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1.
Fertil Steril ; 2022 Sep 13.
Article in English | MEDLINE | ID: covidwho-2104920

ABSTRACT

OBJECTIVE: To study the potential effect of coronavirus disease (COVID-19) on the endometrial transcriptome of affected, symptomatic women for the detection of altered gene expression. DESIGN: Pilot study of the endometrial transcriptomes of women manifesting COVID-19 compared with those of women without COVID-19 undergoing hysteroscopic procedures for benign gynecologic disorders using RNA sequencing. SETTING: Hospital and university laboratories. PATIENT(S): Women with (n = 14) and without a COVID-19 (n = 10) diagnosis based on a nasopharyngeal swab analysis using quantitative reverse-transcription polymerase chain reaction. The endometrium of the patients with COVID-19 had previously been tested for severe acute respiratory syndrome coronavirus 2 infection, revealing the absence of the virus in this tissue. INTERVENTION(S): Endometrial biopsy sample collection. MAIN OUTCOMES MEASURE(S): Endometrial gene expression and functional analysis of symptomatic patients with COVID-19 vs. individuals without the infection. RESULT(S): The systemic disease COVID-19 altered endometrial gene expression in 75% of the women, with the patients exhibiting a preponderance of 163 up-regulated (e.g., UTS2, IFI6, IFIH1, and BNIP3) and 72 down-regulated genes (e.g., CPZ, CDH3, and IRF4) (false discovery rate<0.05). A total of 161 dysregulated functions (36 up-regulated and 125 down-regulated) were typically enriched in the endometria of the patients with COVID-19, including up-regulation in pathways involved in the development of immune responses to viruses and cytokine inflammation, reflecting elicitation of a COVID-19 response pathway. CONCLUSION(S): Coronavirus disease 2019 affects endometrial gene expression despite the absence of severe acute respiratory syndrome coronavirus 2 RNA in endometrial tissues.

2.
Bull Exp Biol Med ; 173(6): 740-744, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-2103946

ABSTRACT

The possibility of finding persistent SARS-CoV-2 viral particles in human peripheral blood leukocytes after a novel coronavirus infection was shown. The results of droplet digital PCR showed that 19 of 24 examined subjects had from 4 to 555 copies of the Nsp4 SARS-CoV-2 gene in 5-6 months after infection. The presence of this transcript in peripheral blood leukocytes was associated with reduced expression of FOXP3 gene and increased level of RORγ gene mRNA. The copy number of the Nsp4 gene negatively correlated with the level of FOXP3 gene mRNA (r=-0.45; p=0.028), but showed a positive correlation with the DANCR long non-coding RNA (r=0.94; p<0.001). In SARS-CoV-2-positive healthy individuals, the level of TLR2, NLRP3, and IL1B gene transcripts was higher than in SARS-CoV-2-negative donors. The presence of SARS-CoV-2 in a persistent form is probably associated with impaired immunosuppression and the development of chronic inflammation in apparently healthy volunteers after a new coronavirus infection.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , RNA, Viral/genetics , COVID-19/genetics , RNA, Messenger/genetics , Leukocytes , Forkhead Transcription Factors
3.
South African Journal of Botany ; 151:695-712, 2022.
Article in English | ScienceDirect | ID: covidwho-2096000

ABSTRACT

Critically endangered Aquilaria malaccensis Lam. is known for highly expensive agarwood with unique aroma. Agarwood has been used as a phytomedicine in chronic degenerative neurological disorders, paralysis, rheumatism, asthma, and others. Its production is dependent naturally or artificially on interaction of endophytic fungi, and by nailing, drilling, and microbial inoculation respectively. The majorly produced biomarkers of terpenes, fatty acids, alkanes, chromones, and flavonoids exhibited several biological activities in congruence to their ethnomedicinal claims. During the pandemic, several in-silico, studies showed the potential of a few sesquiterpene hydrocarbons against covid-19. The review aimed to deliver a comprehensive outline of the immunomodulatory potential of agarwood oil with allied traditional medicinal use, biomarkers, pharmacological evaluation, toxicity, and mechanistic action. The review eventually showed the agarwood oil, extracts, and major biomarkers viz., aromadendrene II, valencene, phytol, octacosane, caryophyllene oxide, β-caryophyllene, hinesol, agarospirol, with immunomodulatory, anti-inflammatory, and allied neural, antidiabetic, antimicrobial activity, toxicity, along with molecular target binding potential against 3CLpro, RDRP, Mpro, PLpro, Spike protein S1 of SARS-CoV2 through in-vitro, in-vivo, in silico studies and limited human clinical trials. The expression of HMGR, ASS, ADXPS, ADXPR, FPS, and WRKY genes of sesquiterpenoid biosynthetic pathways were upregulated for signature aroma and immunomodulatory markers viz., δ-guaiene, dodecane, tetracosane, agarospirol, farnesol, and geranylgeraniol acetate as a defensive response. The review would ignite future research on potential immunomodulatory markers viz., caryophyllene oxide, octacosane, heneicosane, agarospirol, n-hexadecanoic acid, α-eudesmol, α-santalol and inoculum guided in-vitro agarwood production restoring the prized aroma, therapeutic efficacy, and wild population.

