West Nile Disease is a zoonotic vector-borne infection involving viral pathogens, human and animal hosts, vectors and habitats with a complex transmission cycle. Cooperation among different disciplines has been promoted by the Italian Public Health Authorities to introduce a robust surveillance system and an integrated West Nile Virus (WNV) Surveillance Plan has been in force in Italy since 2016, in order to establish a medical, veterinary and entomological network. This represents a unique model in Europe. This study aims to present this “One Health” approach applied following the first recorded autochthonous case of West Nile Neuroinvasive Disease (WNND) in Sicily (Southern Italy). Serological and molecular tests were conducted on the blood, liquor and urine of a 38-year-old man with encephalitis and meningitis: WNND was confirmed by serological analysis on liquor and serum. Consequently, a veterinary and entomological surveillance was started. Overall, 160 mosquito catches were collected from six different sampling sites and 2704 adult culicides were morphologically identified. Female mosquitoes were analyzed in pools for WNV RNA detection. Serological and molecular assays for WNV were carried out in 11 horses, 271 chickens and 2 dogs sampled in farms around the man’s residence. Collected mosquito species included Culex pipiens (93.6%), Aedes albopictus (5.25%), Culex hortensis (0.6%), Culiseta longiareolata (0.55%) and Anopheles maculipennis s.l. (0.04%). Mosquito pools were negative for WNV nucleic acid presence. Two dogs (100%) and two horses (18.2%) resulted positive for WNV-specific IgG antibodies. Since WNND epidemiology is influenced by several ecological factors and by the presence of several animal and vector species, the integrated surveillance system was crucial for understanding whether the virus had circulated/was circulating in the suburban, urban area and for preventing the spread of infection.

Letter to the editor

Avian leukosis virus subgroup J (ALV-J) is the most prevalent subgroup in chickens and exhibits increasing pathogenicity and stronger horizontal and vertical transmission ability in different kinds of chicken. Although vertical transmission of ALV-J from hens infected through artificial insemination with ALV-J infected semen was reported before by the detection of swabs and serum, there was no further research on the trasmission pattern of ALVs in the roosters. In the present study, the introduction of Hy-line brown roosters infected with ALV-J significantly increased the p27 positive rate of ALV in a indigenous flock detected by virus isolation. Sequence analysis and IFA showed that it is classified into ALV-J subgroup, locating in a new branch compared with the domestic and foreign referential sequences. Meanwhile, the gp85 gene of the ALV-J isolated in the hens and its albumens had a homology of 94.1-99.7% with that in the roosters, which means that the strain is quite likely transmitted to the hens and their offspring through insemination of the roosters. Moreover, Semens are directly detected by ELISA method is not completely accurate. There are four ALV-J infection status in plasma and semen of rooster (V+S+, V-S+, V+S-, V-S-), so the eradication of ALV in rooster requires simultaneous virus isolation of semen and plasma. Therefore, we speculate that the reason why there are still some sporadic findings of ALV-J in laying hens is probably due to the incomplete eradication process of roosters.

Since the beginning of the current coronavirus 2019 (COVID-19) outbreak, an intense number of studies have been done in an attempt to discover effective therapies, not only from the point of view of discovering new drugs, but also from its repurposing. Recent studies have proposed tranexamic acid (TXA), a hemostatic drug widely used in clinical practice, as a potential therapeutic option for COVID-19 as it reduces plasmin levels. Thus, this letter to the editor aims to provide a critical overview on the use of TXA in the treatment of the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection.

