Adiponectin, Leptin, and Resistin Are Dysregulated in Patients Infected by SARS-CoV-2.

Obesity, through adipose tissue (AT) inflammation and dysregulation, represents a critical factor for COVID-19; here, we investigated whether serum levels of adiponectin, HMW oligomers, leptin, and resistin are modulated and/or correlated with clinical and biochemical parameters of severe COVID-19 patients. This study included 62 severe COVID-19 patients; 62 age and sex-matched healthy subjects were recruited as a control group. Anthropometric and biochemical parameters were obtained and compared. Adiponectin, HMW oligomers, leptin, and resistin were analyzed by ELISA. The adiponectin oligomerization state was visualized by Western blotting. When compared to healthy subjects, total adiponectin levels were statistically lower in severe COVID-19 while, in contrast, the levels of leptin and resistin were statistically higher. Interestingly, HMW adiponectin oligomers negatively correlated with leptin and were positively associated with LUS scores. Resistin showed a positive association with IL-6, IL-2R, and KL-6. Our data strongly support that adipose tissue might play a functional role in COVID-19. Although it needs to be confirmed in larger cohorts, adiponectin HMW oligomers might represent a laboratory resource to predict patient seriousness. Whether adipokines can be integrated as a potential additional tool in the evolving landscape of biomarkers for the COVID-19 disease is still a matter of debate. Other studies are needed to understand the molecular mechanisms behind adipokine's involvement in COVID-19.

Strategies Tackling Viral Replication and Inflammatory Pathways as Early Pharmacological Treatment for SARS-CoV-2 Infection: Any Potential Role for Ketoprofen Lysine Salt?

COVID-19 is an infective disease resulting in widespread respiratory and non-respiratory symptoms prompted by SARS-CoV-2 infection. Interaction between SARS-CoV-2 and host cell receptors prompts activation of pro-inflammatory pathways which are involved in epithelial and endothelial damage mechanisms even after viral clearance. Since inflammation has been recognized as a critical step in COVID-19, anti-inflammatory therapies, including both steroids and non-steroids as well as cytokine inhibitors, have been proposed. Early treatment of COVID-19 has the potential to affect the clinical course of the disease regardless of underlying comorbid conditions. Non-steroidal anti-inflammatory drugs (NSAIDs), which are widely used for symptomatic relief of upper airway infections, became the mainstay of early phase treatment of COVID-19. In this review, we discuss the current evidence for using NSAIDs in early phases of SARS-CoV-2 infection with focus on ketoprofen lysine salt based on its pharmacodynamic and pharmacokinetic features.

Effects of Different Corticosteroid Doses in Elderly Unvaccinated Patients with Severe to Critical COVID-19.

SARS-CoV-2 infection can induce a broad range of clinical symptoms, and the most severe cases are characterized by an uncontrolled inflammatory response with the overproduction of proinflammatory cytokines. Elevated levels of C-reactive protein, interleukin-1B, and interleukin-6 have become key signatures of severe COVID-19. For this reason, the use of 6 mg of dexamethasone has become a standard of care, although this regime may not be optimal. Even though various glucocorticoid doses have been proposed, it is still unclear which dose should be used to prevent adverse effects while at the same time reducing the inflammatory response. Here, we compared two different doses of corticosteroids in 52 elderly hospitalized patients with severe to critical COVID-19 to assess efficacy and safety. We showed that in patients receiving a higher dose of prednisone, the time to negative swab was significantly longer. Furthermore, although neither dose was correlated with the risk of death, patients receiving the high dose were more likely to have adverse events such as hyperglycemia, leukocytosis, an increase in systemic blood pressure, and others. Finally, the BMI, WBC number, and NLR value were directly related to death. In conclusion, although the optimal glucocorticoid dose is still undefined, our retrospective study supports the absence of beneficial effects in the utilization of higher doses of corticosteroids in elderly patients with severe to critical COVID-19.

Mucolytic and Antioxidant Properties of Carbocysteine as a Strategy in COVID-19 Therapy.

SARS-CoV-2 infection leads to a heterogenous spectrum of clinical conditions ranging from self-limiting upper airway infection to severe respiratory failure. Carbocysteine is a thioether mucolytic with antioxidant and anti-inflammatory activities. Carbocysteine has been shown to have anti-viral effects on human rhinovirus, RSV and the influenza virus as well as interfering with upper airway ciliary motility, the first site of SARS-CoV-2 infection, leading to more effective mucus clearance and potential containment of viral spread towards the lower airway. Positive effects, in terms of limiting superimposed bacterial infection and reducing oxidative stress, have also been documented in COPD patients. Accordingly, Carbocysteine should also be considered in both post-exposure prophylaxis and early-phase treatment of COVID-19 in combination with other agents (monoclonal antibodies, antivirals, non-steroidal anti-inflammatory agents, and inhaled corticosteroids). In this review, we explored the pharmacokinetic and pharmacodynamic aspects of Carbocysteine to delineate its potential therapeutic impact in patients with COVID-19.

Exploring the Role of Krebs von den Lungen-6 in Severe to Critical COVID-19 Patients.

