Susceptibility of turkeys, chickens and chicken embryos to SARS-CoV-2 virus was evaluated by experiment inoculation. Turkeys and chickens were inoculated using a combination of intranasal, oral and ocular routes. Both turkeys and chickens did not develop clinical disease or antibodies to the virus following inoculation. Viral RNA was not detected in oral and cloacal swabs and in tissues using quantitative real-time RT-PCR. In addition, chicken embryos were inoculated using the yolk sac, intravenous, chorioallantoic membrane and allantoic cavity routes did not support replication of the virus. SARS-COV-2 virus does not affect both turkeys and chickens in the current genetic state and does not pose any potential risk to establish in both species of domestic poultry.

BACKGROUND: The coronavirus disease-2019 (COVID-19) is still rapidly spreading worldwide, and remains a global health crisis. We investigated the impact of asthma on the prevalence and outcomes of COVID-19 and identify the risk factors for delayed viral clearance. METHODS: Adult patients with COVID-19 admitted to 10 hospitals in Daegu were retrospectively registered, and their clinical information was collected. Delayed viral clearance was divided into two groups based on 30 days. RESULTS: A total of 2,200 patents were evaluated, and the prevalence of asthma in COVID-19 was 3.2%. Compared with Korea nationwide survey data, there were no differences in asthma prevalence. In the univariate analysis, the risk of death (13.6% vs 6.4%, P = 0.021) and high flow oxygen therapy (18.2% vs 10.5%, P = 0,048) was increased in asthma patients, with a stronger tendency among elderly, women, and overweight patients. However, in a multivariate analysis using the logistic regression model, any clinical outcomes according to asthma was not significant. The risk factors for delayed viral clearance were older age >65 years (Odds ratio [95% confidence interval] 2.002 [1.292–3101]), dementia (3.123 [1.833–5.321]), skin rash (15.943 [1.613–157.535]), and anemia (2.156 [1.061–2.377]), whereas headache (0.673 [0.485–0.932]) lowered the risk. CONCLUSIONS: There may be a difference depending on phenotypes, but asthma prevalence was not significantly different in patients with COVID-19, and asthma did not affect outcomes of COVID-19. Older age, dementia, headache, skin rash, and anemia were independently associated with delayed viral clearance.

INTRODUCTION: The SARS-CoV-2 coronavirus pandemic has caused more than fifteen million infections worldwide. Our aim is to investigate the differentiating characteristics in asthmatic patients with SARS-CoV-2 infection in the community of Castilla la Mancha. METHODS: We used the Savana® software and its algorithm based on Big Data and artificial intelligence, performed a retrospective search of the diagnoses of COVID 19 and asthma in the digitized medical records with positive RT-PCR results for SARS-CoV-2, and analysed the demographic characteristics, comorbidities, hospitalization data and deaths. RESULTS: 6,310 patients with positive RT-PCR for SARS-CoV-2 were selected, of which 577 had a diagnosis of asthma with a prevalence of 9.14%. The mean age in SARS-CoV-2 (SC2) was 59 ±19 years of age and in SARS-CoV2-asthma (SC2-A) 55 ±20 years of age. SC2 included 2983 (41%) men and 3327 (59%) women, while SC2-A included 198 (31%) men and 379 (69%) women. High blood pressure (BP) was the most common comorbidity in both groups (51%). 2,164 SC2 (34.2%) and 131 SC2-A (22.7%) required hospitalization with an asthma prevalence of 6.05%. 250 SC2 (3.96%) and 21 SC2-A (3.64%) died. CONCLUSION: The prevalence of asthma in our SARS-CoV-2 positive RT-PCR population was 9.14% and 6.05% in hospitalized patients. HBP is the most frequent comorbidity in both groups, and smoking is the only one with significant differences, more frequent in asthmatics. Mortality is lower in patients with asthma

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage were associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin converting enzyme 2 (ACE2). As a result of SARS-Cov-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT1R) axis associated with oxidative stress. This leads to insulin resistance, lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block the AT1R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects helpful in mitigating COVID-19 severity.

