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1.
Gastroenterology Clinics of North America ; JOUR
Article in English | ScienceDirect | ID: covidwho-2104988
2.
Cephalalgia ; 42(1 Supplement):71-72, 2022.
Article in English | EMBASE | ID: covidwho-2079254

ABSTRACT

Introduction: Calcitonin gene-related peptide (CGRP) a is well-known to be implicated in migraine pathophysiology. Its b isoform, released mainly in the enteric nervous system, has not been as extensively studied. Previous research prompt CGRP has a role in gastrointestinal motility, as well as immune and intestinal blood flow regulation. It is postulated to help peptic ulcer healing, and immune cell migration and regulation in acute gastrointestinal infections. In COVID-19 between 2% and 50% of patients develop diarrhea, and its prevalence increases with the severity of the disease. The pathophysiology of the diarrhea in this infection is not completely clear but CGRP has been proposed to play a role in different aspects of the symptomatology. Inflammatory bowel disease (IBD), known to be associated with migraine, is a chronic gastrointestinal autoimmune disease. Neuropeptides like CGRP might play a role in the complex pathophysiology of the disease, but this has not been well established yet. On the other hand, the most frequent adverse event of new monoclonal antibodies against CGRP for migraine is constipation, which points out that the blockage may affect CGRPbeta release. Objective(s): To assess the role of CGRPbeta in two gastrointestinal disorders: COVID-19 with acute diarrhea;and IBD. Method(s): CGRPbeta were measured by ELISA (CUSABIO, China) in early morning serum samples in patients with IBD at diagnosis, as well as in COVID-19 inpatients experiencing diarrhea. We compared each group with a cohort of healthy controls matched by age and sex. Image: Results: Twenty-six COVID-19 inpatients with diarrhea were included (mean age=62+/-16 years, range 31-91 years;69.2% females) who were matched with 30 healthy controls (mean age=61+/-15 years, range 29-89 years, 66.6% women). Fifty-nine patients with early IBD (mean age 48.9+/-16.4 years, range 21-79 years;62,7% females were matched with 59 healthy controls (mean age 49.0+/-14.9 years, range 23-77 years;62,7% females). While CGRPbeta levels were significantly elevated in COVID-19 patients (6,3+/-2.6 pg/mL) vs controls (4.2+/-2.4 pg/mL) (+26.2%;p<0.01), CGRPbeta levels in patients with IBD were significantly decreased (3.1+/-1.8 pg/mL) as compared to controls (4.8+/-2.6 pg/mL) (-35.4%, p<0.001). Conclusion(s): CGRPbeta seems to exert different actions depending on the underlying conditions. While its increase with diarrhea in COVID-19 patients fits very well with the known acute effects of increase gastrointestinal motility in CGRP infusion in volunteers, the decrease in CGRPbeta levels in IBD confirm a protective role of this peptide in the homeostasis of the intestinal mucosa. These findings may help to explain the role of CGRPbeta in digestive manifestations of migraine and in the constipation seen in migraine patients on CGRP antibodies as well.

3.
Viruses ; 14(10)2022 10 16.
Article in English | MEDLINE | ID: covidwho-2071840

ABSTRACT

Host-virus protein interactions are critical for intracellular viral propagation. Understanding the interactions between cellular and viral proteins may help us develop new antiviral strategies. Porcine epidemic diarrhea virus (PEDV) is a highly contagious coronavirus that causes severe damage to the global swine industry. Here, we employed co-immunoprecipitation and liquid chromatography-mass spectrometry to characterize 426 unique PEDV nucleocapsid (N) protein-binding proteins in infected Vero cells. A protein-protein interaction network (PPI) was created, and gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) database analyses revealed that the PEDV N-bound proteins belong to different cellular pathways, such as nucleic acid binding, ribonucleoprotein complex binding, RNA methyltransferase, and polymerase activities. Interactions of the PEDV N protein with 11 putative proteins: tripartite motif containing 21, DEAD-box RNA helicase 24, G3BP stress granule assembly factor 1, heat shock protein family A member 8, heat shock protein 90 alpha family class B member 1, YTH domain containing 1, nucleolin, Y-box binding protein 1, vimentin, heterogeneous nuclear ribonucleoprotein A2/B1, and karyopherin subunit alpha 1, were further confirmed by in vitro co-immunoprecipitation assay. In summary, studying an interaction network can facilitate the identification of antiviral therapeutic strategies and novel targets for PEDV infection.


