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1.
ASN Neuro ; 13: 17590914211057635, 2021.
Article in English | MEDLINE | ID: covidwho-1511685

ABSTRACT

Among the plethora of debilitating neurological disorders of COVID-19 syndrome in survivors, the scope of SARS-CoV-2-induced dysautonomia (DNS) is yet to be understood, though the implications are enormous. Herein, we present an inclusive mini-review of SARS-CoV-2-induced DNS and its associated complications. Although, the direct link between Covid-19 and DSN is still speculative, the hypothetical links are thought to be either a direct neuronal injury of the autonomic pathway or a para/post-infectious immune-induced mechanism. SARS-CoV-2 infection-induced stress may activate the sympathetic nervous system (SNS) leading to neuro-hormonal stimulation and activation of pro-inflammatory cytokines with further development of sympathetic storm. Sympathetic over-activation in Covid-19 is correlated with increase in capillary pulmonary leakage, alveolar damage, and development of acute respiratory distress syndrome. Furthermore, SARS-CoV-2 can spread through pulmonary mechanoreceptors and chemoreceptors to medullary respiratory center in a retrograde manner resulting in sudden respiratory failure. Taken together, DSN in Covid-19 is developed due to sympathetic storm and inhibition of Parasympathetic nervous system-mediated anti-inflammatory effect with development of cytokine storm. Therefore, sympathetic and cytokine storms together with activation of Renin-Angiotensin-System are the chief final pathway involved in the development of DSN in Covid-19.


Subject(s)
Angiotensin II Type 1 Receptor Blockers/adverse effects , Angiotensin-Converting Enzyme Inhibitors/adverse effects , COVID-19/mortality , Renin-Angiotensin System/drug effects , Aged , Aged, 80 and over , Cohort Studies , Cytokine Release Syndrome , Female , France , Humans , Male , Middle Aged , Propensity Score , Prospective Studies
2.
Fundam Clin Pharmacol ; 35(6): 1141-1158, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1194121

ABSTRACT

AIMS: The role of renin-angiotensin-aldosterone system (RAAS) blockers on the course of coronavirus disease 2019 (COVID-19) is debated. We assessed the association between chronic use of RAAS blockers and mortality among inpatients with COVID-19 and explored reasons for discrepancies in the literature. METHODS AND RESULTS: We included adult hypertensive patients from a prospective nationwide cohort of 3512 inpatients with COVID-19 up to June 30, 2020. Cox proportional hazard models with various adjustment or propensity weighting methods were used to estimate the hazard ratios (HR) of 30-day mortality for chronic users versus non-users of RAAS blockers. We analyzed data of 1160 hypertensive patients: 719 (62%) were male and 777 (67%) were older than 65 years. The main comorbidities were diabetes (n = 416, 36%), chronic cardiac disease (n = 401, 35%), and obesity (n = 340, 29%); 705 (61%) received oxygen therapy. We recorded 135 (11.6%) deaths within 30 days of diagnosis. We found no association between chronic use of RAAS blockers and mortality (unadjusted HR = 1.13, 95% CI [0.8-1.6]; propensity inverse probability treatment weighted HR = 1.09 [0.86-1.39]; propensity standardized mortality ratio weighted HR = 1.08 [0.79-1.47]). Our comprehensive review of previous studies highlighted that significant associations were mostly found in unrestricted populations with inappropriate adjustment, or with biased in-hospital exposure measurement. CONCLUSION: Our results do not support previous concerns regarding these drugs, nor a potential protective effect as reported in previous poorly designed studies and meta-analyses. RAAS blockers should not be discontinued during the pandemic, while in-hospital management of these drugs will be clarified by randomized trials. NCT04262921.


