Long-term follow-up of cats in complete remission after treatment of feline infectious peritonitis with oral GS-441524

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Abstract

Objectives

Feline infectious peritonitis (FIP), a common disease in cats caused by feline coronavirus (FCoV), is usually fatal once clinical signs appear. Successful treatment of FIP with oral GS-441524 for 84 days was demonstrated recently by this research group. The aim of this study was to evaluate the long-term outcome in these cats.

Methods

A total of 18 successfully treated cats were followed for up to 1 year after treatment initiation (9 months after completion of the antiviral treatment). Follow-up examinations were performed at 12-week intervals, including physical examination, haematology, serum biochemistry, abdominal and thoracic ultrasound, FCoV ribonucleic acid (RNA) loads in blood and faeces by reverse transciptase-quantitative PCR and anti-FCoV antibody titres by indirect immunofluorescence assay.

Results

Follow-up data were available from 18 cats in week 24, from 15 cats in week 36 and from 14 cats in week 48 (after the start of treatment), respectively. Laboratory parameters remained stable after the end of the treatment, with undetectable blood viral loads (in all but one cat on one occasion). Recurrence of faecal FCoV shedding was detected in five cats. In four cats, an intermediate short-term rise in anti-FCoV antibody titres was detected. In total, 12 cats showed abdominal lymphadenomegaly during the follow-up period; four of them continuously during the treatment and follow-up period. Two cats developed mild neurological signs, compatible with feline hyperaesthesia syndrome, in weeks 36 and 48, respectively; however, FCoV RNA remained undetectable in blood and faeces, and no increase in anti-FCoV antibody titres was observed in these two cats, and the signs resolved.

Conclusions and relevance

Treatment with GS-441524 proved to be effective against FIP in both the short term as well as the long term, with no confirmed relapse during the 1-year follow-up period. Whether delayed neurological signs could be a long-term adverse effect of the treatment or associated with a ‘long FIP syndrome’ needs to be further evaluated.

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Compassionate Use of Remdesivir for Patients with Severe Covid-19

Jonathan Grein, Norio Ohmagari, Daniel Sanghoon Shin … (2020)

Abstract Background Remdesivir, a nucleotide analogue prodrug that inhibits viral RNA polymerases, has shown in vitro activity against SARS-CoV-2. Methods We provided remdesivir on a compassionate-use basis to patients hospitalized with Covid-19, the illness caused by infection with SARS-CoV-2. Patients were those with confirmed SARS-CoV-2 infection who had an oxygen saturation of 94% or less while they were breathing ambient air or who were receiving oxygen support. Patients received a 10-day course of remdesivir, consisting of 200 mg administered intravenously on day 1, followed by 100 mg daily for the remaining 9 days of treatment. This report is based on data from patients who received remdesivir during the period from January 25, 2020, through March 7, 2020, and have clinical data for at least 1 subsequent day. Results Of the 61 patients who received at least one dose of remdesivir, data from 8 could not be analyzed (including 7 patients with no post-treatment data and 1 with a dosing error). Of the 53 patients whose data were analyzed, 22 were in the United States, 22 in Europe or Canada, and 9 in Japan. At baseline, 30 patients (57%) were receiving mechanical ventilation and 4 (8%) were receiving extracorporeal membrane oxygenation. During a median follow-up of 18 days, 36 patients (68%) had an improvement in oxygen-support class, including 17 of 30 patients (57%) receiving mechanical ventilation who were extubated. A total of 25 patients (47%) were discharged, and 7 patients (13%) died; mortality was 18% (6 of 34) among patients receiving invasive ventilation and 5% (1 of 19) among those not receiving invasive ventilation. Conclusions In this cohort of patients hospitalized for severe Covid-19 who were treated with compassionate-use remdesivir, clinical improvement was observed in 36 of 53 patients (68%). Measurement of efficacy will require ongoing randomized, placebo-controlled trials of remdesivir therapy. (Funded by Gilead Sciences.)

