Exploration of interethnic variation and repurposed drug efficacy in the treatment of SARS-CoV-2 Infection (COVID-19)

Mapping Intimacies ◽

10.1101/2021.03.07.21253095 ◽

2021 ◽

Author(s):

Ammar Ali Almarzooq

Keyword(s):

Respiratory Infections ◽

East Asian ◽

Drug Efficacy ◽

Asian Populations ◽

South Central ◽

Global Pandemic ◽

Central Asian ◽

Dosage Guidelines ◽

Treatment Safety ◽

Viral Respiratory Infections

ABSTRACTThe COVID-19 global pandemic has led to repurposing of drugs, with little underlying evidence for treatment safety and efficacy. This may increase complications for patients with acute viral respiratory infections. UGT1A1 and CYP2D6 enzymes are involved in the metabolism of atazanavir and fluvoxamine repurposed for COVID-19. This study aimed to elucidate the role of interethnic variation in these enzymes in the efficacy of repurposed drug therapies. A retrospective cohort of 101 Jordanian Arab samples were genotyped using Affymetrix DMET Plus Premier Package. Comprehensive global population genetic structure analyses were performed for CYP2D6 and UGT1A1 allele frequencies across multi-ethnic populations of over 131,000 global subjects from 417 published reports, revealing that Jordanian Arabs share the closest sequence homology to European and Near East populations. The East Asian populations have significantly over-representaiton of individuals with diplotype pairs for reduced atazanavir metabolism compared to the African populations and are more likely to show impaired UGT1A1 metabolism. East Asian populations are also 4.4x more likely to show impaired fluvoxamine metabolism than South Central Asian and Oceanian populations, and 8x more likely than other ancestry populations. The results here support previous findings that interethnic variation should be used for developing proper population-specific dosage guidelines.

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Next-Generation Probiotics and Their Metabolites in COVID-19

Microorganisms ◽

10.3390/microorganisms9050941 ◽

2021 ◽

Vol 9 (5) ◽

pp. 941

Author(s):

Thomas Gautier ◽

Sandrine David-Le Gall ◽

Alaa Sweidan ◽

Zohreh Tamanai-Shacoori ◽

Anne Jolivet-Gougeon ◽

...

Keyword(s):

Immune Response ◽

Respiratory Infections ◽

Current Knowledge ◽

Next Generation ◽

Secondary Bile Acid ◽

Global Pandemic ◽

Tract Infections ◽

Viral Respiratory Infections ◽

Gut Microbiota Composition ◽

Viral Respiratory

Since December 2019, a global pandemic has been observed, caused by the emergence of a new coronavirus, SARS CoV-2. The latter is responsible for the respiratory disease, COVID-19. The infection is also characterized by renal, hepatic, and gastrointestinal dysfunctions suggesting the spread of the virus to other organs. A dysregulated immune response was also reported. To date, there is no measure to treat or prevent SARS CoV-2 infection. Additionally, as gut microbiota composition is altered in patients with COVID-19, alternative therapies using probiotics can be considered to fight SARS CoV-2 infection. This review aims at summarizing the current knowledge about next-generation probiotics (NGPs) and their benefits in viral respiratory tract infections and in COVID-19. We describe these bacteria, highlighted by studies using metagenomic approaches. In addition, these bacteria generate metabolites such as butyrate, desaminotyrosine, and secondary bile acid, suggested to prevent viral respiratory infections. Gut microbial metabolites transported via the circulation to the lungs could inhibit viral replication or improve the immune response against viruses. The use of probiotics and/or their metabolites may target either the virus itself and/or the immunologic process. However, this review showed that more studies are needed to determine the benefits of probiotics and metabolite products in COVID-19.

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Assessment of the effectiveness of the EUROFORGEN NAME and Precision ID Ancestry panel markers for ancestry investigations

Scientific Reports ◽

10.1038/s41598-021-97654-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

D. Truelsen ◽

T. Tvedebrink ◽

H. S. Mogensen ◽

M. S. Farzad ◽

M. A. Shan ◽

...

