An outbreak of a pathogenic canine coronavirus type 2 in captive snow leopards (Panthera uncia) in the U.S, with severe gastrointestinal signs (preprint)

The species alphacoronavirus-1 comprises a set of diverse viruses of cats, dogs, and pigs, and is highly recombinogenic. Within this species, canine coronavirus type 2 (CCoV-2) can infect multiple species of canids, causing a range of clinical outcomes. CCoV-2 is genetically related to feline coronavirus type 1 (FCoV-1) and type 2 (FCoV-2), with FCoV-2 being a recombinant genotype of FCoV-1 and CCoV-2. Recently, a novel FCoV (FCoV-23) resulting from recombination with a highly pathogenic (pantropic) CCoV-2 (pCCoV-2) has been identified as the cause of a widespread outbreak among stray/feral cats in Cyprus. To understand the origin of recombinant variants it is crucial to identify hosts that can be infected with viruses in the species alphacoronavirus-1. Experimental evidence indicates that domesticated cats likely play a central role in the emergence of recombinant variants, as they can also be infected with CCoV-2. Wild felids are genetically closely related to domestic cats and may also be susceptible to FCoV and CCoV infection; however, there have been no reports of natural infection with CCoV in domesticated or wild felids. In this study, we retrospectively investigated a localized outbreak of severe enteritis in snow leopards (Panthera uncia) housed in a zoological institute in the U.S. Molecular screening and whole genome sequencing revealed the shedding of CCoV-2 in the feces of the three sick leopards. Phylogenetic analyses of the spike gene revealed it is genetically related to pathogenic variants of CCoV-2 identified in domesticated dogs in the U.S., and to pCCoV-2 CB/05 circulating in Europe. This study provides the first genetic evidence of CCoV-2 infection in a wild felid and highlights the necessity of conducting surveillance of both FCoV and CCoV in domesticated and wild felids.

Necrotic enteritis in a commercial turkey flock coinfected with hemorrhagic enteritis virus.

Four turkeys from a commercial flock with acutely elevated mortality levels were submitted for postmortem examination and diagnostic workup. No clinical signs had been observed before death. On gross examination, hemorrhage and necrosis were present throughout the intestinal tracts, and the spleens were markedly enlarged and speckled. Microscopically, numerous, large basophilic-to-amphophilic intranuclear inclusion bodies were observed in mononuclear cells of the spleen and the lamina propria of the small intestine. In addition, there were lesions of diffuse villus blunting and necrosis of the small intestine, with large numbers of rod-shaped bacteria adhered to the epithelium and in the intestinal lumen. Hemorrhagic enteritis virus (HEV) infection was confirmed via PCR on the spleen. Clostridium perfringens was demonstrated in the small intestine by anaerobic culture and immunohistochemistry. The C. perfringens isolate was type F by PCR and, to our knowledge, necrotic enteritis in turkeys has not been described in association with C. perfringens type F infection.

Postmortem examination of equids >1-year-old with enterotyphlocolitis in Ontario: a retrospective descriptive study.

Equine enterotyphlocolitis is an inflammatory process of the intestinal tract of horses that is associated with multiple etiologic agents and risk factors. Most clinical cases do not have an etiologic diagnosis. We describe here the pathogens detected and the histologic lesions found in horses with enterotyphlocolitis in Ontario that were submitted for postmortem examination, 2007-2019. We reviewed the medical records of 208 horses that fulfilled inclusion criteria. Cultures were positive in 67 of 208 (32%) equids for Clostridium perfringens, in 16 of 208 (8%) for Clostridioides difficile, and in 14 of 208 (7%) for Salmonella spp.; 6 of 208 (3%) were positive for Neorickettsia risticii by PCR assay. One horse was positive in a Rhodococcus equi PCR assay. All horses tested by PCR assay for equine coronavirus and Lawsonia intracellularis were negative. The histologic lesions were characterized as follows: 6 of 208 (3%) enteritis, 5 of 208 (2%) typhlitis, 104 of 208 (50%) colitis, 37 of 208 (18%) enterocolitis, 45 of 208 (22%) typhlocolitis, and 11 of 208 (5%) enterotyphlocolitis. We strongly recommend standardized testing of diarrheic horses during and/or after postmortem examination, as well as standardized reporting of histologic lesions in enterotyphlocolitis cases.

