Radiological lung sequelae, functional status and symptoms in older patients 3 and 6 months after hospitalization for COVID-19 pneumonia.

The aim of our study was to assess the lung sequelae and clinical consequences 3 and 6 months after hospitalization for COVID-19 pneumonia in older patients. An observational study was conducted on 55 patients aged 65 years and older. Activities of daily living (ADL) and clinical frailty scale (CFS) were assessed at baseline and after 3 months. Both quantitative assessment at chest high-resolution computed tomography (CT) and semi-quantitative severity score (CTSS) were performed at baseline and after 3 and 6 months. Mean age: 82.3 ± 7.1 years. Male prevalence: 56.4%. After 6 months, ground-glass opacities (GGO) were still detectable in 22% of subjects, while consolidations were no longer appreciable. During follow-up, CTSS reached an overall median score of zero after 6 months. Fibrotic-like changes were found in 40% of subjects with an overall median score of 0 (0-5) points, being more prevalent in males. Patients reporting worsening ADL and CFS were 10.9% and 45.5%, respectively. They were associated with the burden of comorbidities, especially history of heart failure and chronic obstructive pulmonary disease at baseline. Amnesic disorders, exertional dyspnea, and fatigue were the most relevant symptoms reported. No association emerged between persistent or new-onset symptoms and evidence of fibrotic-like changes. The typical chest CT abnormalities of the COVID-19 pneumonia acute phase resolved in most of our older patients. Mild fibrotic-like changes persisted in less than half of the patients, especially males, without significantly affecting the functional status and frailty condition, which instead were more likely associated with pre-existing comorbidities.

Renin-Angiotensin-System Inhibitors Are Associated With Lower In-hospital Mortality in COVID-19 Patients Aged 80 and Older.

Background: Older adults are at higher risk of morbidity and mortality for coronavirus disease 2019 (COVID-19). Renin-angiotensin-system inhibitors (RASi) were found to have a neutral or protective effect against mortality in COVID-19 adult patients. Aims: We investigated whether this association was confirmed also in COVID-19 older patients. Methods: This is a prospective observational study on 337 hospitalized older adults (aged 80 years and older). We classified the study population according to usage of RASi before and during hospitalization. A propensity score analysis was also performed to confirm the findings. Results: The mean age was 87.4 ± 6.1 years. Patients taking RASi at home were 147 (43.6%). During hospitalization, 38 patients (11.3% of the entire study population) discontinued RASi, while 57 patients (16.9% of the entire study population) started RASi. In-hospital mortality was 43.9%. Patients taking RASi during hospitalization (patients who maintained their home RASi therapy + patients who started RASi during hospitalization) had a significantly lower in-hospital mortality than untreated patients [HR 0.48 (95% CI: 0.34-0.67)], even after adjustment for required respiratory support, functional status, albumin, inflammation, and cardiac biomarkers. The analysis of the groups derived from the "propensity score matching" (58 patients in each group) confirmed these results [HR 0.46 (95% CI: 0.23-0.91)]. Discussion: Despite the high risk of death in older COVID-19 patients, RASi therapy during hospitalization was associated with a clinically relevant lower in-hospital mortality, likely due to the benefit of RAS modulation on the cardiopulmonary system during the acute phase of the disease. Conclusion: Our findings confirm the protective role of RASi even in COVID-19 patients aged 80 years and older.

Renin-Angiotensin-System Inhibitors Are Associated With Lower In-hospital Mortality in COVID-19 Patients Aged 80 and Older

