RAHWAY, N.J. - Merck & Co. (NYSE: MRK) has presented new data from its Phase 3 STRIDE-10 trial of V116, an investigational vaccine aimed at preventing invasive pneumococcal disease in adults. The findings, announced at the European Society of Clinical Microbiology and Infectious Diseases meeting in Barcelona, Spain, suggest that V116 could be a significant advancement in adult pneumococcal disease prevention.
The STRIDE-10 study compared the immunogenicity, tolerability, and safety of V116 with the current PPSV23 vaccine in adults aged 50 and older who had not previously received a pneumococcal vaccine. The trial involved 1,484 participants who were randomized to receive a single dose of either V116 or PPSV23.
Results from the trial indicated that V116 triggered immune responses that were noninferior to those of PPSV23 for the 12 serotypes common to both vaccines. Moreover, V116 showed superior immune responses for the nine serotypes unique to it, not included in PPSV23. The safety profile of V116 was also comparable to that of PPSV23.
These results build upon previous Phase 3 trial data and suggest that V116 could offer broader protection against pneumococcal disease, a significant health concern, especially among older adults and those with certain health conditions. The serotypes targeted by V116 account for approximately 83% of invasive pneumococcal disease in individuals aged 65 and older, based on U.S. Centers for Disease Control and Prevention data from 2018-2021.
V116 is currently under review by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA). The FDA has granted the vaccine priority review, with a target action date of June 17, 2024.
Merck also presented research suggesting that V116 may help to reduce the health and economic burden associated with invasive pneumococcal disease and non-bacteremic pneumococcal pneumonia among adults in several European countries.
The development of V116 is part of Mercks broader commitment to pneumococcal disease prevention. The company has a history of over 40 years in vaccine development and is focused on addressing the specific needs of different populations through its vaccine program.
The information in this article is based on a press release statement from Merck & Co., Inc.
As Merck & Co. (NYSE: MRK) continues to make strides in the healthcare sector with its latest vaccine developments, its financial health remains a key consideration for investors. The company's commitment to innovation is reflected in its robust performance metrics. The following insights from InvestingPro could help investors understand Merck's financial landscape as it progresses with its vaccine program:
InvestingPro Data: Merck's market capitalization stands strong at $332.33 billion, underlining its significant presence in the pharmaceutical industry. The company's P/E ratio, as of the last twelve months leading up to Q1 2024, is adjusted to 88.04, which indicates a high earnings multiple that investors are willing to pay for a share of its earnings. Despite a PEG ratio of -1.75 suggesting potential concerns over future earnings growth relative to its P/E ratio, Merck has demonstrated a solid revenue growth of 6.11% over the last twelve months, with a quarterly increase of 8.89% in Q1 2024, showcasing its ability to expand its financial top line.
Two notable InvestingPro Tips for Merck include the company's consistent history of raising its dividend, with payments maintained for 54 consecutive years, signaling a reliable return to shareholders. Additionally, analysts have revised their earnings upwards for the upcoming period, reflecting optimism in the company's financial prospects. For investors seeking more in-depth analysis, there are 16 additional InvestingPro Tips available at https://www.investing.com/pro/MRK, providing a comprehensive outlook on Merck's financial health and stock performance.
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This article was generated with the support of AI and reviewed by an editor. For more information see our T&C.
The scientist who led the efforts to develop Chinas first anti-Covid vaccine has now been expelled from the parliament and is facingseriouscharges, reported Hong-based media outlet South China Morning Post.
Yang Xiaoming is a veteran researcher and former chairman of China National Biotec Group, a vaccine subsidiary of state-owned Sinopharm. It was only under his leadership that China developed Sinopharms BBIBP-CorV vaccine, Chinas first coronavirus shot.
Chinas National Peoples Congress (NPC) on Friday (Apr 26) said in a statement that hewas removedfor alleged serious violations of discipline and law.
An investigation has alreadybeen launchedagainst the 62-year-old scientist by the party disciplinary body, SCMP reported.
Sinopharms BBIBP-CorV vaccine was one of the most used vaccines in the country andwas exportedto at least 112 nations.Lateron, it causedhugeembarrassment for the Chinese government asquestions were raisedoverthe vaccines efficacy.