To the Editor: Bronchial asthma is characterized by restricted airflow due to chronic airway inflammation, and frequent lower respiratory viral infections in early life are a significant risk factor for development of the disease. Previous studies demonstrated that anti-viral interferon (IFN) production, including of IFN-α, IFN-β and IFN-λ, by leukocytes and bronchial epithelial cells can be impaired in asthma patients.1 An epidemiological study found that allergic sensitization precedes wheeze during asthma development in children, suggesting that Type 2 (T2) conditions play a key role in the impaired anti-viral IFN production. Furthermore, a prospective cohort study showed that, regardless of the type of virus, each successive lower respiratory viral infection with wheeze increases the risk of asthma by about 1.5 fold.2 However, we still don’t have a full understanding of the precise mechanism(s) of how respiratory viral infections under T2 conditions lead to development of asthma.A meta-analysis of large-scale genome-wide association studies revealed that both IL-33 and its receptor, IL-33 receptor(IL-33R ; also known as ST2 ), are closely associated with asthma development.3 Indeed, IL-33 expression was reportedly increased in rhinovirus-infected bronchial epithelial cells and correlated significantly with the disease severity of asthma.4 This suggests that virus-induced IL-33 in the airway may be fundamentally involved in the mechanistic links between viral infection and development and/or exacerbation of asthma. In addition, impairment of anti-viral IFN production was reported to cause necrosis—but not apoptosis—of the virus-infected epithelium,5 which results in release of bioactive IL-33.MicroRNAs (miRNAs) are small, non-coding RNA molecules (containing about 22 nucleotides) that are found in diverse organisms. miRNAs regulate expression of a broad spectrum of target genes through RNA silencing and/or post-transcriptional regulation. Among them, microRNA-29a (miR-29a) was induced by respiratory syncytial virus (RSV) infection in a human lung adenocarcinoma cell line, A549, and suppressed expression of IFN (α, β and ω) receptor 1 (IFNAR1).6 Furthermore, miR-29a regulated the expression of soluble ST2 (sST2), a decoy receptor for IL-33, in human tenocytes.7 Based on those earlier findings, we focused on miR-29 in the present study. We hypothesized that T2 cytokine induces miR-29 expression in bronchial epithelial cells, leading to suppression of both sST2 release and IFNAR1 expression by epithelial cells, and culminating in asthma development and/or exacerbation.Based on that hypothesis, we first examined whether T2 cytokine and inflammatory cytokine induced sST2 production in a human bronchial epithelial cell line, BEAS-2B. The detailed methods are described in Supporting Information. Specific ELISA showed that IL-4 and TNF-α synergistically induced sST2 release from BEAS-2B, in a dose-dependent manner (Figure 1A). Next, to examine the effects of miR-29 overexpression or inhibition on that cytokine-induced sST2 release, BEAS-2B cells were first transfected with miR-29 mimics or inhibitors for 24 hours and then stimulated with a combination of IL-4 and TNF-α for 48 hours.The human miR-29 family consists of three mature members, i.e., miR-29a, miR-29b, and miR-29c. These miR-29s are encoded by the miR-29a/b-1 cluster on chromosome 7q32.3 and the miR-29c/b-2 cluster on chromosome 1q32.2, respectively (Figure 1B).8 The three family members share an identical seed sequence (Figure 1B), and their functional properties are thought to be similar. We examined the effects of miR-29a and miR-29b in this study. ELISA of the culture supernatants showed that inhibition of miR-29a or miR-29b significantly enhanced cytokine-induced sST2 release (Figure 1C). In contrast, overexpression of miR-29a or miR-29b almost completely inhibited that release, indicating that these miR-29s regulate sST2 release from bronchial epithelial cells under T2 conditions. Of note, neither inhibition nor overexpression of miR-29a or miR-29b had any effects on the protein levels of the ST2 receptor in the BEAS-2B cells (Figure 1D, upper panel). These results suggest that T2 cytokine-induced miR-29 plays a critical role in IL-33-dependent allergic inflammation through regulation of sST2 release from bronchial epithelial cells.Furthermore, transfection of either miR-29a or miR-29b inhibitors significantly enhanced IFNAR1 protein expression in the BEAS-2B cells (Figure 1D, middle panel), which is consistent with earlier findings for miR-29a in A549 cells.6 Conversely, transfection of miR-29 mimics resulted in reduced IFNAR1 expression in BEAS-2B cells, suggesting that overproduction of miR-29s in bronchial epithelial cells may lead to suppression of antiviral responses by IFNs. Thus, we found that miR-29s simultaneously regulate the expression of both sST2 and IFNAR1 in bronchial epithelial cells. Our findings suggest the possibility that T2 cytokine-induced miR-29s in airway epithelial cells are key players in the development and/or exacerbation of asthma triggered by respiratory viral infections through both decreasing IFN-regulated antiviral activities and exacerbating IL-33-dependent allergic inflammation.miRNAs are released from cells into the extracellular environment via exosomes, which can then fuse with target cells. This process can deliver various proteins and nucleic acids, including miRNAs, into even distant target/receiving cells.9 We, therefore, examined whether exosomes similarly export miR-29s from bronchial epithelial cells. BEAS-2B cells were stimulated with a combination of IL-4 and TNF-α for 48 hours, and exosomal fractions were collected from the culture supernatants. Although qPCR detected both miR-29a and miR-29b in the exosomes even without that T2 cytokine stimulation (control), both of their copy numbers were significantly increased by that stimulation (Figure 2A). Furthermore, Western blot analysis also found that expression of CD81, an exosome marker, was enhanced by the cytokine stimulation (Figure 2B). These results suggest that T2 cytokine-stimulated epithelial cells release more exosomes containing more miR-29s than unstimulated cells.This study has several limitations. First, no functional experiments were performed in this study to confirm the effects of the changes in sST2 release or IFNAR1 expression. In addition, we did not measure the expression levels of miR-29s in clinical samples.Figure S1 summarizes our findings as a schematic illustration of bronchial epithelial cells. Based on those findings, we hypothesize that elevated nasal, bronchial and/or exosomal levels of miR-29s in infancy may be useful biomarker(s) for predicting later development of asthma, and further studies are needed. Our data suggest a new perspective that miRNAs are crucially involved in the association between viral infection and asthma development. We believe that our research has great significance in pointing to a novel direction for further studies and the existence of a new key player, i.e., miRNAs, in the relationship between viral infections and asthma development.