Subject(s)
Angiotensin II Type 1 Receptor Blockers/adverse effects , Angiotensin-Converting Enzyme Inhibitors/adverse effects , COVID-19/mortality , Renin-Angiotensin System/drug effects , Aged , Aged, 80 and over , Cohort Studies , Female , France , Humans , Hypertension , Male , Middle Aged , Pandemics , Propensity Score , Prospective Studies
3.
PLoS One ; 15(12): e0244708, 2020.
Article in English | MEDLINE | ID: covidwho-999851

ABSTRACT

BACKGROUND: Retrospective studies on the use of Renin-Angiotensin-Aldosterone System blockade in patients with Coronavirus Disease 2019 (COVID-19) have been informative but conflicting, and prospective studies are required to demonstrate the safety, tolerability, and outcomes of initiating these agents in hospitalized patients with COVID-19 and hypertension. METHODS AND FINDINGS: This is a single center feasibility study encompassing two cohorts: (1) prospective cohort (April 21, 2020 to May 29, 2020) and (2) retrospective cohort (March 7, 2020 to April 1, 2020) of hospitalized patients with real-time polymerase chain reaction (PCR) positive SARS-CoV-2 by nasopharyngeal swab. Key inclusion criteria include BP > 130/80 and a requirement of supplemental oxygen with FiO2 of 25% or higher to maintain SpO2 > 92%. Key exclusion criteria included hyperkalemia and acute kidney injury (AKI) at the time of enrollment. Prospective cohort consisted of de novo initiation of losartan and continuation for a minimum of 7 days and assessed for adverse events (AKI, hyperkalemia, transaminitis, hypotension) and clinical outcomes (change in SpO2/FiO2 and inflammatory markers, need for ICU admission and mechanical ventilation). Retrospective cohort consisted of continuation of losartan (prior-to-hospitalization) and assessment of similar outcomes. In the prospective cohort, a total of 250 hospitalized patients were screened and inclusion/exclusion criteria were met in 16/250 patients and in the retrospective cohort, a total of 317 hospitalized patients were screened and inclusion/exclusion criteria were met in 14/317 patients. Most common adverse event was hypotension, leading to discontinuation in 3/16 (19%) and 2/14 (14%) patients in the prospective and retrospective cohort. No patients developed AKI in the prospective cohort as compared to 1/14 (7%) patients in the retrospective cohort, requiring discontinuation of losartan. Hyperkalemia occurred in 1/16 (6%) and 0/14 patients in the prospective and retrospective cohorts, respectively. In the prospective cohort, 3/16 (19%) and 2/16 (13%) patients required ICU admission and mechanical ventilation. In comparison, 3/14 (21%) required ICU admission and mechanical ventilation in the retrospective cohort. A majority of patients in both cohorts (14/16 (88%) and 13/14 (93%) patients from the prospective and retrospective cohort) were discharged alive from the hospital. A total of 9/16 (prospective) and 5/14 (retrospective) patients completed a minimum 7 days of losartan. In these 9 patients in the prospective cohort, a significant improvement in SpO2/FiO2 ratio was observed from day 1 to 7. No significant changes in inflammatory markers (initiation, peak, and day 7) were observed in either cohort. CONCLUSION: In this pilot study we demonstrate that losartan was well-tolerated among hospitalized patients with COVID-19 and hypertension. We also demonstrate the feasibility of patient recruitment and the appropriate parameters to assess the outcomes and safety of losartan initiation or continuation, which provides a framework for future randomized clinical trials.


Subject(s)
Angiotensin II Type 1 Receptor Blockers/therapeutic use , COVID-19/pathology , Hypertension/drug therapy , Losartan/therapeutic use , Aged , Angiotensin II Type 1 Receptor Blockers/adverse effects , Blood Pressure/drug effects , Female , Humans , Losartan/adverse effects , Male , Middle Aged , Pilot Projects , Prospective Studies , Retrospective Studies , SARS-CoV-2
6.
J Physiol Pharmacol ; 71(2)2020 Apr.
Article in English | MEDLINE | ID: covidwho-635661

