Identification of FasL as a crucial host factor driving COVID-19 pathology and lethality.

The dysregulated immune response and inflammation resulting in severe COVID-19 are still incompletely understood. Having recently determined that aberrant death-ligand-induced cell death can cause lethal inflammation, we hypothesized that this process might also cause or contribute to inflammatory disease and lung failure following SARS-CoV-2 infection. To test this hypothesis, we developed a novel mouse-adapted SARS-CoV-2 model (MA20) that recapitulates key pathological features of COVID-19. Concomitantly with occurrence of cell death and inflammation, FasL expression was significantly increased on inflammatory monocytic macrophages and NK cells in the lungs of MA20-infected mice. Importantly, therapeutic FasL inhibition markedly increased survival of both, young and old MA20-infected mice coincident with substantially reduced cell death and inflammation in their lungs. Intriguingly, FasL was also increased in the bronchoalveolar lavage fluid of critically-ill COVID-19 patients. Together, these results identify FasL as a crucial host factor driving the immuno-pathology that underlies COVID-19 severity and lethality, and imply that patients with severe COVID-19 may significantly benefit from therapeutic inhibition of FasL.

Building a predictive model for assessing the risk of Salmonella shedding at slaughter in fattening pigs.

Salmonellosis continues to be a major cause of foodborne outbreaks worldwide, and pigs are one of the main sources of human infection. Salmonella pork contamination is a major concern for abattoirs and is related to the presence of Salmonella in pigs' feces at slaughter. Being able to predict the risk of Salmonella shedding in pigs arriving at the slaughterhouse could help mitigate abattoir and carcass contamination. For this purpose, 30 batches of 50 pigs each were selected from 30 different fattening units. The pigs were tagged and bled for the detection of antibodies against Salmonella approximately one month before slaughter. Pooled floor fecal samples were also collected from 10 pens per unit for Salmonella detection, and a questionnaire on biosecurity was administered to each farm. At the abattoir, colon content was collected from each tagged pig for the Salmonella shedding assessment. A predictive model for Salmonella shedding at slaughter was built with two-third of the pigs by employing random-effects logistic regression analysis, with Salmonella shedding as the dependent variable and pig serology and other farm/environmental characteristics as the independent variables. The model included farm as the grouping factor. Data from the remaining one-third of the pigs were used for model validation. Out of 1,500 pigs initially selected, 1,341 were identified at the abattoir and analyzed. Salmonella was detected in 13 (43.3%; 95%CI = 27.4-60.8) of the fattening units. The mean batch seroprevalence (cut-off OD% ≥40) among the fattening units was 31.7% (95%CI = 21.8-41.0), and a total of 316 pigs (23.6%; 95%CI = 21.4-25.9) shed Salmonella at slaughter. The model predicted reasonably well (Area under the curve = 0.76; P < 0.05) whether a pig would shed Salmonella at slaughter, with estimates of sensitivity and specificity at 71.6% and 73.6%, respectively. Serology, the percentage of Salmonella-positive pens on the farm, and the internal biosecurity score were significantly associated (P < 0.05) with Salmonella shedding at the abattoir, and several scenarios were observed by the model. The study highlighted that although serology may be helpful for identifying batches of pigs at risk of shedding Salmonella upon their arrival at the abattoir, it may not be necessary in some scenarios.

Placental Infection Associated with SARS-CoV-2 Wildtype Variant and Variants of Concern.

