Viral enteritis in cattle: To well known viruses and beyond

Livestock products supply about 13 percent of energy and 28 percent of protein in diets consumed worldwide. Diarrhea is a leading cause of sickness and death of beef and dairy calves in their first month of life and also affecting adult cattle, resulting in large economic losses and a negative impact on animal welfare. Despite the usual multifactorial origin, viruses are generally involved, being among the most important causes of diarrhea. There are several viruses that have been confirmed as etiological agents (i.e., rotavirus and coronavirus), and some viruses that are not yet confirmed as etiological agents. This review summarizes the viruses that have been detected in the enteric tract of cattle and tries to deepen and gather knowledge about them.Copyright © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

[Anaphylaxis and COVID-19 vaccines]. / L'anaphylaxie et les vaccins COVID-19.

Vaccines against COVID-19 are an essential global intervention to control the current pandemic situation. Anaphylactic reactions have rapidly been reported after SARS-CoV2 RNA vaccines. This risk is now measured at 2.5-11/1,000,000 in the context of vaccine safety surveillance programs and only one case was documented to be due to polyethylene glycol. Suggestions for its role are indirect. The COVID-19 vaccination is rolling out vastly and surveillance programs are key to monitor severe adverse reactions, such as anaphylaxis. It is important to restore confidence about vaccination with COVID-19 mRNA and other vaccines and current data confirm their safety with no greater mortality than previous vaccines. Anaphylaxis is a complication that should be recognized immediately, be treated with epinephrine and which is not limiting and allows re-vaccination of some patients with pre-medication. It is important to recognize populations at risk such as women, patients with a history of allergies and anaphylaxis and to recognize the rare patients who have mast cell activating diseases. Anaphylaxis due to vaccine is extremely rare and specific cases should receive individualized investigation and care, highlighting the key role of allergists in the vaccination programmes.

Mast Cells in COVID-19-Associated Lung Damage

Background: SARS-CoV-2 infection results in acute respiratory distress and multiple organ failure, but the pathogenesis of the disease is poorly understood. Recent data suggest that viral RNA may be found in mast cells, but patients with asthma who have hyperplasia of mucosal mast cells do not experience asthma exacerbations during infection and do not suffer from increased mortality due to COVID-19-associated lung damage. Mast cells from bone marrow do not express the ACE2 receptor used for SARS-CoV-2 entry into human cells, and patients with mast cell activation disorders such as systemic mastocytosis do not show mast cell activation during infection. Because activated mast cells can release potent inflammatory mediators including IL-6 and have been implicated in fibrotic lung damage, the purpose of this study was to investigate the role of mast cells in COVID-19 fatal lung disease. Design: We evaluated 19 autopsies and post-mortem biopsies performed on patients who died of COVID-19 in April and May 2020. Representative sections of lung tissue with typical histological changes of diffuse alveolar damage (DAD;both acute and organizing) were selected. Mast cells were identified by immunohistochemistry for KIT (CD117), tryptase, and chymase. Mean values for mast cells were obtained by counting 3 different areas each with the highest and lowest density of CD117/tryptasepositive cells with 40x magnification. Results: Patients in this cohort were mostly obese with systemic hypertension or diabetes and had elevated CRP and IL-6. All mast cells in COVID-19 lung autopsies were positive for tryptase and chymase, indicating a connective tissue phenotype (Figure 1). While both acute and organizing forms of non-COVID-19-related lung injury showed a 3-5-fold increase in mast cell numbers between low and high-density areas, acute COVID-19 showed a <2-fold increase. In contrast, organizing DAD in COVID-19 showed a 3-fold increase in mast cells between low and high-density areas (Figure 2). Few mast cells were co-localized with SARS-CoV-2 mRNA. Conclusions: During the early phase of DAD in SARS-CoV-2 infection, mast cells are suppressed, potentially due to an interferon surge, which is reversed during the organizing DAD phase of infection. Viral RNA is rarely present in mast cells, consistent with the reported lack of ACE2 receptors in bone marrow mast cells.

