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• Most antiviral drugs available for treatment of feline and canine viral infections are nucleoside analogues with greatest activity against retroviruses, herpesviruses and coronaviruses. • Antiviral drugs also affect the function of host cell machinery;therefore, they have considerable potential for toxicity. • Antiviral drugs are widely used in human medicine for treatment of HIV infection, herpesvirus infection, and other viral. Much less is known about these medications in cats and dogs, and there are only few diseases of cats and dogs for which efficacy has been demonstrated. • There are important differences between human and animal virus infections;therefore, it should not be assumed that the use of an antiviral agent in humans can be translated to a use in animals unless there is evidence of safety and efficacy. • The most common indication for antiviral drugs in animals is treatment of FHV-1 infections with famciclovir and cidofovir. Zidovudine, an antiretroviral drug, has been used to treat FIV and FeLV infections. In addition, new antiviral drugs are now used to treat FIP. • Antiviral drugs can act synergistically with immunomodulatory agents. • Immunomodulators include microbial products, plant-derived immunomodulators, naturally occurring mammalian proteins, and synthetic drugs. The effect of many of these drugs on outcome in cats and dogs with infectious diseases has not been fully evaluated with well-designed studies. • The parenteral use of natural or recombinant human cytokines in cats and dogs can produce neutralizing antibodies after 1 to 2 weeks of treatment, which can cross-react with endogenous proteins. • Antiviral treatments are intended to suppress viral entry, multiplication, or transmission. Some of these antiviral agents can produce a remission or assist the patient's immune system to limit the course of the viral disease. © 2021 Elsevier Inc. All rights reserved.
ABSTRACT
Case report Trometamol (tromethamine, tris(hydroxymethyl)aminomethane (TRIS)) is an excipient frequently used as buffer in fluids and semisolid agents, including many drugs such as antibiotics, iodinated contrast agents and the COVID-19 vaccine mRNA-1273. Here, we report the first case of a delayed-type hypersensitivity after oral intake of trometamol. A 64-year- old female patient presented to our emergency department with generalized erythematous rash, pruritus and swelling of the face five hours after the intake of one tablet of fosfomycin trometamol for a urinary tract infection. Further medical history revealed a previous erythematous rash five to six hours after administration of the iodinated contrast agent iopromide. We performed skin prick and intradermal tests with trometamol, fosfomycin trometamol and various iodinated contrast agents, including iopromide, iomeprol, iobitridol, iopamidol and iodixanol. These tests showed no reactions initially. However, 48 hours after intradermal testing, macular erythematous lesions developed at the sites tested with trometamol 0.1%, trometamol 0.01% and all sites tested with iodinated contrast agents. Furthermore, when we performed a lymphocyte transformation test with trometamol, fosfomycin trometamol and iopromide, we recorded a positive reaction with cytokine release after stimulating T cells with trometamol and iopromide. In contrast, basophil activation testing showed a negative result for these agents. Based on these results and our patient's history, we diagnosed a clinically relevant type IV sensitization to trometamol. There are only a few case reports about immediate-type allergic reactions to gadolinium contrast agents caused by the excipient trometamol. There are some published cases which report contact dermatitis after topical administration of trometamol-containing agents. To our knowledge, ours is the first case to report a delayed hypersensitivity reaction to oral administration of trometamol. Excipients are indispensable for drugs, vaccines and other products since they stabilize and preserve the active agents. Nevertheless, excipients should always be considered during an allergy workup, especially if the patient reports prior drug reactions that cannot be explained by a chemical cross-reaction. In our case, we diagnosed delayed-type hypersensitivity to the excipient trometamol. This is a consequential diagnosis for the patient, because trometamol is contained in many drugs and in the COVID-19 vaccine mRNA-1273.
ABSTRACT
Feline infectious peritonitis (FIP) caused by feline coronavirus (FCoV) is a fatal disease if untreated. A recent prospective controlled treatment trial in field cats with confirmed FIP demonstrated excellent efficacy of GS-441524. The aims of this study were to investigate the effect of GS-441524 treatment on fecal FCoV RNA shedding and presence of FCoV spike (S-) gene mutations in different body compartments in treated FIP cats as well as in 12 companion cats cohabitating with the FIP cats. Eighteen cats with confirmed FIP were treated with oral GS-441524 for 84 days. Viral loads in feces, blood, and effusion were determined by RT-qPCR. In the first three days of treatment, 11/18 treated FIP cats (61%) shed FCoV RNA in feces, but all of them tested negative by day six. In one of them, fecal shedding reoccurred on day 83. Two cats initially negative in feces were transiently positive 1-4 weeks into the treatment. FCoV RNA loads in feces decreased in all treated FIP cats with time, comparable with those in blood and effusion. Sgene mutations linked to systemic FCoV spread were consistently found in blood and effusion from treated FIP cats, but not in feces from treated or companion cats. Phylogenetic analyses of the S-gene revealed a clustering of fecal samples of the companion cats with the corresponding FIP cats. Oral treatment with GS-441524 effectively decreased viral RNA loads in feces, blood, and effusion in cats with FIP. Nonetheless, reshedding can occur, most likely if cats are re-exposed to FCoV.