The original SARS-CoV-2 lineages have been replaced by successive variants of concern (VOCs) over time. The aim of this study was to perform an assessment of the placental infection by SARS-CoV-2 according to the predominant variant at the moment of COVID-19 diagnosis. This was a prospective study of SARS-CoV-2-positive pregnant women between March 2020 and March 2022. The population was divided into pregnancies affected by COVID-19 disease during 2020 (Pre-VOC group) and pregnancies affected after December 2020 by SARS-CoV-2 variants of concern (VOC group). The presence of virus was assessed by RT-PCR, and the viral variant was determined by whole genome sequencing. A total of 104 placentas were examined, among which 54 cases belonged to the Pre-VOC group and 50 cases belonged to the VOC group. Sixteen positive placental RT-PCR tests for SARS-CoV-2 were reported. The NGS analysis confirmed the SARS-CoV-2 lineage in placenta tissue. All samples corresponded to the Pre-VOC group, whereas no placental presence of SARS-CoV-2 was detected in the VOC group (16, 29.6% vs. 0, 0.0% p = 0.000). Preterm birth (9, 16.7% vs. 2, 4%; p = 0.036) and hypertensive disorders of pregnancy (14, 25.9% vs. 3, 6%; p = 0.003) were more frequent in the Pre-VOC group than in the VOC group. Finally, the VOC group was composed of 23 unvaccinated and 27 vaccinated pregnant women; no differences were observed in the sub-analysis focused on vaccination status. In summary, SARS-CoV-2-positive placentas were observed only in pregnancies infected by SARS-CoV-2 wildtype. Thus, placental SARS-CoV-2 presence could be influenced by SARS-CoV-2 variants, infection timing, or vaccination status. According to our data, the current risk of SARS-CoV-2 placental infection after maternal COVID disease during pregnancy should be updated.

Salmonella Infection in Nursery Piglets and Its Role in the Spread of Salmonellosis to Further Production Periods.

Few studies have focused on assessing Salmonella infection in the nursery and its role in further pig production periods. Mesenteric lymph nodes, intestinal content, and meat juice from 389 6-week-old male piglets intended for human consumption from five breeding farms and 191 pooled floor fecal samples from gilt development units (GDU) from the same farms were analyzed to estimate and characterize (by pulsed-field gel electrophoresis and antimicrobial resistance analyses) Salmonella infection. The prevalence of infection and shedding among piglets was 36.5% and 37.3%, respectively, shedding being significantly associated with infection (Odds Ratio = 12.7; CI 7.3-22.0). Salmonella Rissen; S. 4,[5],12:i:-; and S. Derby were the most common serotypes. A low level of Salmonella-specific maternal antibodies at the beginning of the nursery period suggested it was a period of high risk of infection. Resistance to 3rd- and 4th-generation cephalosporins was detected in piglet isolates although the piglets never received antibiotics, indicating they could be vectors of antimicrobial resistance. The same Salmonella clones were detected in piglet and GDU isolates, suggesting that infected piglets play a significant role in the infection of gilts and consequently of finishing pigs in the case of production farms. The control of Salmonella infection in nursery piglets may decrease the risk of abattoir and carcass contamination.

Weaned piglets: another factor to be considered for the control of Salmonella infection in breeding pig farms.

Field studies on Salmonella infection in suckling piglets are scarce due to the intrinsic difficulties of collecting proper samples (i.e. tonsils or mesenteric lymph nodes), and most of them rely on the analysis of rectal swabs that limit their accuracy. We used 495 slaughtered 4-weeks-old male piglets intended for human consumption from 5 Salmonella-seropositive breeding farms to collect gastrointestinal packages and perform a thorough detection of Salmonella on mesenteric lymph nodes and intestinal content. The overall prevalence of both infection and shedding was high (≈ 36%) indicating that piglets played an active role in Salmonella maintenance in the farms. Major serotypes found in piglets included 4,[5],12:i: (35.4%), Rissen (17.1%), Derby (10.9%) and Bovismorbificans (10.3%). In most of the infected animals (72.8%) the same serotype was found in mesenteric lymph nodes and feces. Significant higher ELISA OD% values were found in meat juice samples from non-infected piglets compared to infected ones (median OD% of 12.0 and 17.3, respectively; P = 0.002) suggesting some protective effect of sow's colostrum. Salmonella was also isolated from feces from weaned sows contemporary of the slaughtered piglets, and 89% of the serotypes identified in sows were also detected in piglets. Pulsed field gel electrophoresis analyses showed that 75% of the piglet isolates that were compared to those of sows were related to them, suggesting the circulation of Salmonella strains between sows and piglets. It appears that improving piglet colostrum intake along with the reduction of the shedding in sows may favor the control of Salmonella infection in breeding farms.