Clinical protocol for addressing mental health needs of healthcare professionals during COVID-19

Healthcare professionals are in the front line of care for patients with COVID-19, presenting greater risk of contagion and emotional distress. The aim of the study is to describe the results of a psychological intervention protocol for professionals;47 workers from Vall d'Hebron University Hospital who requested psychological support were included during the first month and a half of the crisis. Before and after the intervention a checklist of clinical symptoms, the Clinical Anxiety Scale and the Clinical Global Impression Scale were administered. Professionals who consulted were mostly women, nursing staff, and assistant nursing care technicians, presenting hyperconcern, sadness, sleep, and eating disturbances. Significant improvements were observed on clinical symptoms (z = 4.6, p <= .0001), acute stress (z = 2.5, p = .012), anxiety (z = 5.3, p <= .0001), and clinical impression (z = 4.1, p <= .0001). A brief psychological intervention, based on anxiety management, emotional regulation, and values oriented-behavior, was shown to be effective in reducing emotional symptoms in professionals.

Evidence of increasing diversification of emerging Severe Acute Respiratory Syndrome Coronavirus 2 strains

On 30th January 2020, an outbreak of atypical pneumonia caused by a novel betacoronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was declared a public health emergency of international concern by the World Health Organization. For this reason, a detailed evolutionary analysis of SARS-CoV-2 strains currently circulating in different geographic regions of the world was performed. A compositional analysis as well as a Bayesian coalescent analysis of complete genome sequences of SARS-CoV-2 strains recently isolated in Europe, North America, South America, and Asia was performed. The results of these studies revealed a diversification of SARS-CoV-2 strains in three different genetic clades. Co-circulation of different clades in different countries, as well as different genetic lineages within different clades were observed. The time of the most recent common ancestor was established to be around 1st November 2019. A mean rate of evolution of 6.57 x 10^-4 substitutions per site per year was found. A significant migration rate per genetic lineage per year from Europe to South America was also observed. The results of these studies revealed an increasing diversification of SARS-CoV-2 strains. High evolutionary rates and fast population growth characterizes the population dynamics of SARS-CoV-2 strains.

Evidence of increasing diversification of emerging severe acute respiratory syndrome coronavirus 2 strains. (Special Issue: New coronavirus (2019-nCoV or SARS-CoV-2) and the outbreak of the respiratory illness (COVID-19): part-VI.)

On 30th January 2020, an outbreak of atypical pneumonia caused by a novel betacoronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was declared a public health emergency of international concern by the World Health Organization. For this reason, a detailed evolutionary analysis of SARS-CoV-2 strains currently circulating in different geographic regions of the world was performed. A compositional analysis as well as a Bayesian coalescent analysis of complete genome sequences of SARS-CoV-2 strains recently isolated in Europe, North America, South America, and Asia was performed. The results of these studies revealed a diversification of SARS-CoV-2 strains in three different genetic clades. Co-circulation of different clades in different countries, as well as different genetic lineages within different clades were observed. The time of the most recent common ancestor was established to be around 1st November 2019. A mean rate of evolution of 6.57 10^-4 substitutions per site per year was found. A significant migration rate per genetic lineage per year from Europe to South America was also observed. The results of these studies revealed an increasing diversification of SARS-CoV-2 strains. High evolutionary rates and fast population growth characterizes the population dynamics of SARS-CoV-2 strains.

