Enhanced fatty acid oxidation through Metformin and Baicalin as therapy for COVID-19 and associated inflammatory states in lung and kidney

Progressive respiratory failure is the primary cause of death in the coronavirus disease 2019 (COVID-19) pandemic. It is the final outcome of the acute respiratory distress syndrome (ARDS), characterized by an initial exacerbated inflammatory response and ultimate tissue scarring. Energy balance may be crucial for the recovery of clinical COVID-19. Hence, we asked if two key pathways involved in energy generation, AMP-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) signaling and fatty acid oxidation (FAO) could be beneficial. We tested the drugs Metformin (AMPk activator) and Baicalin (Cpt1A activator) in different experimental models mimicking COVID-19 associated inflammation in lung and kidney. We also studied two different cohorts of COVID19 patients that had been previously treated with Metformin. These drugs ameliorated lung damage in an ARDS animal model, while activation of AMPK/ACC signaling increased mitochondrial function and decreased TGF-beta-induced fibrosis, apoptosis and inflammation markers in lung epithelial cells. Similar results were observed with two new indole derivatives IND6 and IND8 with AMPK activating capacity. Consistently, a reduced stay in the intensive care unit was observed in COVID-19 patients previously exposed to Metformin. Baicalin also reduced kidney fibrosis in two animal models of kidney injury, another key target of COVID-19, while in vitro both drugs improved mitochondrial function and prevented TGF-beta-induced renal epithelial cell dedifferentiation. Our results support that strategies based on energy supply may prove useful in the prevention of COVID-19-induced lung and renal damage.Copyright © 2023

Blood lactate in mild and moderate ARDS secondary to SARS COV 2.

BACKGROUND AND OBJECTIVES: Elevated blood lactate levels are associated with poor outcome in several critical conditions. Patients with SARS-CoV-2 rarely develop hyperlactatemia. The purpose of this study is to evaluate the trend of lactatemia in patients affected by mild/moderate SARS-Co V-2-ARDS and if it affected prognosis. METHODS: We analyzed blood lactate levels in thirty-eight patients with severe SARS-CoV-2 infection admitted to COVID Care Unit of Santa Maria delle Grazie Hospital, Pozzuoli. RESULTS: Twenty patients survived and were discharged at home and 18 patients died. Despite severe hypoxia that affected all patients enrolled, T0 lactate was within normal values. All survivors showed a significant increase in lactate concentration the day prior to clinical improvement. In not-survivors levels of lactate did not increase significantly. CONCLUSION: In our study, patients who survive SARS CoV-2 ARDS have a fleeting increase in lactate, which precedes clinical improvement by one day.

A MECHATRONIC SIMULATOR OF AN AIRCRAFT COCKPIT TO STUDY, BY A VIRTUAL FLIGHT TEST, CARDIOVASCULAR FITNESS IN AIRLINE PILOTS BANNED TO FLY SINCE COVID-19 LOCKDOWN

During flying airline pilots cardio-vascular adaptations occur producing a steady condition of bradycardia and low values in arterial blood pressure. The ability to maintain this optimal level of cardiovascular fitness in aircraft pilots during a prolonged non-driving period is reduced proportionally to this interval. The COVID-19 pandemic has forced pilots to inactivity due to the interruption of many flights at the start of the pandemic. We tested the cardiovascular profile in seven skilled pilots, after 26 weeks of banned to flying for the pandemic lockdown, while they virtually drove an entirely self-built aircraft Airbus A320 simulator. The aim was to investigate on their possible circulatory impairments. Beat-to-beat cardiodynamic profile was non invasively and remotely assessed by a homemade impedance cardiography ICT platform, i.e. the e-Physio tool. Results showed an en route high mean arterial blood pressure (almost 104 Torr) mainly sustained by excessively high values of peripheral vascular resistance (more than 24 Torr per dm3 per minute). Properly central-cardiac hemodynamic and chronotropic modulators of the stroke volume (ventricle end diastolic volume and contractility, heart rate) did not change significantly. Since this hemodynamic picture resembles that of heart failure, it was concluded that (due to the covid-19 dependent long period of inactivity) pilots may go towards a condition of detraining that involved the loss of specific cardiovascular adaptations capable of buffering risks of arterial hypertension. © 2022, Levrotto and Bella. All rights reserved.

