Lock, Stock and Barrel: Role of Renin-Angiotensin-Aldosterone System in Coronavirus Disease 2019

Zanza, Christian; Tassi, Michele Fidel; Romenskaya, Tatsiana; Piccolella, Fabio; Abenavoli, Ludovico; Franceschi, Francesco; Piccioni, Andrea; Ojetti, Veronica; Saviano, Angela; Canonico, Barbara; Montanari, Mariele; Zamai, Loris; Artico, Marco; Robba, Chiara; Racca, Fabrizio; Longhitano, Yaroslava

doi:10.3390/cells10071752

Cited by 12 publications

(9 citation statements)

References 154 publications

(244 reference statements)

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“…In our cohort, the rate of newonset symptoms at follow-up are similar to the data shown by Taboada et al and other authors [9,28,29]. In our cohort, the principal symptom that manifested was a neurological problem such as pain or paresthesia at the extremities, demonstrating that COVID-19 infection, starting through the angiotensin-converting enzyme 2 receptor (ACE2), develops into a systemic disease, with possible endothelium dysfunction, respiratory distress, and even neurological involvement [30][31][32][33][34][35]. The percentage of referred symptoms and clinical data reported are in accordance with the results of the largest follow-up [36][37][38].…”

Section: Discussionsupporting

confidence: 90%

Intensive Care Patients from the First COVID-19 Wave: One-Year Survival after Tocilizumab Treatment

Melegari

Giuliani

Dallai

et al. 2021

JPM

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Introduction: An infection by COVID-19 triggers a dangerous cytokine storm, so tocilizumab has been introduced in Italy as an agent blocking the cytokine storm. This paper aims to describe the one-year survival of ICU patients treated with tocilizumab. Methods: This observational study enrolled all patients confirmed to be infected by COVID-19 who were admitted to the ICU in our center. We offered tocilizumab to all non-septic patients if they did not present any contraindications. Results: We enrolled 68 ICU patients in our center on 72 occasions during the enrollment period; we excluded four patients due to study criteria. The one-year mortality hazard ratio of treated patients was 0.64, with a confidence interval of 0.31 to 1.19, with p = 0.169. Among the survivors, 32 of 35 patients answered the phone interview (14 patients in the treated group and 18 in the untreated group); overall, the effect of COVID-19 on quality of life was 58.14%. These effects were lower in the tocilizumab group, with p = 0.016 *. Conclusions: Our observational data follow the most relevant largest trial. Patients treated with tocilizumab had lower rates of new-onset symptoms later COVID-19 ICU hospitalizations. As reported by recent medical literature, the presence of these symptoms suggests that a follow-up program for these types of patients could be useful.

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Section: Discussionsupporting

confidence: 90%

Intensive Care Patients from the First COVID-19 Wave: One-Year Survival after Tocilizumab Treatment

Melegari

Giuliani

Dallai

et al. 2021

JPM

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“…Our data confirms preceding studies which showed that in patients with COVID-19 pneumonia low P/F, low SpO 2 /FiO 2 ratio, low PCO 2 and the presence of dyspnea at rest predict the need of NIRS [ 12 , 13 , 14 , 34 , 35 ]. Of note, there is a slight discrepancy between PaO 2 /FiO 2 and SpO 2 /FiO 2 cut off, which predicts NIRS requirement (respectively 280 and 438).…”

Section: Discussionsupporting

confidence: 92%

Single-Breath Counting Test Predicts Non-Invasive Respiratory Support Requirements in Patients with COVID-19 Pneumonia

Longhitano

Zanza

Romenskaya

et al. 2021

JCM

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The use of non-invasive respiratory strategies (NIRS) is crucial to improve oxygenation in COVID-19 patients with hypoxemia refractory to conventional oxygen therapy. However, the absence of respiratory symptoms may delay the start of NIRS. The aim of this study was to determine whether a simple bedside test such as single-breath counting test (SBCT) can predict the need for NIRS in the 24 h following the access to Emergency Department (ED). We performed a prospective observational study on 120 patients with COVID-19 pneumonia. ROC curves were used to analyze factors which might predict NIRS requirement. We found that 36% of patients had normal respiratory rate and did not experience dyspnea at rest. 65% of study population required NIRS in the 24 h following the access to ED. NIRS-requiring group presented lower PaO2/FiO2 (235.09 vs. 299.02), SpO2/FiO2 ratio (357.83 vs. 431.07), PaCO2 (35.12 vs. 40.08), and SBCT (24.46 vs. 30.36) and showed higher incidence of dyspnea at rest (57.7% vs. 28.6%). Furthermore, SBCT predicted NIRS requirement even in the subgroup of patients without respiratory symptoms (AUC = 0.882, cut-off = 30). SBCT might be a valuable tool for bedside assessment of respiratory function in patients with COVID-19 pneumonia and might be considered as an early clinical sign of impending respiratory deterioration.

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“…In a second phase, the immune system would recover the ability to effectively fight the virus, but since the latter has been able to replicate undisturbed, it would at that point produce an exaggerated reaction. Some authors have also suggested a role of the renin-angiotensin-aldosterone system (RAAS) [35,42,43]. In fact, the main receptor used by SARS-CoV-2 to enter human cells is angiotensin-converting enzyme 2 (ACE2), a transmembrane glycoprotein with enzymatic activity belonging to RAAS.…”

Section: Covid-19 Related Cytokine Stormmentioning

confidence: 99%

Cytokine Storm in COVID-19: Immunopathogenesis and Therapy

et al. 2022

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A cytokine storm is a hyperinflammatory state secondary to the excessive production of cytokines by a deregulated immune system. It manifests clinically as an influenza-like syndrome, which can be complicated by multi-organ failure and coagulopathy, leading, in the most severe cases, even to death. The term cytokine storm was first used in 1993 to describe the graft-versus-host disease following allogeneic hematopoietic stem cell transplantation. It was then reused to define the adverse syndromes secondary to the administration of immunostimulating agents, such as anti-CD28 antibodies or bioengineered immune cells, i.e., CAR T-cell therapy. Currently, the concept of cytokine storm has been better elucidated and extended to the pathogenesis of many other conditions, such as sepsis, autoinflammatory disease, primary and secondary hemophagocytic lymphohistiocytosis, and multicentric Castleman disease. Moreover, cytokine storm has recently emerged as a key aspect in the novel Coronavirus disease 2019, as affected patients show high levels of several key pro-inflammatory cytokines, such as IL-1, IL-2, IL-6, TNF-α, IFN-γ, IP-10, GM-CSF, MCP-1, and IL-10, some of which also correlate with disease severity. Therefore, since the onset of the pandemic, numerous agents have been tested in the effort to mitigate the cytokine storm in COVID-19 patients, some of which are effective in reducing mortality, especially in critically ill patients, and are now becoming standards of care, such as glucocorticoids or some cytokine inhibitors. However, the challenge is still far from being met, and other therapeutic strategies are being tested in the hope that we can eventually overcome the disease.

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Lock, Stock and Barrel: Role of Renin-Angiotensin-Aldosterone System in Coronavirus Disease 2019

Cited by 12 publications

References 154 publications

Intensive Care Patients from the First COVID-19 Wave: One-Year Survival after Tocilizumab Treatment

Intensive Care Patients from the First COVID-19 Wave: One-Year Survival after Tocilizumab Treatment

Single-Breath Counting Test Predicts Non-Invasive Respiratory Support Requirements in Patients with COVID-19 Pneumonia

Cytokine Storm in COVID-19: Immunopathogenesis and Therapy

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