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In-host mutations in Covid-19 virus reflecting in variants, finds study

July 31, 2021 by admin Leave a Comment

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NEW DELHI: Changes that happen in the genome of the SARS-CoV-2 virus in an infected person reflect at the population level as a variation, according to a study that researchers say will be “of enormous utility” in predicting the spread and infectivity of viral Covid strains.
Tracking the changes that happen in the virus inside a host in individuals and populations might provide important leads to the viral sites that are favourable or disadvantageous for the survival of SARS-CoV-2 that causes Covid-19, the researchers said.
The team behind the recent study included researchers from the National Centre for Disease Control and the CSIR-Institute of Genomics and Integrative Biology (CSIR-IGIB) in Delhi, as well as the Institute of Life Sciences in Bhubaneswar, the Academy for Scientific and Innovative Research in Ghaziabad, the CSIR-Centre for Cellular and Molecular Biology (CSIR-CCMB) in Hyderabad and the Indian Institute of Technology, Jodhpur.
Reacting to the findings of the study, virologist Upasana Ray explained that the emergence of viral variants is dependent on its successful reproduction in the host.
“Mutation is a very common phenomenon in the life cycle of any virus. While a virus undergoes replication and multiplies inside the host cell, small nucleotide alterations occur,” Ray, a senior scientist at Kolkata’s CSIR-Indian Institute of Chemical Biology told PTI.
“As a virus gets transmitted more and more, within its host it gets plenty of chances to accumulate such changes and thus variants emerge,” Ray, who was not involved in the study, said.
In the yet-to-be-published study posted on the preprint repository BioRxiv on July 27, the researchers analysed samples of Covid-19 diagnosed patients from two different time periods of the pandemic.
In phase 1 of the study, the team analysed 1,347 samples collected latest by June 2020 from China, Germany, Malaysia, UK, US and different subpopulations of India to perceive a genome-wide intra-host single nucleotide variation (iSNV) map in SARS-CoV-2 infected populations.
A single nucleotide variation (SNV) is a substitution of a nucleotide — a basic building block of the genetic material of the virus.
According to Ray, iSNV are the variations happening inside the host. She added that these mutations might or might not ultimately reflect at the population level.
“For an intra-host SNV to survive, such a variant should be able to multiply and spread and hence establish itself,” the scientist said.
The researchers observed 18,146 iSNV sites spanning the viral genome, including those that defined the B.1 and B.6 lineages.
The Alpha variant, first identified in the UK, the Beta variant first found in South Africa and Delta variant, first reported from India, belong to this lineage of SARS-CoV-2.
“Interestingly, 41 per cent of all unique iSNVs identified in these samples were found to be reported as an SNV by 30th September 2020 in one or more samples submitted in GISAID, increasing to 80 per cent by 30th June 2021,” the authors of the study noted.
GISAID is a global science initiative and primary source that provides open access to genomic data of influenza viruses and the coronavirus responsible for the Covid-19 pandemic.
In phase 2 of the study, the authors analysed 1,798 samples sequenced in India between November 2020 and May 2021.
They found evidence that iSNVs can over time manifest into SNVs in populations.
“In these samples, iSNVs could be recorded to be present in the population in most of the Delta (B.1.617.2) and Kappa (B.1.617.1) lineage-defining genomic positions prior to their fixation as SNVs by February 2021,” the researchers said.
“These results highlight the importance of recording iSNVs as an extension to the genomic surveillance programmes to enable more accurate models for viral epidemiology,” they said.
The authors also observed iSNVs in 87 per cent of the sites in the spike protein — which the virus uses to enter and infect the human cells — that have been recently reported to confer antibody resistance.
Current vaccines are directed against the spike protein of SARS-COV-2 virus.
“These mutations can have major implications in vaccine response as they could alter the immunogenicity,” the authors said.
Immunogenicity is the ability of a vaccine to provoke an immune response in the body.
“The study reveals important insights about residues favourable or not favourable for the survival of this virus and thus might help to engineer the next generation therapeutics which targets these mutation prone proteins,” Ray added



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Study finds more reliable rapid tests for Covid-19