To the Editor, A COVID-19 epidemic started in China and then disseminated to other Asian countries before becoming a pandemic. It appears that the pandemic has so far resulted in proportionately fewer deaths in China and most Eastern Asian countries. Many reasons can explain this picture.1 One of them is the type of diet in the low mortality countries. 2This paper is the sixth of a series attempting to understand the role of diet in the differences of COVID-19 death rates between and within countries with the aim to identify potential preventive measures against COVID-19. The concept paper 2 was followed by two ecological studies comparing death rates in European countries and the consumption of vegetables or fermented foods. 3,4 We then proposed that sulforaphane from cruciferous vegetables1 and lactobacilli from fermented foods (submitted) were possibly involved in the reduction of insulin resistance in COVID-19.It is noteworthy that fermented foods are largely used in Asia.5,6 It is therefore important to check whether some commonly eaten fermented foods in these countries may explain geographic differences in COVID-19. Kimchi will be used as a model of fermented cabbage.

The world has been under terror of another morbid viral pandemic which is a virus belongs to the corona virus family as SARS-COV2 (Severe acute respiratory syndrome-corona virus) related to previously existing SARS-COV (Severe acute respiratory syndrome) and MERS-COV (Middle East respiratory syndrome). It is considered to be zoonotic in origin as it is transmitted from animals to human. It presents crown like morphology with spike like protein which adheres to the surfaces of the body mainly in respiratory system. Mild symptoms like fever, dry cough, and body pain, loss of smell and taste, headache, shortness of breath appear on exposure to virus leading to major symptoms damaged lungs and drop in oxygen saturation. Pharmacological drug trials and various nutritional therapies are being used to prevent the symptoms of the infection. Researchers are developing proper vaccination to cure the infection.

Rabies is a viral zoonotic disease present in two thirds of all countries, and causes the death of one person every 10 minutes (~70,000 deaths/year). The reservoirs of the Rabies Virus (RABV) are bats and canids, and it has also been found in other animals, including Cerdocyon thous (crab-eating fox) and Pseudalopex vetulus (hoary fox). Here we used Next Generation Sequencing (NGS), phylogenetic, and in vitro/in vivo analyses, to characterized the genome of a new subtype of RABV circulating in foxes of the Northeastern region of Brazil. We verified that although these variants were similar to existing strains from wild canids and domestic canines from Brazil, the samples contained escape mutants, suggesting that it was a heterogeneous virus population. In all, we used several molecular techniques to characterize a new RABV strain circulating in wild-foxes in Northeastern Brazil, and verified still manifested its notorious pathogenic characteristics.

