Vaccine-Boosted CCP Decreases Virus Replication and Hastens Resolution of Infection Despite Transiently Enhancing Disease in SARS-CoV-2-Infected Hamsters.

Definitive data demonstrating the utility of coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) for treating immunocompromised patients remains elusive. To better understand the mechanism of action of CCP, we studied viral replication and disease progression in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected hamsters treated with CCP obtained from recovered COVID-19 patients that were also vaccinated with an mRNA vaccine, hereafter referred to as Vaxplas. Vaxplas transiently enhanced disease severity and lung pathology in hamsters treated near peak viral replication due to immune complex and activated complement deposition in pulmonary endothelium, and recruitment of M1 proinflammatory macrophages into the lung parenchyma. However, aside from one report, transient enhanced disease has not been reported in CCP recipient patients, and the transient enhanced disease in Vaxplas hamsters may have been due to mismatched species IgG-FcR interactions, infusion timing, or other experimental factors. Despite transient disease enhancement, Vaxplas dramatically reduced virus replication in lungs and improved infection outcome in SARS-CoV-2-infected hamsters.

Administration of vaccine-boosted COVID-19 convalescent plasma to SARS-CoV-2 infected hamsters decreases virus replication in lungs and hastens resolution of the infection despite transiently enhancing disease and lung pathology.

The utility of COVID-19 convalescent plasma (CCP) for treatment of immunocompromised patients who are not able to mount a protective antibody response against SARS-CoV-2 and who have contraindications or adverse effects from currently available antivirals remains unclear. To better understand the mechanism of protection in CCP, we studied viral replication and disease progression in SARS-CoV-2 infected hamsters treated with CCP plasma obtained from recovered COVID patients that had also been vaccinated with an mRNA vaccine, hereafter referred to as Vaxplas. We found that Vaxplas dramatically reduced virus replication in the lungs and improved infection outcome in SARS-CoV-2 infected hamsters. However, we also found that Vaxplas transiently enhanced disease severity and lung pathology in treated animals likely due to the deposition of immune complexes, activation of complement and recruitment of increased numbers of macrophages with an M1 proinflammatory phenotype into the lung parenchyma.

N-dihydrogalactochitosan reduces mortality in a lethal mouse model of SARS-CoV-2.

The rapid emergence and global dissemination of SARS-CoV-2 that causes COVID-19 continues to cause an unprecedented global health burden resulting in nearly 7 million deaths. While multiple vaccine countermeasures have been approved for emergency use, additional treatments are still needed due to sluggish vaccine rollout, vaccine hesitancy, and inefficient vaccine-mediated protection. Immunoadjuvant compounds delivered intranasally can guide non-specific innate immune responses during the critical early stages of viral replication, reducing morbidity and mortality. N-dihydrogalactochitosan (GC) is a novel mucoadhesive immunostimulatory polymer of ß-0-4-linked N-acetylglucosamine that is solubilized by the conjugation of galactose glycans with current applications as a cancer immunotherapeutic. We tested GC as a potential countermeasure for COVID-19. GC was well-tolerated and did not produce histopathologic lesions in the mouse lung. GC administered intranasally before and after SARS-CoV-2 exposure diminished morbidity and mortality in humanized ACE2 receptor expressing mice by up to 75% and reduced infectious virus levels in the upper airway. Fluorescent labeling of GC shows that it is confined to the lumen or superficial mucosa of the nasal cavity, without involvement of adjacent or deeper tissues. Our findings demonstrate a new application for soluble immunoadjuvants such as GC for preventing disease associated with SARS-CoV-2 and may be particularly attractive to persons who are needle-averse.

Sylvatic Transmission of Chikungunya Virus among Nonhuman Primates in Myanmar.

Nonhuman primates living in proximity to humans increase risks for sylvatic arbovirus transmission. We collected serum samples from nonhuman primates in Hlawga National Park near Yangon, Myanmar, and detected antibodies against chikungunya (33%) and Japanese encephalitis (4%) viruses. Buffer zones between primate and human communities might reduce cross-species arbovirus transmission.

Unique Isospora-associated histologic lesions in white-rumped shama (Copsychus malabaricus).

Twenty-one white-rumped shamas (19 necropsied, 2 biopsied) (Copsychus malabaricus) housed at the San Diego Zoo between 1992 and 2020 were diagnosed with Isospora infection based on evaluation of histologic sections. Review of these cases revealed a consistent histologic lesion characterized by nodular aggregates of atypical epithelioid macrophages containing few intracytoplasmic protozoa, with or without lymphocytic infiltrates. Of the 19 necropsied cases, 16 (84%) had systemic lesions variably affecting the liver, spleen, gastrointestinal tract, lung, pancreas, connective tissues, or bone marrow, while all 21 diagnosed cases had skin involvement. The findings suggest that white-rumped shamas have a unique inflammatory response to isosporosis with a predilection for the skin. Skin may be a diagnostically sensitive sampling site for histologic diagnosis of Isospora in this species.

Bacterial meningitis after dental extraction in a 17-year-old horse.

Dental extractions in horses may result in bacteremia, which can lead to systemic complications. Bacterial meningitis following oral cheek tooth extractions in a 17-year-old Thoroughbred gelding is described in this report. The bacterial meningitis was confirmed by histopathology. The gelding was presented for evaluation of intermittent fever, loose feces, and mild colic signs which started 5 days after cheek tooth extraction. This case illustrates a rare complication associated with oral tooth extraction in a horse and highlights the unusual presenting features of meningitis. Key clinical message: Bacterial meningitis secondary to oral cheek tooth extraction should be considered as differential diagnosis; particularly in cases with the development of pyrexia a few days after the procedure.