Persistent infection and tumourigenesis by papillomaviruses (PVs) require viral manipulation of various of cellular processes, including those involved in innate immune responses. Herein, we showed that bovine PV (BPV) E5 oncoprotein interacts with a tripartite motif-containing 25 (TRIM25) but not with Riplet in spontaneous BPV infection of urothelial cells of cattle. Statistically significant reduced protein levels of TRIM25, retinoic acid-inducible gene I (RIG-I), and melanoma differentiation-associated gene 5 (MDA5) were detected by Western blot analysis. Real-time quantitative PCR revealed marked transcriptional downregulation of RIG-I and MDA5 in E5-expressing cells compared with healthy urothelial cells. Mitochondrial antiviral signalling (MAVS) protein expression did not vary significantly between diseased and healthy cells. Co-immunoprecipitation studies showed that MAVS interacted with a protein network composed of Sec13, which is a positive regulator of MAVS-mediated RLR antiviral signalling, phosphorylated TANK binding kinase 1 (TBK1), and phosphorylated interferon regulatory factor 3 (IRF3). Immunoblotting revealed significantly low expression levels of Sec13 in BPV-infected cells. Low levels of Sec13 resulted in a weaker host antiviral immune response, as it attenuates MAVS-mediated IRF3 activation. Furthermore, western blot analysis revealed significantly reduced expression levels of pTBK1, which plays an essential role in the activation and phosphorylation of IRF3, a prerequisite for the latter to enter the nucleus to activate type 1 IFN genes. Our results suggested that the innate immune signalling pathway mediated by RIG-I-like receptors (RLRs) was impaired in cells infected with BPVs. Therefore, an effective immune response is not elicited against these viruses, which facilitates persistent viral infection.

Porcine parvoviruses (PPVs) and porcine circoviruses (PCVs) infect pigs worldwide, with PPV1-7 and PCV2 infections common in pigs. Although PPV7 was only identified in 2016, co-infection of PPV7 and PCV2 is already common and PPV7 may stimulate PCV2 replication. PCV3, a novel type of circovirus, is prevalent worldwide and believed to cause reproductive disorders and dermatitis nephrotic syndrome. In recent studies, pigs were commonly infected with both PCV3 and PPV7. Our objective was to investigate co-infections between PPV7 and PCV3 in samples from swine on farms in Hunan, China, and assess potential impacts of PPV7 on PCV3 viremia. A total of 399 porcine serum samples, negative or positive for PCV3, were subjected to real-time PCR to detect PPV7; of these samples, 190 were from farms with long-standing histories of reproductive failure (RF) and were selected to determine whether PPV7 affected PCV3 viremia. Among 209 serum samples, 23% (48/209) were positive for PPV7 and the PPV7-positive rate was significantly higher in PCV3 positive serum (31.4%) than negative serum (14.4%). Among 190 serum samples, 45.1% (28/62) were positive for PPV7 and PCV3 and the PPV7-positive rate was significantly higher in PCV3 positive RF-serum (51.2%) than in non-PCV3 RF-serum (34.8%); furthermore, there was a higher PPV7 prevalence (55%) in PCV3-positive aborted fetus samples. In addition, the Ct value of PCV3 in PPV7 positive samples was significantly lower than that in PPV7 negative serum samples. Based on our findings, we concluded that PPV7 may stimulate PCV3 replication.

Caprine parainfluenza virus type 3 (CPIV3) was first identified in goats named JS2013 in China. In 2019, a sheep herd broke a disease with respiratory disease in Hebei province, China. In order to confirm the pathogen of the disease, the nasal swabs, stool swabs and blood samples were collected from the sheep. Virus isolation was performed on MDBK cells and identification was conducted by RT-PCR. The complete genome of the isolate was sequenced and phylogenetic analyzed. In order to evaluate the pathogenicity of the virus, five seronegative sheep were experimental infected with the virus suspension. The phylogenetic analyses based on the complete genome and the M gene indicated that the isolate strain was distinguished distinct from previously reported CPIV3 lineage of JS2013. The virus-inoculated sheep displayed the syndrome with depression, cough, and fever. Virus shedding were detected by RT-PCR from nasal swabs. All infected showed virus shedding during 2 - 21dpi and viremia could be detected in serum samples. Gross pathological assessment of sheep in infected group showed gross lesion in the lungs. Histopathological observation results indicated that lungs had mild to moderate interstitial pneumonia , with thickened alveolar walls, decreased alveolar space, and increased amounts of inflammatory cells infiltration. This is the first report of pathogenicity of the novel lineage of sheep-derived CPIV3. The results would be helpful for further studies on the prevention and control strategies for CPIV3 infections in goat and sheep.

