Insight into molecular mechanisms underlying hepatic dysfunction in severe COVID-19 patients using systems biology

Hammoudeh, Sarah; Hammoudeh, Arabella Musa; Bhamidimarri, Poorna Manasa; Mahboub, Bassam; Halwani, Rabih; Hamid, Qutayba; Rahmani, Mohamed; Hamoudi, Rifat

doi:10.3748/wjg.v27.i21.2850

Cited by 17 publications

(12 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We found that this protein was significantly higher in COVID-19 patients (P < 1.5×10 -14 ) across all three outcomes. HDGF has been shown to be significantly upregulated in transcriptome of liver autopsy samples of severe COVID-19 patients ( 35 ). We found high HDGF levels in our COVID-19 patients across all three outcomes (P < 4.1×10 -14 ).…”

Section: Resultsmentioning

confidence: 99%

Plasma proteomics of SARS-CoV-2 infection and severity reveals impact on Alzheimer and coronary disease pathways

Cruchaga

Wang

Sung

et al. 2022

Preprint

View full text Add to dashboard Cite

Identification of the plasma proteomic changes of Coronavirus disease 2019 (COVID-19) is essential to understanding the pathophysiology of the disease and developing predictive models and novel therapeutics. We performed plasma deep proteomic profiling from 332 COVID-19 patients and 150 controls and pursued replication in an independent cohort (297 cases and 76 controls) to find potential biomarkers and causal proteins for three COVID-19 outcomes (infection, ventilation, and death). We identified and replicated 1,449 proteins associated with any of the three outcomes (841 for infection, 833 for ventilation, and 253 for death) that can be query on a web portal (https://covid.proteomics.wustl.edu/). Using those proteins and machine learning approached we created and validated specific prediction models for ventilation (AUC>0.91), death (AUC>0.95) and either outcome (AUC>0.80). These proteins were also enriched in specific biological processes, including immune and cytokine signaling (FDR < 3.72x10-14), Alzheimer's disease (FDR < 5.46x10-10) and coronary artery disease (FDR < 4.64x10-2). Mendelian randomization using pQTL as instrumental variants nominated BCAT2 and GOLM1 as a causal proteins for COVID-19. Causal gene network analyses identified 141 highly connected key proteins, of which 35 have known drug targets with FDA-approved compounds. Our findings provide distinctive prognostic biomarkers for two severe COVID-19 outcomes (ventilation and death), reveal their relationship to Alzheimer's disease and coronary artery disease, and identify potential therapeutic targets for COVID-19 outcomes.

show abstract

Section: Resultsmentioning

confidence: 99%

Plasma proteomics of SARS-CoV-2 infection and severity reveals impact on Alzheimer and coronary disease pathways

Cruchaga

Wang

Sung

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…As it is a systemic inflammatory disease, COVID-19 affects, among others, the gastrointestinal system ( 48 ). Individuals who developed the severe form of the disease had pathological tissue changes in the liver parenchyma, developing liver cirrhosis and non-alcoholic liver steatosis ( 49 ). An increased liver parenchyma density is suggestive of hepatic steatosis and was observed in 57% of individuals in Group 1.…”

Section: Discussionmentioning

confidence: 99%

Chest Computed Tomography Is an Efficient Method for Initial Diagnosis of COVID-19: An Observational Study

et al. 2022

View full text Add to dashboard Cite

Coronavirus disease (COVID-19) is an infectious disease that can lead to pneumonia, pulmonary oedema, acute respiratory distress syndrome, multiple organ and system dysfunction, and death. This study aimed to verify the efficacy of chest computed tomography (CT) for the initial diagnosis of COVID-19. This observational, retrospective, cross-sectional study included 259 individuals who underwent clinical evaluation, blood collection, chest CT, and a reverse transcription polymerase chain reaction (RT-PCR) diagnostic test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during their course of treatment at a reference hospital in Belém, Pará, Brazil between April and June 2020. Inclusion criteria were flu-like symptoms in adults of both sexes. Individuals with an inconclusive COVID-19 molecular test or who had artifacts in the chest CT images were excluded. Parametric data were analyzed using Student-t-test and non-parametric data were analyzed using average test and Fisher exact test. Participants were divided into two groups: Group 1 (COVID-19 positive), n = 211 (124 males, 87 females), 51.8 ± 17.9 years old and Group 2 (COVID-19 negative), n = 48 (22 males, 26 females), 47.6 ± 18.6 years old. Most frequent symptoms were cough [Group 1 n = 199 (94%)/Group 2 n = 46 (95%)], fever [Group 1 n = 154 (72%)/Group 2 n = 28 (58%)], myalgia [Group 1 n = 172 (81%)/Group 2 n = 38 (79%)], dyspnoea [Group 1 n = 169 (80%) / Group 2 n = 37 (77%)], headache [Group 1 n = 163 (77%)/Group 2 n = 32 (66%)], and anosmia [Group 1 n = 154 (73%)/Group 2 n = 29 (60%)]. Group 1 had a higher proportion of ground-glass opacity [Group 1 n = 175 (83%)/Group 2 n = 24 (50%), 0.00], vascular enhancement sign [Group 1 n = 128 (60%)/Group 2 n = 15 (31%), 0.00], septal thickening [Group 1 n = 99 (47%)/Group 2 n = 13 (27%), 0.01], crazy-paving pattern [Group 1 n = 98 (46%) / Group 2 n = 13 (27%), 0.01], consolidations [Group 1 n = 92 (43%)/Group 2 n = 8 (16%), 0.00], and CO-RADS 4 and 5 [Group 1 n = 163 (77.25%)/Group 2 n = 24 (50%), 0.00] categories in chest CT. Chest CT, when available, was found to be an efficient method for the initial diagnosis and better management of individuals with COVID-19.