The action against Yang Xiaoming comes amidst an ongoing crackdown against corruption in Chinas health sector by President Xi Jinping.
WATCH: Tornado in China: Five killed & 140 factory buildings damaged in tornado
The crackdownisspecificallytargetinghospitals, drug companies and insurance funds, which also resulted in the arrest of several hospital chiefs last year.
The campaign is an extension of Xis 2012 anti-corruption drive.
Yang Xiaoming is a big name in Chinas vaccine development industry.In past, he served as a chief engineer andchiefscientist at Sinopharm.
He is also serving as the chief scientist of the vaccine project under Chinas national 863 programme.
The COVID-19 vaccine developed under his leadership was approved for use in December 2020, which also got the nod from the World Health Organization (WHO) for international use.
In a 2021 interview, Xiaoming had described his vaccine as a miracle, developed in a record time of just 330 days.
Earlier, he was rewarded forhis role infighting the pandemic and was given a national award in September 2020.
(With inputs from agencies)
Geopolitical writer at WION, follows Indian foreign policy and world politics, a truth seeker.
In a milestone study led by the Peter Doherty Institute of Infection and Immunity (Doherty Institute), researchers have identified fragments from influenza B viruses that the immune system consistently recognize, offering promising targets for a universal influenza B vaccine.
Often underestimated, influenza B viruses can cause significant illness and mortality, especially in children. Despite the burden of influenza B viruses globally, they remain understudied and little is known about how the immune system interacts with these viruses.
A team of scientists, led by University of MelbourneProfessor Katherine Kedzierska, Head of the Human T cell Laboratory at the Doherty Institute, set out to change this by delving into the intricacies of the immune response toinfluenza B viruses, revealing a wealth of insights previously overlooked.
Published inNature Communications,the study focused on killer T cells, also known as CD8+T cells, whichplay a crucial role in the antiviral immune response, and discovered how they targetinfluenza B virusesto combat infection.
University of MelbourneTejas Menon, Graduate Researcher at the Doherty Institute and co-first author of the paper, described the challenge of identifying the specific parts of the influenza B viruses that killer T cells bind to as like searching for a needle in a haystack.
To tackle a virus, killer T cells need to be able to recognize the virus and find the best viral parts to target, explained Mr Menon.
As new variants of a virus emerge, killer T cells can recognize fragments that are unchanged among those influenza variants. This makes killer T cells an attractive immune population to stimulate with vaccines.
In the context of influenza B viruses, we were excited to discover nine viral fragments which provoked a strong immune response from killer T cells and remained unchanged in the virus' history. This finding, reached after sieving through hundreds of influenza B virus particles, which was done in collaboration Professor Purcell and Dr Illing from Monash University, is a significant advancement in our understanding of influenza B immunity.
Until now, only 18 such viral fragments had been identified, limiting the ability to generate new vaccines against influenza B viruses that prevent severe illness and death. This comprehensive study brings the total to 27, offering more options for vaccine development.
Researchers also explored how this immune response changes with age, providing valuable information for tailoring health strategies for different age groups.
University of MelbourneDr Carolien van de Sandt, a Senior Research Fellow at the Doherty Institute and co-author of the study, said that this research gives valuable insights into age-related immune responses to influenza B viruses.
As we age, our immune system responds differently to the flu, said Dr van de Sandt.
While we detected killer T cells that recognize influenza B viral fragments across the human lifespan, from young children to the elderly, those T cell responses substantially peaked in adults. This may help explain why this particular age group is protected from severe influenza B infections.
Our findings also showed that killer T cells that recognize influenza B viruses have a very good memory, but are not as numerous in elderly people and children. This is fascinating, as children have a higher burden from influenza B than adults and the elderly.
Professor Kedzierska explained that the clinical implications of the study are substantial, and the research presents the first step toward the development of new T cell-based influenza B vaccines.
The influenza B viral T cell targets that we have found could be included in new T cell-based vaccines, which could significantly reduce severe cases and death caused by influenza B, especially in children, and alleviate the burden of seasonal influenza epidemics.
