ORCID Profile
0000-0002-9363-1869
Current Organisation
Tel Aviv University
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Publisher: Cold Spring Harbor Laboratory
Date: 16-05-2022
DOI: 10.1101/2022.05.12.22274991
Abstract: Anosmia is common in COVID-19 patients, lasting for weeks or months following recovery. The biological mechanism underlying olfactory deficiency in COVID-19 does not involve direct damage to nasal olfactory neurons, which do not express the proteins required for SARS-CoV-2 infection. A recent study suggested that anosmia results from downregulation of olfactory receptors. We hypothesized that anosmia in COVID-19 may also reflect SARS-CoV-2 infection-driven elevated expression of regulator of G protein signaling 2 ( RGS2 ), a key regulator odorant receptor, thereby silencing their signaling. To test our hypothesis, we analyzed gene expression of nasopharyngeal swabs from SARS-CoV-2 positive patients and non-infected controls (two published RNA-sequencing datasets, 580 in iduals). Our analysis found upregulated RGS2 expression in SARS-CoV-2 positive patients (FC=14.5, Padj=1.69e-05 and FC=2.4 Padj=0.001, per dataset). Additionally, RGS2 expression was strongly correlated with PTGS2, IL1B, CXCL8, NAMPT and other inflammation markers with substantial upregulation in early infection. These observations suggest that upregulated expression of RGS2 may underlie anosmia in COVID-19 patients. As a regulator of numerous G-protein coupled receptors, RGS2 may drive further neurological symptoms of COVID-19. Studies are required for clarifying the cellular mechanisms by which SARS-CoV-2 infection drives the upregulation of RGS2 and other genes implicated in inflammation. Insights on these pathways may assist in understanding anosmia and additional neurological symptoms reported in COVID-19 patients.
Publisher: Informa UK Limited
Date: 17-08-2022
DOI: 10.1080/23744235.2022.2111464
Abstract: Alpha 1 antitrypsin (A1AT) is the major human blood serine protease inhibitor. Transmembrane serine protease 2 (TMPRSS2), which is crucial for SARS-CoV-2 cell entry, is inhibited by A1AT. Therefore, we hypothesized that in iduals with diminished levels of A1AT may be more prone to SARS-CoV-2 infection and severe COVID-19 disease. Our aim in this study was to evaluate the level of A1AT in hospitalized COVID-19 patients in comparison to hospitalized patients with non-COVID-19 pneumonia. We conducted an observational prospective study between October 2020 and April 2021 in Rabin Medical Centre in Israel. A1AT levels were measured from the routine serum s les of hospitalized patients with COVID-19 and non-COVID-19 pneumonia (control group). The primary outcome was A1AT level, secondary outcomes were clinical outcomes and predictors of morality. Overall, 145 patients were included in the study, 98 in the COVID-19 group and 47 in the control group. The median A1AT level was 222 mg/dL (interquartile range (IQR) 188-269) and 258 mg/dL (IQR 210-281) in the COVID-19 and control groups, respectively ( Patients admitted due to severe COVID-19 had lower A1AT levels in comparison to patients admitted due to non-COVID pneumonia. This observation may suggest an association between mildly diminished A1AT and higher risk of SARS-CoV-2 infection with severe COVID-19 disease.
Publisher: Springer Science and Business Media LLC
Date: 05-09-2018
DOI: 10.1038/S41398-018-0237-0
Abstract: Lithium is the first-line treatment for bipolar affective disorder (BPAD) but two-thirds of patients respond only partially or not at all. The reasons for this high variability in lithium response are not well understood. Transcriptome-wide profiling, which tests the interface between genes and the environment, represents a viable means of exploring the molecular mechanisms underlying lithium response variability. Thus, in the present study we performed co-expression network analyses of whole-blood-derived RNA-seq data from n = 50 lithium-treated BPAD patients. Lithium response was assessed using the well-validated ALDA scale, which we used to define both a continuous and a dichotomous measure. We identified a nominally significant correlation between a co-expression module comprising 46 genes and lithium response represented as a continuous (i.e., scale ranging 0–10) phenotype (cor = −0.299, p = 0.035). Forty-three of these 46 genes had reduced mRNA expression levels in better lithium responders relative to poorer responders, and the central regulators of this module were all mitochondrially-encoded ( MT-ND1 , MT-ATP6 , MT-CYB ). Accordingly, enrichment analyses indicated that genes involved in mitochondrial functioning were heavily over-represented in this module, specifically highlighting the electron transport chain (ETC) and oxidative phosphorylation (OXPHOS) as affected processes. Disrupted ETC and OXPHOS activity have previously been implicated in the pathophysiology of BPAD. Our data adds to previous evidence suggesting that a normalisation of these processes could be central to lithium’s mode of action, and could underlie a favourable therapeutic response.