Understanding African swine fever virus (ASFV) transmission in a population is essential for strategies to minimize virus spread during an outbreak. ASFV can survive for extended periods of time in animal products, carcasses, and the environment. Recent studies have shown that wild boar demonstrate interest in carcasses at an advanced stage of decay and in the soil where the remains of wild boar once were. While ASFV nucleic acids have been found in the environment around infected farms, data on the survival of the virus in soil are scarce. We investigated different soil matrices spiked with ASFV-positive blood from infected wild boar to see if ASFV can remain viable in the soil beneath infected carcasses. Moreover, we tried different mitigation strategies that could be used in affected regions. As expected, ASFV genome detection was reliably possible over the full range of sampling days. Soil pH, structure, and ambient temperature played a significant role for the stability of infectious ASFV. Infectious ASFV was demonstrated in specimens originating from sterile sand for at least three weeks, and from ordinary beach sand for up to two weeks. In yard soil, infectious ASFV was demonstrated for one week, and in soil from a swampy area for three days. Virus was not recovered from two acidic forest soils. All risk mitigation experiments with citric acid or calcium hydroxide resulted in complete inactivation in our experimental setup. In conclusion, stability of infectious ASFV is almost non-existent in forest soils but rather high in sandy soils. However, given the high variability, treatment of carcass collection points with disinfectants should be considered for additional risk reduction. In this respect, biocidal nature and occupational safety have to be considered.

Rotaviruses (RVs) are a major cause of viral gastroenteritis in both animals and humans worldwide. According to the molecular and serological properties of Viral Protein 6 (VP6), RVs are classified into nine species or groups (RVA-RVD and RVF-RVJ). RVA, RVB and RVC are well-recognized as etiological agents of enteric disease on swine farms and have been identified in all countries with a relevant pork production. Contrarily, RVH has only been identified on swine farms from Japan and more recently from Brazil, USA, South Africa and Vietnam but not yet in Europe. The occurrence of RVH was investigated in 103 Spanish pig herds. Nine farms were positive and the complete nucleotide sequences were achieved for four RVH isolates. Mean nucleotide identities with the RVH sequences available in GenBak ranged between 69.4 and 93.7 %. Phylogenetically, all genomic segments of Spanish RVH isolates clustered closely with other porcine RVH strains but were distantly related to human RVH as well as bat RVH strain. Moreover, based on the available tentative genotyping system for RVH, a new genotype for VP7 was proposed. To the best of our knowledge this is the first report of RVH on swine farms in Europe including its characterization by means of complete genome sequencing.

The SARS-CoV-2 pandemic has radically changed the sta tus quo of the global society. The fast spread of the new coronavirus is governed by nonlinear dynamics. The purpose of this paper is to investigate the complex dynamics inherent by the dissemination of COVID-19 into 27 Brazilian States. Because of this, we have investigated the time series of daily death caused by COVID-19. Our analysis taking into account the Bandt & Pompe method (BPM) to estimate the Information Theory quantifiers, the Permutation entropy (Hs), and the Fisher information measure (Fs). Based on the Information Theory quantifiers we build up the Shannon-Fisher causality plane, which made it possible to study the temporal evolution inherent of the phenomenology associated with the number of daily deaths by COVID-19, as well as their respective locations along the SFCP were mapped. Our results show that the number of death cases due to COVID-19 for Brazilian States present a dynamical behavior that tends to have their starting positions close to the lower-right region at the 2-D plane (Hs x Fs). Thus, the Brazilian States located in this region or its surroundings show high entropy and lowest disorder (highest efficiency). While the Brazilian States located in the middle region of the 2-D plane (Hs x Fs) or its surroundings are depicted by a less entropic and highest disorder (lowest efficiency). We also employed the Permutation entropy and the Fisher information measure to rank the conjuncture of the Brazilian States considering the number of daily death due to COVID-19 based on the complexity hierarchy. From a mathematical point of view, we found an inverse relationship between the Permutation entropy and Fisher information measure. Given this, we concluded that the higher value of the permutation entropy (Hs)the lower value related to the Fisher information measure (Fs).