ABSTRACT

COVID-19, which is caused by the single-stranded RNA severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has introduced significant therapeutic dilemmas in several areas. One of these is concern regarding the use of renin-angiotensin system (RAS) inhibitors. Dysfunction of the RAS has been observed in COVID-19 patients, but whether RAS inhibitors, such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type-1 receptor blockers (ARBs), are associated with improved or worse clinical outcomes, remains unclear. RAS inhibitors are currently widely used in the treatment of hypertension. Emerging data suggest an increased association and a heightened mortality in patients of COVID-19 with co-morbidities such as hypertension, coronary heart disease, and diabetes mellitus, particularly in the elderly. Therefore, several recently published research papers have focused on the management of hypertension during the COVID-19 pandemic, as this co-morbidity was found to be the most common in patients with coronavirus infections. SARS-CoV-2 viral surface protein is known to attach angiotensin converting enzyme-2 (ACE-2) on the cell membrane to facilitate viral entry into the cytoplasm. While the SARS-CoV-2 viral load remains the highest in upper respiratory tract of COVID-19 patients, it has also been reported in multiple sites in COVID-19, and patients not infrequently require the Intensive Care Units (ICU) admission. However, despite the theoretical concerns of possible increased ACE2 expression by RAS blockade, there is no evidence that RAS inhibitors are harmful during COVID-19 infection, and indeed they have been shown to be beneficial in some animal studies. In this review we summarise the pathophysiology of the interaction between RAS, ACEIs/ARBs inhibitors and COVID-19, and conclude, on the basis of current data, that RAS blockade should be maintained during the current coronavirus pandemic.


Subject(s)
Angiotensin II Type 1 Receptor Blockers/administration & dosage , Angiotensin-Converting Enzyme Inhibitors/administration & dosage , Coronavirus Infections/physiopathology , Pneumonia, Viral/physiopathology , Angiotensin II Type 1 Receptor Blockers/adverse effects , Angiotensin II Type 1 Receptor Blockers/pharmacology , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Animals , Betacoronavirus/isolation & purification , COVID-19 , Coronavirus Infections/virology , Humans , Hypertension/drug therapy , Pandemics , Pneumonia, Viral/virology , Renin-Angiotensin System/drug effects , SARS-CoV-2
7.
Hipertens Riesgo Vasc ; 37(4): 176-180, 2020.
Article in Spanish | MEDLINE | ID: covidwho-615690

ABSTRACT

The association between hypertension, diabetes, cardio and cerebrovascular disease and severe and fatal COVID-19, described in different countries, is remarkable. Myocardial damage and myocardial dysfunction are postulated as a possible causal nexus. Frequent findings of elevated troponin levels and electrocardiographic anomalies support this concept. On the other hand, hypotheses in favour and against a deleterious effect of angiotensin converting enzyme inhibitors and angiotensin receptor blockers, a usual treatment for cardiovascular disease, have been raised. There is currently no solid evidence and thus properly designed studies on this subject are urgently needed. In this context, patients with cardiovascular disease should especially avoid being exposed to the virus, should not self-medicate and rapidly seek medical advice should they show symptoms of infection.


Subject(s)
Betacoronavirus , Cardiovascular Diseases/physiopathology , Coronavirus Infections/physiopathology , Pandemics , Pneumonia, Viral/physiopathology , Age Factors , Aged , Angiotensin II Type 1 Receptor Blockers/adverse effects , Angiotensin II Type 1 Receptor Blockers/pharmacology , Angiotensin II Type 1 Receptor Blockers/therapeutic use , Angiotensin-Converting Enzyme 2 , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antihypertensive Agents/adverse effects , Antihypertensive Agents/pharmacology , Antihypertensive Agents/therapeutic use , Betacoronavirus/drug effects , COVID-19 , Cardiovascular Diseases/complications , Coronavirus Infections/complications , Early Diagnosis , Heart/physiopathology , Humans , Hypertension/complications , Hypertension/drug therapy , Hypertension/physiopathology , Middle Aged , Myocarditis/etiology , Myocarditis/physiopathology , Peptidyl-Dipeptidase A/drug effects , Peptidyl-Dipeptidase A/physiology , Pneumonia, Viral/complications , Receptors, Virus/drug effects , Receptors, Virus/physiology , Renin-Angiotensin System/drug effects , Renin-Angiotensin System/physiology , Risk Factors , SARS-CoV-2 , Self Medication
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