Assessment of the Epidemic Potential of the Marek’s Disease Virus in the Russian Federation (preprint)

Abstract. Marek's disease virus is an oncogenic avian herpesvirus and the problem of oncogenicity of this virus for humans remains unexplored. This pathology appeared in broiler chickens of 30 days and older, that is from now on the contact with poultry meat carries the risk of infecting people. This article analyzes the risks of the emergence of the epidemic potential of the Marek's disease virus in the Russian Federation taking into account the characteristics of modern pig and poultry farming. It was found that COVID 19 can serve as an additional factor in reducing the resistance of the population to herpesvirus infections. The COVID 19 epidemic is accompanied by folic acid deficiency which also increases the risk of contamination of diseases associated with DNA viruses, including an extended risk of animal viruse infection. Since, according to our estimates, Marek's disease occurred in at least 25% of broiler poultry farms in the Russian Federation, a possible expand in mortality from neoplasms of the reproductive system for the Russian Federation as a whole can contribute to the dynamics of oncological diseases of reproductive organs and breast cancer. Since 2011 a contagious form of intestinal pathology, vesicular enteritis, has widely spread at poultry farms in the Russian Federation. During periods of extending incidence of vesicular enteritis, we recorded cases of inflammation of the facial nerves and subfebrile temperature in contact persons, bursts of oncological diseases in veterinary personnel (ovarian cancer, breast cancer), abnormal and synchronous increases in the incidence of infectious larengotracheitis and Marek's disease in chickens under the age of 40 days which requires additional monitoring studies.

Calpain-1: a Novel Antiviral Host Factor Identified in Porcine Small Intestinal Mucus.

The thick mucus layer covering of the intestinal epithelium has received increasing attention, owing to its protective role in intestinal infection. However, the exact mechanisms by which the mucus increases intestinal resistance against viral infection remain largely unclear. Here, we identify prominent antiviral activity of the small intestinal mucus and extracted total mucus proteins, as evidenced by their inhibitory effects against porcine epidemic diarrhea virus (PEDV) infection. Of all the extracted mucus proteins, mucin 2 and fraction III (~70 kDa) exhibited potent antiviral activity. We further evaluated the antiviral effects of three candidate factors in fraction III and found that calpain-1 contributed substantially to its antiviral activity. In vivo studies demonstrated that oral administration of calpain-1 provided effective protection against intestinal PEDV infection. As a calcium-activated cysteine protease, calpain-1 inhibited viral invasion by binding to and hydrolyzing the S1 domain of the viral spike protein. The region between amino acids 297 and 337 in the b domain of PEDV S1 protein was critical for calpain-1-mediated hydrolysis. Further investigation indicated that calpain-1 could be produced by goblet cells between intestinal epithelia. Taken together, the results of our study revealed calpain-1 to be a novel antiviral protein in porcine small intestinal mucus, suggesting that calpain-1 has potential for defending against intestinal infections. IMPORTANCE Although the antiviral activity of the intestinal mucus was recognized 20 years ago, the antiviral active ingredients in the mucus are poorly understood. Currently, most research on antiviral molecules in the intestinal mucus remains limited to members of the mucin family. This study identified the cysteine protease calpain-1 as a novel antiviral protein in porcine small intestinal mucus and revealed its underlying protective mechanism for the first time. This mechanism involves inhibiting porcine epidemic diarrhea virus (PEDV) invasion by binding and hydrolyzing the S1 domain of the viral spike protein. Furthermore, the results of our PEDV-challenge experiment in piglets indicated that calpain-1 provides effective protection against intestinal PEDV infection. Our findings provide new insights into the protective function of the small intestinal mucus. In addition to potential therapeutic implications for the swine industry, our analysis of antiviral proteins in the small intestinal mucus may have implications for the prevention and control of coronavirus infection in humans.

mRNA COVID-19 Vaccine-Associated Subserosal Eosinophilic Gastroenteritis: A Case Report.

The World Health Organization declared coronavirus disease 2019 (COVID-19) a global pandemic in March 2020. Several vaccines have been developed to overcome the COVID-19 pandemic, and messenger RNA vaccines, commonly known as mRNA vaccines, were the first COVID-19 vaccines to be authorized in Korea. With the worldwide increase in vaccinations, reports of adverse reactions are increasing. However, to the best of our knowledge, there have been no reports of eosinophilic gastroenteritis (EGE) following mRNA vaccination. Here, we present the first case of EGE in a patient who received a second dose of the mRNA vaccine, BNT162b2 (Pfizer-BioNTech). A previously healthy 34-year-old woman presented to the emergency department with generalized abdominal pain for the preceding 2 weeks. She had received a second dose of the mRNA COVID-19 vaccine 2 weeks prior. Subserosal EGE was diagnosed, oral prednisolone was administered, and she recovered completely.