Abstract – Highly pathogenic bovine Delta papillomaviruses (δPVs) were detected and quantified for the first time using digital droplet polymerase chain reaction (ddPCR) by liquid biopsy in 103 clinically healthy sheep. Overall, ddPCR detected bovine δPVs in 68 blood samples (66%). Bovine papillomavirus (BPV) infection by a single genotype was revealed in 59% of the blood samples, and BPV coinfection by double, triple or quadruple genotypes was observed in 41% of liquid biopsies. The BPV-2 genotype was most frequently seen in sheep, whereas BPV-1 was the least common. Furthermore, ddPCR was very useful for detection and quantification; the BPV-14 genotype was observed for the first time in ovine species, displaying the highest prevalence in some geographical areas (Apulia). In 42 of the positive samples (61.8%), a single BPV infection was observed, 26 of which were caused by BPV-2 (61.9%) and 7 by BPV-13 (16.7%). BPV-14 was responsible for 7 single infections (16.7%) and BPV-1 for 2 single infections (4.7%). Multiple BPV coinfections were observed in the remaining 26 positive samples (38.2%), with dual BPV-2/BPV-13 infection being the most prevalent (84.6%). BPV infection by triple and quadruple genotypes was also observed in 11.5% and 3.8% of cases, respectively. The present study showed that ddPCR, a biotechnological refinement of conventional PCR, is by far the most sensitive and accurate assay for BPV detection. Therefore, ddPCR displayed diagnostic and epidemiological value resulting in the identification of otherwise undetectable BPV genotypes as well as their geographical distributions and suggesting that animal husbandry practices contribute to cross-species transmission of BPVs.

Peste des petits ruminants (PPR) is an acute, highly contagious, world organization for animal health (OIE) notifiable and economically important transboundary viral disease of sheep and goats and caused by PPR virus (PPRV), which belongs to the genus Morbillivirus of the family Paramyxoviridae. The disease is endemic across Asia, the Middle East and African regions and is considered to be a major obstacle to the development of sustainable agriculture across the developing world due to huge burden for the economy and development of the affected countries and has recently been targeted by the OIE and the Food and Agriculture Organization (FAO) for eradication with the aim of global elimination of the disease by 2030. In this review, the regional epidemiology of PPR outbreaks and associated risk factors with special reference to the PPR-affected countries in South， Central and East Asia is comprehensively discussed.

Objective: This systematic review and meta-analysis was aimed to evaluate the therapeutic benefits and safety of tocilizumab (TCZ) in treating severe coronavirus disease 2019 (COVID-19) and associated health complications. Methods: The electronic search was performed using PubMed, Scopus, CENTRAL (Cochrane Central Register of Controlled Trials (RCTs) and Google scholar databases to identify the randomized control trials. Mortality, incidences of ICU admission, need of mechanical ventilation (MV), length of stay in the hospital (LOS) and length of stay in the ICU (LOS-ICU) and the incidences of super-infection, bacteraemia, fugleman, pneumonia and pulmonary thrombosis were evaluated as the primary outcomes. The comparison will be between TCZ versus standard of care (SOC)/placebo. Results: Based on the inclusion criteria there were 24 retrospective studies involving 5686 subjects were included. The outcomes of the meta-analysis have revealed that the TCZ has reduced the mortality (Mantel-Haenszel (M-H), random effects risk difference (RE-RD) of -0.11 (-0.18 to -0.04), at 95% CI, p = 0.001, I2 = 88%) and increased the incidences of super-infections (M-H, RE-Risk ratio (RR) of 1.49 (1.13 to 1.96) at 95% CI, p=0.004, I2 = 47%). However, there is no significant difference in ICU admissions rate, need of MV, LOS, LOS-ICU, and incidences of pulmonary thrombosis compared to SOC/control. Conclusion: Based on the outcomes of the meta-analysis we can conclude that administration of TCZ would reduce the risk of mortality, and however there is no much difference observed between the TCZ and SOC/control groups in other parameters.