June 16, 2021 by admin Leave a Comment

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WASHINGTON: During a recent study, researchers at the University of Maryland School of Medicine (UMSOM) developed two rapid diagnostic tests for Covid-19 that are nearly as accurate as the gold-standard test currently used in laboratories.
Unlike the gold standard test, which extracts RNA and uses it to amplify the DNA of the virus, these new tests can detect the presence of the virus in as little as five minutes using different methods. The findings were published in the journal Nature Protocols.
One test is a Covid-19 molecular diagnostic test, called Antisense, which uses electrochemical sensing to detect the presence of the virus. The other uses a simple assay of gold nanoparticles to detect a color change when the virus is present. Both tests were developed by Dipanjan Pan, PhD, Professor of Diagnostic Radiology and Nuclear Medicine and Pediatrics at UMSOM, and his research team. Dr. Pan has a joint appointment at the University of Maryland Baltimore County (UMBC).
“These tests detect the presence of the virus within 5 to 10 minutes and rely on simple processes that can be performed with little lab training,” said Dr. Pan. They do not require the extraction of the virus’s RNA – which is both complicated and time-consuming.
They also are more reliable than the rapid antigen tests currently on the market, which detect the virus only in those with significantly high viral levels. “These two newer tests are extremely sensitive and can detect the presence of the virus, even in those with low levels of the virus,” Dr. Pan said.
Dr. Pan’s team included UMSOM research fellow Maha Alafeef, UMSOM research associate Parikshit Moitra, PhD, and research fellow Ketan Dighe, from UMBC.
Last month, the U.S. Food and Drug Administration (FDA) registered the laboratory of Dr. Pan as an approved laboratory development site for the Antisense test. The move paves the way for Dr. Pan’s laboratory to begin conducting the test at the university, in research settings, as it undergoes further development.
In February, RNA Disease Diagnostics, Inc. (RNADD) received an exclusive global license from UMB and UMBC to commercialize the test. Dr. Pan serves as an unpaid scientific advisor to the company.
This test detects the virus in a swab sample using an innovative technology called electrochemical sensing. It uses a unique dual-pronged molecular detection approach that integrates electrochemical sensing to rapidly detect the SARS-CoV-2 virus.
“The final prototype is like a glucometer, which patients with diabetes use at home to measure their blood glucose levels,” said Dr. Pan, “and is just as easy for people to do themselves.”
Dr. Pan and his colleagues, in collaboration with RNA Disease Diagnostics, are launching a study of NBA basketball players in New York City to compare the Antisense test to rapid Covid tests that the NBA is using to monitor Covid infections in its players.
“We would like to see whether our test can yield more reliable results compared to the existing platforms,” he said. “Current antigen-based rapid Covid tests miss infections about 20 percent of the time and also have high rates of false-positive results. Our Antisense test appears to be about 98 percent reliable, which is similar to the PCR test.”
Similar to the Antisense test, the second rapid test also does not require the use of any advanced laboratory techniques, such as those commonly used to extract RNA, for analysis. It uses a simple assay containing plasmonic gold nanoparticles to detect a color change when the virus is present. In April, Dr. Pan and his colleagues published a stepwise protocol in the journal Nature Protocols, explaining how the nano-amplified colorimetric test works and how it can be used.
Once a nasal swab or saliva sample is obtained from a patient, the nucleic acid (bits of genetic material) in the sample is amplified via a simple process that takes about 10 minutes. The test uses a highly specific molecule attached to the gold nanoparticles to detect a particular protein. This protein is part of the genetic sequence that is unique to the novel coronavirus. When the biosensor binds to the virus’s gene sequence, the gold nanoparticles respond by turning the liquid reagent from purple to blue.
“Innovations in Covid-19 testing remain incredibly important even as the epidemic appears to be waning in this country,” said E. Albert Reece, MD, PhD, MBA, Executive Vice President for Medical Affairs, UM Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor and Dean, University of Maryland School of Medicine. “As we continue to monitor infections in unvaccinated segments of our population and the potential spread of new variants, there will be a vital need for inexpensive rapid tests to ensure that we continue to maintain low infection rates.”



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Covid-19 patients at greater risk of mental disorders find Oxford University study