Keyword(s):

Middle East ◽

Central Asia ◽

North Africa ◽

Middle Eastern ◽

North African ◽

Likelihood Ratios ◽

North East ◽

Asian Populations ◽

South Central ◽

Central Asian

AbstractThe EUROFORGEN NAME panel is a regional ancestry panel designed to differentiate individuals from the Middle East, North Africa, and Europe. The first version of the panel was developed for the MassARRAY system and included 111 SNPs. Here, a custom AmpliSeq EUROFORGEN NAME panel with 102 of the original 111 loci was used to sequence 1098 individuals from 14 populations from Europe, the Middle East, North Africa, North-East Africa, and South-Central Asia. These samples were also sequenced with a global ancestry panel, the Precision ID Ancestry Panel. The GenoGeographer software was used to assign the AIM profiles to reference populations and calculate the weight of the evidence as likelihood ratios. The combination of the EUROFORGEN NAME and Precision ID Ancestry panels led to fewer ambiguous assignments, especially for individuals from the Middle East and South-Central Asia. The likelihood ratios showed that North African individuals could be separated from European and Middle Eastern individuals using the Precision ID Ancestry Panel. The separation improved with the addition of the EUROFORGEN NAME panel. The analyses also showed that the separation of Middle Eastern populations from European and South-Central Asian populations was challenging even when both panels were applied.

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Assessment of the effectiveness of the EUROFORGEN NAME and Precision ID Ancestry panel markers for ancestry investigations

10.21203/rs.3.rs-331678/v1 ◽

2021 ◽

Author(s):

Ditte Truelsen ◽

Torben Tvedebrink ◽

Helle Smidt Mogensen ◽

Maryam Sharafi Farzad ◽

Muhammad Adnan Shan ◽

...

Keyword(s):

Middle East ◽

Central Asia ◽

North Africa ◽

Middle Eastern ◽

Likelihood Ratios ◽

North East ◽

Asian Populations ◽

South Central ◽

Central Asian ◽

Second Tier

Abstract The EUROFORGEN NAME panel is a second-tier ancestry panel designed to differentiate individuals from the Middle East, North Africa, and Europe. The first version of the panel was developed for the MassARRAY® system and included 111 SNPs. Here, a custom AmpliSeq™ EUROFORGEN NAME panel with 102 of the original 111 loci was used to sequence 1,098 individuals from 14 populations from Europe, the Middle East, North Africa, North-East Africa, and South-Central Asia. These samples were also sequenced with the first-tier Precision ID Ancestry Panel. The GenoGeographer software was used to assign the AIM profiles to reference populations and calculate the weight of the evidence as likelihood ratios. The combination of the EUROFORGEN NAME and Precision ID Ancestry panels led to fewer ambiguous assignments, especially for individuals from the Middle East and South-Central Asia. The likelihood ratios showed that North African individuals could be separated from European and Middle Eastern individuals using the Precision ID Ancestry Panel. The separation improved with the addition of the EUROFORGEN NAME panel. The analyses also showed that the separation of Middle Eastern populations from European and South-Central Asian populations was challenging even when both panels were applied.

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LRRK2 Mutations and Asian Disease-Associated Variants in the First Parkinson’s Disease Cohort from Kazakhstan

Parkinson s Disease ◽

10.1155/2020/2763838 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10

Author(s):

Rauan Kaiyrzhanov ◽

Akbota Aitkulova ◽

Chingiz Shashkin ◽

Nazira Zharkinbekova ◽

Mie Rizig ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Early Onset ◽

East Asian ◽

Asian Populations ◽

Medical Centers ◽

Central Asian ◽

Fast Progression ◽

Allele Specific ◽

University College London

Background. LRRK2 mutations have emerged as the most prevalent and potentially treatable determinants of Parkinson’s disease (PD). Peculiar geographic distribution of these mutations has triggered an interest in genotyping PD cohorts of different ethnic backgrounds for LRRK. Objective. Here, we report on the results of LRRK2 screening in the first Central Asian PD cohort. Methods. 246 PD patients were consecutively recruited by movement disorder specialists from four medical centers in Kazakhstan, and clinicodemographic data and genomic DNA from blood were systematically obtained and shipped to the Institute of Neurology University College London together with DNAs from 200 healthy controls. The cohort was genotyped for five LRRK2 mutations (p.Gly2019Ser, p.Arg1441His, p.Tyr1699Cys, p.Ile2020Thr, and p.Asn1437His) and three East Asian disease-associated variants (p.Gly2385Arg, p.Ala419Val, and p.Arg1628Pro) via Kompetitive allele-specific polymerase chain reaction assay analysis. Results. None of the study subjects carried LRRK2 mutations, whereas the following Asian variants were found with insignificant odds ratios (OR): p.Gly2385Arg (1.2%, minor allele frequency (MAF) 0.007, OR 1.25, p=0.8), p.Ala419Val (3.7%, MAF 0.02, OR 1.5, p=0.4), and p.Arg1628Pro was found only in 1% of controls. p.Gly2385Arg was positive in a big family with PD and tremor, although with incomplete segregation. One early-onset PD subject was homozygous for p.Ala419Val who developed fast progression and severe dyskinesias. p.Ala419Val was associated with early-onset PD. Conclusions. We showed that East Asian LRRK variants could be found in Central Asian populations but their pathogenicity remains to be elucidated in larger PD cohorts.