Katherine Kedzierska,Professor, University of Melbourne
Current influenza vaccines primarily rely on antibodies that target specific strains, necessitating frequent updates due to mutations in the virus. However, the study suggests exploring T cell-based vaccine strategies, highlighting their potential to provide broad immune protection across all variants of influenza B viruses for various age groups.
Cotonou/Freetown/Monrovia In a significant step forward for malaria prevention in Africa, three countriesBenin, Liberia and Sierra Leonetoday launched a large-scale rollout of the life-saving malaria vaccine targeting millions of children across the three West African nations. The vaccine rollout, announced on World Malaria Day, seeks to further scale up vaccine deployment in the African region.
Todays launch brings to eight the number of countries on the continent to offer the malaria vaccine as part of the childhood immunization programmes, extending access to more comprehensive malaria prevention. Several of the more than 30 countries in the African region that have expressed interest in the vaccine are scheduled to roll it out in the next year through support from Gavi, the Vaccine Alliance, as efforts continue to widen its deployment in the region in coordination with other prevention measures such as long-lasting insecticidal nets and seasonal malaria chemoprevention.
Benin, which received 215 900 doses, has added the malaria vaccine to its Expanded Programme on Immunization. The malaria vaccine should be provided in a schedule of 4 doses in children from around 5 months of age.
The introduction of the malaria vaccine in the Expanded Programme on Immunization for our children is a major step forward in the fight against this scourge. I would like to reassure that the malaria vaccines are safe and effective and contribute to the protection of our children against this serious and fatal diseases, said Prof Benjamin Hounkpatin, Minister of Health of Benin.
In Liberia, the vaccine was launched in the southern Rivercess County and will be rolled out afterwards in five other counties which have high malaria burden. At least 45 000 children are expected to benefit from the 112 000 doses of the available vaccine.
"For far too long, malaria has stolen the laughter and dreams of our children. But today, with this vaccine and the unwavering commitment of our communities, healthcare workers and our partners, including GAVI, UNICEF and WHO, we break the chain. We have a powerful tool that will protect them from this devastating illness and related deaths, ensuring their right to health and a brighter future. Let's end malaria in Liberia and pave the way for a healthier, more just society," said Dr Louise Kpoto, Liberias Minister of Health.
Two safe and effective vaccines RTS,S and R21 recommended by World Health Organization (WHO), are a breakthrough for child health and malaria control. A pilot malaria vaccine programme in Ghana, Kenya and Malawi reached over 2 million children from 2019 to 2023, showing a significant reduction in malaria illness and a 13% drop in overall child mortality and substantial reductions in hospitalizations.
In Sierra Leone, the first doses were administered to children at a health centre in Western Area Rural where the authorities kicked off the rollout of 550000 vaccine doses. The vaccine will then be delivered in health facilities nationwide.
With the new, safe and efficacious malaria vaccine, we now have an additional tool to fight this disease. In combination with insecticide-treated nets, effective diagnosis and treatment, and indoor spraying, no child should die from malaria infection, said Dr Austin Demby, Minister of Health of Sierra Leone.
Malaria remains a huge health challenge in the African region, which is home to 11 countries that carry approximately 70% of the global burden of malaria. The region accounted for 94% of global malaria cases and 95% of all malaria deaths in 2022, according to the World Malaria Report 2023.
The African region is advancing in the rollout of the malaria vaccine a game-changer in our fight against this deadly disease, said Dr Matshidiso Moeti, WHO Regional Director for Africa. Working with our member states and partners, were supporting the ongoing efforts to save the lives of young children and lower the malaria burden in the region.
Aurelia Nguyen, Chief Programme Officer at Gavi, the Vaccine Alliance, noted: Today we celebrate more children gaining access to a new lifesaving tool to fight one of Africas deadliest diseases. This introduction of malaria vaccines into routine programmes in Benin, Liberia, and Sierra Leone alongside other proven interventions will help save lives and offer relief to families, communities and hard-pressed health systems.
Progress against malaria has stalled in these high-burden African countries since 2017 due to factors including climate change, humanitarian crises, low access to and insufficient quality of health services, gender-related barriers, biological threats such as insecticide and drug resistance and global economic crises. Fragile health systems and critical gaps in data and surveillance have compounded the challenge.
