Endothelial dysfunction, oxidative stress and low-grade endotoxemia in COVID-19 patients hospitalised in medical wards.

BACKGROUND: Endothelial dysfunction, assessed by flow-mediated dilation (FMD), is related to poor prognosis in patients with COVID-19 pneumonia (CP). In this study, we explored the interplay among FMD, NADPH oxidase type 2 (NOX-2) and lipopolysaccharides (LPS) in hospitalised patients with CP, community acquired pneumonia (CAP) and controls (CT). METHODS: We enrolled 20 consecutive patients with CP, 20 hospitalised patients with CAP and 20 CT matched for sex, age, and main cardiovascular risk factors. In all subjects we performed FMD and collected blood samples to analyse markers of oxidative stress (soluble Nox2-derived peptide (sNOX2-dp), hydrogen peroxide breakdown activity (HBA), nitric oxide (NO), hydrogen peroxide (H2O2)), inflammation (TNF-α and IL-6), LPS and zonulin levels. RESULTS: Compared with controls, CP had significant higher values of LPS, sNOX-2-dp, H2O2,TNF-α, IL-6 and zonulin; conversely FMD, HBA and NO bioavailability were significantly lower in CP. Compared to CAP patients, CP had significantly higher levels of sNOX2-dp, H2O2, TNF-α, IL-6, LPS, zonulin and lower HBA. Simple linear regression analysis showed that FMD inversely correlated with sNOX2-dp, H2O2, TNF-α, IL-6, LPS and zonulin; conversely FMD was directly correlated with NO bioavailability and HBA. Multiple linear regression analysis highlighted LPS as the only predictor of FMD. CONCLUSION: This study shows that patients with COVID-19 have low-grade endotoxemia that could activate NOX-2, generating increased oxidative stress and endothelial dysfunction.

At the Crossroads of One Health: Lessons Learned from Foot and Mouth Disease in COVID-19 Pandemic

Foot-and-mouth disease (FMD) and Coronavirus Disease 2019 (COVID-19) are transboundary diseases caused by single-stranded positive-sense RNA viruses with similarities in genome replication and viral protein synthesis. In FMD, asymptomatic infection leads to carrier status and persistently infected animals that threaten the animals vaccinated with a trivalent inactivated whole virus vaccine. Similar information on COVID-19 is not yet available. As COVID-19 vaccination is introduced in January 2021 (since 16 January 2021 in India), its outcome can be assessed by the year-end;and while doing so, the experiences gained in the control of FMD in livestock worldwide can be applied, including monitoring of vaccination response, duration of immunity, level of herd immunity developed, and antigenic matching of the vaccine virus. Antigenic divergence of the virus is a major issue in FMD, and different geographical regions in the world use different virus strains in vaccine preparations to antigenically match circulating virus strains in respective regions for control of the disease. Non-synonymous mutations in the critical antigenic determinants of SARS-CoV-2 have been observed, and there is likely the existence/development of antigenic variants. Therefore, during the post-COVID-19 vaccination regime, it will be essential to monitor the suitability of the in-use vaccine strain region-wise from time to time, as there could be an eruption of isolated outbreaks in a country arising due to antigenic variation and variants. In the context of the present scenario of COVID-19 around the Globe and multiple ongoing efforts to develop suitable vaccine(s) to control the disease, it is a must to develop NSP-antibody (that differentiate infected from vaccinated) assays to differentiate infected from vaccinated individuals(DIVI;DIVA in veterinary epidemiology). The techniques used and experiences gained in ongoing FMD control programs in the endemic countries can be applied to COVID-19 control in a country;and finally, the Globe. After achieving the control of COVID-19, the aim would be to eradicate the virus, which will be tough even with vaccination, as the disease/infection may become endemic during the time to come. To achieve this, applying the principles of Progressive Control Pathway for Foot-and-Mouth Disease (PCP-FMD;FAO/OIE) to COVID-19 control will be beneficial in its control. The present review discusses the issue of control of COVID-19. © 2021 by the authors.

The effect of ozone short-term exposure on flow-mediated dilation: Using data before and after COVID-19 lockdown in Shanghai.