Dealing with the unknown: perceptions and fears of SARS-CoV-2 infection among hospital workers : Mireia Utzet

Introduction This study aims to explore perceptions, fears and worries regarding SARS-CoV-2 risk of infection and transmission to relatives and/or co-workers and non-pharmacological preventive interventions among hospital workers. Materials and Methods The research used an explorative qualitative approach. Six focus groups and ten individual interviews across multidisciplinary workers (physicians, nurses, aides, cleaners, maintenance, and security staff) were conducted online and audio-recorded, transcribed verbatim and analysed using thematic analysis and mixed coding. Results Forty professionals participated in the study. Four common themes emerged in all groups: challenges related to the lack of pandemic preparedness, concerns about personal protective equipment, unclear guidelines for case and contact tracing, and communication-related difficulties. Conclusions This study emphasizes the key recommendations to improve non-pharmacological preventive interventions to reduce workers’ fears and worries about the risk of infection and spreading the infection to others, including families. Above all, these should include ensuring the availability, and correct use of adequate personal protective equipment, improve guidelines on case and contact tracing, and setting effective communication channels for all workers of the organization. These recommendations must be reinforced in maintenance and security personnel, as well as night shift nurses and aides, in order to reduce also health inequalities. Key messages • Lack of pandemic preparedness increased HCW’ fear of infection, which could be reduced by ensuring the availability and good use of proper PPE, and by clear guidelines on case/contact detection. • The improvement on non-pharmacological preventive interventions must be underpinned by effective communication channels and/or communication staff, and should reach all workers in the institution.

Innovative Smart Face Mask to Protect Workers from COVID-19 Infection

The most frequent prodromes of COVID-19 infection are fever and signs/symptoms of incipient respiratory diseases such as cough and shortness of breath or tachypnea. However, it is not infrequent that in patients infected with COVID-19, in addition to respiratory manifestations, cardiac rhythm alterations are also present which can be an early sign of an acute cardiovascular syndrome. It is therefore of utmost importance, especially for health care and civil protection workers who are most exposed to the infection, to detect the prodromal symptoms of this infection in order to be able to make a diagnosis of possible positivity to COVID-19 infection as quickly as possible and therefore to provide their immediate insertion in the isolation/therapy protocols. Here a prototype of a smart face mask is presented: the AG47-SmartMask. In addition to having the function of both an active and passive anti COVID-19 filter, the latter by an electro-heated filter brought to a minimum temperature of 38 degrees C, the AG47-SmartMask also allows the continuous monitoring of numerous cardio-pulmonary variables. Several specific sensors are incorporated into the mask in an original way that assess the inside mask temperature, relative humidity and air pressure together with the auricular assessment of body temperature, heart rate and percentage of oxygen saturation of haemoglobin. Sensors work in synergy with an advanced telemedicine platform. To validate the device, twenty workers engaged in a vegetable packaging chain tested the tool simulating, while working, both tachypnea and cough, and the AG47-SmartMask faithfully quantified the simulated dyspnoic events.

Is there an etiological role for polyethylene glycol (PEG)-2000 in COVID arm due to mRNA vaccines?