Background Older adults are at higher risk of morbidity and mortality for coronavirus disease 2019 (COVID-19). Renin-angiotensin-system inhibitors (RASi) were found to have a neutral or protective effect against mortality in COVID-19 adult patients. Aims We investigated whether this association was confirmed also in COVID-19 older patients. Methods This is a prospective observational study on 337 hospitalized older adults (aged 80 years and older). We classified the study population according to usage of RASi before and during hospitalization. A propensity score analysis was also performed to confirm the findings. Results The mean age was 87.4 ± 6.1 years. Patients taking RASi at home were 147 (43.6%). During hospitalization, 38 patients (11.3% of the entire study population) discontinued RASi, while 57 patients (16.9% of the entire study population) started RASi. In-hospital mortality was 43.9%. Patients taking RASi during hospitalization (patients who maintained their home RASi therapy + patients who started RASi during hospitalization) had a significantly lower in-hospital mortality than untreated patients [HR 0.48 (95% CI: 0.34–0.67)], even after adjustment for required respiratory support, functional status, albumin, inflammation, and cardiac biomarkers. The analysis of the groups derived from the “propensity score matching” (58 patients in each group) confirmed these results [HR 0.46 (95% CI: 0.23–0.91)]. Discussion Despite the high risk of death in older COVID-19 patients, RASi therapy during hospitalization was associated with a clinically relevant lower in-hospital mortality, likely due to the benefit of RAS modulation on the cardiopulmonary system during the acute phase of the disease. Conclusion Our findings confirm the protective role of RASi even in COVID-19 patients aged 80 years and older.

The Identikit of Patient at Risk for Severe COVID-19 and Death: The Dysregulation of Renin-Angiotensin System as the Common Theme.

Since the first months of the coronavirus disease 2019 (COVID-19) pandemic, several specific physiologic traits, such as male sex and older age, or health conditions, such as overweight/obesity, arterial hypertension, metabolic syndrome, and type 2 diabetes mellitus, have been found to be highly prevalent and associated with increased risk of adverse outcomes in hospitalized patients. All these cardiovascular morbidities are widespread in the population and often coexist, thus identifying a common patient phenotype, characterized by a hyper-activation of the "classic" renin-angiotensin system (RAS) and mediated by the binding of angiotensin II (Ang II) to the type 1-receptor. At the same time, the RAS imbalance was proved to be crucial in the genesis of lung injury after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, where angiotensin-converting-enzyme-2 (ACE2) is not only the receptor for SARS-CoV-2, but its down-regulation through internalization and shedding, caused by the virus binding, leads to a further dysregulation of RAS by reducing angiotensin 1-7 (Ang 1-7) production. This focused narrative review will discuss the main available evidence on the role played by cardiovascular and metabolic conditions in severe COVID-19, providing a possible pathophysiological link based on the disequilibrium between the two opposite arms of RAS.

Possible harm from glucocorticoid drugs misuse in the early phase of SARS-CoV-2 infection: a narrative review of the evidence.

Since the publication of the RECOVERY trial, the use of glucocorticoid drugs (GC) has spread for the treatment of severe COVID-19 worldwide. However, the benefit of dexamethasone was largest in patients who received mechanical ventilation or supplemental oxygen therapy, while no benefit was found among patients without hypoxemia. In addition, a positive outcome was found in patients who received dexamethasone after several days of symptoms, while possible harm could exist if administered early. The right time interval for GC administration is still a matter of debate. Previous studies showed that an early GC use during the first phase of the disease, when viral replication peaks, may negatively affect the innate immune response through several mechanisms, such as the inhibition of pro-inflammatory and antiviral cytokine production and signaling pathway, including type I interferon, that is fundamental to counteract the virus and that was found to be impaired in several patients with life-threatening COVID-19. The GC misuse can lead to a more severe disease even in patients who do not have the established risk factors, such as obesity and cardiovascular diseases. In our focused review, we describe the role of immune response in viral infections, especially SARS-CoV-2, and discuss the potential harms of GC misuse in COVID-19.

Covid-19 and the role of smoking: the protocol of the multicentric prospective study COSMO-IT (COvid19 and SMOking in ITaly).