BACKGROUND: Short-term ambient ozone exposure has been shown to have an adverse impact on endothelial function, contributing to major cardiovascular diseases and premature death. However, only limited studies have focused on the impact of short-term ozone exposure on Flow-mediated Dilation (FMD), and their results have been inconsistent. The current study aims to explore the relationship between short-term ambient ozone exposure and FMD. In addition, the study aims to investigate how lockdown measures for COVID-19 may influence ozone concentration in the atmosphere. METHODS: Participants were recruited from a hospital in Shanghai from December 2020 to August 2022. Individuals' ozone exposure was determined using residential addresses. A distributed lag nonlinear model was adopted to assess the exposure-response relationship between short-term ozone exposure and FMD. A comparison was made between ambient ozone concentration and FMD data collected before and after Shanghai's lockdown in 2022. RESULTS: When ozone concentration was between 150 and 200 µg/m3, there was a significant reduction in FMD with a 2-day lag. Elderly individuals (age ≥ 65), females, non-drinkers, and non-smokers were found to be more susceptible to high concentrations of ozone exposure. The lockdown did elevate ambient ozone concentration compared to the same period previously. INTERPRETATION: This study proposes that an ambient ozone concentration of 150-200 µg/m3 is harmful to endothelial function, and that a reduction in human activity during lockdown increased the concentration, which in turn reduced FMD. However, the underlying mechanism requires further research.

Current understanding of the airborne transmission of important viral animal pathogens in spreading disease

Current research on airborne transmission of African swine fever virus (ASFV), porcine epidemic diarrhoea virus (PEDV), avian influenza (AIV), porcine reproductive and respiratory syndrome virus (PRRSV), and foot and mouth disease virus (FMDV) was reviewed to evaluate commonalities, knowledge gaps, and methodologies of studying airborne transmission of animal diseases. The reviewed studies were categorised as short-range transmission (within a single facility) and long-range transmission (beyond a single site). Short-range airborne transmission was demonstrated for at least one strain of the above-mentioned pathogens in experimental settings. Most studies reported in the literature concern FMDV, with limited information for ASFV and PEDV, particularly for short-range airborne transmission. Air sampling upwind, downwind, and within infected facilities has been commonly used to demonstrate long-range airborne transmission. The amount of evidence from air sampling for each of the reviewed viruses varies from no evidence on ASFV to evidence from multiple settings for AIV. Computer modelling has been used to study past outbreaks of infectious diseases to assess the contribution of airborne transmission with a multitude of computer models reported in the literature for simulating long-range airborne transmission of FMDV based on past outbreaks. This has resulted in predictive tools for assessing future risk of airborne transmission. Some important computer models are based on epidemiology analysis, weather analysis, and air dispersion. Few models are reported for ASFV, PEDV, and PRRSV. Studies in the literature indicate that airborne transmission is generally affected by virus strain, aerosol type, shedding duration and concentration, environmental conditions, and infectious dose.

The impact of statin therapy on in-hospital prognosis and endothelial function of patients at high-to-very high cardiovascular risk admitted for COVID-19.

Statins may protect against adverse outcomes from Coronavirus disease 2019 (COVID-19) through their pleiotropic effects. Endothelial dysfunction seems to be implicated in the pathophysiology of COVID-19, and can be attenuated by statins. This study assessed the role of preadmission statin therapy and its interaction with endothelial function, measured using flow-mediated dilation (FMD) at hospital admission, in predicting in-hospital outcomes among patients with COVID-19 having high-to-very high cardiovascular (CV) risk. We conducted a retrospective cohort study of hospitalized patients with COVID-19 having high-to-very high CV risk, including a subgroup of patients who underwent FMD assessment. Among 342 patients, 119 (35%) were treated with statins at study baseline. Preadmission statin therapy was independently associated with a 75% risk reduction of intensive care unit admission/in-hospital death (adjusted hazard ratio 0.252, 95% confidence interval 0.122-0.521, p < 0.001). In the subgroup of patients with an FMD assessment (245 patients, 40% statin-treated), preadmission statin therapy was independently associated with higher FMD values (ß = 0.159, p = 0.013). However, preadmission statin therapy × FMD interaction was not associated with in-hospital outcomes (F = 0.002, pinteraction = 0.960). Preadmission statin therapy is associated with better in-hospital outcomes among patients with COVID-19 having high-to-very high CV risk, independent of the endothelium-protective effects of these drugs.