The emergence of novel coronavirus infectious disease-2019 (COVID-19) in December 2019, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has traumatized the whole world with the ongoing devastating pandemic. After droplet mediated transmission of infectious virus particle, and subsequent tissue tropism through the upper and lower respiratory tract, the acute clinical disease is manifested by severe respiratory illness accompanied by shortness of breath, progressive pneumonia, multi-organ dysfunction and ultimate death in SARS-CoV-2 infected patients. The involvement of other microbial co-infections leading to extortionate ailment in critically ill patients has not been significantly reviewed along with conclusive reporting on underlying molecular mechanisms in COVID-19 patients. Although the incidence of co-infections could be up to 94.2% in laboratory-confirmed COVID-19 cases, the fate of co-infections among SARS-CoV-2 infected hosts often depends on the balance between the host’s protective immunity and immunopathology. The cross-talk between co-pathogens (especially lung microbiomes), SARS-CoV-2 and host is an important factor that ultimately increases the difficulty of diagnosis, treatment, and prognosis of COVID-19, and even increase the symptoms and mortality of the disease. Simultaneously, co-infecting microorganisms may use new strategies to escape host defense mechanisms (by altering both innate and adaptive immune responses) to further aggravate SARS-CoV-2 pathogenesis. This review of literature suggests that clinicians should rule out SARS-CoV-2 infection by ruling in other respiratory co-pathogens, and must have a high index of suspicion for co-infection among COVID-19 patients. Thus, after recognizing the possible pathogens causing co-infection among COVID-19 patients, and the underlying molecular mechanisms of co-infections appropriate curative and preventive interventions can be recommended.

An experimental compound (CNS004), reported to have various biological activities including antiviral, antimalarial, antiprotozoal and immunomodulatory effects, has been identified to potentiate NMDA subtype of glutamate receptors that are expressed in human lungs and central nervous system. We hypothesize that potentiating NMDA receptors will increase calcium ion influx and promote downstream signaling mechanisms associated with cellular contractions which is disrupted in severe acute respiratory syndrome. Pharmacological effects generated by triggering central nervous system glutamate receptor function, coupled with concurrent stimulation of the respiratory tract, may produce a synergetic effect in improving the airway smooth muscle function. Further, an antiviral activity combined with immunomodulatory effect of this experimental compound may improve the symptoms of viral diseases. This novel multipronged intervention to simultaneously inhibit viral proteins and promote host cell functions would be helpful to develop clinically useful compounds for the treatment of emerging viral diseases that deteriorate peripheral and central nervous system function before causing death in human beings.

The global distribution of canine parvovirus (CPV-2), derived from a closely related carnivore parvovirus, has caused a considerable threat to the dog population. The virus continuously underwent genetic evolution, giving rise to several variants. To investigate the prevalence of Chinese CPV-2 strains in recent years, a total of 25 CPV-2 strains were isolated from 33 canine samples collected from 2018 to 2020, and then sequenced and analyzed. Two variants, New CPV-2a and CPV-2c were identified. Contrary to previous reports, the CPV-2c variant has gained an epidemiological advantage over the New CPV-2a variant in China. To make up for the relatively limited sample, 683 Chinese CPV-2 records identified between 2014 to 2019 were retrieved from Genbank and associated publications, whose result further supported our finding. That should be caught concern since the CPV-2c variant has been frequently related to vaccine failure in adult dogs. VP2 protein sequences analysis revealed several amino acid substitutions, including Ala5Gly, Pro13Ser, Phe267Tyr, Tyr324Ile, Gln370Arg, Thr440Ala, and Lys570Arg. Phylogenetic analysis indicated a close relationship between Chinese strains with Asian strains, suggesting the mutual transmission between Asian countries. Furthermore, the intercontinental transmission should be a cause for concern. Surprisingly, two feline panleukopenia (FPLV) strains with Ile101Thr mutation in VP2 protein were also successfully isolated from canine fecal samples, which was considered incapable of infecting dogs. This study clarified the epidemic characteristics of Chinese CPV-2 strains between 2014 and 2019, offering a reference for epidemic control. Besides, the detection of FPLV in canine samples may provide information for future studies on the evolution of carnivore parvovirus.

Influenza viruses are highly variable pathogens that infect a wide range of mammalian and avian species. According to the internal conserved proteins (nucleoprotein: NP, and matrix proteins: M), these viruses are classified into type A, B, C, and D. Influenza A virus in swine is of significant importance to the industry since it is responsible of endemic infections that lead to high economic loses derived from poor weight gain, reproductive disorders, and the role it plays in Porcine Respiratory Disease Complex (PRDC). To the date, swine influenza virus (SIV) diagnosis keeps on being based in complex and expensive technologies such as RT-qPCR. In this study, we aimed to improved actual tools by the implementation of new bioreceptors molecules; aptamers. First, three different aptamers have been selected using the recombinant NP of Influenza A virus expressed in insect cells, as target. Then, these molecules have been used for the development of an Enzyme-Linked AptaSorbent Assay (ELASA) in combination with specific monoclonal antibodies for Influenza A detection. A total of 171 field samples (nasal swabs) have been evaluated with the newly developed assay obtaining a 79.7 % and 98.1 % sensitivity and specificity respectively, using real time RT-PCR as standard assay. These results suggest that the assay is a promising method that could be used for Influenza A detection in analysis laboratories facilitating surveillance labours.

