Angiotensin-converting enzyme 2 and COVID-19: patients, comorbidities, and therapies

Pathangey, Girish; Fadadu, Priyal; Hospodar, Alexandra Raye; Abbas, Amr E.

doi:10.1152/ajplung.00259.2020

Cited by 37 publications

(38 citation statements)

References 349 publications

(348 reference statements)

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“…Binding of SARS-CoV-2 to the angiotensin-converting enzyme 2 (ACE2) coreceptor for viral entry has focused attention on the renin-angiotensin system (RAS) in the pathophysiology of COVID-19. The prevailing hypothesis is that SARS-CoV-2-ACE2 binding/internalization increases the ratio of angiotensin II (ANG II) to ANG-(1–7) due to loss of ACE2 activity, promoting oxidative stress, inflammation, fibrosis, and increased vascular tone ( 1 , 2 ). This finding has prompted speculation on the role of the RAS as a disease modifier, and whether pharmacological manipulation of the RAS might improve outcomes in patients with COVID-19.…”

Section: Introductionmentioning

confidence: 99%

A pilot study to assess the circulating renin-angiotensin system in COVID-19 acute respiratory failure

Files

Gibbs

Schaich

et al. 2021

American Journal of Physiology-Lung Cellular and Molecular Phys

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The renin-angiotensin system (RAS) is fundamental to COVID-19 pathobiology, due to the interaction between the SARS-CoV-2 virus and the angiotensin-converting enzyme-2 (ACE2) co-receptor for cellular entry. The prevailing hypothesis is that SARS-CoV-2-ACE2 interactions lead to an imbalance of the RAS, favoring pro-inflammatory Ang II related signaling at the expense of the anti-inflammatory Ang-(1-7) mediated alternative pathway. Indeed, multiple clinical trials targeting this pathway in COVID-19 are underway. Therefore, precise measurement of circulating RAS components is critical to understand the interplay of the RAS on COVID-19 outcomes. Multiple challenges exist in measuring the RAS in COVID-19 including improper patient controls, ex-vivo degradation and low concentrations of angiotensins, and unvalidated laboratory assays. Here, we conducted a prospective pilot study to enroll thirty-three moderate and severe COVID-19 patients and physiologically matched COVID-19 negative controls to quantify the circulating RAS. Our enrollment strategy led to physiologic matching of COVID-19 negative and positive moderate hypoxic respiratory failure cohorts, in contrast to the severe COVID-19 cohort which had increased severity of illness, prolonged ICU stay and increased mortality. Circulating Ang II and Ang-(1-7) levels were measured in the low picomolar (pM) range. We found no significant differences in circulating RAS peptides or peptidases between these three cohorts. The combined moderate and severe COVID-19 positive cohorts demonstrated a mild reduction in ACE activity compared to COVID-19 negative controls (2.2±0.9x105 vs. 2.9±0.8x105 RFU/mL, p=0.03). These methods may be useful in designing larger studies to physiologically match patients and quantify the RAS in COVID-19 RAS augmenting clinical trials.

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Section: Introductionmentioning

confidence: 99%

A pilot study to assess the circulating renin-angiotensin system in COVID-19 acute respiratory failure

Files

Gibbs

Schaich

et al. 2021

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…[ 8 , 17 ] The lungs are the most affected organs because the virus accesses host cells through angiotensin-converting enzyme 2 (ACE2), which is most abundant on type II alveolar cells. [ 7 , 16 ] However, extra-respiratory manifestations of SARS-CoV-2 infection have recently been observed in the rapidly increasing number of COVID-19 cases. [ 1 , 5 , 11 , 18 ] About one-third of infected patient’s present neurological symptoms during the course of the disease and, even in some cases, neurologic symptoms may be the initial or only presentation of the COVID-19.…”

Section: Discussionmentioning

confidence: 99%

Ventricular empyema associated with severe pyogenic meningitis in COVID-19 adult patient: Case report