4.
JACC Basic Transl Sci ; 2022 Oct 19.
Article in English | MEDLINE | ID: covidwho-2076294

ABSTRACT

SARS CoV-2 enters host cells via its Spike protein moiety binding to the essential cardiac enzyme angiotensin-converting enzyme (ACE) 2, followed by internalization. COVID-19 mRNA vaccines are RNA sequences that are translated into Spike protein, which follows the same ACE2-binding route as the intact virion. In model systems, isolated Spike protein can produce cell damage and altered gene expression, and myocardial injury or myocarditis can occur during COVID-19 or after mRNA vaccination. We investigated 7 COVID-19 and 6 post-mRNA vaccination patients with myocardial injury and found nearly identical alterations in gene expression that would predispose to inflammation, coagulopathy, and myocardial dysfunction.

5.
Comput Struct Biotechnol J ; 20: 5713-5728, 2022.
Article in English | MEDLINE | ID: covidwho-2068856

ABSTRACT

Since COVID-19 emerged in 2019, significant levels of suffering and disruption have been caused on a global scale. Although vaccines have become widely used, the virus has shown its potential for evading immunities or acquiring other novel characteristics. Whether current drug treatments are still effective for people infected with Omicron remains unclear. Due to the long development cycles and high expense requirements of de novo drug development, many researchers have turned to consider drug repositioning in the search to find effective treatments for COVID-19. Here, we review such drug repositioning and combination efforts towards providing better handling. For potential drugs under consideration, aspects of both structure and function require attention, with specific categories of sequence, expression, structure, and interaction, the key parameters for investigation. For different data types, we show the corresponding differing drug repositioning methods that have been exploited. As incorporating drug combinations can increase therapeutic efficacy and reduce toxicity, we also review computational strategies to reveal drug combination potential. Taken together, we found that graph theory and neural network were the most used strategy with high potential towards drug repositioning for COVID-19. Integrating different levels of data may further improve the success rate of drug repositioning.

6.
Neurology Asia ; 27(3):783-786, 2022.
Article in English | EMBASE | ID: covidwho-2067763

ABSTRACT

Neutropenia during recovery after coronavirus disease 2019 (COVID-19), as well as neutropenia after intravenous immunoglobulin (IVIG) administration are very rare hematological abnormalities. We report the first case of agranulocytosis following IVIG administration in patients with Guillain-Barre syndrome (GBS) triggered by COVID-19. A 62-year-old female patient was admitted to the Emergency Department due to progressive limb weakness and sensory disturbances that began two weeks before admission. Five weeks before admission she was treated for COVID-19 and has fully recovered. She was diagnosed with Guillain-Barre syndrome (GBS), and treatment with IVIG was started. Twenty hours after the first dose of IVIG, blood analysis showed neutropenia and thrombocytopenia, and after the fifth dose she developed agranulocytosis followed by mild increase in body temperature. Granulocyte colony-stimulating factor (G-CSF) was administered and after 12 hours the leukocyte lineage recovered. According to the previous findings, neutropenia after IVIG administration might be related to CD11b, and COVID-19 is associated with an increase in immature neutrophil populations in the later stages of the disease defined by their expression of CD11b. Meanwhile, some finding suggests that corticosteroid pretreatment prevent neutropenia after IVIG administration, which might be important because many patients with post-COVID GBS have been treated with corticosteroids for COVID-19. Copyright © 2022, ASEAN Neurological Association. All rights reserved.

7.
Journal of Food and Drug Analysis ; 30(3):440-453, 2022.
Article in English | EMBASE | ID: covidwho-2067698

ABSTRACT

The jelly from achenes of Ficus pumila var. awkeotsang (FPAA) is a famous beverage ingredient in Taiwan. In this work, ficumarin (1), a new compound was obtained from its twigs (FPAT) and elucidated with comprehensive spectroscopic data. The biosynthetic origin was proposed from the p-coumaroyl-CoA pathway. Alloxanthoxyletin, betulinic acid, and catechin were identified as the major and active constituents responsible for relieving neutrophilic inflammation by FPAT. Among them, the most potent alloxanthoxyletin was found to interact with PRO350 and GLU377 of human INOSOX. Further, Nrf2 activating capacity of the FPAT fraction and its coumarins was confirmed. With the analysis of LC-MS/MS data and feature-based molecular networking, coumarins were found as the dominant and responsible components. Notably, alloxanthoxyletin increased Nrf2 expression by up to 816.8 +/- 58% due to the interacting with the VAL561, THR560 and VAL420 residues of 5FNQ protein. COVID-19 Docking Server simulation indicated that pyranocoumarins would promisingly interfere with the life cycle of SARS-CoV-2. FPAT was proven to exert. Copyright © 2022 Taiwan Food and Drug Administration.