Here we described brain lesion in young captive lions after exhibiting ataxia. The histopathological analyses of the brain showed typical encephalitis with glial cell proliferation, neuronal atrophy and necrosis, and encephalomalacia. We used a variety of identification methods, including next-generation sequencing, polymerase chain reaction (PCR), virus isolation, immunofluorescence staining (IFA), and electron microscopy. Combined with clinical manifestations of the infected cub, it determined that the dead cub have resulted from an FPV embryonic infection. Through sequence analysis, it was found that the infected virus may be a recombinant virus between FPV and CPV. this study not only provides new gene sequences for the global study of FPV-infected lions but also helps to further study the incidence and genetic diversity of FPV.

Background: Most recently, murine kobuvirus (MuKV), a novel recognized member of the family Picornaviridae, has been initially identified from fecal samples of Rattus norvegicus in China. The circulation of MuKV from other murine rodent species is not fully understood, prompted us to investigate the prevalence and genetic characterization of MuKV in Rattus losea, Rattus tanezumi and Rattus norvegicus in Southern China. Results: Between 2015 and 2017, a total of 243 fecal samples from three murine rodent species were screened for the presence of murine kobuvirus (MuKV) from three cities in Southern China, with an overall prevalence of 23.0% (56/243). Phylogenetic analysis based on the complete VP1 gene suggested our sequences were genetically closely related to each other and the Chinese strains. Three complete polyprotein nucleotide sequences of MuKV and the genome organization were acquired in the present study. Phylogenetic analyses also showed our sequences belong to the members of genus Kobuvirus within the genotype of Achivirus A. Conclusion: The present study indicated that MuKV is very common in murine rodent populations.

Background: Although avian coronavirus infectious bronchitis virus (IBV) and SARS-CoV-2 belong to different genera of the Coronaviridae family, exposure to IBV may result in the development of cross-reactive antibodies to SARS-CoV-2 due to homologous epitopes. We aimed to investigate whether antibody responses to IBV cross-react with SARS-CoV-2 in poultry farm personnel who are occupationally exposed to aerosolized IBV vaccines. Methods: We analyzed sera from poultry farm personnel, COVID-19 patients, and pre-pandemic controls. IgG levels against the SARS-CoV-2 antigens S1, RBD, S2, and N and peptides corresponding to the SARS-CoV-2 ORF3a, N, and S proteins as well as whole virus antigens of the four major S1-genotypes 4/91, IS/1494/06, M41, and D274 of IBV were investigated by in-house ELISAs. Moreover, live-virus neutralization test (VNT) was performed. Results: A subgroup of poultry farm personnel showed elevated levels of specific IgG for all tested SARS-CoV-2 antigens compared to pre-pandemic controls. Moreover, poultry farm personnel, COVID-19 patients, and pre-pandemic controls showed specific IgG antibodies against IBV strains. These antibody titers were higher in long-term vaccine implementers. We observed a strong correlation between IBV-specific IgG and SARS-CoV-2 S1-, RBD-, S2-, and N-specific IgG in poultry farm personnel compared to pre-pandemic controls and COVID-19 patients. However, no neutralization was observed for these cross-reactive antibodies from poultry farm personnel using the VNT. Conclusion: We report here for the first time the detection of cross-reactive IgG antibodies against SARS-CoV-2 antigens in humans exposed to IBV vaccines. These findings have implications for future vaccination strategies and possibly cross-reactive T cell immunity.