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Background and Aim Obesity and type 2 diabetes (T2D) show an increased risk for a severe COVID-19 disease. Treatment with DPP4 inhibitor (DPP4i) results in reduced mortality and better clinical outcome. Here, we aimed to identify potential mechanisms for the observed DPP4i effect in COVID-19. Methods We compared T2D subjects with (cases) and without (controls) DPP4i treatment (N=69), as well as patients hospitalised for severe COVID-19 and healthy controls (N=34) with regard to serum concentrations of soluble frizzle receptor protein 5 (sFRP5) using univariate statistics. Furthermore, we isolated pre-adipocytes, mature adipocytes and macrophages from adipose tissue biopsies (N=100) and performed western-blotting for sFRP5 and Wnt5a expression. Results In T2D patients, we identified a significant increase of the anti-inflammatory adipokine sFRP5 in relation to DPP4 inhibition. sFRP5 is a specific antagonist to Wnt5a, a glycopeptide secreted by adipose tissue macrophages acting proinflammatory in various diseases. We therefore examined sFRP5 levels in patients hospitalised for severe COVID-19 and found significant lower levels compared to healthy controls. Since sFRP5 might consequently be a molecular link for the beneficial effects of DPP4i in COVID-19, we further aimed to identify the exact source of sFRP5 in adipose tissue on cellular level. Results from western-blotting in adipose tissues showed a sFRP5 expression specifically in mature adipocytes of subcutaneous and omental adipose tissue. Conclusion In summary, our data suggest that DPP4i increase serum levels of anti-inflammatory sFRP5 which might be beneficial in COVID-19, reflecting a state of sFRP5 deficiency.
Subject(s)
Family/psychology , Health Services Accessibility/ethics , Maternal Health Services/ethics , Patient Acceptance of Health Care/psychology , Pregnant Women/psychology , Women's Rights/ethics , COVID-19/prevention & control , Europe , Female , Humans , Infection Control , Maternal Health Services/organization & administration , Parturition/psychology , Pregnancy , Quality of Health Care/ethics , SARS-CoV-2ABSTRACT
Aims Dipeptidylpeptidase is a key regulator of the incretin system. Initially, it's soluble form (sDPP-4) was described as an adipokine mediating metabolic inflammation. This is recently questioned in mechanistic rodent studies. To further clarify sDPP-4's role in physiology and metabolic diseases, we examined sDPP-4 in a large human cohort and during weight-loss interventions. Like ACE2, sDPP-4 serves as a binding partner for certain corona-like viruses enabling virus entry. As metabolic diseases are major risk factors for the COVID-19 pandemic, we additionally examined sDPP-4 in patients suffering severe Sars-CoV-2 infection. Methods sDPP-4 serum concentrations were measured using ELISA and related to various metabolic variables. Using a case-control-design, sDPP-4 was assessed in acute COVID-19 and sepsis infection. Results sDPP-4 increased with body weight, insulin resistance and hypertriglyceridemia but reduced in type 2 diabetes and arterial hypertension. Altered serum concentrations appeared with impaired liver and kidney but not cardiac function. No association to systemic inflammation was observed. Having found increased sDPP-4 in obesity, surgical (gastric bypass/sleeve gastrectomy) and non-surgical weight-loss interventions revealed a significant association of sDPP-4 with the improvement of liver function but neither with changes in body weight nor fat mass. Complementary, the case control study revealed reduced sDPP-4 concentrations specific for COVID-19 infection. Conclusions We suggest that sDPP-4 is rather related to hepatic abnormalities in obesity than primarily functioning as an adipokine. sDPP-4 is implicated in glucose and lipid metabolism, but not fundamentally in systemic inflammation. Additional to ACE-2, sDPP-4 might also have a regulatory role in COVID-19 infection.
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BACKGROUND: The clinical knowledge about the course, complications and treatment of COVID-19 in children and adolescents is so far limited. AIM: This systematic review summarizes the current scientific evidence regarding the clinical presentation of COVID-19 in hospitalized children based on available case series from China. In addition, first data from a nationwide pediatric hospital survey conducted by the German Society for Pediatric Infectious Diseases (DGPI) are presented. METHODS: This study evaluated 12 case series from China with 6-2143 children infected with SARS-CoV2, which were identified by a literature search in PubMed up to 31 March 2020. The database of the German nationwide DGPI COVID-19 survey was accessed on 6 April 2020. RESULTS: The median patient age in the case series was between 2 and 7 years and 18-45% were infants <1 year of age. The duration of hospital stay was 5-20 days. Most commonly reported symptoms were fever and cough; in 40-100% of cases involvement of the lower respiratory tract was reported, usually confirmed by computed tomography (CT). Severe and critical courses of disease were reported in up to 8% of the children including 2 fatalities. So far the German DGPI COVID-19 survey reported 33 hospitalized children up to 6 April 2020, mostly with upper airway infections. Of these children, 45% were infants and 32% had an underlying medical condition. So far 3 children (9%) needed admission to an intensive care unit. CONCLUSION: COVID-19 in hospitalized children usually presented as an uncomplicated febrile upper airway infection or mild pneumonia. Severe cases or fatalities rarely occurred in children. Information on neonates and children with underlying chronic conditions as well as on therapeutic and preventive measures are urgently needed.