Subject(s)
Coronavirus Infections , Nucleic Acids , Porcine epidemic diarrhea virus , Swine Diseases , Chlorocebus aethiops , Swine , Animals , Porcine epidemic diarrhea virus/genetics , Vimentin/metabolism , Vero Cells , Nucleocapsid/metabolism , Nucleocapsid Proteins/genetics , Viral Proteins/metabolism , Coronavirus Infections/metabolism , Antiviral Agents/metabolism , RNA/metabolism , Heat-Shock Proteins/metabolism , Methyltransferases/metabolism , Heterogeneous-Nuclear Ribonucleoproteins/metabolism , DEAD-box RNA Helicases/metabolism , Ribonucleoproteins/metabolism , Karyopherins/metabolism , Nucleic Acids/metabolism
4.
Res Vet Sci ; 152: 236-244, 2022 Dec 20.
Article in English | MEDLINE | ID: covidwho-2069657

ABSTRACT

Porcine epidemic diarrhea virus (PEDV) envelope protein (E) is recognized as a viroporin that plays important functions in virus budding, assembly and virulence. Our previous study found that PEDV E protein induces endoplasmic reticulum stress (ERS), as well as suppresses the type I interferon (IFN) response, but their link and underlying mechanism remain obscure. To better understand this relationship, we investigated the roles of PEDV E protein-induced ERS in regulating cellular type I IFN production. Our results showed that PEDV E protein localized in the ER and triggered ERS through activation of PERK/eIF2α branch, as revealed by the up-regulated phosphorylation of PERK and eIF2α. PEDV E protein also significantly inhibited both poly(I:C)-induced and RIG-I signaling-mediated type I interferon production. The PERK/eIF2α branch of ERS activated by PEDV E protein led to the translation attenuation of RIG-I signaling-associated antiviral proteins, resulting in the suppression of type I IFN production. However, PEDV E protein had no effect on the mRNA transcription of RIG-I-associated molecules. Moreover, suppression of ERS with 4-PBA, a widely used ERS inhibitor, restored the expression of RIG-I-signaling-associated antiviral proteins and mRNA transcription of IFN-ß and ISGs genes to their normal levels, suggesting that PEDV E protein blocks the production of type I IFN through inhibiting expression of antiviral proteins caused by ERS-mediated translation attenuation. This study elucidates the mechanism by which PEDV E protein specifically modulates the ERS to inhibit type I IFN production, which will augment our understanding of PEDV E protein-mediated virus evasion of host innate immunity.


Subject(s)
Coronavirus Infections , Interferon Type I , Porcine epidemic diarrhea virus , Swine Diseases , Swine , Animals , Antiviral Agents , Endoplasmic Reticulum Stress , Cell Line , Eukaryotic Initiation Factor-2 , RNA, Messenger , Coronavirus Infections/veterinary
5.
Pakistan Journal of Medical and Health Sciences ; 16(8):88-91, 2022.
Article in English | EMBASE | ID: covidwho-2067739

ABSTRACT

Background: The COVID-19 first surfaced when cluster of pneumonia patients arose in Wuhan, Hubei Province, China. Although the current gold standard for COVID-19 diagnosis is reverse transcriptase-polymerase chain reaction (RT-PCR), chest x-ray (CXR) and computed tomography (CT) play a vital role in sickness diagnosis due to their limited sensitivity and availability. Aim: To evaluate retrospectively the role of CXR, the main radiological findings in it and its diagnostic accuracy in COVID-19 pneumonia. Methods: This is a cross sectional study involving 264 PCR positive COVID-19 patients with their clinical-epidemiological findings admitted at Ziauddin Hospital from May-July 2020. CXRs were taken as digital radiographs in our emergency department's isolation wards using the same portable X-ray device, according to local norms. CXRs were taken in two directions: antero-posterior (AP) and postero-anterior (PA). The hospitals' database had all of the images. To determine the number of radiological findings, multiple radiologists on duty completed an independent and retrospective examination of each CXR. In the event of disagreement, a mutual agreement was reached. SPSS version 20 was used for statistical analysis. Results: We were able to find 264 patients who met our criteria. With a mean age of 56.4214.89, the majority of individuals were determined to be males 189(71.6%) and females 75(28.4%). (Range of 16 to 87 years). 127 patients (48.1%) had severe illness symptoms and were admitted to the ICU, while the remaining 102(38.6%) had mild to moderate disease 35(13.3%). Diffuse (29.2%) and middle and lower co-existing distribution (25.8%) whereas just lower lobe (13.3%) were the most common predominance in severity. Peripheral involvement was also seen in (8.7%) cases. Conclusion: Both lungs are equally affected with the disease having the consolidation and opacifications while the effusion is the major complication in the severe cases. Diffuse involvement of the lung lobes is seen in the study followed by the middle and lower lobe involvement.

6.
Pakistan Journal of Medical and Health Sciences ; 16(8):24-26, 2022.
Article in English | EMBASE | ID: covidwho-2067738