Background: Delayed local reactions due to mRNA vaccines or COVID arm have been reported. COVID arm commonly presents as an itchy and painful erythematous plaque with swelling and is characterized by a delayed onset of 7 to 10 days after vaccination. New excipients used in mRNA vaccines (polyethylene glycol (PEG)-2000, tromethamol and 1,2-distearoyl-sn-glicero-3-phosphocholine) have increased the awareness about their role in such cutaneous adverse reactions. Objectives: To define the excipient accountability in COVID arm through specific skin provocation testing. Methods: Health workers of a tertiary level hospital suffering COVID arm were patch, skin prick (SP) and intradermal (ID) tested with PEG-400, PEG-2000, tromethamol and 3-phosphocholine at different concentrations (0.001%, 0.01%, 0.1% and 1%). Positive long standing ID reactions were biopsied. Results: Eleven patients were included. Patch tests were always negative. PEG-2000 presented positive SP at 1% (4 patients) and 0.1% (1 patient). PEG-2000 ID was positive at 1% (10 patients), 0.1% (7 patients) and 0.01% (6 patients). Three showed long standing positive reactions to ID of PEG-2000 on day 2, whose biopsies depicted perivascular lymphocytes, occasional eosinophils and dermal edema. In addition, 6 patients reacted to PEG-400, all of which also reacted to PEG-2000. SP and ID for the other excipients were negative. Conclusions: The presence of immediate and delayed reactions to PEG-2000 in patients. with COVID arm poses a challenge on whether PEG-2000 acts as a delayed sensitizer or. these infrequent reactions are irritative.

Mental impact of Covid-19 among Spanish healthcare workers. A large longitudinal survey.

AIMS: Longitudinal data on the mental health impact of the coronavirus disease 2019 (Covid-19) pandemic in healthcare workers is limited. We estimated prevalence, incidence and persistence of probable mental disorders in a cohort of Spanish healthcare workers (Covid-19 waves 1 and 2) -and identified associated risk factors. METHODS: 8996 healthcare workers evaluated on 5 May-7 September 2020 (baseline) were invited to a second web-based survey (October-December 2020). Major depressive disorder (PHQ-8 ≥ 10), generalised anxiety disorder (GAD-7 ≥ 10), panic attacks, post-traumatic stress disorder (PCL-5 ≥ 7), and alcohol use disorder (CAGE-AID ≥ 2) were assessed. Distal (pre-pandemic) and proximal (pandemic) risk factors were included. We estimated the incidence of probable mental disorders (among those without disorders at baseline) and persistence (among those with disorders at baseline). Logistic regression of individual-level [odds ratios (OR)] and population-level (population attributable risk proportions) associations were estimated, adjusting by all distal risk factors, health care centre and time of baseline interview. RESULTS: 4809 healthcare workers participated at four months follow-up (cooperation rate = 65.7%; mean = 120 days s.d. = 22 days from baseline assessment). Follow-up prevalence of any disorder was 41.5%, (v. 45.4% at baseline, p < 0.001); incidence, 19.7% (s.e. = 1.6) and persistence, 67.7% (s.e. = 2.3). Proximal factors showing significant bivariate-adjusted associations with incidence included: work-related factors [prioritising Covid-19 patients (OR = 1.62)], stress factors [personal health-related stress (OR = 1.61)], interpersonal stress (OR = 1.53) and financial factors [significant income loss (OR = 1.37)]. Risk factors associated with persistence were largely similar. CONCLUSIONS: Our study indicates that the prevalence of probable mental disorders among Spanish healthcare workers during the second wave of the Covid-19 pandemic was similarly high to that after the first wave. This was in good part due to the persistence of mental disorders detected at the baseline, but with a relevant incidence of about 1 in 5 of HCWs without mental disorders during the first wave of the Covid-19 pandemic. Health-related factors, work-related factors and interpersonal stress are important risks of persistence of mental disorders and of incidence of mental disorders. Adequately addressing these factors might have prevented a considerable amount of mental health impact of the pandemic among this vulnerable population. Addressing health-related stress, work-related factors and interpersonal stress might reduce the prevalence of these disorders substantially. Study registration number: NCT04556565.