Active smoking and severity of COVID-19 infection in cancer patients

Background: Smoking is the leading cause of cancer worldwide. Active smoking alters the inflammatory environment of the respiratory epithelium, increasing the production of potent pro-inflammatory cytokines that promote the recruitment of macrophages and neutrophils, leading to lung damage. We hypothesize that smoking-induced inflammation can impact on COVID-19 infection severity and mortality related to the proinflammatory cascade. Methods: Multicenter retrospective cohort of cancer patients (pts) with COVID-19 infection diagnosed by PCR/Ag detection (n=274) and CT-scan (N=13) in Mar-Apr/20r in 12 centers. Clinical and biological data were collected. Smoker was defined as active tobacco consumption and heavy smoker as >30 pack-year (PY). Primary endpoints were 30-day mortality rate and the rate of severe acute respiratory failure (SARF), defined by oxygen requirements >15 L/min. Results: A total of 287 pts were enrolled: 25 (9%) were active smokers, 127 (47%) were former and 116 (43%) never smoker. Among active smokers: 73% were heavy smokers, median age was 62y, 60% were male and median body mass index was 22. Regarding their comorbidities: 25% had hypertension, 8% cardiovascular disease, 28% chronic obstructive pulmonary disease and 24% diabetes. Thoracic tumors were the most common (52%), 72% had advanced disease and 56% were under systemic therapy. 92% of active smokers required hospitalization, 68% developed pneumonia and 58% required oxygen. Only 4% were escalated to the intensive care unit. Active smokers received treatment with hydroxychloroquine (91%), azithromycin (61%), antiviral therapy (33%) and steroids (29%). Only 4% received immunomodulatory drugs. SARF was the most common complication (25%) and no thromboembolic events were observed. A pro-inflammatory status was observed at COVID-19 diagnosis in active smokers, e.g. median of absolute neutrophil count was 6.35 (vs. 5.4), mean ferritin was 1269 (vs. 991) and D-Dimer was 2422 (vs. 1816);but with no significant differences. Overall mortality rate was 27%. Mortality rate was higher in active smokers (40% vs. 24% in non-smokers;p=0.08). Conclusions: Active smoking might be associated with severe COVID-19 infection and early death in cancer patients. Smoking induced-inflammation should be further explored. Legal entity responsible for the study: Aleix Prat. Funding: Has not received any funding. Disclosure: E. Auclin: Travel/Accommodation/Expenses: Mundifarma;Speaker Bureau/Expert testimony: Sanofi Genzime. S. Pilotto: Speaker Bureau/Expert testimony: Astra-Zeneca;Speaker Bureau/Expert testimony: Boehringer Ingelheim;Speaker Bureau/Expert testimony: Eli-Lilly;Speaker Bureau/Expert testimony: BMS. A. Prat: Honoraria (institution), Speaker Bureau/Expert testimony: Roche;Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer;Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis;Amgen;Speaker Bureau/Expert testimony: BMS;Honoraria (institution), Speaker Bureau/Expert testimony: Daiichi Sankyo;Nanostring;Advisory/Consultancy: Puma;Oncolytics Biotech;MSD;Honoraria (institution), Advisory/Consultancy: Lilly;Boehringer;Sysmex Europa GmbH;Medican Scientia inno. Research;Celgene;Astellas;Officer/Board of Directors: Breast International Group;Solti's Foundation;Actitud frente al cancer foundation. L. Mezquita: Speaker Bureau/Expert testimony, Research grant/Funding (self), Travel/Accommodation/Expenses: Bristol-Meyers Squibb;Speaker Bureau/Expert testimony: Tecnofarma;Honoraria (institution), Speaker Bureau/Expert testimony: Astrazeneca;Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche;Research grant/Funding (self): Boehringer Intelligence. All other authors have declared no conflicts of interest.