ABSTRACT

Aim: To evaluate the potential use of ivermectin with standard therapy among mild to moderate covid-19 illness. Methods: This is a single-centered, prospective observational, randomized, parallel group (1:1 ratio), standard versus controlled ivermectin study recruited 210 confirmed COVID-19 positive patients who were admitted in COVID treatment center of Dr Ruth Kum Pafu Civil hospital Karachi, Pakistan from 1st November 2020 to 30th May 2021. Data were analyzed using SPSS version Results: Total of 210 patients were enrolled in the study and aged matched patients were divided in two groups 105 patients received ivermectin 6 mg twice a day for five days along with standard therapy while remaining 105 patients received standard therapy as per local and international guidelines. Male were 140(66.7%) and female 70(33.3%);age ranges between 26 to 77 years and majority 140( 66.7%) were more than 50 years of age. Fever, dry cough and dyspnea were the major symptoms seen;112(53.3%) patients had DM as a comorbid illness . Total of 21(20%) of 105 patients of ivermectin group had negative PCR for COVID 19 on day seven while the other group had positive covid test in all of 105 patients . On day 10 total of 49 more patients from ivermectin group found COVID negative along with 21 previously negative had second PCR was found negative in this way total of 70( 66.7%) of ivermectin group had negative PCR for COVID 19 while 21(20%) patients from non ivermectin got negative PCR for COVID 19 on day 10 . Conclusion: Use of ivermectin with standard therapy clear the virus earlier than standard therapy in mild to moderate COVID-19 infected patients admitted in COVID treatment center of Dr Ruth Kum Pafu Civil Hospital Karachi.

7.
Iatreia ; 35(4):414-423, 2022.
Article in Spanish | EMBASE | ID: covidwho-2067412

ABSTRACT

Objective: To identify the clinical presentation and factors associated with anosmia and ageusia in patients with COVID-19 in a health center in a province of Peru for the period 2020-2021. Method(s): Cross-sectional analytical study through data from the COVID-19 program of the Essalud Po-lyclinic in Jauja, Peru. Sociodemographic characte-ristics, symptoms and comorbidities of the patients were detailed. A bivariate analysis identified the factors associated with anosmia and ageusia. Result(s): 356 patients were identified: 53.1 % were wo-men, mean age was 48.7 years (+/-17.8) and 261 (73.3%) with mild COVID-19. Of the total, 22.2% had anosmia and 19.9% ageusia;of which the majority were un-der 65 and female. Associated symptoms were found in 86.1% of patients with anosmia and 83.1% with ageusia. The main factors associated with anosmia were age younger than 65 years (p=0.027), cough (p<0.001), headache (p<0.001), dyspnea (p<0.001), nasal congestion (p<0.001) and fever (p<0.001);and ageusia: age younger than 65 years (p=0.006), cough (p=0.001), headache (p<0.001), dyspnea (p<0.001), nasal congestion (p<0.001) and diarrhea (p<0.001). Conclusion(s): Anosmia and ageusia are common symptoms of COVID-19. Most patients had these symptoms associated with common symptoms. Many of those who had anosmia had nasal congestion, so it is advisable to consider differentiating them when making the diagnosis. Copyright © 2022, Universidad de Antioquia. All rights reserved.

8.
Viruses ; 14(10)2022 10 08.
Article in English | MEDLINE | ID: covidwho-2066562

ABSTRACT

Pig diarrhea is a universal problem in the process of pig breeding, which seriously affects the development of the pig industry. Porcine enteric coronaviruses (PECoVs) are common pathogens causing diarrhea in pigs, currently including transmissible gastroenteritis virus (TGEV), porcine epidemic diarrhea virus (PEDV), porcine deltacoronavirus (PDCoV) and swine acute diarrhea syndrome coronavirus (SADS-CoV). With the prosperity of world transportation and trade, the spread of viruses is becoming wider and faster, making it even more necessary to prevent PECoVs. In this paper, the host factors required for the efficient replication of these CoVs and the compounds that exhibit inhibitory effects on them were summarized to promote the development of drugs against PECoVs. This study will be also helpful in discovering general host factors that affect the replication of CoVs and provide references for the prevention and treatment of other CoVs.


Subject(s)
Coronavirus Infections , Coronavirus , Porcine epidemic diarrhea virus , Swine Diseases , Swine , Animals , Coronavirus Infections/drug therapy , Coronavirus Infections/prevention & control , Coronavirus Infections/veterinary , Diarrhea/drug therapy , Diarrhea/veterinary
9.
Journal of Interdisciplinary Medicine ; 7(2):44-46, 2022.
Article in English | EMBASE | ID: covidwho-2065359

ABSTRACT

Background: BNT162b2 is a widely used mRNA COVID-19 vaccine for which 8.2% of participants above the age of 56 years have reported diarrhea as an adverse event. This case report highlights the possibility of eosinophilic colitis in post-vaccination diarrhea. Case report: A 72-year-old male patient presented with generalized colicky abdominal pain and acute diarrhea after receiving the first dose of the BNT162b2 vaccine. Laboratory examination revealed peripheral blood eosinophilia with cecal and ascending colon mucosal eosinophilia with 100-130 cells/HPF and eosinophilic cryptitis. The patient's symptoms and eosinophilia resolved spontaneously and did not recur after the second dose of vaccination. More research is needed to confirm eosinophilic colitis as a possible vaccine adverse reaction. Copyright © 2022 Selva Yuwaraj Vadioaloo et al., published by Sciendo.