8.
NeuroQuantology ; 20(11):1858-1865, 2022.
Article in English | EMBASE | ID: covidwho-2067333

ABSTRACT

Background: Fighting the Covid-19 pandemic is one of the global priorities now, and the most important type of pandemic control is vaccination. Pfizer-Biotech is considered one of the most important vaccines currently because of its high effectiveness in stimulating the immune system, despite limited data regarding the duration of the response and its side effects. The goal of this study is to assess the response ofSARS CoV-2 S1-RBD IgG andInterleukin-15 after 30 and 120days fromthe 2nd dose ofPfizer-BioNTech vaccine which applied on themedical college students at Diyala university. Methodology: This study began after the obtainment of the Medical College of the University of Diyala, the Medical College of Al-IraqiaUniversity, and the Iraqi Ministry of Health approvals . It continued from October 2021 until March 2022.A total of45 male and femaleparticipants from the College of Medicine( DiyalaUniversity)students who took thetwo doses of Pfizer-BioNTech and were divided into two groups: 1 month (30 days) and 4 months (120 days) after the full vaccination (two doses).A 5 ml of their blood was taken two times (30 days and 120 days after the 2nd dose of thePfizer-BioNTech vaccine) in the postgraduate laboratories inside the Diyala Medical College. A serological analysis to quantify IL-15 and SARS CoV-2 S1-RBD IgG has been done using BT LAB/ Bioassay Technology Laboratory/ Human Interleukin 15 ELISA Kit from CHINA andDiasino/ SARS CoV-2 S1-RBD IgG ELISA Kit/ CHINA respectively. All the lab work happened in the postgraduate laboratories inside the Diyala Medical College. Demographic information (Age and Gender) has been collected from the participants. These participants were split into two groups depending on the time after the 2nd of Pfizer-BioNTech vaccine dose (1 month and 4 months, respectively). STATISTICA (version 12 )and SPSS (version 26 ) were used to input, review and data analysis. Essential approaches of percentages and frequencies were used for qualitative variables, while, average and standard deviation were used for quantitative variables. For both IL-15 and SARS CoV-2 S1-RBD IgG, less than 0.05 of a P-value was considered considerable. Result(s): The ratio, according to gender, was (17.8: 82.2) while the age Average was (20.9 years old). The serum data of IL-15 and SARS-CoV-2 S1-RBD IgG levels after 1 month (30 days) and 4 months (120 days) were statistically non-parametric. Mann-Whitney test (Independent two samples), showeda considerabledrop(P<0.05) of IL-15as well as SARS CoV-2 S1-RBD IgGserum levels in the 4th-monthsgroup compared to the 1-monthgroup. Conclusion(s): Interleukin-15 and SARS CoV-2 S1-RBD IgG serum levels significantly droped after 120days of the 2nd dose of Pfizer-BioNTech vaccine. Copyright © 2022, Anka Publishers. All rights reserved.

9.
Journal of Clinical and Diagnostic Research ; 16(8):DC53-DC57, 2022.
Article in English | EMBASE | ID: covidwho-2067196

ABSTRACT

Introduction: In the search of effective medicines against Coronavirus Disease-2019 (COVID-19) besides the conventional mode of treatment many medicines belonging to alternative therapeutics claimed to be effective in this disease. In homeopathy-a branch of alternative medicine some medicines are claimed to be effective in COVID-19 after human trials. Aim: To study whether ultradiluted preparation of Phosphorus 6CH (centesimal (C) dilutions, using Hanhemann's (H) dilution method) can protect damaging action of Delta Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) spike protein Receptor Binding Domain (RBD) in Gallus gallus embryo in relation to their gross appearances, histopathological changes and cytokine changes. Materials and Methods: An in-vivo fertilized chick embryo model experimental analysis was carried out at the Genetic Research Laboratory of Heritage Institute of Technology, Kolkata, West Bengal, India. The whole experimental study was done in a time period of November 2021 to January 2022 and the data collected were analysed using statistical software Minitab. About 14 days old Gallus gallus embryonated eggs were inoculated with the antigen along with the vehicle alcohol controls. The Phosphorus 6CH was used to see whether it can prevent or cure the damaging action of the spike protein in the embryo in different experimental sets. results: The notable finding in this experiment is the remarkable elevated expression of Interleukin (IL)-10 gene in the curative, preventive sets as well as in the medicine control sets in comparison to antigen and alcohol control sets. In case of Transforming Growth Factor, (TGF) β1 there was enhanced expression of TGF β1 gene in the alcohol 6C set and antigen set which gets ameliorated with Phosphorus 6CH. The morbid anatomy of the embryo and the histopathological picture of the liver of the embryo also reflected similar findings in these two experimental sets. After statistical analysis it was found that there was significant correlation in between Interferon (IF) γ and IL-10 in these experimental results which appears very important. conclusion: The homeopathic medicine phosphorus 6CH is capable of maintaining cytokine balance in Delta SARS-CoV-2 spike protein RBD induced pathogenecity in Gallus gallus embryo.