COVID-19 encompasses a broad spectrum of clinical conditions caused by SARS-CoV-2 infection. More severe cases experience acute respiratory and/or multiorgan failure. KL-6 is a glycoprotein expressed mainly from type II alveolar cells with pro-fibrotic properties. Serum KL-6 concentrations have been found in patients with COVID-19. However, the relevance of KL-6 in patients with severe and critical COVID-19 has not been fully elucidated. METHODS: Retrospective data from consecutive severe to critical COVID-19 patients were collected at UOC Clinica Pnuemologica "Vanvitelli", A.O. dei Colli, Naples, Italy. The study included patients with a positive rhinopharyngeal swab for SARS-CoV-2 RNA with severe or critical COVID-19. RESULTS: Among 87 patients, 24 had poor outcomes. The median KL-6 value in survivors was significantly lower when compared with dead or intubated patients (530 U/mL versus 1069 U/mL p < 0.001). KL-6 was correlated with body mass index (BMI) (r: 0.279, p: 0.009), lung ultrasound score (LUS) (r: 0.429, p < 0.001), Chung Score (r: 0.390, p < 0.001). KL-6 was associated with the risk of death or oro-tracheal intubation (IOT) after adjusting for gender, BMI, Charlson Index, Chung Score, and PaO2/FIO2 (OR 1.003 95% CI 1.001-1.004, p < 0.001). Serum KL-6 value of 968 has a sensitivity of 79.2%, specificity of 87.1%, PPV 70.4%, NPV 91.5%, AUC: O.85 for risk of death or IOT. CONCLUSIONS: The presented research highlights the relevance of serum KL-6 in severe to critical COVID-19 patients in predicting the risk of death or IOT.

Mechanisms and Clinical Implications of Endothelial Dysfunction in Arterial Hypertension.

The endothelium is composed of a monolayer of endothelial cells, lining the interior surface of blood and lymphatic vessels. Endothelial cells display important homeostatic functions, since they are able to respond to humoral and hemodynamic stimuli. Thus, endothelial dysfunction has been proposed as a key and early pathogenic mechanism in many clinical conditions. Given the relevant repercussions on cardiovascular risk, the complex interplay between endothelial dysfunction and systemic arterial hypertension has been a matter of study in recent years. Numerous articles have been published on this issue, all of which contribute to providing an interesting insight into the molecular mechanisms of endothelial dysfunction in arterial hypertension and its role as a biomarker of inflammation, oxidative stress, and vascular disease. The prognostic and therapeutic implications of endothelial dysfunction have also been analyzed in this clinical setting, with interesting new findings and potential applications in clinical practice and future research. The aim of this review is to summarize the pathophysiology of the relationship between endothelial dysfunction and systemic arterial hypertension, with a focus on the personalized pharmacological and rehabilitation strategies targeting endothelial dysfunction while treating hypertension and cardiovascular comorbidities.

Clinical Characteristics, Exercise Capacity and Pulmonary Function in Post-COVID-19 Competitive Athletes.

BACKGROUND: Limited evidence exists regarding adverse modifications affecting cardiovascular and pulmonary function in physical active adults affected by COVID-19, especially in athletic populations. We aimed to describe the clinical presentation of COVID-19 in a cohort of competitive athletes, as well as spirometry and echocardiography findings and cardio-respiratory performance during exercise. METHODS: Twenty-four competitive athletes with COVID-19 were recruited for this study after ending self-isolation and confirmation of negative laboratory results. All athletes underwent clinical evaluation, spirometry, echocardiography and cardiopulmonary exercise testing (CPET). These data were compared to a group of healthy control athletes. RESULTS: Anosmia was the most frequent symptom present in 70.83% patients, followed by myalgia, fatigue and ageusia. The most frequent persisting symptoms were anosmia 11 (45.83%) and ageusia 8 (33.33%). Compared to controls, COVID-19 patients presented lower FEV1%: 97.5 (91.5-108) vs. 109 (106-116) p = 0.007. Peak Oxygen Uptake (VO2) in COVID-19 patients was 50.1 (47.7-51.65) vs. 49 (44.2-52.6) in controls (p = 0.618). CONCLUSIONS: Reduced exercise capacity was not identified and pulmonary and cardiovascular function are not impaired during early recovery phase in a population of physical active adults except FEV1 reduction.

SARS-CoV-2: One Year in the Pandemic. What Have We Learned, the New Vaccine Era and the Threat of SARS-CoV-2 Variants.

Since the beginning of 2020, the new pandemic caused by SARS-CoV-2 and named coronavirus disease 19 (COVID 19) has changed our socio-economic life. In just a few months, SARS-CoV-2 was able to spread worldwide at an unprecedented speed, causing hundreds of thousands of deaths, especially among the weakest part of the population. Indeed, especially at the beginning of this pandemic, many reports highlighted how people, suffering from other pathologies, such as hypertension, cardiovascular diseases, and diabetes, are more at risk of severe outcomes if infected. Although this pandemic has put the entire academic world to the test, it has also been a year of intense research and many important contributions have advanced our understanding of SARS-CoV-2 origin, its molecular structure and its mechanism of infection. Unfortunately, despite this great effort, we are still a long way from fully understanding how SARS-CoV-2 dysregulates organismal physiology and whether the current vaccines will be able to protect us from possible future pandemics. Here, we discuss the knowledge we have gained during this year and which questions future research should address.