Porcine circovirus 3 (PCV3) is a newly emerged circovirus discovered in 2016, and since then is threatening the swine industry worldwide. In this study, we evaluated the presence of different PCV3 strains in swine herds from Brazil. PCV3 was detected by qPCR in different samples from different life stages. Sequencing was performed with seventeen positive samples. This study reported the coinfection of different PCV3 strains in one animal. This study provides insights into the genetic diversity of PCV3 strains circulating in the Brazilian swine herds.

Amongst newly developed approaches to analyse molecular data, phylodynamic models are receiving much attention because of their potential to reveal changes to viral populations over short periods. This knowledge can be very important for understanding disease impacts. However, their accuracy needs to be fully understood, especially in relation to wildlife disease epidemiology, where sampling and prior knowledge may be limited. The release of the rabbit haemorrhagic disease virus (RHDV) as biological control in naïve rabbit populations in Australia in 1996 provides a unique dataset with which to validate phylodynamic models. By comparing the results obtained for RHDV1 with our current understanding of the RHDV epidemiology in Australia, we evaluated the performances of these recently developed models. In line with our expectations, coalescent analyses detected a sharp increase in the virus trajectory in the first few months after the virus release, followed by a more gradual increase. The phylodynamic analyses with a birth-death tree prior generated effective reproductive number estimates (the average number of secondary infections per each infectious case, Re) larger than one for most of the epochs considered. However, the possible range of the initial Re included estimates lower than one despite the known rapid spread of RHDV1 in Australia. Furthermore, the analyses that took into account the geographical structuring failed to converge. We argue that the difficulties that we encountered most likely stem from the fact that the samples available from 1996 to 2014 were too sparse with respect to geographic and within outbreak coverage to adequately infer some of the model parameters. In general, while these Bayesian analyses proved to be greatly informative in some regards, we caution that their interpretation may not be straight forward and recommend further research in evaluating the robustness of these models to assumption violations and sensitivity to sampling regimes.

The entry of SARS-CoV-2 into host cells proceeds by a two-step proteolysis process, which involves the lysosomal peptidase cathepsin L. Inhibition of cathepsin L is therefore considered an effective method to prevent the virus internalization. Analysis from the perspective of structure-functionality elucidates that cathepsin L inhibitory proteins/peptides found in food share specific features: multiple disulfide crosslinks (buried in protein core), lack or low contents of α-helix structures (small helices), and high surface hydrophobicity. Lactoferrin can inhibit cathepsin L, but not cathepsins B and H. This selective inhibition might be useful in fine targeting of cathepsin L. Molecular docking indicated that only the carboxyl-terminal lobe of lactoferrin interacts with cathepsin L and that the active site cleft of cathepsin L is heavily superposed by lactoferrin. Food protein-derived peptides might also show cathepsin L inhibitory activity.

Background and Purpose: Currently there are no licensed vaccines and limited antivirals for the treatment of COVID-19. Heparin (delivered systemically) is currently being used to treat anticoagulant anomalies in COVID-19 patients. In addition, in the UK, nebulised unfractionated heparin (UFH) is currently being trialled in COVID-19 patients as a potential treatment. A systematic comparison of the potential antiviral effect of various heparin preparations on live wild-type SARS-CoV-2, in vitro, is thus urgently needed. Experimental Approach: A range of heparin preparations both UFH (n=4) and low molecular weight heparins (LMWH) (n=3) of porcine or bovine origin were screened for antiviral activity against live SARS-CoV-2 (Victoria/01/2020) using a plaque reduction neutralisation assay and Vero E6 cells. ND50 values for each heparin were calculated using a mid-point probit analysis. Key Results: UFH had potent antiviral effects, with ND50 values of 12.5 and 23 μg/ml for two porcine mucosal UFH tested. Bovine mucosal UFH had similar antiviral effects although it was ~50% less active (ND50, 50-75 μg/ml). In contrast, LMWHs such as Clexane and Fragmin were markedly less active by ~100-fold (ND50 values of 2.6-6.8 mg/ml). Conclusions and Implications: This comparison of a panel of clinically relevant heparins, including the UFH preparation under trial in the UK, demonstrated that distinct products exhibit different degrees of antiviral activity against live SARS-CoV-2. Porcine mucosal UFH has the strongest antiviral activity followed by bovine mucosal UFH, whereas LMWHs had the lowest amount of antiviral activity (by 100-fold). Overall the data strongly support further clinical investigation of UFH as a potential treatment for patients with COVID-19.