Predominance and first complete genomic characterization of canine parvovirus 2b in Turkey.

Viral enteritis is a significant threat to domestic dogs. The two primary pathogens that cause viral enteritis in dogs are canine coronavirus (CCoV) and canine parvovirus (CPV). In this study, we investigated the occurrence of CPV-2, CCoV, and canine circovirus coinfection by characterizing circulating subtypes of CPV-2 in faecal samples from symptomatic dogs admitted to veterinary clinics located in Ankara, Elazig, Kayseri, and Kocaeli provinces of Turkey, between 2019 and 2022. Virus detection by PCR and RT-PCR revealed that CPV-2 was present in 48 (77.4%) samples, and no other agents were detected. Based on the occurrence of the codon GAT at positions 1276 to 1278 (coding for aspartate at residue 426) of VP2, all CPV-2 isolates were confirmed to be of the CPV-2b subtype. The complete genome sequences of two CPV-2b isolates showed a high degree of similarity to and phylogenetic clustering with Australian and East Asian strains/isolates. The predominant CPV strain circulating in the three different regions of Turkey was found to be a CPV-2b strain containing the amino acid substitutions at Y324I and T440A, which commonly contribute to immune escape. This is the first report of complete genomic analysis of CPV-2 isolates circulating in symptomatic domestic dogs in Turkey. The evolution of CPV-2 has raised questions about the efficacy of current vaccination regimes and highlights the importance of monitoring the emergence and spread of new CPV-2 variants.

Modeling and Role-Modeling Theory on Stunting Children in the Perspective of Philosophy (preprint)

Stunting, during the Covid-19 pandemic, is increasingly becoming a big problem in the world, especially in poor and developing countries. Observational studies have shown that stunting is associated with poor nutrition, especially a plant-based diet, inflammation, caused by infection, enteric dysfunction, an environment with clean water, inadequate sanitation and hygiene (WASH), and endogenous inflammation associated with excess adiposity. This causes nutritional interventions to be often unsuccessful (Kemenkes RI, 2018).The government intervenes to reduce stunting to the target party, which is divided into two categories. The first category is specific nutrition intervention, namely monitoring children under five at the posyandu, giving immunizations, giving vitamin A, giving Supplementary Foods (PMT), and others. The second category is sensitive nutrition interventions, namely the provision of drinking water and proper sanitation, postnatal family planning (KB) services, providing information related to stunting, food social assistance, conditional cash assistance, and others. (KEMEN-PMK, 2018). WHO states, that the impact of stunting can be divided into short-term and long-term impacts. The short-term impacts are; increased incidence of morbidity and mortality; cognitive, motor, and verbal development in children is not optimal; and increased healthcare costs. While the long-term impact; Posture that is not optimal as an adult (shorter than usual); Increased risk of obesity and other diseases; The decline in reproductive health; Less than optimal learning capacity and performance during school years; and Low productivity and work capacity (Kemenkes RI, 2018). The nursing goal is to help people achieve quality, holistic health. Implementation of Modeling and Role Modeling Theory is an option in implementing nursing care for children with stunting. “Modeling” is gaining an understanding of the client’s world from the client’s perspective. That is to build a “model” of the client’s worldview. “Role‑Modeling” is based on the assumption that all humans want to interact with others, they want to carry out selected roles in society. Role-Modeling is using the client’s model of the world to plan interventions that meet his or her perceived needs, grow, develop and heal. Role-Modeling requires that we aim to build trust, promote a positive orientation and a sense of control, affirm strengths and set specific mutual goals.

Seasonality of Common Human Coronaviruses in the United States, 2014-2021 (preprint)

The four common human coronaviruses (HCoVs), including two alpha (HCoV-NL63 and HCoV-229E) and two beta (HCoV-HKU1 and HCoV-OC43) types, generally cause mild, upper respiratory illness. HCoVs are known to have seasonal patterns and variation in predominant types each year, but defined measures of seasonality are needed. We defined seasonality of HCoVs during July 2014 to November 2021 in the United States using a retrospective method applied to National Respiratory and Enteric Virus Surveillance System (NREVSS) data. In the six HCoV seasons prior to 2020-2021, onsets ranged from October to November, peaks from January to February, and offsets from April to June; most (>93%) HCoV detections occurred within the defined seasonal onsets and offsets. The 2020-2021 HCoV season onset was delayed by 11 weeks compared to prior seasons, likely due to COVID-19 mitigation efforts. Better defining HCoV seasonality can inform clinical preparedness and the expected patterns of emerging HCoVs. Article Summary Line The typical common HCoV season in the United States starts between October and November, peaks towards the end of January, and ends between April and June, but the 2020-2021 season was markedly delayed compared to prior seasons.