10.
Indian Journal of Critical Care Medicine ; 26(10):1091-1098, 2022.
Article in English | EMBASE | ID: covidwho-2066996

ABSTRACT

Background: It is known that coronavirus disease-2019 (COVID-19) pneumonia causes cytokine storm, and treatment modalities are being developed on inhibition of proinflammatory cytokines. We aimed to investigate the effects of anticytokine therapy on clinical improvement and the differences between anticytokine treatments. Method(s): A total of 90 patients with positive COVID-19 polymerase chain reaction (PCR) test were divided into three groups, group I (n = 30) was given anakinra, group II (n = 30) was given tocilizumab, and group III (n = 30) was given standard treatment. Group I was treated with anakinra for 10 days;tocilizumab, intravenously, was given in group II. Group III patients were selected from those who did not receive any anticytokine treatment other than the standard treatment. Laboratory values, Glasgow coma scale (GCS), and PaO2/FiO2 values were analyzed on days 1, 7, and 14. Result(s): The seventh-day mortality rates were 6.7% in group II, 23.3% in group I, and 16.7% in group III. In group II, the ferritin levels on the 7th and 14th days were significantly lower (p = 0.004), and the lymphocyte levels on the seventh day were significantly higher (p = 0.018). Examining the changes between the first intubation days, in the early period (seventh day), group I was found to be 21.7%, group II was 26.9%, and group III was 47.6%. Conclusion(s): We observed the positive effects of the use of tocilizumab on clinical improvement in the early period;mechanical ventilation requirement was delayed and at a lower rate. Anakinra treatment did not change mortality and PaO2/FiO2 rates. Mechanical ventilation requirements occurred earlier in the patients who were not receiving any anticytokine therapy. Studies with larger patient populations are needed to demonstrate the potential efficacy of anticytokine therapy. Copyright © The Author(s).

11.
Open Access Macedonian Journal of Medical Sciences ; 10:2029-2033, 2022.
Article in English | EMBASE | ID: covidwho-2066705

ABSTRACT

BACKGROUND: Mycobacterium tuberculosis infection causes the release of pro-inflammatory cytokines affecting hemostasis. Although the plasminogen activator inhibitor-1 (PAI-1) has a vital role in the fibrinolysis system, little is known about its profile among people with latent tuberculosis (TB). METHODS: This is a cross-sectional study that involves 80 healthcare workers. The study was conducted in two academic medical centers of Makassar city, Indonesia, from September to October 2021. PAI-1 levels were measured using the enzyme-linked immunosorbent assay technique. The statistical test results were significant if p < 0.05. RESULTS: Although there was no statistically significant difference (p > 0.05) in PAI-1 levels, PAI-1 level among participants in the latent TB infection (LTBI) group was found to be lower (4.9 ng/mL) than in the healthy control group (6.0 ng/mL). In addition, participants in the LTBI group with a history of being infected (9.6 ng/mL) with the COVID-19 had higher PAI-1 levels than those who had never been infected (2.3 ng/mL), which is statistically significant (p = 0.004). Although there was no statistically significant difference (p > 0.05) in PAI-1 levels among participants in the healthy control group, those with a history of being infected (6.7 ng/mL) demonstrated higher PAI-1 levels than those who had never been infected (4.8 ng/mL). CONCLUSIONS: PAI-1 levels were lower in LTBI participants, which potentially is due to more participants in the healthy control group having a history of COVID-19 infection.