To put malaria progress back on track, WHO recommends robust commitment to malaria responses at all levels, particularly in high-burden countries; greater domestic and international funding; science and data-driven malaria responses; urgent action on the health impacts of climate change; harnessing research and innovation; as well as strong partnerships for coordinated responses. WHO is also calling attention to addressing delays in malaria programme implementation.
BATON ROUGE - A group fighting against anti-vaccination legislation protested at the Capitol on Monday.
The nonprofit group Louisiana Families for Vaccines is hoping six of the 13 proposed bills will not become law. Group leaders said some of the bills would prohibit the requirement of vaccines in schools, ban COVID-19 vaccine requirements and require blood donors to disclose their vaccination status. Protest organizers said these bills are spreading mistruths.
"Ultimately, disinformation is deadly and it deserves no hospitality of the legislature floor," vaccine advocate Crystal Rommen said. "A lot of the legislation that we're seeing come through the House and the Senate are trying to limit access to vaccines. We see things that are based in misinformation."
One bill, HB 866, will allow for individuals to submit vaccine exemptions to allow them access into any public facility regardless of their vaccination status.
"Louisiana has one of the broadest vaccination exemption policies in the nations. We have non-medical exemptions including religious and philosophical. Of course, we also have medical exemptions for people who truly can't be vaccinated," Rommen said.
Pediatrician Mikki Bouquet says the legislature should be recommending vaccines to promote a healthier state.
"We need strong public policies that are evidence-based that state vaccines are safe, effective and healthy," Bouquet said.
HB 288, which would require autopsy reports for infants include immunization records, failed to pass.
The following bills are still making their way through the legislature:
- Allow unvaccinated students to remain in class with immunocompromised students during an outbreak (HB 908) - Require teenagers to have parental consent for immunizations (HB 711) - Prohibit businesses, schools and government entities from requiring COVID-19 vaccines or masks (HB 87) - Prohibit schools from requiring COVID-19 vaccines (HB 46) - Require blood donors to disclose vaccination status (HB 822) - Prohibit Louisiana from using CDC Public Health recommendations (HB 809)
In a large study, remdesivir (RDV) use was associated with a reduction of mortality in seniors 65 years of age and older who were hospitalized with severe COVID-19 during the period when the Omicron variant was the dominant strain of the virus. The results were shared as late-breaking research at the ongoing ESCMID Global Congress.
Unadjusted mortality rates were 9.9% vs. 13.0% at 14-days and 13.3% vs. 16.9% at 28-days for RDV vs. non-RDV, respectively, the investigators wrote. RDV was associated with a significantly lower 14-day mortality (adjusted hazard ratio [95% CI]: 0.74[0.70-0.79]) and 28-day mortality (0.77[0.73-0.81]) as compared to non-RDV in the overall study cohort.
Jason Okulicz, MD, executive director, Global Medical Affairs, COVID-19 and Emerging Viruses, reiterates the severity and toll of COVID-19 within this patient population.
The elderly populations are a very important population to [consider] for treatment, Okulicz said. In the US in 2023, almost two thirds of patients hospitalized for COVID-19 were over the age 65. And among those who were hospitalized, nearly 90% of deaths that occurred in the hospital due to COVID-19 were in this population.
Study Parameters and Methods Using the PINC AI Healthcare database, the investigators examined patients 65 years of age and older who were hospitalized with a primary diagnosis of COVID-19 between Dec 2021 to April 2023. Their analysis was broken into 3 different groups including: no supplemental oxygen charges (NSOc); low-flow oxygen (LFO); and high-flow oxygen/non-invasive ventilation (HFO/NIV) or invasive mechanical ventilation (IMV)/ECMO, as well as by age groups.
Patients were either in a cohort that included administration of remdesivir in the first 2 days of admission or those not initiating the treatment during their hospitalization, and were matched using 1:1 preferential within-hospital propensity matching (PS) with replacement. They examined the time to 14- and 28-day in-hospital mortality. Okulicz said that over 45,000 patients were given remdesivir to over 20,000, patients who were not given remdesivir.