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COVID-19: the older adult and the importance of vitamin D sufficiency

Journal of Nutritional Science ◽

10.1017/jns.2020.36 ◽

2020 ◽

Vol 9 ◽

Author(s):

Paula M. O'Shea ◽

Tomás P. Griffin ◽

Michelle Brennan ◽

Eamon C. Mulkerrin

Keyword(s):

Vitamin D ◽

Vitamin D Deficiency ◽

Protective Factor ◽

Respiratory Infections ◽

Hypovitaminosis D ◽

The Novel ◽

Global Pandemic ◽

Inflammatory Cytokine Response ◽

Novel Coronavirus ◽

Viral Respiratory Infections

Abstract In December 2019, in Wuhan, China, the novel coronavirus ‘severe acute respiratory syndrome 2’ (SARS-CoV-2) was discovered as the cause of a pneumonia-like illness and subsequently named coronavirus disease 2019 (COVID-19). COVID-19 spread and is now a global pandemic. With few exceptions, countries in the Northern hemisphere have higher mortality rates from COVID-19. This may be due to an increased prevalence of older people in Northern Europe at higher risk of having cardio-pulmonary and metabolic comorbidities as well as hypovitaminosis D. With increasing age, immunosenescence and ‘inflammaging’ lead to impaired and maladaptive immune responses to SARS-CoV-2 infections, contributing to the enhanced prevalence of severe COVID-19 in older patients. The association of ageing with increased vitamin D deficiency, which is associated with cardiovascular risk factors and disease and worse prognosis in COVID-19 infection, is discussed. Considerable experimental evidence demonstrates the immuno-modulatory properties of vitamin D, in particular, its role in regulating and suppressing the inflammatory cytokine response to viral respiratory infections links the importance of vitamin D sufficiency as a potential protective factor in COVID-19. There is an urgent need for prospective randomised studies to examine whether hypovitaminosis D correlates with severity of COVID-19 disease and the actual benefit of repletion. Moreover, given what has been described as a ‘pandemic of vitamin D deficiency’, especially in Europe, and in the context of the SARS-CoV-2 contagion, the authors support the call for public health doctors and physicians, with support from Governments, to prioritise and strengthen recommendations on vitamin D intake and supplementation.

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Prediction of Inflammatory Bowel Diseases using Genetic Risk Score in Asian populations

10.21203/rs.3.rs-153287/v1 ◽

2021 ◽

Author(s):

Shifteh Abedian ◽

Sunny H Wong ◽

Suzanne Van Sommeren ◽

Atsushi Takahashi ◽

Jae Hee Cheon ◽

...

Keyword(s):

Genetic Risk ◽

Rare Variants ◽

Genetic Risk Score ◽

East Asian ◽

Risk Scores ◽

Total Load ◽

Asian Populations ◽

Central Asian ◽

Disease Occurrence ◽

Inflammatory Bowel

Abstract Background and Aims: The incidence of Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and Ulcerative colitis (UC), is rising in Asian populations. We undertook a cross-population study to explore whether genetic risk scores (GRS) of IBD, CD and UC could explain their occurrence, and whether they can be used to predict disease occurrence in general populations from East Asia (EA) and Central Asia (CA). Methods We studied 9,698 subjects – 4,733 IBD patients (2,003 CD; 2,730 UC) and 4,965 matched controls – who had been genotyped using Immunochip. The subjects were from three East Asian (Japan, South Korea and China) and two Central Asian populations (India and Iran). We generated GRS for each population by combining information from up to 201 genome-wide significant IBD-associated variants to summarize the total load of genetic risk for each phenotype. We then estimated the explained variance and predictability of IBD using the GRS. Results IBD GRS could explain up to 4.40% and 4.14% of IBD variance at a significant level in East Asian and Central Asian populations, respectively, but, given a prevalence of 0.01% and 0.04% for IBD, these yield limited predictive probability. GRS for CD and UC separately proved less significant than GRS for IBD. Conclusion GRS alone can explain only a limited percentage of disease occurrence (< 5% of disease susceptibility) and cannot be used to predict IBD in Asian populations at this time. Our results highlight the significant missing heritability, which may be due to genetic epistasis, gene-environment interactions, or rare variants.