The results of the investigation of the exact nature of the mechanisms that ensure the organism's survival in the face of the pathogen's pathological effects reveal those severe co-occurring manifestations that are temporally linked to a pathogen, such as those which appear in COVID-19 patients, to be manifestations of different diseases which are brought about through the same pathway under the influence of different causes which include the pathogen. Since the single pathway through which all of such diseases, which have the same "immunological nature," are brought about must be blocked for the attenuation of the influence of the pathogen to bring about the remission of the disease it causes, such diseases will undergo simultaneous remission when conditions permit immune mechanisms to attenuate the causative influences of the pathogen. Therefore, when conditions do not permit immune mechanisms to attenuate the influence under which any of the diseases in the same "immunological spectrum" as the disease the pathogen causes is produced through the pathway, the manifestations of such diseases that are linked with the pathogen will persist despite treatments that reduce pathogen load and the pathogen will appear to be resistant to treatment. These results throw light on the different immunological phenomena which include those that inspired variolation and vaccination, remissions that are temporally linked with infection, the multiorgan manifestations that are seen in COVID-19 as well as long COVID.

Background and Purpose: Peptides derived from retroviral envelope proteins have been shown to possess a wide range of immunosuppressive and anti-inflammatory activities. We have previously reported identification of such a peptide derived from the envelope protein coded by a human endogenous retrovirus (HERV). In this study we assessed effects of this peptide treatment on inhibition of immune response in the DSS-induced mice model of colitis. Furthermore, we identified that in vitro the peptide inhibits the KCa3.1 potassium channel, a potential target for therapy of immune diseases. Experimental Approach: We characterized an immunosuppressive peptide ENV59, from a specific HERV envelope protein, in vivo effects on inflammation control in acute colitis mice model and in vitro on the production of pro-inflammatory cytokines. Furthermore, we described in vitro ENV59-GP3 effects with respect to potency of inhibition on KCa3.1 channels and calcium influx. Key Results: ENV59-GP3 peptide treatment showed reduction of the disease score in the DSS-induced acute colitis mice model, which was comparable to effects of the KCa3.1 channel blocker NS6180. Analysis of cytokine production from DSS-mice model treated animals revealed equipotent inhibitory effects of the ENV59-GP3 and NS6180 compounds on the production of IL-6, TNF-α, IL-1β. Patch clamp studies show that the peptide ENV59-GP3 is a blocker of the potassium channel KCa3.1. Conclusion and Implications: Env59-GP3 represents KCa3.1 channel inhibitor underlining the implications of using virus derived channel blockers for treatment of autoimmune diseases. There are no drugs with a similar mechanism of action currently on the market.

Non-steroidal anti-inflammatory drugs (NSAIDs) and other eicosanoid pathway modifiers are among the most ubiquitously used medications in the general population. Their broad anti-inflammatory, antipyretic and analgesic effects are applied against symptoms of respiratory infections, including SARS-CoV-2, as well as in other acute and chronic inflammatory diseases that often coexist with allergy and asthma. However, the current pandemic of COVID-19 also revealed the gaps in our understanding of their mechanism of action, selectivity and interactions not only during viral infections and inflammation, but also in asthma exacerbations, uncontrolled allergic inflammation, and NSAIDs-exacerbated respiratory disease (NERD). In this context, the consensus report summarises currently available knowledge, novel discoveries and controversies regarding the use of NSAIDs in COVID-19, and the role of NSAIDs in asthma and viral asthma exacerbations. We also describe here novel mechanisms of action of leukotriene receptor antagonists (LTRAs), outline how to predict responses to LTRA therapy and discuss a potential role of LTRA therapy in COVID-19 treatment. Moreover, we discuss interactions of novel T2 biologicals and other eicosanoid pathway modifiers on the horizon, such as prostaglandin D2 antagonists and cannabinoids, with eicosanoid pathways, in context of viral infections and exacerbations of asthma and allergic diseases. Finally, we identify and summarise the major knowledge gaps and unmet needs in current eicosanoid research.