show abstract

“…For example, a recent study indicated that SARS-CoV-2 may hijack the GPCR signaling pathway to alter fluid and ion transport within the lungs, which leads to lung edema-a deadly clinical sign of COVID-19 infection (58). Similarly, Hammoudeh et al (59) suggested that SARS-CoV-2 manipulation of the GPCR pathways could facilitate viral infection within the host leading to dysregulation of intracellular transport within the livers of infected patients. Given its role in infectivity of other coronaviruses, further investigation into GPCR signaling and its association with BCoV and BRD in cattle is warranted.…”

Section: Discussionmentioning

confidence: 99%

Identifying Loci Associated With Bovine Corona Virus Infection and Bovine Respiratory Disease in Dairy and Feedlot Cattle

Kiser

Neibergs

2021

Front. Vet. Sci.

View full text Add to dashboard Cite

Bovine coronavirus (BCoV) is associated with respiratory and enteric infections in both dairy and beef cattle worldwide. It is also one of a complex of pathogens associated with bovine respiratory disease (BRD), which affects millions of cattle annually. The objectives of this study were to identify loci and heritability estimates associated with BCoV infection and BRD in dairy calves and feedlot cattle. Dairy calves from California (n = 1,938) and New Mexico (n = 647) and feedlot cattle from Colorado (n = 915) and Washington (n = 934) were tested for the presence of BCoV when classified as BRD cases or controls following the McGuirk scoring system. Two comparisons associated with BCoV were investigated: (1) cattle positive for BCoV (BCoV+) were compared to cattle negative for BCoV (BCoV−) and (2) cattle positive for BCoV and affected with BRD (BCoV+BRD+) were compared to cattle negative for BCoV and BRD (BCoV−BRD−). The Illumina BovineHD BeadChip was used for genotyping, and genome-wide association analyses (GWAA) were performed using EMMAX (efficient mixed-model association eXpedited). The GWAA for BCoV+ identified 51 loci (p < 1 × 10−5; 24 feedlot, 16 dairy, 11 combined) associated with infection with BCoV. Three loci were associated with BCoV+ across populations. Heritability estimates for BCoV+ were 0.01 for dairy, 0.11 for feedlot cattle, and 0.03 for the combined population. For BCoV+BRD+, 80 loci (p < 1 × 10−5; 26 feedlot, 25 dairy, 29 combined) were associated including 14 loci across populations. Heritability estimates for BCoV+BRD+ were 0.003 for dairy, 0.44 for feedlot cattle, and 0.07 for the combined population. Several positional candidate genes associated with BCoV and BRD in this study have been associated with other coronaviruses and respiratory infections in humans and mice. These results suggest that selection may reduce susceptibility to BCoV infection and BRD in cattle.

show abstract

Insight into molecular mechanisms underlying hepatic dysfunction in severe COVID-19 patients using systems biology

Cited by 17 publications

References 52 publications

Plasma proteomics of SARS-CoV-2 infection and severity reveals impact on Alzheimer and coronary disease pathways

Plasma proteomics of SARS-CoV-2 infection and severity reveals impact on Alzheimer and coronary disease pathways

Chest Computed Tomography Is an Efficient Method for Initial Diagnosis of COVID-19: An Observational Study

Identifying Loci Associated With Bovine Corona Virus Infection and Bovine Respiratory Disease in Dairy and Feedlot Cattle

Contact Info

Product

Resources

About