12.
Genome Med ; 14(1): 18, 2022 02 21.
Article in English | MEDLINE | ID: covidwho-1688773

ABSTRACT

BACKGROUND: Measuring host gene expression is a promising diagnostic strategy to discriminate bacterial and viral infections. Multiple signatures of varying size, complexity, and target populations have been described. However, there is little information to indicate how the performance of various published signatures compare to one another. METHODS: This systematic comparison of host gene expression signatures evaluated the performance of 28 signatures, validating them in 4589 subjects from 51 publicly available datasets. Thirteen COVID-specific datasets with 1416 subjects were included in a separate analysis. Individual signature performance was evaluated using the area under the receiving operating characteristic curve (AUC) value. Overall signature performance was evaluated using median AUCs and accuracies. RESULTS: Signature performance varied widely, with median AUCs ranging from 0.55 to 0.96 for bacterial classification and 0.69-0.97 for viral classification. Signature size varied (1-398 genes), with smaller signatures generally performing more poorly (P < 0.04). Viral infection was easier to diagnose than bacterial infection (84% vs. 79% overall accuracy, respectively; P < .001). Host gene expression classifiers performed more poorly in some pediatric populations (3 months-1 year and 2-11 years) compared to the adult population for both bacterial infection (73% and 70% vs. 82%, respectively; P < .001) and viral infection (80% and 79% vs. 88%, respectively; P < .001). We did not observe classification differences based on illness severity as defined by ICU admission for bacterial or viral infections. The median AUC across all signatures for COVID-19 classification was 0.80 compared to 0.83 for viral classification in the same datasets. CONCLUSIONS: In this systematic comparison of 28 host gene expression signatures, we observed differences based on a signature's size and characteristics of the validation population, including age and infection type. However, populations used for signature discovery did not impact performance, underscoring the redundancy among many of these signatures. Furthermore, differential performance in specific populations may only be observable through this type of large-scale validation.


Subject(s)
Bacterial Infections/diagnosis , Datasets as Topic/statistics & numerical data , Host-Pathogen Interactions/genetics , Transcriptome , Virus Diseases/diagnosis , Adult , Bacterial Infections/epidemiology , Bacterial Infections/genetics , Biomarkers/analysis , COVID-19/diagnosis , COVID-19/genetics , Child , Cohort Studies , Diagnosis, Differential , Gene Expression Profiling/statistics & numerical data , Genetic Association Studies/statistics & numerical data , Humans , Publications/statistics & numerical data , SARS-CoV-2/pathogenicity , Validation Studies as Topic , Virus Diseases/epidemiology , Virus Diseases/genetics
13.
Int J Mol Sci ; 23(19)2022 Sep 23.
Article in English | MEDLINE | ID: covidwho-2066118

ABSTRACT

Echinacea purpurea (L.) Moench is one of the most economically important medicinal plants, cultivated worldwide for its high medicinal value and with several industrial applications in both pharmaceutical and food industries. Thanks to its various phytochemical contents, including caffeic acid derivatives (CADs), E. purpurea extracts have antioxidant, anti-inflammatory, and immuno-stimulating properties. Among CADs, chicoric acid is one of the most important compounds which have shown important pharmacological properties. The present research was aimed at optimizing the production of chicoric acid in E. purpurea cell culture. Methyl jasmonate (MeJa) at different concentrations and for different duration of treatments was utilized as elicitor, and the content of total polyphenols and chicoric acid was measured. Several genes involved in the chicoric acid biosynthetic pathway were selected, and their expression evaluated at different time points of cell culture growth. This was performed with the aim of identifying the most suitable putative molecular markers to be used as a proxy for the early prediction of chicoric acid contents, without the need of expensive quantification methods. A correlation between the production of chicoric acid in response to MeJa and an increased response to oxidative stress was also proposed.


Subject(s)
Biological Products , Echinacea , Acetates , Antioxidants/metabolism , Biological Products/metabolism , Caffeic Acids , Cell Culture Techniques , Cyclopentanes , Echinacea/chemistry , Echinacea/metabolism , Oxylipins , Pharmaceutical Preparations/metabolism , Plant Extracts/metabolism , Plant Extracts/pharmacology , Succinates
14.
American Journal of Transplantation ; 22(Supplement 3):875-876, 2022.
Article in English | EMBASE | ID: covidwho-2063548

ABSTRACT

Purpose: The purpose of this study was to assess the clinical characteristics of serologic non-responders to COVID-19 booster vaccination in a cohort of solid organ transplant recipients. Method(s): All solid organ transplant recipients our center who received COVID-19 booster vaccination and had SARS-CoV-2 Spike IgG antibodies checked at least 4 weeks after the dose were included. We evaluated the patients who were found to have negative SARS-CoV-2 Spike IgG antibodies despite booster vaccination (i.e. serologic non-responders). Result(s): Among 657 solid organ transplant patients who had received a booster COVID-19 vaccination, 168 patients had Spike IgG antibodies checked during the study period. Forty-nine patients (29.2%) were found to be seronegative and were included in the analysis. 69% were male with a median age of 60 years. The majority of the cohort (47%) were kidney transplant recipients who had received primary vaccination series at a median of 206 days post-transplant. 65% had received basiliximab for induction immunosuppression. Most of the patients (65%) received primary vaccination with Pfizer COVID-19 vaccine and 67% received Pfizer COVID-19 booster vaccination at a median of 187 days after primary vaccination series. Spike IgG antibodies were checked at a median of 41 days from booster vaccination. No patients received rATG within 90 days of booster administration. Similarly, no patients received high dose (>250mg methylprednisolone equivalent) steroids within 30 days prior to booster vaccination. For immunosuppression, 27% were maintained on belatacept and 82% were on anti-metabolites at the time of the booster vacciantion. Ten patients (20%) experienced a COVID-19 infection postcompletion of their booster vaccination. Conclusion(s): In our solid organ transplant cohort, the majority of serologic nonresponders underwent basiliximab induction and were on an antimetabolite for maintenance immunosuppression. A limitation of our study was the use of different laboratory assays for determining IgG levels. Future work includes evaluating the clinical characteristics of COVID 19 booster serologic responders and comparing the two populations. (Table Presented).