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Coronavirus Susceptibility to the Antiviral Remdesivir (GS-5734) Is Mediated by the Viral Polymerase and the Proofreading Exoribonuclease

Maria Agostini, Erica L. Andres, Amy Sims … (2018)

ABSTRACT Emerging coronaviruses (CoVs) cause severe disease in humans, but no approved therapeutics are available. The CoV nsp14 exoribonuclease (ExoN) has complicated development of antiviral nucleosides due to its proofreading activity. We recently reported that the nucleoside analogue GS-5734 (remdesivir) potently inhibits human and zoonotic CoVs in vitro and in a severe acute respiratory syndrome coronavirus (SARS-CoV) mouse model. However, studies with GS-5734 have not reported resistance associated with GS-5734, nor do we understand the action of GS-5734 in wild-type (WT) proofreading CoVs. Here, we show that GS-5734 inhibits murine hepatitis virus (MHV) with similar 50% effective concentration values (EC50) as SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). Passage of WT MHV in the presence of the GS-5734 parent nucleoside selected two mutations in the nsp12 polymerase at residues conserved across all CoVs that conferred up to 5.6-fold resistance to GS-5734, as determined by EC50. The resistant viruses were unable to compete with WT in direct coinfection passage in the absence of GS-5734. Introduction of the MHV resistance mutations into SARS-CoV resulted in the same in vitro resistance phenotype and attenuated SARS-CoV pathogenesis in a mouse model. Finally, we demonstrate that an MHV mutant lacking ExoN proofreading was significantly more sensitive to GS-5734. Combined, the results indicate that GS-5734 interferes with the nsp12 polymerase even in the setting of intact ExoN proofreading activity and that resistance can be overcome with increased, nontoxic concentrations of GS-5734, further supporting the development of GS-5734 as a broad-spectrum therapeutic to protect against contemporary and emerging CoVs.

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Are we facing a crashing wave of neuropsychiatric sequelae of COVID-19? Neuropsychiatric symptoms and potential immunologic mechanisms ☆

Emily A. Troyer, Jordan Kohn, Suzi Hong (2020)

Highlights • The COVID-19 pandemic is a significant source of psychological distress globally. • The novel coronavirus and host immunologic response may also directly affect brain and behavior. • Acute and delayed neuropsychiatric sequelae have been associated with past viral pandemics. • Prospective monitoring of COVID-19 patients is needed to determine neuropsychiatric outcomes. • A psychoneuroimmunology perspective will aid in promoting post-pandemic public mental health.

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Author and article information

Contributors

Katharina Zwicklbauer: (View ORCID Profile)

Daniela Krentz: (View ORCID Profile)

Michèle Bergmann: (View ORCID Profile)

Roswitha Dorsch: (View ORCID Profile)

Regina Hofmann-Lehmann: (View ORCID Profile)

Marina L Meli: (View ORCID Profile)

Andrea M Spiri: (View ORCID Profile)

Laura Kolberg: (View ORCID Profile)

Yury Zablotski: (View ORCID Profile)

Ulrich von Both: (View ORCID Profile)

Journal

Title: Journal of Feline Medicine and Surgery

Abbreviated Title: Journal of Feline Medicine and Surgery

Publisher: SAGE Publications

ISSN (Print): 1098-612X

ISSN (Electronic): 1532-2750

Publication date Created: August 2023

Publication date (Electronic): August 07 2023

Publication date (Print): August 2023

Volume: 25

Issue: 8

Affiliations

[1 ]Clinic of Small Animal Medicine, Centre for Clinical Veterinary Medicine, LMU Munich, Munich, Germany

[2 ]Clinical Laboratory, Department of Clinical Diagnostics and Services, Center for Clinical Studies, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland

[3 ]Division of Paediatric Infectious Diseases, Dr. von Hauner Children’s Hospital, University Hospital, LMU Munich, Munich, Germany

[4 ]Section of Clinical and Comparative Neuropathology, Institute of Veterinary Pathology, Centre for Clinical Veterinary Medicine, LMU Munich, Munich, Germany

[5 ]German Center for Infection Research (DZIF), partner site Munich, Munich, Germany

Article

DOI: 10.1177/1098612X231183250

SO-VID: cd03ac85-a56f-4890-bcb0-4f8f861554f3

License:

https://creativecommons.org/licenses/by-nc/4.0/

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Long-term follow-up of cats in complete remission after treatment of feline infectious peritonitis with oral GS-441524

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Abstract

Objectives

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Point-of-Care Testing for Infectious Diseases Super Collection

Most cited references 34

Compassionate Use of Remdesivir for Patients with Severe Covid-19

Coronavirus Susceptibility to the Antiviral Remdesivir (GS-5734) Is Mediated by the Viral Polymerase and the Proofreading Exoribonuclease

Are we facing a crashing wave of neuropsychiatric sequelae of COVID-19? Neuropsychiatric symptoms and potential immunologic mechanisms ☆

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