10.
J Vet Med Sci ; 84(11): 1543-1550, 2022 Nov 14.
Article in English | MEDLINE | ID: covidwho-2065087

ABSTRACT

In this study, the viral genome extraction performance of automatic nucleic acid extractors and manual nucleic acid extraction kits was compared. We showed that compared with manual kits, the automatic extractors showed superior genome extraction performance using bovine viral diarrhea virus (BVDV) genome-positive cattle sera and bovine coronavirus/infectious bovine rhinotracheitis virus-spiked cattle nasal swabs. In addition, the subgenotyping of BVDV strains detected in Tokachi Province in Japan during 2016-2017 was performed. Results showed that most of these BVDV strains belonged to subgenotype 1b, while few strains belonged to subgenotypes 1a and 2a. This study showed the high applicability of automatic nucleic acid extractors in extracting multiple viral genomes and the dominant subgenotype of BVDV in Tokachi.


Subject(s)
Bovine Virus Diarrhea-Mucosal Disease , Cattle Diseases , Diarrhea Virus 1, Bovine Viral , Diarrhea Viruses, Bovine Viral , Nucleic Acids , Cattle , Animals , RNA, Viral/genetics , Japan , Genotype , Diarrhea Viruses, Bovine Viral/genetics , Diarrhea/veterinary , Magnetic Phenomena , Diarrhea Virus 1, Bovine Viral/genetics , Phylogeny
11.
Journal of Indian Association for Child and Adolescent Mental Health ; 18(1):82-91, 2022.
Article in English | EMBASE | ID: covidwho-2064575

ABSTRACT

Background: Pandemics are known to cause an increase in the prevalence of posttraumatic stress disorder (PTSD). The current COVID-19 pandemic has led to a surge in the same along with other problems such as anxiety and depression. Aim(s): To find out the prevalence of PTSD and other mental health abnormalities among adolescent girls who have contracted COVID-19 infection and the factors associated with it. Method(s): This was a cross-sectional study carried out for 6 months at RL Jalappa Hospital and Research Center, Kolar. Adolescent girls infected with COVID-19 were included. A total of 100 girls took part in the study after matching inclusion and exclusion criteria. To assess for PTSD, the Mini International Neuropsychiatry Interview-KID (MINI-KID) and CPSS-5 Interviewer Version (CPSS 5-I) questionnaire were used. Data entered in Microsoft office excel were analyzed using SPSS v 22 (IBM Corp., Armonk, NY, USA). To check for the association between factors, chi-square test was applied. Result(s): The majority of girls were aged 18 years, belonged to nuclear families, and had a hospital stay for 7 days to14 days. About 15% of the girls had PTSD diagnosed using two tools. Panic disorder and separation anxiety were commonly seen. Duration of COVID symptoms adolescent girls had before being diagnosed with COVID-19 by RT-PCR and duration of the hospital stay along with symptoms like throat pain, headache, and diarrhea were a few clinical factors that had a statistically significant association with PTSD. Mental health screening seems to be disregarded in COVID-19 cases. COVID-19 can be a traumatic stressor event among adolescents which can elicit PTSD-like responses and also exacerbate mental health problems. Conclusion(s): Early screening for PTSD or other mental health abnormalities among adolescents post COVID-19 infection should be considered. Copyright © 2022 Indian Association for Child and Adolescent Mental Health, unless otherwise noted. Manuscript content on this site is licensed under Creative Commons Licenses.

12.
American Journal of Transplantation ; 22(Supplement 3):644-645, 2022.
Article in English | EMBASE | ID: covidwho-2063525

ABSTRACT

Purpose: Immunocompromised hosts are at risk for severe complications or death from SARS-CoV-2 infection. Few studies describe the clinical features, outcomes and treatment strategies in this population across multiple sites. Method(s): A multi-center retrospective analysis from academic medical centers in the Midwestern US was conducted for hospitalized patients with SARS-CoV-2 infection. Data was collected electronically using standardized intake and 28-day follow up case report forms. The centers included Northwestern University, University of Nebraska, Cleveland Clinic, University of Chicago, Indiana University and University of Kansas. Result(s): The cohort included 272 patients hospitalized from March 2020 to November 2021. Demographics are in Table 1. Mean admission was 6.84 +/- 6.42 days after symptom onset. The most commonly reported symptoms were cough (71.4%), dyspnea (59.6%), fatigue (55.3%), fever (54.9%), and diarrhea (43.9%). Admission CXR had pneumonia in 31.6%;63% with multifocal or patchy opacities. 87 patients had a chest CT;72 (82.7%) showed pneumonia. 97 patients (36.1%) required ICU admission. Treatments included remdesivir (58.5%), dexamethasone (54.4%), convalescent plasma (3.0%), IL-6 inhibitor (4.5%). Immunosuppression management included holding (44.2%) or decreasing (26.6%) the dose of antimetabolite. 76 patients (28.3%) had documented bacterial co-infection, in blood (34.1%), lung (30.6%) and urine (30.6%). 6 (2.2%) patients experienced rejection within 30 days and 8 patients (3.0%) developed CMV viremia. 26 patients (9.7%) died by day 28. Conclusion(s): This cohort had high rates of ICU admission (36.1%), bacterial coinfection (28.3%), rehospitalization (31.5%) and mortality (9.7%).