Foot-and-mouth disease status in India during the second decade of the twenty-first century (2011-2020).

Foot-and-mouth disease (FMD) is a major disease of livestock in India and causes huge economic losses. The formal FMD control program started in 2003-04 in selected districts and was gradually expanded. The present study provides a descriptive review of the FMD outbreaks, prevalent serotypes, and genetic and antigenic features of the FMD virus (FMDV) that circulated in the country between 2011 and 2020. FMD outbreaks were regularly reported in cloven-hoofed domestic livestock and wildlife, with three serotypes including O, A, and Asia1. During the study period, a total of 2226 FMD outbreaks were documented and serotypes confirmed. FMDV serotype O dominated the outbreak scenario, accounting for about 92% of all outbreaks, followed by Asia1 (5% of all outbreaks) and A (3% of all outbreaks). Two major epidemics of FMD on an unprecedented scale during the years 2013 and 2018 by serotype O were recorded. The spatial distribution of FMD was characterized by a larger number of outbreaks in the southern region of the country. In an annual-scale analysis, 2020 was the year with the lowest outbreaks, and 2013 was the year with the highest. The month-scale analysis showed that outbreaks were reported throughout the year, with the highest numbers between October and March. The emergence of three major lineages (O/ME-SA/Ind2001d, O/ME-SA/Ind2001e, and O/ME-SA/Ind2018) of serotype O was observed during the period. In the cases of serotype A and Asia1, the appearance of at least one novel lineage/genetic group, including A/G-18/non-deletion/2019 and Asia1/Group-IX, was documented. While serotype A showed the advent of antigenic variants, serotypes O and Asia1 did not show any antigenic diversity. It was noticed during the course of an outbreak that animal movement contributes significantly to disease transmission. Except for 2018, when numerous FMD outbreaks were recorded, the number of annual outbreaks reported after 2016 has been lower than in the first half of the decade, probably due to mass vaccination and COVID-19 pandemic-linked movement restrictions. Even during outbreaks, disease symptoms in ruminant populations, including cattle, were found to be less severe. Regular six-monthly immunization certainly has a positive impact on the reduction of disease burden and should be followed without fail and delay, along with intensive disease surveillance.

Targeting Histone Deacetylases in Idiopathic Pulmonary Fibrosis: A Future Therapeutic Option.

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease with limited therapeutic options, and there is a huge unmet need for new therapies. A growing body of evidence suggests that the histone deacetylase (HDAC) family of transcriptional corepressors has emerged as crucial mediators of IPF pathogenesis. HDACs deacetylate histones and result in chromatin condensation and epigenetic repression of gene transcription. HDACs also catalyse the deacetylation of many non-histone proteins, including transcription factors, thus also leading to changes in the transcriptome and cellular signalling. Increased HDAC expression is associated with cell proliferation, cell growth and anti-apoptosis and is, thus, a salient feature of many cancers. In IPF, induction and abnormal upregulation of Class I and Class II HDAC enzymes in myofibroblast foci, as well as aberrant bronchiolar epithelium, is an eminent observation, whereas type-II alveolar epithelial cells (AECII) of IPF lungs indicate a significant depletion of many HDACs. We thus suggest that the significant imbalance of HDAC activity in IPF lungs, with a "cancer-like" increase in fibroblastic and bronchial cells versus a lack in AECII, promotes and perpetuates fibrosis. This review focuses on the mechanisms by which Class I and Class II HDACs mediate fibrogenesis and on the mechanisms by which various HDAC inhibitors reverse the deregulated epigenetic responses in IPF, supporting HDAC inhibition as promising IPF therapy.

Special Issue: Microbiologists making waves around the South Pacific. (Special Issue: Microbiologists making waves around the South Pacific.)