The disbalance of the renin-angiotensin system was suggested to play an important role in the pathogenesis of the COVID-19 disease. Previously it has been shown that ACE2 expression in downregulated in the murine model in response to SARS-CoV infection and may be also induced by the recombinant spike protein alone. We hypothesize that the soluble SARS-CoV-2 spike protein S1 subunits shed from the infected cells and from the virions in vivo may bind to the ACE2 receptor and trigger ACE2 downregulation. Decreased ACE2 activity on the background of the constant or increased ACE activity in the lungs may lead to the prevalence of angiotensin II effects over angiotensin(1-7) connected to increased thrombosis, inflammation and pulmonary damage.

EDITORIAL Coronavirus disease‐19 (COVID‐19) is a new disease caused by SARS‐CoV2. Since the beginning of 2020, it has become one of the main challenges of our times, causing a high incidence of severe pneumonia, acute respiratory distress syndrome (ARDS), multiorgan failure and death1. At the root of COVID-19 lies the sudden development of ‘cytokine storms’, hyper-inflammatory responses involving the release of pro-inflammatory cytokines (e.g., TNF-α, IL-6, IL-1, IL-8, and MCP-1) that impair the gas exchange function of the lung and lead in select patients, mostly with underlying comorbidities, to multiorgan failure and death1,2. Additional complications triggered by ‘cytokine storms’ include endothelial dysfunction and hypercoagulation, increasing the risk of thromboembolytic events, and life-threatening cardiovascular complications. Anti-inflammatory therapies are thus being considered for alleviating the damaging side effects of hyper-inflammation with many trials including anti-cytokine biologicals, disease-modifying antirheumatic drugs (DMARDs) and corticosteroids being ongoing3. Surprisingly, among them dexamethasone has taken center stage as initial results from the RECOVERY trial, a large multicenter randomized open-label trial for hospitalized patients run in the United Kingdom, revealed notable efficacy in the treatment of critically ill COVID-19 patients4.Dexamethasone is one of the oldest synthetic glucocorticoid agonists synthesized in 1957 and introduced into the clinic in 1961. When administered at 6 mg daily, either orally or intravenously for 10 days, dexamethasone was shown in the RECOVERY trial to improve survival rates of hospitalized patients with severe COVID-19 receiving oxygen or being on mechanical ventilation by a remarkable 30%4. Benefit was restricted to patients requiring respiratory support whereas in milder cases this was not clear. This notable efficacy of dexamethasone treatment goes against the current view of corticosteroid use in respiratory viral infections which remains contradictory. Although corticosteroids improve ventilator weaning and can lower the intensity of the host response to the virus, tempering the ‘cytokine storm’ and limiting immunopathology, they can also reduce viral clearance and lead to more severe disease. Understanding therefore how dexamethasome mediates its effects is of paramount importance.Dexamethasone, as other corticosteroids, is held to mediate its anti-inflammatory and immunosuppressive effects via the glucocorticoid receptor. Upon ligand binding, the receptor-corticosteroid molecule complex moves into the cell nucleus, where it dimerizes and binds to glucocorticoid response elements (GRE), acting as transcriptional repressor or transactivator of diverse sets of genes. This results in the inhibition of inflammatory cell activity, including neutrophils, macrophages and lymphocytes, and the suppression of pro-inflammatory cytokines such as TNF and interleukins and other genes such as cyclooxygenase-2 and inducible nitric oxide synthase5. However, we have recently uncovered that dexamethasone can also induce the D-series proresolving lipid mediator pathway leading to the production of 17-HDHA and the protectins D1 and DX6. These are potent major players of the molecular machinery driving the resolution of inflammation, i.e. the proper regulated termination of pro-inflammatory responses involving the catabolism of pro-inflammatory mediators, the removal of inflammatory cells and the restoration of the tissue in a timely and highly coordinated manner7. Although resolution of inflammation has long been considered to occur spontaneously as a result of the waning of pro-inflammatory responses, this is now known to be an ordered and highly regulated process involving the timely production of enzymatically oxygenated lipid-derived mediators such as protectins, D-series resolvins and maresins derived from the omega-3 fatty acid docosahexaenoic acid (DHA), E-series resolvins derived from eicosapentaenoic acid (EPA), and lipoxins biosynthesized from omega-6 fatty acids following eicosanoid class