13.
American Journal of Transplantation ; 22(Supplement 3):787-788, 2022.
Article in English | EMBASE | ID: covidwho-2063448

ABSTRACT

Purpose: Ritonavir (RTV), a component of the oral antiviral agent nirmatrelvir-RTV (Paxlovid) for COVID-19 infection, increases tacrolimus concentrations through strong competitive inhibition of gastrointestinal and hepatic CYP3A4 enzymes. The prescribing information for nirmatrelvir-RTV recommends against its use in combination with tacrolimus when close monitoring of serum concentrations is not feasible. Method(s): Herein we report a multicenter case series of 3 patients started on nirmatrelvir-RTV without the knowledge of the transplant team while taking concomitant tacrolimus. Result(s): Figure 1 outlines the time course and lab values for each patient. The first case is a 29 year old male 8 years post-kidney transplant, maintained on immediate release tacrolimus (IR-Tac) (goal 4-6 ng/mL), mycophenolate mofetil (MMF) 500 mg twice daily, and prednisone 5 mg daily. He took 5 doses of nirmatrelvir-RTV before discontinuing due to diarrhea. Six days after his first nirmatrelvir-RTV dose, his tacrolimus level was 95.5 ng/mL and serum creatinine (SCr) 2.8 mg/dL (baseline 2.2 mg/dL). Tacrolimus was discontinued, and 5 days later the level was 9.5 ng/mL. The second case is a 41 year old female 22 years post-kidney transplant, maintained on extended-release tacrolimus (XR-Tac;Envarsus) (goal 4-6 ng/mL) and prednisone 5 mg daily. She took 4 doses of nirmatrelvir-RTV before discontinuing due to diarrhea and headache, and continued her doses of XR-Tac throughout this time. Ten days after her first nirmatrelvir-RTV dose, her tacrolimus level was 4.4 ng/mL and SCr 2.6 mg/dL (baseline 2.0 mg/dL). The third case is a 66 year old male 1.5 years post-liver transplant, maintained on XR-Tac (goal 4-8 ng/mL) and MMF 500 mg twice daily. He took 4 doses of nirmatrelvir-RTV and then XR-Tac was held while completing nirmatrelvir-RTV therapy. Five days after his first nirmatrelvir- RTV dose and 3 days after his XR-Tac was held, his tacrolimus level was 23.9 ng/ mL and SCr 2.4 mg/dL (baseline 1.4 mg/dL). Conclusion(s): In this case series of 3 patients who took nirmatrelvir-RTV while on tacrolimus, duration of nirmatrelvir-RTV and time course of tacrolimus adjustment were variable, and all patients had a rise in SCr from baseline. Given the extreme elevation of tacrolimus concentrations in the patient taking IR-Tac, further study is needed to systematically characterize the variability of this drug interaction between tacrolimus formulations.

14.
American Journal of Transplantation ; 22(Supplement 3):645-646, 2022.
Article in English | EMBASE | ID: covidwho-2063439

ABSTRACT

Purpose: Kidney transplant recipients (KTRs) are at higher risk for severe COVID- 19 caused by the severe acute respiratory syndrome coronavirus-2 (SARS646 All Infections (Excluding Kidney & Viral Hepatitis) I CoV-2). Sotrovimab decreases the risk of disease progression in the general population, but efficacy and safety in KTRs is unknown. Herein, we describe our experience in treating COVID-19 infected KTRs with sotrovimab. Method(s): We performed a retrospective, single-center cohort study of KTRs diagnosed with COVID-19 by polymerase chain reaction from 07/15/21-11/30/21. KTRs with COVID-19 were admitted to the hospital to expedite evaluation and treatment. KTRs with COVID-19 were eligible for sotrovimab if they 1) were not requiring oxygen at admission, 2) were unvaccinated or if SARS-CoV-2 spike antibody (SAb) after vaccination was <100 U/mL, and 3) duration of symptoms/day of illness (DOI) was <=7 days. COVID-19 disease requiring oxygen therapy was treated with remdesevir + dexamethasone. Immunomodulator therapy (baricitinib or tocilizimab) was given for rapidly progressive disease requiring high-flow oxygen or ICU care. Baseline characteristics, treatments, and outcomes including oxygen supplementation, ICU admission, and mortality were manually ed and evaluated. Result(s): In all, 36 KTRs were diagnosed with COVID-19 - mean age 59 years, 72% male, 67% Chinese, 64% diabetic and 17% obese;72% were deceased donor and 28% were living donor KTRs presenting a mean 11 years from transplant. The majority (69%) were vaccinated with >=2 doses of mRNA-based SARS-CoV-2 vaccines, 22% received 3 doses, and 15% were unvaccinated. Among KTRs who received >=2 doses, SAb was reactive in 36% and >100 U/mL in 16%. In all, 14 (39%) required oxygen, 11 (31%) required ICU admission, 5 (14%) were mechanically ventilated, and 4 (11%) died (Table). Sotrovimab was given to 27 eligible KTRs at median DOI 2 (range 0-6). Of these, 8 (30%) required oxygen, 5 (19%) required ICU admission, 2 (7%) were mechanically ventilated, and 1 died (4%). KTRs receiving sotrovimab at DOI <=3 vs >3 were less likely to require oxygen (p=0.01) or ICU admission (p=0.02). Sotrovimab was well tolerated with one associated adverse event (self-limiting diarrhea). Conclusion(s): KTRs remain at high risk for severe COVID-19. Sotrovimab administered early in the disease course is associated with a lower rate of severe COVID-19. Outcomes of KTRs with COVID-19 overall and among those receiving sotrovimab by day of illness (Figure Presented).