15.
American Journal of Transplantation ; 22(Supplement 3):1016, 2022.
Article in English | EMBASE | ID: covidwho-2063533

ABSTRACT

Purpose: Torque tenovirus (TTV), a highly prevalent virus which is not known to cause pathology in humans, is currently being investigated as a marker of immunosuppression. In this study we investigated if the TTV load measured prior to COVID-19 vaccination can predict the serological response to the COVID-19 vaccine, measured 28 days after the second vaccination dose. Method(s): The humoral response to the mRNA 1273 vaccine (Moderna) was assessed in Lung transplant recipients (LTR) who received a transplant between 4 and 237 months prior, by measuring Spike-specific IgG levels at 28 days after the second vaccination. Antibody concentrations of >10 BAU/ml were considered reactive. TTV loads were determined by PCR and Pearson's correlation coefficient was calculated to correlate serological responses to TTV load. Patient characteristics, including reasons for transplantation, antirejection treatment, age and time since transplantation, were recorded to assess associations between these factors and vaccination response or TTV levels. Result(s): 103 LTR were included of which 41 (40%) showed some response (>10 BAU/ml) to the vaccine at 28 days after the second vaccination. 61 (60%) were non-responders. TTV loads at baseline varied between negative and 10E9 copies/ ml. The TTV loads were found to correlate with IgG levels and the with the percentage of responders 28 days after the second vaccination (=<0.001). TTV loads also correlated strongly with the time since transplantation. High TTV levels occurred predominantly in patients who were shorter after transplantation (p=0.0001). Conclusion(s): This study shows an association between pre-vaccination TTV load and humoral response to the SARS-CoV-2 vaccine, which correlate with the time after transplantation. We recommend that TTV load measurements are included in further vaccination efficacy studies in immunocompromised cohorts. If the TTV load is indeed a predictor of vaccine response, this could be used as a potential guidance for optimizing vaccination response.

16.
American Journal of Transplantation ; 22(Supplement 3):909-910, 2022.
Article in English | EMBASE | ID: covidwho-2063523

ABSTRACT

Purpose: Kidney transplant recipients (KTRs) have poor outcomes compared to non-KTRs with acute COVID-19. To provide insight into management of immunosuppression (IS) during COVID-19, we studied immune signatures from the peripheral blood during and after COVID-19 infection from a multicenter KTR cohort. Method(s): Clinical data were collected by chart review. Paxgene blood RNA was polyA-selected and sequenced at enrollment Results: A total of 64 KTRs affected with COVID-19 were enrolled (31 Early cases (<4weeks from a positive SARS-CoV-2 PCR test) and 33 late cases). Out of the 64 patients, eight died and three encountered graft losses during follow-up. Among 31 early cases, we detected differentially expressed genes (nominal p-value < 0.01) in the blood transcriptome that were positively or negatively associated with the COVID-19 severity score (scale of 1 to 7 with increasing severity;Fig 1A). Enrichment analyses showed upregulation of neutrophil and innate immune pathways and downregulation of adaptive immune activation pathways with increasing severity score (Fig 1B). This observation was independent of lymphocyte count, despite reduction in immunosuppression (IS) in 75% of KTRs. Interestingly, compared with early cases, the blood transcriptome in late cases showed "normalization" of these enriched pathways after 4 weeks, suggesting return of adaptive immune system activation despite re-initiation of immunosuppression (Fig 1C). The latter analyses were adjusted for the severity score. Interestingly, similar pathway enrichment with worsening severity of COVID-19 was identifiable from a public dataset of non-KTRs (GSE152418), showing overlapped signatures for acute COVID-19 between KTRs and non-KTRs (overlap P<0.05) (Fig 1D). Conclusion(s): Blood transcriptome of COVID-KTRs shows marked decrease in adaptive immune system activation during acute COVID-19, even during IS reduction, which show recovery after acute illness. (Figure Presented).