switching7. Interestingly, certain lipid mediators have been shown to exert additional non-conventional functions; resolvin D4 can attenuate pathologic thrombosis, reduce NETosis and promote clot removal8 which is now recognized as a key pathology of COVID-19 infection, while resolvin E4 (RvE4) stimulates efferocytosis of senescent erythrocytes in hemorrhagic exudates especially under hypoxic conditions that characterize COVID-199. Moreover, corticosteroids have been reported to reduce fibrinogen and procoagulant factors under pro-inflammatory conditions and increase anticoagulant factors10.The ability of viral infections to induce proresolving lipids has been reported earlier. Toll-like receptor 7 (TLR7), a major pattern recognition receptor of viral RNA, activates PD1 and PDX production11. Moreover, influenza virus infection has been demonstrated to drive proresolving lipid mediator networks including the production of PD1 which limits influenza pathogenicity by directly interacting with the RNA replication machinery to inhibit viral RNA nuclear export12,13. Notably, in particularly virulent strains of influenza virus such as the H5N1 avian strain, PD1 formation is not sufficiently upregulated, leading to more efficient viral replication and host demise12. It is therefore plausible that the efficacy of dexamethasone in COVID-19 is due at least in part to its ability to induce proresolving lipid mediators that possess multiple anti-inflammatory and proresolving actions tempering down inflammation and promoting its resolution, preventing coagulation and enhancing viral and bacterial clearance (Figure 1) yet are not immunosuppressive . Whether other corticosteroids beyond dexamethasone can also mediate such effects, and to what extent, is not known. Whether inhalable corticosteroids, such as those given to asthmatic patients, can also induce proresolving lipid mediator networks locally and thus prevent the development of severe SARS‐CoV‐2 infection remains to be determined. There is evidence that asthmatic patients exhibit reduced incidence of severe and/or critical COVID-1914.Recently, COVID-19 patients showed increased association of serum arachidonate-derived proinflammatory lipid mediators, e.g. prostaglandins, in severe COVID -19 infections while some pro-resolving mediators such as resolvin E3 were up-regulated in the moderate COVID-19 group suggesting that an imbalance in lipid mediators with a swift toward pro-inflammatory mediators in severe disease may contribute to COVID-19 disease severity15. Although the involvement of proresolving lipid mediator pathways in COVID-19 is an attractive hypothesis, further evidence from human trials is needed as there are no studies at present reporting the induction or modulation of such networks in the context of the various disease stages and treatments. It is thus of uttermost priority to investigate proresolving lipid mediators in COVID-19, in a temporal and longitudinal manner, as modulating these networks either through drug treatment or direct administration of resolvin and protectins agonists has the potential to affect this highly lethal and devastating disease in a way other approaches cannot. Such studies are therefore eagerly awaited.

Poly (ADP-ribose) polymerase 1 (PARP1) is a post-translational modifying enzyme and is also known to act as transcription factor and co-activator. PARP1 has been shown to be involved with diseases resulting in increased inflammation and several viral diseases have also been associated with PARP1 activation. PARP1 facilitates influenza A virus entry in host cells by degrading interferon receptor type I. PARP1 regulates expression of NFkB and downstream cytokine production and its inhibition is known to attenuate the expression of inflammatory cytokines. Thus, PARP1 plays an important role in host-pathogen interactions and pathogenesis. Moreover, pre-clinical and in vitro studies have shown that PARP1 inhibition may affect viability of several viruses including affecting replication of the SARS-CoV virus, a distant relative of the SARS-CoV-2 virus, the one which caused the SARS epidemic of 2002. Covid-19 has been declared a global pandemic; with symptoms of the disease now not limited to respiratory distress alone. Severe inflammation is observed in the lungs leading to a surge of cytokine release systemically, affecting heart function, ischemia and stroke. Inflammatory cytokines which are associated with severe comorbidities and mortalities due to chronic diseases are being upregulated in an acute fashion. There is no immediate treatment, and only palliative care is being provided. The current review will discuss mechanisms of PARP1 activation during viral infection, inflammatory diseases, cytokine expression and possibility of PARP1 in regulating cytokine storm and hyper-inflammation seen with Covid-19.