MITIGATING THE COVID-19 PANDEMIC: A PORTRAIT OF THE EXPERIENCE FROM THE LUSOPHONE WORLD

This article aims to provide a reflection on the World Health Organization sponsored Project: "Responsibility for Public Health in the Lusophone World: Doing Justice In and Beyond the Covid Emergency". This initiative was designed to gather experiences and data regarding the preparedness and response to the SARS-CoV-2 Pandemic in Angola, Brazil, Mozambique, Portugal and the Macao Special Administrative Region. Launched in November 2020, it combines the in-depth analysis of the most recent legislation and bibliography on the matter with data obtained through a Questionnaire, addressed to a significant number of participants (from healthcare workers to academics and non-government organisations (NGOs), of which there were 41 respondents), which aims to gather different experiences and analyse ethical difficulties, identified in the response to the Pandemic.

Four-month incidence of suicidal thoughts and behaviors among healthcare workers after the first wave of the Spain COVID-19 pandemic.

Healthcare workers (HCW) are at high risk for suicide, yet little is known about the onset of suicidal thoughts and behaviors (STB) in this important segment of the population in conjunction with the COVID-19 pandemic. We conducted a multicenter, prospective cohort study of Spanish HCW active during the COVID-9 pandemic. A total of n = 4809 HCW participated at baseline (May-September 2020; i.e., just after the first wave of the pandemic) and at a four-month follow-up assessment (October-December 2020) using web-based surveys. Logistic regression assessed the individual- and population-level associations of separate proximal (pandemic) risk factors with four-month STB incidence (i.e., 30-day STB among HCW negative for 30-day STB at baseline), each time adjusting for distal (pre-pandemic) factors. STB incidence was estimated at 4.2% (SE = 0.5; n = 1 suicide attempt). Adjusted for distal factors, proximal risk factors most strongly associated with STB incidence were various sources of interpersonal stress (scaled 0-4; odds ratio [OR] range = 1.23-1.57) followed by personal health-related stress and stress related to the health of loved ones (scaled 0-4; OR range 1.30-1.32), and the perceived lack of healthcare center preparedness (scaled 0-4; OR = 1.34). Population-attributable risk proportions for these proximal risk factors were in the range 45.3-57.6%. Other significant risk factors were financial stressors (OR range 1.26-1.81), isolation/quarantine due to COVID-19 (OR = 1.53) and having changed to a specific COVID-19 related work location (OR = 1.72). Among other interventions, our findings call for healthcare systems to implement adequate conflict communication and resolution strategies and to improve family-work balance embedded in organizational justice strategies.

Mechatronic face mask anti covid-19 to remotely record cardiorespiratory variables in farm’s workers engaged in jobs at high risk of infection

The most frequent prodromes of COVID-19 infection are fever, signs of respiratory diseases, cough and shortness of breath. Nevertheless, it is not infrequent that patients with COVID-19 also show cardiac symptoms. So, it is of importance to detect the prodromal symptoms of the COVID-19 infection in order to be able to make a diagnosis as quickly as possible to provide the immediate insertion of the infected people in isolation/therapy protocols. Here is presented a prototype of a smart face mask, named AG47-SmartMask that, in addition to the function of both an active and passive anti COVID-19 filter by an electro-heated filter brought to a minimum temperature of 38°C, it also allows the continuous monitoring of numerous cardio-pulmonary variables. Several specific sensors are incorporated into the mask to assess the inside mask temperature from which synchronous waving with the breathing was acquired the breath frequency, relative humidity, air pressure together and end tidal carbon dioxide percentage, and an auricular assessment of the body temperature, the heart rate and the percentage of oxygen saturation of haemoglobin. Sensors are embedded within an advanced ICT platform. To validate the AG47-SmartMask tool, were engaged twenty seven Farm’s workers of a vegetable packaging chain and they dressed the face mask device to simulate, while working, both tachypnea and cough, and the AG47-SmartMask faithfully quantified the simulated dyspnoic events. © 2021, Levrotto and Bella. All rights reserved.