17.
American Journal of Transplantation ; 22(Supplement 3):949-950, 2022.
Article in English | EMBASE | ID: covidwho-2063519

ABSTRACT

Purpose: The COVID-19 pandemic portends significant morbidity and mortality in immunocompromised individuals. Vaccination against COVID-19 among immunocompromised population is an essential step to minimize deadly complications. Numerous studies have shown an association between immune status, disease severity, and suboptimal responsiveness to vaccination. Additionally, data suggests that elevated IgG levels correlated with host viral neutralization. We herein present data indicating that induction and maintenance immunosuppression therapy affects responsiveness to vaccination among kidney transplant recipients. Method(s): The study data was retrospectively analyzed for 48 kidney transplant patients who received mRNA type COVID-19 vaccine at our institution. Majority of patients received vaccination between January and March 2021;two doses in total. The 30 days post-vaccination SARS-CoV-2 spike antigen-specific IgG levels were measured to assess immunological response to vaccine. Result(s): The included patients underwent kidney transplantation between 1983 and 2020. Among these patients, 35% showed detectable peak COVID IgG serum levels 30 days after the 2nd vaccine dose. A total of 31 patients (65%) did not show any response;majority of these non-responders (62%) were heavily immunocompromised, either on high dose Mycophenolate (at least 720 mg twice daily) in addition to standard Calcineurin inhibitor/Sirolimus+/-Prednisone), or had received high dose Thymoglobulin (6 mg/kg or more) within a year of vaccination. Among immunocompetent patients, over 95% immunological responsiveness or viral neutralization after the second vaccination dose has been reported. Conclusion(s): Anti-thymocyte globulin as induction immunosuppression and antimetabolites like Mycophenolate as maintenance immunosuppression serve as the cornerstone of transplantation management. However, their utilization impacts B cell proliferation, thereby reducing antibody production and the effectiveness of the SARS-CoV-2 vaccine in transplant patients. The ability of these immunosuppressive medications to suppress responsiveness to the SARS CoV-2 vaccine supports the need for 1) regular immunological surveillance post-vaccination among transplant patients, and 2) the need for a third or possibly fourth booster dose to achieve a sustained and effective response.

18.
American Journal of Transplantation ; 22(Supplement 3):1102, 2022.
Article in English | EMBASE | ID: covidwho-2063518

ABSTRACT

Purpose: Vaccination against SARS-CoV-2 is essential. Complicating this effort are reports of a suboptimal response to the SARS-CoV-2 spike protein in patients on immunosuppressive medications and possible thrombotic microangiopathy (TMA) in renal transplant patients who receive the mRNA type vaccines. Method(s): 48 year old male with end stage renal disease who received a living unrelated transplant in 2015. Pre-operative creatinine was 10.42 mg/dL and decreased to 2.48 mg/dL within a week. Patient received Basiliximab induction and maintained on tacrolimus and mycophenolate (MMF). One month post-transplant patient was diagnosed with TMA. Tacrolimus was stopped and patient was switched to Sirolimus and continued on MMF. Patient was followed closely by transplant nephrology for the next 5 years with a baseline creatinine of 1.9 mg/dL, protein to creatinine ratio below 0.5 mg/mg and well controlled diabetes. No DSA Class I or II detected on regular testing. Patient was compliant with all prescribed medications. On January 25 2021 patient received Pfizer Vaccine. Second Pfizer vaccine administered on February 18 2021. A week later creatinine was noted to be 3.44 mg/dL. Repeat creatinine of 4.27 mg/dL. Biopsy revealed diffuse lymphocytic interstitial inflammation, peritubular capillaritis, and C4D negative. Findings consistent with chronic TMA. DSA testing revealed Class II DSA:DQ2 (SI-5933), Allosure 1.2 %. BK < 500 and CMV undetected. Patient received therapeutic plasma exchange, IV Ig infusion and steroids while on MMF and sirolimus. His creatinine decreased to 2.9 mg/dL on discharge. Over the next 6 months graft function deteriorated. He is now CKD stage 5 and under evaluation for a second transplant. Result(s): There are case reports of COVID-19 vaccine administration and transplant graft dysfunction. A possible mechanism involves the mRNA lipid nanoparticleencapsulated platform producing such a robust CD4 and CD8 T-cell response that pro-inflammatory cytokines are activated or that immune complex associated glomerular disease occurs resulting in the development of TMA in susceptible patients. Conclusion(s): A possible link between SARS CoV-2 vaccination and kidney transplant TMA warrants the implementation of close surveillance of vaccinated transplant patients, particularly susceptible individuals. More research is needed to determine if this link exists.