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Cellular Immunotherapy and the Lung

Vaccines ◽

10.3390/vaccines9091018 ◽

2021 ◽

Vol 9 (9) ◽

pp. 1018

Author(s):

Sorcha Daly ◽

Andrew O’Sullivan ◽

Ronan MacLoughlin

Keyword(s):

Viral Infections ◽

Nk Cell ◽

Respiratory Infections ◽

Checkpoint Inhibitors ◽

Cellular Immunotherapy ◽

Cell Therapies ◽

Routes Of Administration ◽

Global Pandemic ◽

Area Of Concern ◽

Viral Respiratory Infections

The new era of cellular immunotherapies has provided state-of-the-art and efficient strategies for the prevention and treatment of cancer and infectious diseases. Cellular immunotherapies are at the forefront of innovative medical care, including adoptive T cell therapies, cancer vaccines, NK cell therapies, and immune checkpoint inhibitors. The focus of this review is on cellular immunotherapies and their application in the lung, as respiratory diseases remain one of the main causes of death worldwide. The ongoing global pandemic has shed a new light on respiratory viruses, with a key area of concern being how to combat and control their infections. The focus of cellular immunotherapies has largely been on treating cancer and has had major successes in the past few years. However, recent preclinical and clinical studies using these immunotherapies for respiratory viral infections demonstrate promising potential. Therefore, in this review we explore the use of multiple cellular immunotherapies in treating viral respiratory infections, along with investigating several routes of administration with an emphasis on inhaled immunotherapies.

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The Buhl Burial: A Paleoindian Woman from Southern Idaho

American Antiquity ◽

10.2307/2694629 ◽

1998 ◽

Vol 63 (3) ◽

pp. 437-456 ◽

Cited By ~ 59

Author(s):

Thomas J. Green ◽

Bruce Cochran ◽

Todd W. Fenton ◽

James C. Woods ◽

Gene L. Titmus ◽

...

Keyword(s):

East Asian ◽

Isotopic Analysis ◽

Skeletal Remains ◽

Time Of Death ◽

Human Skeletal Remains ◽

Asian Populations ◽

South Central ◽

Minimum Age ◽

North American Indian ◽

The Town

In January 1989 highway workers encountered human skeletal remains in a gravel quarry in south-central Idaho near the town of Buhl. Excavation revealed the remains of a young Paleoindian woman, 17–21 years of age at the time of death, with craniofacial attributes similar to other North American Indian and East Asian populations. She was buried in windblown and colluvial sediments immediately overlying Bonneville flood gravel. Grave goods include a large stemmed biface, an eyed needle, and a bone implement of unknown function. Isotopic analysis suggests a diet of meat and fish, including anadromous fish. Radiographs show numerous periods of dietary stress throughout the woman's childhood. AMS (accelerator mass spectrometry) dating indicates an age of 10,675±95 B.P., and geomorphological studies verify this single radiocarbon date suggesting it is the burial's minimum age. Following Idaho State law, the skeleton was claimed by the Shoshone-Bannock tribes of Idaho and reburied.

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Neuropsychiatric and Cognitive Sequelae of COVID-19

Frontiers in Psychology ◽

10.3389/fpsyg.2021.577529 ◽

2021 ◽

Vol 12 ◽

Author(s):

Sanjay Kumar ◽

Alfred Veldhuis ◽

Tina Malhotra

Keyword(s):

Mental Health ◽

Mental Health Problems ◽

Psychiatric Symptoms ◽

Respiratory Infections ◽

Global Pandemic ◽

Neuropsychiatric Manifestations ◽

Long Term Impact ◽

Viral Respiratory Infections

Coronavirus disease 2019 (COVID-19) is likely to have long-term mental health effects on individuals who have recovered from COVID-19. Rightly, there is a global response for recognition and planning on how to deal with mental health problems for everyone impacted by the global pandemic. This does not just include COVID-19 patients but the general public and health care workers as well. There is also a need to understand the role of the virus itself in the pathophysiology of mental health disorders and longer-term mental health sequelae. Emerging evidence suggests that COVID-19 patients develop neurological symptoms such as headache, altered consciousness, and paraesthesia. Brain tissue oedema and partial neurodegeneration have also been observed in an autopsy. In addition, there are reports that the virus has the potential to cause nervous system damage. Together, these findings point to a possible role of the virus in the development of acute psychiatric symptoms and long-term neuropsychiatric sequelae of COVID-19. The brain pathologies associated with COVID-19 infection is likely to have a long-term impact on cognitive processes. Evidence from other viral respiratory infections, such as severe acute respiratory syndrome (SARS), suggests a potential development of psychiatric disorders, long-term neuropsychiatric disorders, and cognitive problems. In this paper, we will review and evaluate the available evidence of acute and possible long-term neuropsychiatric manifestations of COVID-19. We will discuss possible pathophysiological mechanisms and the implications this will have on preparing a long-term strategy to monitor and manage such patients.

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