15.
American Journal of Transplantation ; 22(Supplement 3):406-407, 2022.
Article in English | EMBASE | ID: covidwho-2063395

ABSTRACT

Purpose: To date studies of children with a kidney transplant and COVID-19 are limited. The Improving Renal Outcomes Collaborative (IROC) is a learning health network in the US comprised of 36 pediatric kidney transplant programs that provides infrastructure to efficiently conduct multicenter studies. Method(s): We collected COVID-19 testing, indications, and outcomes data. Data were linked to patient demographic and clinical data in the IROC registry. We previously reported the results of this effort from April 6-September 3, 2020 (era 1). Here we report data from September 4, 2020 - February 28, 2021 (era 2). We describe the differences in testing frequency and positive testing over the two eras. Result(s): In era 1, 22 centers submitted testing data;in era 2, 21 centers submitted testing data. There were 281 tests in 281 patients analyzed in era 1 and 648 tests for 465 patients in era 2. From era 1 to era 2, the proportion of positive tests increased from 24/281 (8.54%) to 109/465 (23%). Testing frequency and results from eras 1 and 2 are displayed in Figure 1. 133 patients tested positive for COVID-19 over both eras, and there was no difference in the symptoms at the time of testing between the two eras. The most common symptoms for both eras were fever (35%), cough (33%), rhinorrhea (23%), vomiting (14%), and diarrhea (14%). Over both eras, 41/133 (31%) that tested positive for COVID-19 had no symptoms at the time of testing. There were no differences in outcomes between the two eras. 117 patients (88%) had no transplant complications. 1 (0.8%) patient had T cell-mediated rejection, 3 (2%) had antibody-mediated rejection, 1 (0.8%) had mixed T cell- and antibodymediated rejection, 10 (7.5%) had acute kidney injury, 1 (0.8%) experienced graft failure, and 1 patient (0.8%) died from their COVID-19 infection. Conclusion(s): In this cohort, there was overall more testing and more positive COVID-19 tests in era 2. The dates of era 2 correspond with children returning to school and the Winter surge in cases in the US. Despite the increased number and proportion of positive patients, the clinical outcomes are consistent with reported outcomes for their non-immunosuppressed peers. Follow-up studies will be required to evaluate whether the availability of vaccines for adolescents and the rise of the delta variant as the predominant strain affect clinical outcomes. (Table Presented).

16.
American Journal of Transplantation ; 22(Supplement 3):602, 2022.
Article in English | EMBASE | ID: covidwho-2063386

ABSTRACT

Purpose: Nirmatrelvir/ritonavir use has not yet been described in solid organ transplant recipients (SOTR) who become infected with COVID-19. The objective of our study was to evaluate outcomes among a heterogeneous population of SOTR and quantify the drug-drug interaction with commonly used immunosuppressive medications. Method(s): This is an IRB-approved, retrospective study of all adult SOTR on a calcineurin inhibitor or mammalian target of rapamycin inhibitor who were prescribed nirmatrelvir/ritonavir between 12/28/21 and 1/6/2022. Result(s): A total of 26 adult SOTR were included (n=20 tacrolimus, n=4 cyclosporine, n=3 everolimus, n=1 sirolimus). All patients were instructed to follow the following standardized protocol during treatment with 5 days of nirmatrelvir/ritonavir: hold tacrolimus, reduce cyclosporine dose to 20% of baseline daily dose, and/or hold everolimus/sirolimus. Two patients (7.7%) were hospitalized;one patient for symptoms related to COVID-19 and the other for infectious diarrhea. No patients died within 12 days of receipt of nirmatrelvir/ritonavir. Median time to first CNI trough from completion of nirmatrelvir/ritonavir was 2 days (IQR, 1 - 3). Median tacrolimus trough concentration pre- and post-nirmatrelvir/ritonavir were 7.7 ng/mL (IQR, 6.6 - 8.6) and 5.3 ng/mL (IQR, 3.6 - 8.5), respectively. One patient on cyclosporine had trough concentrations pre- and post- nirmatrelvir/ritonavir of 73 ng/mL and 45 ng/ mL (day 9), while the other patient had a trough of 75.9 ng/mL prior and 190 ng/mL and 80 ng/mL on days 6 and 9, respectively. Median everolimus trough concentration prior to receipt of nirmatrelvir/ritonavir was 4.8 ng/mL (IQR, 3 - 4.9). Everolimus trough concentrations post-nirmatrelvir/ritonavir were undetectable in two patients on day 7 and day 9, and 1.4 ng/mL on day 8 in the third patient. Conclusion(s): Our results suggest that nirmatrelvir/ritonavir may be an effective therapy to prevent COVID-19-related hospitalization and death in SOTR. Furthermore, the clinically significant interaction between nirmatrelvir/ritonavir and immunosuppressive agents can be reasonably managed with a standardized dosing protocol.