Meguins¹,

Rocha²,

Laurenti³

et al. 2021

Surgical Neurology International

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Background: Coronavirus Disease 2019 (COVID-19) pandemic raised global attention especially due to the severe acute respiratory symptoms associated to it. However, almost one third of patients also develop neurological symptoms. The aim of the present study is to describe the case of a previously health adult that evolved cerebral ventricular empyema in the IV ventricle during COVID-19 infection treatment. Case Description: A 49-year-old man with COVID-19 developed pneumonia caused by multidrug-resistant Acinetobacter baumannii. After treating adequate treatment, sedation was switched off without showing appropriate awakening. Brain CT was performed with evidence of communicating hydrocephalus. External ventricular shunt (EVD) was implant with intraoperative cerebrospinal fluid suggestive of meningitis with a positive culture for oxacillin-sensitive Staphylococcus hominis. Twenty days after EVD, meningitis treatment was finished and with 2 negative cultures, conversion to ventriculoperitoneal shunt was performed. In the following week, during the evaluation of the patient in intensive care, quadriplegia and absence of spontaneous respiratory movement were evidenced, just maintaining head movement. Brain MRI was performed with a diagnosis of ventriculitis associated with pus collections on the IV ventricle. The patient underwent microsurgical drainage removal of the shunt, with a positive intraventricular collection culture for Klebsiella pneumoniae carbapenemase and multidrug-resistant Pseudomonas aeruginosa, without improvement in the neurological condition. After 14 weeks of hospitalization, the patient died. Conclusion: It is well known that COVID-19 has potential to directly attack and cause severe damage to the central nervous system; however, ventricular empyema is an extremely rare life-threatening complication.

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“…The ACE-2 upregulation may increase infectiousness and therefore infection severity risk, as the SARS-COV-2 virus uses this receptor for host entry. Paradoxically, it is stated that it may be useful in protecting people from acute lung injury (Pathangey et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Correlation between Pregnancy Status and Severe Corona-Virus Disease Characterized by Cytokine Storm: Systematic Review and Meta-Analysis

Muthuka

Kiptoo

Oluoch

et al. 2021

Preprint

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Background. Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SAR2-COV-2) that identified first in Wuhan, China, in December 2019, rapidly spreading to the rest of the globe, becoming a pandemic. Some studies have eluded to an association between pregnancy status and severe COVID-19 cytokine storm, some, in contrast, have demonstrated such. The aim of the current study was to find the relationship between pregnancy status and clinical COVID-19 severity characterized by cytokine storm through a systematic review and meta-analysis approach. Methods. We searched Google Scholar, PubMed, Scopus, Web of Science, and Embase databases to identify clinical studies suitable for inclusion in this meta-analysis. Studies reporting pregnancy status and comparing the COVID-19 severity cytokine storm outcome were included. The COVID-19 severity characterized by cytokine storm was described using parameters such as; Intensive Care Unit Admission, Invasive Mechanical Ventilation, Mechanical Ventilation, Hospital Admission, Pro and Inflammatory cytokine levels, consolidation on chest CT scan, pulmonary infiltration, extreme fevers as characteristic of cytokine storm, syndromic severity, higher neutrophil count indicative of cytokine storm and severe COVI-19 presentation. Results. A total of 17 articles detailing 840332 COVID-19 women were included. Our meta-analysis revealed a relationship between positive pregnancy status and severe COVID-19 cytokine storm case (random effect model, OR=2.47; 95% CI: 1.63-3.73; P < 0.0001), with a cumulative incidence of 6432 (14.1%) among the pregnant women with COVID-19 and 24352 (3.1%) among the non-pregnant women with COVI-19. Further to this, we found that the sub-analysis between Single Centre and Multiple Centre studies demonstrated seemingly the same as heterogeneity (I2 = 72 and (I2 = 98), respectively. Sensitivity analysis on each sub-group revealed that pregnancy was significantly related to severe COVID-19 with cytokine storm from single Centre studies, (fixed effect model, OR= 3.97; 95% CI: 2.26-6.95; P< 0.00001) with very low heterogeneity (I2 = 2 %; P = 0.42). Conclusion. Being pregnant is clearly associated with experiencing a severe COVID-19 characterized by a cytokine storm. The SARS-COV-2 epidemic should serve as an impetus for pregnant women diagnosed with COVID-19, and map out salient risk factors associated with its severity. The trial is registered with the International Prospective Register of Systematic Reviews (PROSPERO) CRD42021242011.

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Angiotensin-converting enzyme 2 and COVID-19: patients, comorbidities, and therapies

Cited by 37 publications

References 349 publications

A pilot study to assess the circulating renin-angiotensin system in COVID-19 acute respiratory failure

A pilot study to assess the circulating renin-angiotensin system in COVID-19 acute respiratory failure

Ventricular empyema associated with severe pyogenic meningitis in COVID-19 adult patient: Case report

Correlation between Pregnancy Status and Severe Corona-Virus Disease Characterized by Cytokine Storm: Systematic Review and Meta-Analysis

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