pasien dengan penyakit kardiovaskular dapat bermanifestasi klinis lebih berat karena ekspresi ACE2 yang lebih tinggi pada populasi ini. Komplikasi kardiovaskular pada COVID-19 dapat meliputi jejas miokardium, miokarditis, infark miokard akut, gagal jantung akut, tromboemboli, dan aritmia. Pada pasien dengan komorbid kardiovaskular, optimalisasi terapi medis konservatif perlu diprioritaskan. Tindakan intervensi darurat dapat dipertimbangkan pada kasus tertentu dengan instabilitas hemodinamik.Kata kunci: sistem kardiovaskular, COVID-19, SARS-CoV-2, ACE2

The role of renin-angiotensin system and angiotensin-converting enzyme 2 (ACE2) in the development and course of viral infection COVID-19 in patients with diabetes mellitus

Diabetes Mellitus ◽

10.14341/dm12501 ◽

2020 ◽

Vol 23 (3) ◽

pp. 242-249

Author(s):

O. K. Vikulova ◽

Zamira Zuraeva ◽

L. V. Nikankina ◽

M. V. Shestakova

Keyword(s):

Diabetes Mellitus ◽

Viral Infection ◽

Ace Inhibitors ◽

Renin Angiotensin System ◽

Converting Enzyme ◽

Angiotensin System ◽

Renin Angiotensin

The role of renin-angiotensin system (RAS) in general and angiotensin-converting enzyme 2 (ACE2) in particular in the pathogenesis and course of viral infection caused by SARS-CoV-2 (COVID-19) is of particular interest. This is due not only to the fact that ACE2 is a receptor for the virus the target cells. RAS hyperactivation in patients with arterial hypertension, cardiovascular disease and diabetes mellitus, is considered one of the most important factors for a more severe infection in persons with concomitant pathology. In addition, the effects of PAS blockage with angiotensin converting enzyme inhibitors (ACE inhibitors) and angiotensin II receptor blockers (ARBs) remains one of the most discussed topics in the literature on COVID-19. Thisreview presents the data on the interaction between the virus and the main components of RAS and the factors influencing their expression level, the impact of ACE inhibitors and ARBs therapy on the disease outcome, and presents theperspectives of the treatment with recombinant ACE 2.