19.
American Journal of Transplantation ; 22(Supplement 3):696, 2022.
Article in English | EMBASE | ID: covidwho-2063494

ABSTRACT

Purpose: Recent data has shown poor antibody response to SARS-CoV-2 vaccination among adult kidney transplant (tx) recipients, with seroconversion ranging between 22%-58% after two mRNA vaccine doses. Here, we evaluated the antibody and T cell response to SARS-CoV-2 vaccination and evaluate the effects of intensified immunosuppression on such response in pediatric (ped) kidney tx recipients. Method(s): Between April and November 2021, 31 ped renal tx patients (pts)aged 13-22 years old had SARS-CoV-2 spike IgG assessment after receiving 2 doses of SARS-CoV-2 mRNA or 1 dose of viral vector vaccine. Pts were evaluated by their level of immunosuppression: A) standard immunosuppression (tacrolimus, mycophenolate mofetil +/- steroids) or B) intensified immunosuppression (standard immunosuppression + solumedrol pulse, IVIG, rituximab, and/or tocilizumab within 11 months prior to and up to 5 months after SARS-CoV-2 vaccination). A subgroup of 18 pts had SARS-CoV-2 Tc assessment post-vaccination. Result(s): 23 of 31 (74.2%) pts seroconverted at a median assessment time of 83 days (IQR 43-124) post-vaccination. There was no difference in the use of steroid-based or steroid-free immunosuppression between the two groups or the type of vaccine received (Table 1). 15 of 17 (88.2%) of those who received standard immunosuppression seroconverted post-vaccination compared to 8 of 14 (57.1%) in those who received intensified immunosuppression (Table 1;p = 0.10). In a subgroup of pts who had SARS-CoV-2 spike-specific Tc testing, 7 of 7 (100%) in the standard immunosuppression group had positive Tc compared to 7 of 11 (63.6%) in the intensified immunosuppression group (Table 1, p = 0.12). There was no leukopenia or difference in the WBC count in either group at the time of Tc testing (Table 1;p = 0.97). No pts developed symptomatic SARS-CoV-2 infection. Conclusion(s): Ped renal tx recipients appear to have higher rates of seroconversion after the standard 2-dose mRNA or 1-dose viral vector SARS-CoV-2 vaccination compared to adult renal tx recipients. The intensified immunosuppression group appears to have a trend towards lower SARS-CoV-2 spike IgG and Tc conversion, however, results are limited by the small sample size. Larger studies are needed to better understand the humoral and cellular response to SARS-CoV-2 vaccination in this group. (Figure Presented).

20.
American Journal of Transplantation ; 22(Supplement 3):660, 2022.
Article in English | EMBASE | ID: covidwho-2063476

ABSTRACT

Purpose: Kidney transplantation (KT) from coronavirus disease 2019 (COVID-19) positive donors has been avoided due to concerns for donor-derived transmission and possibility of the kidney being a viral reservoir. There is no long-term safety data, and sensitive molecular testing for SARS-CoV-2 in donor kidney is not routinely performed. We report a case of successful KT from a deceased donor who died from severe COVID-19 respiratory illness whose donor kidney and aorta were probed for virus using in situ hybridization (ISH) and quantitative reverse transcriptionpolymerase chain reaction (qRT-PCR). Method(s): A 30-year-old female was admitted to the hospital with severe COVID-19 pneumonia with a positive RT-PCR test for SARS-CoV-2 on nasopharyngeal swab. With clinical worsening, she was placed on extracorporeal membrane oxygenation, but developed hypoxic brain injury and progressed to brain death. Renal function was stable during her hospital course with serum creatinine concentration of 0.7 mg/dL. SARS-CoV-2 RT-PCR on bronchoalveolar lavage and nasopharyngeal samples tested again three days prior to donation was negative. A 55-year-old male recipient with an end-stage renal disease secondary to hypertension was transplanted with the left kidney from the above donor. The donor kidney was studied using pre-implantation surgical biopsy tissues to investigate the presence of SARS-CoV-2 RNA. Aorta tissue with the kidney was also studied given high expression of angiotensin-converting enzyme 2 receptors in vasculature. Result(s): ISH analyses did not show any positive signal for SARS-CoV-2 RNA in the donor kidney sample compared to a SARS-CoV-2 positive lung control. All samples tested by qRT-PCR were also negative for SARS-CoV-2. We found no evidence of SARS-CoV-2 mRNA in the donor kidney and aorta. The recipient has been free of COVID-19 related signs or symptoms and tested negative for SARSCoV- 2 by nasopharyngeal swab RT-PCR on days 20, 30, and 90 following KT. After an initial period of delayed graft function requiring hemodialysis, the recipient now has excellent renal recovery over 6 months following the transplant, and the most recent creatinine is 1.3 mg/dL. Conclusion(s): Taken together with recent observations of successful KT outcomes from mild or asymptomatic COVID-19 donors, we believe that the transmission risk of SARS-CoV-2 through KT is likely to be very low. Use of deceased donors who died after severe COVID-19 can be considered for KT. Larger scale studies are needed to confirm our findings.

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