Oxygen Requirements vs Nonrequirements One of the important findings was that there was a consistent result across baseline supplemental oxygen requirements and different age groups.
"Even among the elderly, with different types of oxygen requirements or nonrequirements, they were shown to have reduced mortality with the use of remdesivir, Okulicz said.
Reference Mozaffari E, et al. Remdesivir reduces mortality in elderly patients 65+ years hospitalised for COVID-19 during Omicron.Late-breaking abstract. Presented at ESCMID. April 27-30, 2024. Barcelona, Spain.
For the 15th consecutive week, reported coronavirus cases decreased statewide.
And in the 10 communities covered by The Sun Chronicle in the week ending April 20, reported cases decreased by 5, from 17 to 12. Thats a decrease of 29.41%.
The 10 communities covered by The Sun Chronicle are Attleboro, North Attleboro, Plainville, Norton, Mansfield, Foxboro, Wrentham, Norfolk, Rehoboth and Seekonk.
Statewide, the number of reported cases fell to 488 reported cases from 575 a decrease of 87 cases. Thats a drop of 15.13%.
Its the seventh consecutive week the number of reported cases statewide has been under 1,000.
Overall, reported cases have dropped 12 consecutive weeks statewide from 4,999 to 488 cases, which is a decrease of 90.23%.
In Plainville, Rehoboth and Wrentham, there were zero cases.
There were 328 coronavirus tests administered by health professionals in the 10 communities covered by The Sun Chronicle, with 12 positives, which is a percentage of 3.65%, or 0.93 points lower than last week.
Thats a decrease of 43 tests, which equals 11.59%.
The number of COVID-19 cases in the area and state is not accurate and the figure is likely higher because of the prevalence of home-testing kits. Not all positive cases found through home-testing are reported to health officials. Also, many people who become ill, do not bother testing as the virus has weakened and the symptoms caused by the virus are less severe.
For context, the highest number of reported new cases statewide for one week was recorded on Jan. 14, 2022, at 132,557.
The highest number locally for one week was 3,463 recorded on Jan. 13, 2022.
All told, since the beginning of the pandemic in March 2020, the area has recorded 50,787 cases. Thats 25.29% of the 200,793 population in the 10 communities covered by The Sun Chronicle.
Percentages of the disease in each community range from 22% to 29% (rounded up) and the average is 24.68%
In the week ending April 20, the case counts in each of the 10 communities was:
Statewide, the number was 488 confirmed cases with 157 probable cases for a total statewide of 2,151,607 confirmed and probable cases since the beginning of the pandemic in March 2020.
The number of confirmed deaths statewide was 6, and the number of probable deaths was 1.
The number of confirmed deaths statewide since the beginning of the pandemic in March 2020 is 23,449 and the number of confirmed and probable deaths is 29,957.
A poll for the 10 communities covered by The Sun Chronicle was taken and the total number of deaths was 520. Thats a death rate of 1.02%.
Death totals per community covered by The Sun Chronicle are:
Most of the deaths were suffered by the elderly.
According to the states Department of Public Health, most deaths occur in people at or over the age of 65.
According to the Centers for Disease Control and Prevention, the rate of positive tests for coronavirus nationwide was 3.0% as of April 20.
In the Attleboro area, its 3.65% as of April 20.
Emergency room visits nationwide were down 17.9% as of April 20. Hospital admissions for coronavirus are down 14.4% nationwide as of April 20. And deaths nationwide were down 10% as of April 20.
The percentage rate for all deaths nationwide is 1.1%.
In the 10 communities covered by The Sun Chronicle, its 1.02%
George W. Rhodes can be reached at 508-236-0432.
A major bivalent COVID-19 vaccine induces production of neutralizing antibodies against the coronavirus that circulated at the start of the pandemic as well as subvariants of omicron, albeit less abundantly, according to a Brazilian studyreportedin theJournal of Medical Virology.
The study confirmed the vaccine's effectiveness and its importance to control of the disease, while also showing that, more than three years after the first application of a COVID-19 vaccine in Brazil, the vaccination model should be similar to that adopted for influenza, with frequent adjustments to the formulation to prioritize more recent variants.