17.
American Journal of Transplantation ; 22(Supplement 3):442, 2022.
Article in English | EMBASE | ID: covidwho-2063368

ABSTRACT

Purpose: This study aimed to investigate the clinical consequences at 3 months after symptom onset among kidney transplant recipients surviving COVID-19. Method(s): This is an ongoing single-center observational prospective study including adult kidney transplant recipients who were diagnosed and survived after COVID-19 between 03/20/2020 and 05/31/2021. Patients who lost their graft were excluded. The patients are scheduled to receive a telephone contact at 3 months after symptom onset from the clinical research team. The call consisted of a structured questionnaire of symptoms with binary answers (yes or no). The questionnaire included the following symptoms: headache, dizziness, anosmia/ageusia, weakness, myalgia, inappetence, diarrhea, and dyspnea, which could be presented before and/or after the COVID-19 diagnosis. Those patients with at least one symptom presented only after the disease, were defined as having Long-COVID-19. Subsequently, the clinical research team included a question about the work status. Adjusted multivariable logistic regression models were used to identify the risk factors associated with Long-COVID-19. Result(s): There were 1,731 patients with COVID-19, with 455 deaths and 36 graft losses. Of the remaining 1,240 patients, 454 (36%) didn't answer our calls, yielding a final cohort of 786 patients. Of them, 217 (28%) developed Long-COVID-19. The incidence of each symptom at 3 months was: dyspnea (7%), myalgia (12%), weakness (11%), headache (10%), dizziness (7%), diarrhea (4%), inappetence (4%) and anosmia/ageusia (3%). About 1% of our patients needed domiciliary O2. Of those who we obtained the working status (n=239), 95 (40%) were employed before COVID-19 and 79 of them (83%) had returned to their original work at 3 months. After COVID-19 diagnosis, 44% of the patients were hospitalized (31% in ICU), 35% used supplemental O2, and 5% required mechanical ventilation. Fever (53%), shiver (39%), nausea (3%), anosmia/ageusia (59%), hospitalization (67%), and adverse cardiovascular events (3%), such as thrombosis or myocardial infarction, were risk factors associated with subsequent development of Long-COVID-19, using adjusted multivariable logistic regression. Conclusion(s): The incidence of Long-COVID-19 at 3 months was 28% and was associated with reduced quality of life and return to work. Several COVID-19 associated symptoms and disease severity markers were associated with Long- COVID-19.

18.
Therap Adv Gastroenterol ; 15: 17562848221118403, 2022.
Article in English | MEDLINE | ID: covidwho-2064680

ABSTRACT

Background: Prolonged symptoms after COVID-19 are an important concern due to the large numbers affected by the pandemic. Objectives: To ascertain the frequency of gastrointestinal (GI) manifestations as part of long GI COVID. Design: A systematic review and meta-analysis of studies reporting GI manifestations in long COVID was performed. Data Sources and Methods: Electronic databases (Medline, Scopus, Embase, Cochrane Central Register of Controlled Trials, and Web of Science) were searched till 21 December 2021 to identify studies reporting frequency of GI symptoms in long COVID. We included studies reporting overall GI manifestations or individual GI symptoms as part of long COVID. We excluded pediatric studies and those not providing relevant information. We calculated the pooled frequency of various symptoms in all patients with COVID-19 and also in those with long COVID using the inverse variance approach. All analysis was done using R version 4.1.1 using packages 'meta' and 'metafor'. Results: A total of 50 studies were included. The frequencies of GI symptoms were 0.12 [95% confidence interval (CI), 0.06-0.22, I 2 = 99%] and 0.22 (95% CI, 0.10-0.41, I 2 = 97%) in patients with COVID-19 and those with long COVID, respectively. The frequencies of abdominal pain, nausea/vomiting, loss of appetite, and loss of taste were 0.14 (95% CI, 0.04-0.38, I 2 = 96%), 0.06 (95% CI, 0.03-0.11, I 2 = 98%), 0.20 (95% CI, 0.08-0.43, I 2 = 98%), and 0.17 (95% CI, 0.10-0.27, I 2 = 95%), respectively, after COVID-19. The frequencies of diarrhea, dyspepsia, and irritable bowel syndrome were 0.10 (95% CI, 0.04-0.23, I 2 = 98%), 0.20 (95% CI, 0.06-0.50, I 2 = 97%), and 0.17 (95% CI, 0.06-0.37, I 2 = 96%), respectively. Conclusion: GI symptoms in patients were seen in 12% after COVID-19 and 22% as part of long COVID. Loss of appetite, dyspepsia, irritable bowel syndrome, loss of taste, and abdominal pain were the five most common GI symptoms of long COVID. Significant heterogeneity and small number of studies for some of the analyses are limitations of the systematic review.