Background and Purpose: People with COPD are susceptible to respiratory infections which exacerbate pulmonary and/or cardiovascular complications, increasing their likelihood of death. The mechanisms driving these complications remain unknown but increased oxidative stress has been implicated. Here we investigated whether influenza A virus (IAV) infection, following chronic cigarette smoke (CS) exposure, worsens vascular function and if so, whether the antioxidant ebselen alleviates this vascular dysfunction. Experimental Approach: Male BALB/c mice were exposed to either room air or CS for 8 weeks followed by inoculation with IAV (Mem71, 1 x 104.5 pfu)). Mice were treated with ebselen (10 mg/kg) or vehicle (5% w/v CM-cellulose in water) daily. Mice were culled 3- and 10-days post-infection, and their lungs lavaged to assess inflammation. The thoracic aorta was excised to investigate endothelial and smooth muscle dilator responses, expression of key vasodilatory and oxidative stress modulators and infiltrating immune cells. Key Results: CS increased lung inflammation and caused significant vascular endothelial dysfunction, which was worsened by IAV infection. CS-driven increases in vascular oxidative stress and suppression of eNOS were not affected by IAV infection. CS and IAV infection significantly enhanced T-cell recruitment into the aortic wall. Ebselen abolished the exaggerated lung inflammation, vascular dysfunction and increased aortic T-cell infiltration in CS and IAV-infected mice. Conclusion and Implications: Ebselen abolished vascular dysfunction in IAV-induced exacerbations of cigarette smoke-induced lung inflammation indicating it may have potential for the treatment of cardiovascular comorbidities seen in acute exacerbations of COPD.

Vaccines have reduced the transmission and severity of COVID-19 but there remains a paucity of efficacious treatment for drug resistant strains and more susceptible individuals. Repurposing existing drugs is a timely, safe and scientifically robust method for treating pandemics such as COVID-19. Here, we review the pharmacology and scientific rationale for repurposing niclosamide, an anti-helminth already in human use as a treatment for COVID-19. In addition to potent antiviral activity, niclosamide has shown pleiotropic anti-inflammatory, antibacterial, bronchodilatory and anticancer effects in numerous pre-clinical and early clinical studies. The advantages and rationale for nebulised and intranasal formulations of niclosamide, which target the site of primary infection in COVID-19, are reviewed. Finally, we discuss the TACTIC-E clinical trial, an international COVID-19 therapeutic platform trial for the use of licensed and novel therapeutic agents, which is investigating niclosamide as a promising candidate against SARS-CoV-2.

We would like to draw attention to the potential of immunomodulatory tetracyclines for severe COVID-19. The COVID-19 pandemic is having a devastating impact on developing countries. A successful approach to manage the scarcity of cost-effective therapies worldwide is drug repurposing. Predictions of direct anti-viral activity of tetracyclines against SARS-CoV2 have been confirmed experimentally. Furthermore, their effectiveness in experimental ARDS has been proven extensively, counteracting the overt inflammatory reaction and fibrosis sequelae due to a synergic combination of pharmacological activities. Finally, a few clinical reports have confirmed their potentiall in COVID-19 patients, encouraging the development of this novel indication. We believe that the benefits of their multi-target pharmacology and their safety profile place immunomodulatory tetracyclines as gold repurposing candidates for COVID-19.

Objetives. To perform a description of the etiology of hospitalized children with community-acquired pneumonia (CAP) in Spain and analyze predictors related to etiology. Hypothesis. The different etiological groups of pediatric CAP are associated to different clinical, radiographic and analytical data. Design. Observational, multi-center, prospective study. Patient selection. Patients from 1 month to 17 years admitted because of CAP from April 2012 to May 2019. Methods. An extensive microbiological workup was done. Clinical, radiographic and analytical parameters were analyzed in order to differentiate viral, atypical bacteria (AB) and typical bacteria (TyB) pneumonia. Results. 495 children were enrolled. At least one likely causative pathogen was identified in 262 (52.9%). Pathogenic viruses in 155/262 (59.2%), AB in 84/262 (32.1%) and TyB in 40/262 (15.3%). Consolidation was found in 89/138 (64.5%) CAP attributed to virus only, in 74/84 (88.1%) of CAP attributed to AB and 40/40 (100%) of CAP attributed to TyB. Para-pneumonic pleural effusion (PPE) was found in 112/495 (22.6%) patients, 61/112 (54.5%) with a likely causative pathogen: virus 12/61 (19.7%), AB 23/61 (37.7%) and TyB 26/61 (42.6%). Viral etiology was significantly more frequent in younger patients and those with lower oxygen saturation, wheezing, no-consolidation and higher lymphocyte counts. Patients with AB were significantly more likely to have more days of fever at admission and a higher rate of use of antibiotics before admission. Conclusions. Viruses and AB are the main cause of pediatric CAP in Spain. Wheezing, younger age and no-consolidation on the X-ray support viral etiology. Viruses and AB can also cause PPE. The use of antibiotic in pediatric CAP can be restricted.