April 7, 2021 by admin Leave a Comment

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LONDON: Patients are at an estimated 44 per cent greater risk of neurological and mental health diagnoses after Covid-19 than after flu, and a 16 percent greater risk than with other respiratory tract infections, the largest study of its kind by the University of Oxford revealed on Wednesday.
Overall, the estimated incidence of being diagnosed with a neurological or mental health disorder following Covid-19 infection was 34 percent, and for 13 per cent of these people, it was their first recorded neurological or psychiatric diagnosis.
The most common diagnoses after Covid-19 were anxiety disorders (occurring in 17 per cent of patients), mood disorders (14 per cent), substance misuse disorders (7 percent), and insomnia (5 per cent). The incidence of neurological outcomes was lower, including 0.6 per cent for a brain haemorrhage, 2.1 per cent for ischaemic stroke, and 0.7 per cent for dementia.
“These are real-world data from a large number of patients. They confirm the high rates of psychiatric diagnoses after Covid-19 and show that serious disorders affecting the nervous system (such as stroke and dementia) occur too. While the latter is much rarer, they are significant, especially in those who had severe Covid-19,” said Professor Paul Harrison, lead author of the study, from the Department of Psychiatry at Oxford University.
“Although the individual risks for most disorders are small, the effect across the whole population may be substantial for health and social care systems due to the scale of the pandemic and that many of these conditions are chronic. As a result, health care systems need to be resourced to deal with the anticipated need, both within primary and secondary care services,” he said.
This latest study analyzed data from the electronic health records of 236,379 Covid-19 patients from the US-based TriNetX network, which includes more than 81 million people.
This group was compared with 105,579 patients diagnosed with influenza and 236,038 patients diagnosed with any respiratory tract infection (including influenza).
“Our results indicate that brain diseases and psychiatric disorders are more common after Covid-19 than after flu or other respiratory infections, even when patients are matched for other risk factors,” Dr. Max Taquet, a co-author of the study from Oxford University.
“We now need to see what happens beyond six months. The study cannot reveal the mechanisms involved, but does point to the need for urgent research to identify these, with a view to preventing or treating them,” he said.
Their peer-reviewed paper, published in ‘Lancet Psychiatry’, was funded by the National Institute for Health Research (NIHR) Oxford Health Biomedical Research Centre.

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Cancer patients less protected after first Covid vaccine jab, UK study finds

March 11, 2021 by admin Leave a Comment

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LONDON: Cancer patients may not be protected to the same degree as the rest of the population after they receive their first of two doses of a Covid-19 vaccine, a new UK study has found on Thursday.
A team of experts from King’s College London and Francis Crick Institute found in the first real-world study of its kind that a shorter than the stipulated 12-week gap between the two vaccine doses for such patients appeared to be the answer.
The study’s senior authors, Dr Sheeba Irshad and Professor Adrian Hayday, believe that there should be urgent re-evaluation of UK policy for the dosing interval for all cancer patients, and likewise for many other high-risk groups of immuno-suppressed patients.
“Our data provides the first real-world evidence of immune efficacy following one dose of the Pfizer vaccine in immunocompromised patient populations,” said Dr Sheeba Irshad, a senior clinical lecturer from the School of Cancer and Pharmaceutical Sciences at King’s College London.
“We show that following the first dose, most solid and haematological cancer patients remained immunologically unprotected up until at least five weeks following primary injection; but this poor one dose efficacy can be rescued with an early booster at day 21,” she said.
Data from the world’s first reported trial to examine the level of immune protection after the Pfizer/BioNTech vaccine in cancer patients has found that anti-SARS-CoV-2 – the virus which causes Covid-19 – antibody responses at week three following the first dose of the vaccine were only 39 per cent and 13 per cent in the solid and haematological cancers, compared to 97 per cent in those without cancer.
The preprint study, which is to be peer-reviewed, also reports that when the second dose of the vaccine was given three weeks after the first dose, the immune response improved significantly for solid cancer patients with 95 per cent of them showing detectable antibodies to the SARS-CoV-2 virus within just two weeks.
By contrast, those who did not get a vaccine boost at three weeks did not see any real improvement, with only 43 per cent of solid cancer patients and 8 per cent of blood cancer patients developing antibodies to the Pfizer vaccine at five weeks compared to 100 per cent of healthy controls.
The evidence of vaccine responses in cancer patients shows that a gap of 12 weeks between doses of the Pfizer-BioNTech vaccine could leave many cancer patients vulnerable to serious Covid-19, the study finds.
Prof. Adrian Hayday from King’s College London and the Francis Crick Institute said: “Cancer patients should be vaccinated and boosted quickly and their responses, particularly those of blood cancer patients, should be intensively monitored so that those who mix with family, friends and carers can be confident of their environment.”
Dr Simon Vincent, Director of Research, Support and Influencing at Breast Cancer Now, called on the Joint Committee on Vaccination and Immunisation (JCVI), which determines the UK’s vaccine rollout cohorts, to urgently review the evidence and to consider adapting its strategy to ensure that cancer patients can receive both the first and second dose of the Pfizer/BioNTech Covid-19 vaccine within a three-week timeframe to minimise their risk of both contracting and becoming seriously ill with coronavirus.
“Worryingly, this study suggests that people affected by cancer, including breast cancer, get little protection against the virus when they only receive a single dose of the Pfizer Covid-19 vaccine, and then do not receive their vaccine boost in the following three weeks,” he said.
But Cancer Research UK said the small study had not yet been reviewed by other scientists and people undergoing cancer treatment should continue to follow the advice of their doctors, while the government said that antibody response “was only part of the protection provided by the vaccine”.
Meanwhile, the UK study will continue to follow cancer patients after their vaccinations for up to six months.

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