A document by Cristine Rosário, written on Authorea.

Being able to link clinical outcomes to SARS-CoV-2 virus strains is a critical component of understanding COVID-19. Here we discuss how current processes hamper sustainable data collection to enable meaningful analysis and insights. Following ‘Fast Healthcare Interoperable Resource’ implementation guide, we introduce an ontology-based standard questionnaire to overcome these shortcomings and describe patient “journeys” in coordination with the World Health Organization. We identify steps in the clinical health data acquisition cycle and workflows that likely have the biggest impact in the data-driven understanding of this virus.

The coronavirus disease-2019 (COVID-19) is an infectious respiratory disease attributed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has rapidly spread globally leading to a pandemic. Frequently, COVID-19 contributes to multiple cardiovascular diseases (CVD) including acute myocardial injury, myocarditis, arrhythmias and thromboembolism, due to excessive inflammation and endothelial dysfunction. Moreover, a large proportion of affected patients, especially for elderly patients have been reported to pre-exist comorbidities such as hypertension, diabetes and CVD. However, although some antiviral drugs targeted SARS-CoV-2 have been applied to clinical trial, a few of these investigational agents are associated with excess risk for cardiovascular events in prior studies of non-COVID-19 populations. The objective of this document is to introduce the cardiovascular complications caused by COVID-19 and related investigational therapies, as well as the potential consequences in patients with antiviral drugs and cardiovascular drugs, and then provide recommendations for a systematic approach on the care of patients with CVD during COVID-19 pandemic.

Background and Purpose: Lack of suitable experimental models hinders SARS-CoV-2 research. Reports denote SARS-CoV-2 uses ACE2, TMPRSS-2 as its primary receptors. However, SARS-CoV-2 clinical symptoms were also related to organs with poor or no expressions of primary receptors. Hence, using single-cell RNA sequencing data of human organoids, we analyzed expression levels of primary receptors and array of RNA receptors for their involvement in SARS-CoV-2 pathogenesis. Experimental Approach: From the gene expression omnibus (GEO) or array express database, normalized cell counts of human intestine coventional, intestine improved, prostate, kidney morizane, kidney takasato, brain, retinal, lung organoids were obtained. Individual cell types, RNA receptor expressions in ACE2 (+) and ACE2(-) cells were analyzed. Using immune enrichment analysis, immune pathway activation in ACE2(+) and ACE2(-) cells were determined. Key Results: ACE2 expression is abundant in all organoid, except prostate and brain, while TMPRSS2 is omnipresent. Innate immune component pathways are upregulated in ACE2 (+) cells in all organoids, except lung. Besides, expression of low-density lipoprotein receptor (LDLR) is highly enriched in ACE2 (+) cells in intestinal (conventional and improved), lung, and retinal organoids, with highest expression in lung organoids. Other than primary receptors, LDLR and HDLR might also exert crucial role SARS-CoV-2 pathogenesis. Conclusion and Implications: Mimicing Invivo niche, with array of cell types expressing primary and RNA receptors, immune pathways activation, human organoids will be suitable model for rapid SARS-CoV-2 translational research. Other than ACE2 and TMPRSS2, LDLR and HDLR with moonlighting functions can be useful targets in SARS-CoV-2 clinical management.

Inclusion body hepatitis and hydropericardium syndrome (HHS) associated with fowl adenovirus (FAdV) infections occurred worldwide. In this study, we confirmed an outbreak of HHS in captive peacocks in Henan Province, China. The causative agent fowl adenovirus serotype 4 (FAdV-4) was isolated and designated HN19. Phylogenetic analysis showed that HN19 isolate was clustered in FAdV-C. Animal experiments showed that HN19 exhibited high pathogenicity to chickens. The findings suggested that the possibility risk of cross-host transmission of FAdV-4.

Dear Editor,We read the article on possible effects of BCG vacaccine in COVID-19 management should be discouraged and restricted to research purpose only.2