Remarkable vessel enlargement within lung consolidation in COVID-19 compared to AH1N1 pneumonia: A retrospective study in Italy.

PURPOSE: To investigate the early CT findings in COVID-19 pneumonia as compared to influenza A virus H1N1 (AH1N1), with focus on vascular enlargement within consolidation or ground glass opacity (GGO) areas. METHODS: 50 patients with COVID-19 pneumonia were retrospectively compared to 50 patients with AH1N1 pneumonia diagnosed during the 2009 pandemic. Two radiologists reviewed chest CT scans independently and blindly, with discordance resolved by consensus. Dilated or tortuous vessels within hyperdense lesions were recorded. RESULTS: COVID-19 pneumonia presented with bilateral (96%), peripheral areas of GGO (22%), consolidation (4%) or combined GGO-consolidation (74%). The vascular enlargement sign in COVID-19 pneumonia was much more commonly present in COVID-19 (45/50, 90%) versus AH1N1 pneumonia (12/50, 24%) (p < 0.001). Vascular enlargement was more often present in lower lobes with a peripheral distribution. CONCLUSIONS: Vascular enlargement in consolidative/GGO areas may represent a reasonably common early CT marker in COVID-19 patients and is of uncertain etiology. Although speculative, theoretical mechanisms could potentially reflect acute inflammatory changes, pulmonary endothelial activation, or acute stasis. Further studies are necessary to verify specificity and to study if prognostic for clinical outcomes.

Metabolic Perturbations and Severe COVID-19 Disease: Implication of Molecular Pathways.

Coronavirus disease (COVID-19) is caused by SARS-CoV-2 virus, which can result in serious respiratory illnesses such as pneumonia leading to respiratory failure. It was first reported in Wuhan, Hubei, China, in December 2019 and rapidly spread globally, becoming a pandemic in March 2020. Among comorbidities observed in SARS-CoV-2 positive patients, hypertension (68.3%) and type 2-diabetes (30.1%) are the most frequent conditions. Although symptoms are highly heterogeneous (ranging from absence of symptoms to severe acute respiratory failure), patients with metabolic-associated diseases often experience worse COVID-19 outcomes. This review investigates the association between metabolic disorders and COVID-19 severity, exploring the molecular mechanisms potentially underlying this relationship and those that are responsible for more severe COVID-19 outcomes. In addition, the role of the main biological processes that may connect metabolic alterations to SARS-CoV-2 infection such as hyperglycemia, immune system deregulation, ACE-2 receptor modulation, and inflammatory response is described. The impact of metabolic disorders on the prognosis of COVID-19 has major implications in public health especially for countries affected by a high incidence of metabolic diseases.

Correction to: COVID-19 and the elderly patients: insights into pathogenesis and clinical decision-making.

In the published article, the title was published incorrectly as COVID-19.

Incidental diagnosis of lung adenocarcinoma following coronavirus OC 43 severe pneumonia.

Viral infections are frequent among patients with thoracic malignancies prompted by dysregulation of innate and adaptative immune response. Clinical symptoms and radiological findings of both viral pneumonia and lung adenocarcinoma may overlap resulting in diagnostic and clinical  challenges.We present the case of a women admitted to our department presenting with an acute manifestation of coronavirus OC43 pneumonia with underlying undiagnosed lung adenocarcinoma.

COVID-19 and the elderly: insights into pathogenesis and clinical decision-making.

The elderly may represent a specific cluster of high-risk patients for developing COVID-19 with rapidly progressive clinical deterioration. Indeed, in older individuals, immunosenescence and comorbid disorders are more likely to promote viral-induced cytokine storm resulting in life-threatening respiratory failure and multisystemic involvement. Early diagnosis and individualized therapeutic management should be developed for elderly subjects based on personal medical history and polypharmacotherapy. Our review examines the pathogenesis and clinical implications of ageing in COVID-19 patients; finally, we discuss the evidence and controversies in the management in the long-stay residential care homes and aspects of end-of-life care for elderly patients with COVID-19.

Severe respiratory SARS-CoV2 infection: Does ACE2 receptor matter?

SARS-CoV-2 is a novel virus of the Coronaviridiae family that represents a major global health issue. Mechanisms implicated in virus/host cells interaction are central for cell infection and replication that in turn lead to disease onset and local damage. To enter airway and lung epithelia, SARS-CoV-2 attaches to ACE2 receptors by spike (S) glycoproteins. Molecular mechanisms that promote interaction between SARS-CoV-2 virus and host with particular focus on virus cell entry receptor ACE2 are described. We further explore the impact of underlying medical conditions and therapies including renin-angiotensin inhibitors on modulating ACE 2, which is the major SARS-CoV-2 cell entry receptor.