Méningite bactérienne après extraction dentaire chez un cheval de 17 ans. Les extractions dentaires chez les chevaux peuvent entraîner une bactériémie, ce qui peut amener des complications systémiques. Un cas de méningite bactérienne à la suite d'extractions buccales de dents jugales chez un hongre pur-sang de 17 ans est décrite dans ce rapport. La méningite bactérienne a été confirmée par histopathologie. Le hongre a été présenté pour évaluation d'une fièvre intermittente, de selles molles et de signes de coliques légers qui ont commencé 5 jours après l'extraction de la dent jugale. Ce cas illustre une complication rare associée à l'extraction dentaire orale chez un cheval et met en évidence des caractéristiques inhabituelles de la méningite.Message clinique clé :La méningite bactérienne secondaire à l'extraction buccale des dents jugales doit être considérée comme un diagnostic différentiel, en particulier dans les cas de développement d'une pyrexie quelques jours après l'intervention.(Traduit par Dr Serge Messier).

Stromal cell-derived factor-1 (SDF-1) expression in very preterm human lungs: potential relevance for stem cell therapy for bronchopulmonary dysplasia.

Background: The axis formed by CXC chemokine receptor 4 (CXCR4), expressed on mesenchymal stromal cells (MSCs), and stromal cell-derived factor-1 (SDF-1), expressed in recipient organs, is a critical mediator of MSC migration in non-pulmonary injury models. The role and regulation of SDF-1 expression in preterm lungs, of potential relevance for MSC-based cell therapy for bronchopulmonary dysplasia (BPD), is unknown. The aim of this study was to determine the spatiotemporal pattern of CXCR4/SDF-1 expression in lungs of extremely preterm infants at risk for BPD.Methods: Postmortem lung samples were collected from ventilated extremely preterm infants who died between 23 and 29 wks ("short-term ventilated") or between 36 and 39 wks ("long-term ventilated") corrected postmenstrual age. Results were compared with age-matched infants who had lived <12 h or stillborn infants ("early" and "late" controls). CXCR4 and SDF-1 expression was studied by immunohistochemistry, immunofluorescence/confocal microscopy, and qRT-PCR analysis.Results: Compared with age-matched controls without antenatal infection, lungs of early control infants with evidence of intrauterine infection/inflammation showed significant upregulation of SDF-1 expression, localized to the respiratory epithelium, and of CXCR4 expression, localized to stromal cells. Similarly, pulmonary SDF-1 mRNA levels were significantly higher in long-term ventilated ex-premature infants with established BPD than in age-matched controls. The pulmonary vasculature was devoid of SDF-1 expression at all time points. Endogenous CXCR4-positive stromal cells were preferentially localized along the basal aspect of SDF-1-positive bronchial and respiratory epithelial cells, suggestive of functionality of the CXCR4/SDF-1 axis.Conclusions: Incipient and established neonatal lung injury is associated with upregulation of SDF-1 expression, restricted to the respiratory epithelium. Knowledge of the clinical associations, time-course and localization of pulmonary SDF-1 expression may guide decisions about the optimal timing and delivery route of MSC-based cell therapy for BPD.

Discriminatory features of acute eosinophilic dermatitis with oedema (Wells-like syndrome) and sterile neutrophilic dermatosis (Sweet's-like syndrome) in dogs.

BACKGROUND: Canine acute eosinophilic dermatitis with oedema (CAEDE) and sterile neutrophilic dermatosis have overlapping clinical and histopathological features. HYPOTHESIS/OBJECTIVES: The objective of this study was to identify features that differentiate these entities. ANIMALS: Forty dogs. METHODS AND MATERIALS: Retrospective case series. Forty cases with diagnoses of either CAEDE and/or sterile neutrophilic dermatosis were included based on histopathological review. Medical records (29 of 40 dogs) were reviewed for clinical findings and historical data. Commercially available immunohistochemical stains for granulocytes and a Luna stain were performed (40 of 40 dogs) to assess the granulocytic infiltrate. RESULTS: Nineteen cases had been previously diagnosed as CAEDE, seven cases had been designated as sterile neutrophilic dermatosis and 14 cases had overlapping features. Based on review and receiver operating characteristic (ROC) curve analysis, 30 cases with >12% eosinophils, enumerated by Luna staining, were diagnosed as eosinophilic dermatitis and oedema. Ten cases were diagnosed as sterile neutrophilic dermatosis. Dogs with CAEDE frequently had gastrointestinal signs (24 of 30;80%) and pruritus (11 of 30;33%). In dogs with sterile neutrophilic dermatosis, five of 10 (50%) had diagnoses of or histories compatible with immune-mediated polyarthropathy. CONCLUSIONS AND CLINICAL IMPORTANCE: In this case series, CAEDE was encountered more frequently than neutrophilic dermatosis and could be distinguished by the eosinophilic infiltrate, aided by a Luna stain. Concurrent arthralgia was more frequently identified with neutrophilic dermatosis. It remains unclear whether CAEDE and sterile neutrophilic dermatosis are separate disease entities or varied manifestations of the same disease.