Investigating the Campylobacter enteritis winter peak in Germany, 2018/2019.

Surveillance of notified Campylobacter enteritis in Germany revealed a recurrent annual increase of cases with disease onset several days after the Christmas and New Year holidays ("winter peak"). We suspected that handling and consumption of chicken meat during fondue and raclette grill meals on the holidays were associated with winter peak Campylobacter infections. The hypothesis was investigated in a case-control study with a case-case design where notified Campylobacter enteritis cases served as case-patients as well as control-patients, depending on their date of disease onset (case-patients: 25/12/2018 to 08/01/2019; control-patients: any other date between 30/11/2018 and 28/02/2019). The study was conducted as an online survey from 21/01/2019 to 18/03/2019. Adjusted odds ratios (aOR) were determined in single-variable logistic regression analyses adjusted for age group and sex. We analysed 182 data sets from case-patients and 260 from control-patients and found associations of Campylobacter infections after the holidays with meat fondue (aOR 2.2; 95% confidence interval (CI) 1.2-3.8) and raclette grill meals with meat (aOR 1.5; 95% CI 1.0-2.4) consumed on the holidays. The associations were stronger when chicken meat was served at these meals (fondue with chicken meat: aOR 2.7; 95% CI 1.4-5.5; raclette grill meal with chicken meat: aOR 2.3; 95% CI 1.3-4.1). The results confirmed our initial hypothesis. To prevent Campylobacter winter peak cases in the future, consumers should be made more aware of the risks of a Campylobacter infection when handling raw meat, in particular chicken, during fondue or raclette grill meals on the holidays.

Eosinophilic Esophagitis Patients Are Not at Increased Risk of Severe COVID-19: A Report From a Global Registry.

BACKGROUND: The impact of coronavirus disease 2019 (COVID-19) on eosinophilic esophagitis (EoE) and eosinophilic gastrointestinal diseases (EGIDs) is unknown. OBJECTIVE: We aimed to characterize patients with EoE and EGIDs who had COVID-19, assess severity of COVID-19 in the EoE/EGID population, and evaluate for COVID-19-induced EoE/EGID flares. METHODS: We established an online global registry collecting physician entered, deidentified data related to patient demographics, EoE/EGID disease features, comorbidities, and treatments, COVID-19 source of exposure, symptoms, illness severity, hospitalizations, and deaths. RESULTS: Ninety-four cases were reported between March 2020 and April 2021 (median age, 21 years; range, 1.5-53 years; 73% male). Most had atopy (73%), and 80% had isolated EoE. Before COVID-19, the EoE/EGID activity was reported as clinical remission in 51 (54%) and moderate in 20 (21%). EoE/EGID treatments at the time of COVID-19 included proton pump inhibitors 49 (52%), swallowed/topical steroids 48 (51%), and dietary elimination 34 (36%). COVID-19 symptoms included cough (56%), fever (49%), anosmia (21%), and ageusia (22%). Most patients with COVID-19 had a mild course (70%), with 15% asymptomatic, 12% moderate, and 2% severe. Three patients were hospitalized, and no intensive care unit admissions or deaths were reported. Mean time from first symptoms to resolution in symptomatic patients was 10 days (range, 1-90 days). A single EGID flare was reported during COVID-19. CONCLUSIONS: In a global EoE/EGID registry, relatively few COVID-19 cases have been reported. COVID-19 severity was comparable to the general population. Based on this registry, it does not appear that patients with EoE are at increased risk for severe COVID-19 infection or that COVID-19 leads to EGID flares.

Cutaneous manifestations associated with anosmia, ageusia and enteritis in SARS-CoV-2 infection - A possible pattern? Observational study and review of the literature.

BACKGROUND: The cutaneous manifestations of coronavirus disease 2019 (COVID-19) have been covered insufficiently in the literature. METHODS: Thirty-nine patients admitted to the study hospital with confirmed COVID-19 who experienced various skin manifestations during hospitalization or in the convalescence period, were analysed retrospectively. RESULTS: Thirty-nine patients with COVID-19, admitted to the study hospital between 23 March and 12 September 2020, had intra-infectious rash or lesions of cutaneous vasculitis during convalescence. The most common cutaneous manifestations of COVID-19 were erythematous and erythematous papular rash. Twenty-seven of the 39 patients had anosmia (69.2%), 26 patients had ageusia (66.7%), 34 patients had pneumonia (87.2%) and 24 patients had intra-infectious enterocolitis (61.5%). Skin biopsies were rarely performed in these patients. This article reports the results of biopsies performed in two patients, showing histopathological and immunohistochemical changes in erythematous rash and erythema multiforme-like lesions. Both skin biopsies revealed early fibrous remodelling of the dermis, suggesting similarity with changes that occur in the lungs and other tissues in patients with COVID-19. CONCLUSIONS: Correlations between skin lesions and anosmia, ageusia and enteritis in patients with COVID-19 do not seem to be accidental, but are associated with a similar response to ACE2 receptor expression in these tissues.