Expanding the role of medical oncologist in the management of COVID-19

Background: Cancer patients (pts) have been associated with severe SARS-CoV2 infection and higher mortality compared with the general population. This could be related to the limitation of therapeutic effort based on their prognosis and healthcare prioritization towards non-cancer pts. The oncologist’s role could be crucial for providing high-quality care. We aim to assess the impact of oncologists (ONC) on COVID-19 management. Methods: Multicentre retrospective analysis of cancer pts diagnosed with COVID-19 between Mar-Apr 2020. We classified pts according to an estimated life expectancy (based on tumor/stage/line) in 3 groups: favourable group (FG) mOS >5 years (y), intermediate (IG) 1-5y and poor (PG) <1y. We studied COVID-19 management based on oncologist’s involvement: mainly-ONC vs. mainly other specialists (Other). Primary endpoint: COVID-19 30-day mortality (early-M). Secondary outcomes: intensive care unit admission (ICUa), the incidence of acute respiratory distress syndrome (ARDS) and antiretroviral treatment (ARVt) and immunomodulatory drugs (ImD) administered. Results: 287 pts were enrolled, median age 69 (35-98), 52% male, 67% with an active tumor (of them 76% had advanced stage). Mostly thoracic tumors (26%), followed by gastrointestinal (21%) and breast (19%). Among 170 pts under treatment, 89 (52%) received chemotherapy (CHT). By prognostic group: 49% were included in FG (n=135), 40% in IG (n=113), and 11% in PG (n=30). Overall early-M rate was 27% (ONC 22% vs. Other 27%). Prognostic groups were associated with early-M: 19% (FG) vs. 31% (IG) vs. 37% (PG) (p=0.022). No significant differences regarding rate of ARDS (23% FG vs. 19% IG vs. 17% PG). The ONC-group (n=18) included 4 PG and 14 IG, 94% had an advanced stage disease, 83% receive CHT and 65% had PS≥2 (p=0.05 compared to Other group). In IG (ONC vs. Other): 7% vs. 2% ICUa, 100% vs. 34% ARVt and 57% vs. 7% ImD (all p<0.001). In PG (ONC vs. Other): 25% vs. 0% ICUa, 75% vs. 34% ARVt and 25% vs. 0% ImD (all p<0.001). Finally, FP managed only by Other: 13% ICUa;33% ARVt and 13% ImD. Conclusions: Oncologist mostly treated complex pts compared to other specialists. During COVID-19 crisis, setting prognostic groups helped to individualized therapeutic approaches, reflected by less mortality rate and no differences in terms of complications. Legal entity responsible for the study: Aleix Prat. Funding: Has not received any funding. Disclosure: L. Ghiglione: Licensing/Royalties: Hibor;Licensing/Royalties: Kyowa Kirin;Licensing/Royalties: Vifor Pharma. E. Auclin: Travel/Accommodation/Expenses: Mundipharma;Licensing/Royalties: Sanofi Genzymes. S. Pilotto: Licensing/Royalties: AstraZeneca;Eli-Lilly;BMS;: Boehringer Ingelheim;MSD;Roche. A. Prat: Research grant/Funding (institution), Licensing/Royalties: Roche;Advisory/Consultancy, Research grant/Funding (institution), Licensing/Royalties: Pfizer;Novartis;Amgen;Licensing/Royalties: BMS;Research grant/Funding (institution), Licensing/Royalties: Daiichi Sankyo;Advisory/Consultancy: Puma;Oncolytics Biotech;MSD;Advisory/Consultancy, Research grant/Funding (institution): Lilly;Research grant/Funding (institution), Licensing/Royalties: Nanostring technologies;Officer/Board of Directors: Beast International Group (BIG);Solti's Foundation;Actitud frente al cancer Foundation;Solti;Research grant/Funding (institution): Boehringer;Sysmex Europa GmbH;Medica Scientia inno. Research, SL;Celgene, SLU;Astellas Pharma. L. Mezquita: Research grant/Funding (self), Travel/Accommodation/Expenses, Licensing/Royalties: Bristol-Myers Squibb;Licensing/Royalties: Tecnofarma;Licensing/Royalties, International Mentorship Program: AstraZeneca;Advisory/Consultancy, Travel/Accommodation/Expenses, Licensing/Royalties: Roche;Advisory/Consultancy: Roche Diagnostics;Research grant/Funding (self): Boehringer Ingelheim. All other authors have declared no conflicts of interest.

Effect of the administration of Lactobacillus spp. strains on neonatal diarrhoea, immune parameters and pathogen abundance in pre-weaned calves.

Neonatal calf diarrhoea is one of the challenges faced by intensive farming, and probiotics are considered a promising approach to improve calves' health. The objective of this study was to evaluate the effect of potential probiotic lactobacilli on new-born dairy calves' growth, diarrhoea incidence, faecal score, cytokine expression in blood cells, immunoglobulin A (IgA) levels in plasma and faeces, and pathogen abundance in faeces. Two in vivo assays were conducted at the same farm in two annual calving seasons. Treated calves received one daily dose of the selected lactobacilli (Lactobacillus reuteri TP1.3B or Lactobacillus johnsonii TP1.6) for 10 consecutive days. A faecal score was recorded daily, average daily gain (ADG) was calculated, and blood and faeces samples were collected. Pathogen abundance was analysed by absolute qPCR in faeces using primers directed at Salmonella enterica, rotavirus, coronavirus, Cryptosporidium parvum and three Escherichia coli virulence genes (eae, clpG and Stx1). The faecal score was positively affected by the administration of both lactobacilli strains, and diarrhoea incidence was significantly lower in treated calves. No differences were found regarding ADG, cytokine expression, IgA levels and pathogen abundance. Our findings showed that oral administration of these strains could improve gastrointestinal health, but results could vary depending on the calving season, which may be related to pathogen seasonality and other environmental effects.