This was the first research project conducted to evaluate the immunity induced by the Pfizer-BioNTech bivalent vaccine (COMIRNATY Original/Omicron BA.4-5) in a group of Brazilian subjects. The scientists investigated the antibody neutralization response against different variants of SARS-CoV-2 using serum samples from 93 healthy volunteers (31 males and 62 females) aged between 16 and 84 years and living in Barreiras, Bahia state. Some of the volunteers had previously been given three or four doses of monovalent vaccines based only on the original strain of the virus first identified in Wuhan, China, such as Coronavac (Butantan Institute/Sinovac), Covishield (Oxford/AstraZeneca), or those of Janssen and Pfizer.
Others were also given as an extra booster the bivalent vaccine containing components of the original strain as well as omicron subvariants BA.4 and BA.5.
Serum samples collected from the volunteers were submitted to antibody neutralization assays using different strains of SARS-CoV-2: the original strain from the start of the pandemic; omicron (BA.1), predominant in 2021; and omicron subvariants FE.1.2 and BQ.1.1, predominant in Brazil more recently.
The study was funded by FAPESP (projects20/052047,20/064091,20/089435,21/056611,22/119811 and23/019250), and by the Brazilian Ministry of Science, Technology and Innovation (MCTI).
The study showed that the bivalent vaccine administered as a booster reinforced the immune response and was more effective in neutralizing omicron and its subvariants than in volunteers given only four shots of a monovalent vaccine. However, its main focus was still the original strain that predominated at the start of the pandemic, and the resulting competition limited medium- to long-term immunity against more recent variants, which are now more important epidemiologically.
This was expected because immune memory is based on cells capable of recognizing fractions of the virus and is reinforced by the number of contacts with the contaminant. The immune system will naturally react more against what it already knows, and the participants given the bivalent vaccine had already taken three or four doses of a monovalent vaccine."
Jaime Henrique Amorim, last author of the article
Amorim is a professor at the Federal University of Western Bahia (UFOB) and a visiting researcher at the University of So Paulo's Biomedical Sciences Institute (ICB-USP).
"Controlling a virus with the high transmission capacity of SARS-CoV-2 requires equally high vaccine coverage," saidLus Carlos de Souza Ferreira,head of ICB-USP's Vaccine Development Laboratory and a co-author of the article. "The results of the study show that bivalent vaccines are effective to achieve immunity against subvariants of omicron and that their administration has been fundamental to control novel variants."
According to the researchers, another conclusion to be drawn from the findings is that future planning of vaccination policy should take into account the fact that the immune response induced by existing vaccines is mainly to the original strain, which has ceased circulating since 2020, and vaccines should have their formulation adjusted so that they no longer include these components.
"Forthcoming doses should be designed to combat the variants that are circulating now, instead of those that have disappeared, so that immunity is updated and reinforced in accordance with the current epidemiological situation, as it already is in the case of influenza vaccines," Amorim said.
The joint first authors of the article are Milena Silva Souza and Jssica Pires Farias, researchers at UFOB. The other co-authors are affiliated with institutions in Brazil and the United States.
Source:
Journal reference:
Souza, M. S., et al. (2024). Neutralizing antibody response after immunization with a COVID19 bivalent vaccine: Insights to the future.Journal of Medical Virology. doi.org/10.1002/jmv.29416.
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Despite huge advances in our understanding of COVID-19 over the past four years, the disease is still very much among usand there remains a lot to learn.
One thing we do know: Following infection, it's critical that our cells make new proteins to defend against the virus.
But Talya Yerlici, a post-doctoral researcher at the University of Toronto's Temerty Faculty of Medicine, recently showed how SARS-CoV-2 disrupts the manufacture of proteins.
She is the first author of a paper detailing the process that was published recently in the journal Cell Reports.
Writer Jenni Bozec recently spoke with Yerliciwho is based in the lab of Professor Karim Mekhail in the department of laboratory medicine and pathobiologyabout the findings.
One way SARS-CoV-2 makes us sick is by using a strategy called "host shutoff." This means that while the virus makes copies of itself, it also slows the production of vital components within our cells. As a result, our bodies take longer to respond to the infection.