Publisher: Springer Science and Business Media LLC
Date: 28-07-2021
Publisher: Bentham Science Publishers Ltd.
Date: 05-2013
Publisher: Springer Science and Business Media LLC
Date: 24-12-2014
Publisher: MDPI AG
Date: 28-08-2022
DOI: 10.3390/JPM12091396
Abstract: Anosmia is common in COVID-19 patients, lasting for weeks or months following recovery. The biological mechanism underlying olfactory deficiency in COVID-19 does not involve direct damage to nasal olfactory neurons, which do not express the proteins required for SARS-CoV-2 infection. A recent study suggested that anosmia results from downregulation of olfactory receptors. We hypothesized that anosmia in COVID-19 may also reflect SARS-CoV-2 infection-driven elevated expression of regulator of G protein signaling 2 (RGS2), a key regulator of odorant receptors, thereby silencing their signaling. To test our hypothesis, we analyzed gene expression of nasopharyngeal swabs from SARS-CoV-2 positive patients and non-infected controls (two published RNA-sequencing datasets, 580 in iduals). Our analysis found upregulated RGS2 expression in SARS-CoV-2 positive patients (FC = 14.5, Padj = 1.69 × 10−5 and FC = 2.4 Padj = 0.001, per dataset). Additionally, RGS2 expression was strongly correlated with PTGS2, IL1B, CXCL8, NAMPT and other inflammation markers with substantial upregulation in early infection. These observations suggest that upregulated expression of RGS2 may underlie anosmia in COVID-19 patients. As a regulator of numerous G-protein coupled receptors, RGS2 may drive further neurological symptoms of COVID-19. Studies are required for clarifying the cellular mechanisms by which SARS-CoV-2 infection drives the upregulation of RGS2 and other genes implicated in inflammation. Insights on these pathway(s) may assist in understanding anosmia and additional neurological symptoms reported in COVID-19 patients.
Publisher: Wiley
Date: 10-10-2023
DOI: 10.1002/DDR.22121
Publisher: Wiley
Date: 22-09-2020
DOI: 10.1096/FJ.202002097
Publisher: Cold Spring Harbor Laboratory
Date: 26-08-2020
DOI: 10.1101/2020.08.24.20179226
Abstract: COVID-19 infection and fatality rates vary considerably between countries. We present preliminary evidence that these variations may in part reflect ethnic differences in the frequencies of polymorphic alleles of SERPINA1 , coding for alpha-1 antitrypsin, the major blood serine protease inhibitor.
Publisher: MDPI AG
Date: 30-08-2022
DOI: 10.3390/IJMS23179843
Abstract: Mutations in over 100 genes are implicated in autism spectrum disorder (ASD). DNA SNPs, CNVs, and epigenomic modifications also contribute to ASD. Transcriptomics analysis of blood s les may offer clues for pathways dysregulated in ASD. To expand and validate published findings of RNA-sequencing (RNA-seq) studies, we performed RNA-seq of whole blood s les from an Israeli discovery cohort of eight children with ASD compared with nine age- and sex-matched neurotypical children. This revealed 10 genes with differential expression. Using quantitative real-time PCR, we compared RNAs from whole blood s les of 73 Israeli and American children with ASD and 26 matched neurotypical children for the 10 dysregulated genes detected by RNA-seq. This revealed higher expression levels of the pro-inflammatory transcripts BATF2 and LY6E and lower expression levels of the anti-inflammatory transcripts ISG15 and MT2A in the ASD compared to neurotypical children. BATF2 was recently reported as upregulated in blood s les of Japanese adults with ASD. Our findings support an involvement of these genes in ASD phenotypes, independent of age and ethnicity. Upregulation of BATF2 and downregulation of ISG15 and MT2A were reported to reduce cancer risk. Implications of the dysregulated genes for pro-inflammatory phenotypes, immunity, and cancer risk in ASD are discussed.
No related grants have been discovered for David Gurwitz.