Type 2 Immunity and Age Modify Gene Expression of Coronavirus-induced Disease 2019 Receptors in Eosinophilic Gastrointestinal Disorders.

ABSTRACT: Infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can lead to coronavirus-induced disease 2019 (COVID-19). The gastrointestinal (GI) tract is now an appreciated portal of infection. SARS-CoV-2 enters host cells via angiotensin-converting enzyme-2 (ACE2) and the serine protease TMPRSS2. Eosinophilic gastrointestinal disorders (EGIDs) are inflammatory conditions caused by chronic type 2 (T2) inflammation. the effects of the T2 atopic inflammatory milieu on SARS-COV-2 viral entry gene expression in the GI tract is poorly understood. We analyzed tissue ACE2 and TMPRSS2 gene expression in pediatric eosinophilic esophagitis (EoE), eosinophilic gastritis (EG), and in normal adult esophagi using publicly available RNA-sequencing datasets. Similar to findings evaluating the airway, there was no difference in tissue ACE2/TMPRSS2 expression in EoE or EG when compared with control non-EoE/EG esophagus/stomach. ACE2 gene expression was significantly lower in esophagi from children with or without EoE and from adults with EoE as compared with normal adult esophagi. Type 2 immunity and pediatric age could be protective for infection by SARS-CoV-2 in the gastrointestinal tract because of decreased expression of ACE2.

A comprehensive analysis of outcomes between COVID-19 patients with an elevated serum lipase compared to those with pancreatitis. (preprint)

Background and Aims: COVID-19 patients may have asymptomatic hyperlipasemia without abdominal imaging findings or abdominal pain. In addition, primary and secondary pancreatitis have been described in COVID-19 patients. There is limited information on how the groups compare in outcomes. The aim is to compare outcomes among these groups. Methods: This is a retrospective study from 12 hospitals within one healthcare system examining outcomes between hospitalized COVID-19 patients with a lipase <3x upper limit of normal (ULN), asymptomatic hyperlipasemia (>3x ULN), secondary pancreatitis (typical respiratory COVID-19 symptoms and found to have pancreatitis), and primary pancreatitis (presenting with pancreatitis). Results: Of 11,883 patients admitted with COVID-19, 1,560 patients were included: 1,155 COVID-19 patients with a normal serum lipase (control group), 270 with an elevated lipase <3x ULN, 46 patients with asymptomatic hyperlipasemia with a lipase 3xULN, 57 patients with secondary pancreatitis, and 32 patients with primary pancreatitis. On adjusted multivariate analysis, the elevated lipase <3x ULN and asymptomatic hyperlipasemia groups had worse outcomes. The mortality was OR1.6 (95% CI 1.2-2.2) and 1.1 (95% CI 0.5-2.3), respectively. The need for mechanical ventilation was OR 2.8 (95% CI 1.2-2.1) and 2.8 (95% CI 1.5-5.2), respectively. Longer length of stay was OR 1.5 (95%CI 1.1-2.0) and 3.16 (95%CI 1.5-6.5), respectively. Conclusion: COVID-19 patients with an elevated lipase< 3x ULN and asymptomatic hyperlipasemia have generally worse outcomes than those with pancreatitis. This could be attributed to extrapancreatic causes (liver failure, renal failure, enteritis, etc), which may signify a more severe course of clinical disease. Key words: pancreas; SARS-CoV-2; pancreatitis

Mistaken MIS-C: A Case Series of Bacterial Enteritis Mimicking MIS-C.

Multisystem inflammatory syndrome in children following severe acute respiratory syndrome coronavirus 2 infection is characterized by fever, elevated inflammatory markers, and multisystem organ involvement. Presentations are variable but often include gastrointestinal symptoms. We describe 5 children with fever and gastrointestinal symptoms initially concerning for multisystem inflammatory syndrome in children who were ultimately diagnosed with bacterial enteritis, highlighting the diagnostic challenges presented by the severe acute respiratory syndrome coronavirus 2 pandemic.