This special issue includes 11 articles focusing on development of container laboratories in response to COVID-19;COVID-19 in Fiji;Pacific Regional Infectious Disease Association (PRIDA) - capacity-building for microbiology and infectious disease across the Pacific;meningococcal surveillance in Southeast Asia and the Pacific;tropical fever in remote tropics;movement of arboviruses between Indonesia and Western Australia;Rotavirus surveillance informs diarrhoea disease burden in the WHO Western-Pacific region;surveillance for One Health and high consequence veterinary pathogens (Brucellosis, Coxiellosis and Foot and Mouth Disease) in Southeast Asia - Lao PDR and Cambodia in focus and the importance of international partnerships;Avian influenza H5N1.

Characterization of Foot and Mouth Disease Virus Serotype SAT-2 in Swamp Water Buffaloes (Bubalus bubalis) under the Egyptian Smallholder Production System.

Spontaneous mutations are a common characteristic of the foot and mouth disease virus (FMDV), leading to wide antigenic variations resulting in the emergence of new topotypes and lineages of FMDV, which contributes to occasional vaccination failures. The objectives of the present study were to genetically characterize FMDV isolated from water buffaloes and study the biochemical and histopathological indicators of infected animals. Fifty-four water buffaloes of both sexes and different ages suffered from acute symptoms of FMD were clinically examined and randomly selected for inclusion in this study. Oral desquamated epithelial and oropharyngeal fluid samples have been tested for FMDV by reverse transcriptase PCR (RT-PCR). Tissue and serum samples were also collected from the diseased buffaloes and subjected to histopathological and biochemical analysis. Our findings showed that all examined samples were confirmed to be positive to FMDV serotype SAT-2 and were adjusted to be responsible for the recent disease outbreak in this study. Phylogenetic analysis revealed that the circulating viruses were of the SAT-2 serotype, closely related to the lineage of lib12, topotype VII, with 98.9% identity. The new lineage of SAT-2 showed a high virulence resulting in the deaths of water buffaloes due to heart failure, confirmed by high serum levels of inflammatory and cardiac markers, including haptoglobin, ceruloplasmin, cardiac troponin I and creatine phosphokinase-MB, indicating an unfavorable FMD-infection prognosis. In conclusion, we document the presence of new incursions circulating in water buffalo populations in Egypt in early 2019, explaining the high morbidity rate of FMD outbreak in early 2019. Furthermore, the newly identified serotype SAT-2 lib12 lineage, topotype VII, showed an aggressive pattern in water buffaloes of the smallholder production system.

Endothelial function provides early prognostic information in patients with COVID-19: A cohort study.

BACKGROUND: The prothrombotic phenotype and diffuse intravascular coagulation observed in COVID-19 reflect endothelial dysfunction, which is linked to blood flow delivery deficiencies and cardiovascular risk. Assessments of detect vascular deficiencies among newly diagnosed and hospitalized patients due to COVID-19 have yet to be determined. OBJECTIVE: To assess endothelial function characteristics in relation to length of hospitalization and mortality in patients diagnosed with COVID-19 and compare to patients without COVID-19. METHODS: A prospective observational study involving 180 patients with confirmed COVID-19 (COVID-19 group) or suspected and ruled out COVID-19 (Non-COVID-19 group). Clinical evaluation and flow mediated vasodilation (FMD) were performed between the first 24-48 h of hospitalization. Patients were followed until death or discharge. RESULTS: We evaluated 98 patients (COVID-19 group) and 82 (Non-COVID-19 group), COVID-19 group remained hospitalized longer and more deaths occurred compared to the Non-COVID-19 group (p = 0.01; and p < 0.01). Patients in COVID-19 group also had a significantly greater reduction in both FMDmm and FMD% (p < 0.01 in both). We found that absolute FMD≤0.26 mm and relative FMD≤3.43% were the ideal cutoff point to predict mortality and longer hospital stay. In Kaplan Meyer's analysis patients had a high probability of death within a period of up to 10 days of hospitalization. CONCLUSION: Patients hospitalized for COVID-19 present endothelial vascular dysfunction early, remained hospitalized longer and had a higher number of deaths, when compared with patients without COVID-19.