19.
BMC Vet Res ; 18(1): 369, 2022 Oct 11.
Article in English | MEDLINE | ID: covidwho-2064800

ABSTRACT

BACKGROUND: Swine acute diarrhea syndrome coronavirus (SADS-CoV) causes acute vomiting and diarrhea in piglets, leading to significant financial losses for the pig industry. Recombinase polymerase amplification (RPA) is a rapid nucleic acid amplification technology used under constant temperature conditions. The study established a real-time reverse transcription (RT)-RPA assay for early diagnosis of SADS-CoV.  RESULTS: The detection limit of the real-time RT-RPA was 74 copies/µL of SADS-CoV genomic standard recombinant plasmid in 95% of cases. The assay was performed in less than 30 min and no cross-reactions were observed with eight other common viruses that affect swine, including classical swine fever virus (CSFV), porcine reproductive and respiratory syndrome virus (PRRSV), pseudo rabies virus (PRV), swine influenza virus (SIV), seneca valley virus (SVA), transmissible gastroenteritis virus (TGEV), porcine epidemic diarrhea virus (PEDV) and porcine deltacoronavirus (PDCoV). The coefficient of variation (C.V.) values of the two standards dilutions and three positive clinical sample ranged from 2.95% to 4.71%. A total of 72 clinical fecal samples from swine with diarrheal symptoms were analyzed with the developed RT-RPA and quantitative RT-PCR. There was 98.61% agreement between the RT-RPA and the quantitative real-time PCR results. CONCLUSIONS: These results indicated that the developed RT-RPA assay had good specificity, sensitivity, stability and repeatability. The study successfully established a broadly reactive RT-RPA assay for SADS-CoV detection.


Subject(s)
Alphacoronavirus , Coronavirus Infections , Nucleic Acids , Swine Diseases , Alphacoronavirus/genetics , Animals , Coronavirus Infections/diagnosis , Coronavirus Infections/veterinary , Diarrhea/diagnosis , Diarrhea/veterinary , Real-Time Polymerase Chain Reaction/veterinary , Recombinases , Sensitivity and Specificity , Swine , Swine Diseases/diagnosis
20.
American Journal of Transplantation ; 22(Supplement 3):405, 2022.
Article in English | EMBASE | ID: covidwho-2063339

ABSTRACT

Purpose: Post-acute sequelae of SARS-CoV-2 infection (PASC) is an increasingly recognized phenomenon manifested by long lasting cognitive, mental, and physical symptoms. We aimed to estimate the prevalence of PASC symptoms in solid organ transplant recipients (SOTRs) in the short (1- 6 months) and long-term (> 6 months) periods after SARS-CoV-2 infection. We also compared the prevalence of these symptoms between those with SARS-CoV-2 infection requiring hospitalization and those not requiring hospitalization. Method(s): We surveyed 111 SOTRs with self-reported SARS-CoV-2 infection diagnosed more than 4 weeks prior to survey administration. The survey consisted of 7 validated questionnaires ("Quick Dementia Rating System (QDRS)", "Patient Health Questionnaire (PHQ9)", "Generalized Anxiety Disorder 7 (GAD-7)", "Impact of Events Scale (IES-6)", "EuroQol- 5 Dimension (EQ-5D)", "PROMIS global physical health scale (GHS) "and "Breathlessness, Cough and Sputum Scale (BCSS)"). Result(s): Of the 111 survey participants, 32 (33%) had been hospitalized and 35 (36%) had SARS-CoV-2 infection >6 months ago. Median (IQR) age was 58 years (46, 65). Median time from SARS-CoV-2 diagnosis was 167 days (138, 221). Cognitive impairment, anxiety, depression, insomnia, feeling of trauma, fatigue, pain, breathing problems, cough, abnormal smell, abnormal taste, and diarrhea were reported by 40%, 23%, 36%, 55%, 53%, 41%, 19%, 33%, 33%, 21%, 22%, and 32% of patients respectively. Hospitalized patients had poorer scores in cognition (QDRS survey score of 2 versus 0.75, p=0.048) (Figure 1), quality of life (EQ-5D survey score of 2 versus 1, p=0.043), physical health (PROMIS GHS survey score of 10 versus 11, p=0.013), respiratory status (BCSS survey score of 1 versus 0, p=0.056), and pain (Pain score of 3 versus 0, p 0.006). Among patients who had SARS-CoV-2 infection >6 months ago, abnormal breathing, cough, abnormal smell, abnormal taste, and diarrhea continued to be reported by 31%, 31%, 29%, 32%, and 32% of patients respectively. Conclusion(s): After SARS-CoV-2 infection, SOTRs had a high prevalence of PASC symptoms. Some of the symptoms are more severe in patients who had required hospitalization and persist beyond 6 months. Further studies are needed to understand the long term sequalae of SARS-CoV-2 infection in SOTRs and to develop an evidence-based multidisciplinary approach for caring for these patients beyond the acute phase. (Table Presented).

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