Non-invasive CPAP in mild and moderate ARDS secondary to SARS-CoV-2.

BACKGROUND: During the COVID-19 outbreak, a very high number of infected patients developed pneumonia and many of them complicated with acute respiratory distress syndrome. The optimal management of respiratory failure and the role of lung ultrasound imaging in the evaluation of efficacy of treatment are unknown. METHODS: In March 2020 we treated 18 patients with mild and moderate ARDS secondary to SARS-CoV-2 with non-invasive continuous positive airway pressure therapy (NI-CPAP). All patients underwent lung ultrasound imaging to verify the entity of lung recruitment after NI-CPAP initiation. RESULTS: After one hour of treatment we observed a significant improvement in PaO2/FiO2 ratio in 10 patients. Notably, only 50 % of them reached an effective improvement in lung aeration detectable with lung ultrasound. In the other 50 % or patients the improvement in PaO2/FiO2 might be related to blood redistribution and reverse of hypoxic vasoconstriction. CONCLUSION: NI- CPAP is a valid therapeutic option in mild and moderate ARDS secondary SARS-CoV-2. Lung recruitment detected by means of lung ultrasound is a relevant but not the exclusive mechanism that underlies the therapeutic efficacy of NI-CPAP in this clinical setting.

Eculizumab treatment in patients with COVID-19: preliminary results from real life ASL Napoli 2 Nord experience.

OBJECTIVE: SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2)-related pneumonia, referred to as COVID-19 (Coronavirus Disease 19), is a public health emergency as it carries high morbidity, mortality, and has no approved specific pharmacological treatments. In this case series, we aimed to report preliminary data obtained with anti-complement C5 therapy with eculizumab in COVID-19 patients admitted to intensive care unit (ICU) of ASL Napoli 2 Nord. PATIENTS AND METHODS: This is a case series of patients with a confirmed diagnosis of SARS-CoV2 infection and severe pneumonia or ARDS who were treated with up to 4 infusions of eculizumab as an off-label agent. Patients were also treated with anticoagulant therapy with Enoxaparin 4000 IU/day via subcutaneous injection, antiviral therapy with Lopinavir 800 mg/day + Ritonavir 200 mg/day, hydroxychloroquine 400 mg/day, ceftriaxone 2 g/day IV, vitamine C 6 g/day for 4 days, and were on Non-Invasive Ventilation (NIV). RESULTS: We treated four COVID-19 patients admitted to the intensive care unit because of severe pneumonia or ARDS. All patients successfully recovered after treatment with eculizumab. Eculizumab induced a drop in inflammatory markers. Mean C Reactive Protein levels dropped from 14.6 mg/dl to 3.5 mg/dl and the mean duration of the disease was 12.8 days. CONCLUSIONS: Eculizumab has the potential to be a key player in treatment of severe cases of COVID-19. Our results support eculizumab use as an off-label treatment of COVID-19, pending confirmation from the ongoing SOLID-C19 trial.

COVID-19: biosafety and health education in veterinary establishments in the city of Niteroi, RJ, Brazil

Brazil is currently facing a severe pandemic caused by an emerging viral disease referred to as Covid-19, which has led to thousands of deaths. As a means to control the spread of the disease, total and partial social distancing initiatives have been implemented in several non-essential economic activities. Veterinary clinics and pet shops have not been affected by these measures due to the demand for emergency animal care. This work, as an observational, sectional and descriptive based effort, aimed at describing and evaluating the knowledge among veterinarians regarding the disease and its zoonotic potential, the measures adopted by the clinics to prevent Covid-19 transmission to people and animals, and the recommendations to pet tutors in the municipality of Niteroi. According to the results, veterinarians presented difficulty in recognizing the disease as a zoonosis, despite being aware of its transmission methods and the animals it affected. These professionals also recommended certain actions to pet tutors to avoid the spread of the disease. The surveyed clinics sought to be prepared to face the epidemic, mainly through measures that would not cause them economic impact.