The emergency caused by Covid-19 pandemic raised interest in studying lifestyles and comorbidities as important determinants of poor Covid-19 prognosis. Data on tobacco smoking, alcohol consumption and obesity are still limited, while no data are available on the role of e-cigarettes and heated tobacco products (HTP). To clarify the role of tobacco smoking and other lifestyle habits on COVID-19 severity and progression, we designed a longitudinal observational study titled COvid19 and SMOking in ITaly (COSMO-IT). About 30 Italian hospitals in North, Centre and South of Italy joined the study. Its main aims are: 1) to quantify the role of tobacco smoking and smoking cessation on the severity and progression of COVID-19 in hospitalized patients; 2) to compare smoking prevalence and severity of the disease in relation to smoking in hospitalized COVID-19 patients versus patients treated at home; 3) to quantify the association between other lifestyle factors, such as e-cigarette and HTP use, alcohol and obesity and the risk of unfavourable COVID-19 outcomes. Socio-demographic, lifestyle and medical history information will be gathered for around 3000 hospitalized and 700-1000 home-isolated, laboratory-confirmed, COVID-19 patients. Given the current absence of a vaccine against SARS-COV-2 and the lack of a specific treatment for -COVID-19, prevention strategies are of extreme importance. This project, designed to highly contribute to the international scientific debate on the role of avoidable lifestyle habits on COVID-19 severity, will provide valuable epidemiological data in order to support important recommendations to prevent COVID-19 incidence, progression and mortality.

Disequilibrium between the classic renin-angiotensin system and its opposing arm in SARS-CoV-2-related lung injury.

A dysregulation of the renin-angiotensin system (RAS) has been involved in the genesis of lung injury and acute respiratory distress syndrome from different causes, including several viral infections. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of pneumocytes, the hallmark of the pandemic coronavirus disease 2019 (COVID-19) involving both alveolar interstitium and capillaries, is linked to angiotensin-converting enzyme 2 (ACE2) binding and its functional downregulation. ACE2 is a key enzyme for the balance between the two main arms of the RAS: the ACE/angiotensin (Ang) II/Ang II type 1 receptor axis ("classic RAS") and the ACE2/Ang(1-7)/Mas receptor (MasR) axis ("anti-RAS"). The ACE2 downregulation, as a result of SARS-coronaviruses binding, enhances the classic RAS, leading to lung damage and inflammation with leaky pulmonary blood vessels and fibrosis, when the attenuation mediated by the anti-RAS arm is reduced. ACE inhibitors (ACE-I) and Ang II type 1 receptor blockers (ARB), effective in cardiovascular diseases, were found to prevent and counteract acute lung injury in several experimental models by restoring the balance between these two opposing arms. The evidence of RAS arm disequilibrium in COVID-19 and the hypothesis of a beneficial role of RAS modulation supported by preclinical and clinical studies are the focus of the present review. Preclinical and clinical studies on drugs balancing RAS arms might be the right way to counter COVID-19.

A 95-year-old patient with unexpected coronavirus disease 2019 masked by aspiration pneumonia: a case report.

BACKGROUND: Severe acute respiratory syndrome coronavirus-2 infection has become a pandemic disease (coronavirus disease 2019). The infection has moved from China to the rest of the world and Italy represents one of the most affected countries. Older adults are more susceptible to develop complications with the consequent highest mortality rates. CASE PRESENTATION: We report a case of a 95-year-old Caucasian woman affected by pneumonia, initially defined as common aspiration pneumonia in a bedridden patient with vascular dementia, which later turned out to be coronavirus disease 2019 pneumonia during the initial spread of severe acute respiratory syndrome coronavirus-2 in our district. Some features of a computed tomography scan of her chest and her clinical history with known dysphagia had led at first to a different diagnosis with a consequent exposure of health professionals to infectious risk in two distinct hospitals. In this case report, we describe the clinical/imaging features of coronavirus disease 2019 pneumonia and the diagnostic process that led to a correct diagnosis in a nonagenarian with multiple comorbidities. CONCLUSIONS: This case report highlights both the possible pitfalls in diagnosing coronavirus disease 2019 pneumonia in very old patients with comorbidities and the greater than expected spread of the infection, even in individuals with reduced interpersonal contacts and no defined epidemiological link.