When SARS-CoV-2 enters our cells, it disrupts the process of making proteins, which are essential for our cells to work correctly. A particular SARS-CoV-2 protein called Nsp1 has a crucial role in this process. It stops ribosomes, the machinery that makes proteins, from doing their job effectively. The virus is like a clever saboteur inside our cells, making sure its own needs are met while disrupting our cells' ability to defend themselves.
We found that Nsp1 is good at blocking ribosomes from making new proteins, but also interferes with the production of new ribosomes. In effect, it shuts down the machinery output and the ability to make the machinery itselfa serious double hit.
It does this by blocking the maturation or processing of specialized RNA molecules needed to build ribosomes. This adds a new layer of complexity to our understanding of SARS-CoV-2's interference with the host cell.
Building on our published research, it will be crucial to understand how Nsp1 works to stop different types of human cells, tissues and organs from making proteins when infected with different variants of SARS-CoV-2 and related coronaviruses.
Scientists have been working to find precision medicines that can counteract Nsp1 and help fight against the continually evolving SARS-CoV-2 virus. These drugs aim to help infected cells keep producing proteins and build a robust immune response when dealing with infection. Ongoing research on such drugs should now benefit from testing whether they can block Nsp1 from interfering with both the production and function of ribosomes, and this should help find more effective precision medicines.
This project started because of circumstances during the COVID lockdown. We wanted to help in the fight against the pandemic. However, since I couldn't physically work in the lab, we took the opportunity to analyze next-generation sequencing datasets computationally from home.
Looking at published RNA-sequencing datasets, we realized that cells infected with SARS-CoV-2, compared to uninfected cells, may have difficulty processing the RNA molecules needed to build ribosomes. Through this analysis, together with Dr. Mekhail, we developed hypotheses and designed the project.
I had the privilege of collaborating closely with the talented members of the Mekhail lab, including Alexander Palazzo's group from the department of biochemistry at Temerty Medicine and Brian Raught and Razqallah Hakem's labs at the Princess Margaret Cancer Center (University Health Network).
This work wouldn't have been possible without the collective efforts of our team and collaborators, and I'm grateful for their contributions. My responsibilities included conducting numerous hands-on experiments and bioinformatics analyses, analyzing the results and preparing the paper for peer review and publication.
The most challenging part was conducting research during a global pandemic, which presented many logistical hurdlesfrom disrupted lab routines to limitations on collecting and using samples infected with SARS-CoV-2.
On the other hand, the opportunity to contribute to our understanding of SARS-CoV-2 viral mechanisms and shed light on potential therapeutic targets was incredibly fulfilling. Seeing our research culminate in a published paper and knowing it could inform future strategies for combating coronaviruses is deeply gratifying.
As an independent investigator in my future lab, I want to study how the complex processes of making ribosomes affect the body's natural defense against viruses. It's an area I find compelling and presents ample opportunities for further exploration.
One approach I'm particularly interested in is integrating RNA-sequencing with genetic CRISPR and small-molecule chemical screens, targeting distinct stages of ribosome biogenesis across diverse infection or infection-mimicking conditions.
Such integrated approaches hold promise for uncovering novel mechanisms underlying the regulation of antiviral responses and should help us find innovative and impactful ways to fight viral infections.
More information: V. Talya Yerlici et al, SARS-CoV-2 targets ribosomal RNA biogenesis, Cell Reports (2024). DOI: 10.1016/j.celrep.2024.113891
Journal information: Cell Reports
In a recent study published in the journal BMJ Global Health, researchers compare coronavirus disease 2019 (COVID-19) management guidelines to those published by the World Health Organization (WHO) among different member states.
Study:Comparison of WHO versus national COVID-19 therapeutic guidelines across the world: not exactly a perfect match. Image Credit: Cryptographer / Shutterstock.com
Since the beginning of the COVID-19 pandemic, the therapeutic landscape has changed dramatically, with increasing vaccine coverage, more frequent infections, and viral evolution reducing pathogenicity.
However, the poorest nations have often suffered the worst societal and economic consequences of the pandemic. Variations in treatment recommendations between nations have not been publicly measured or thoroughly investigated, with uneven administration of effective vaccines and medications.
In the present study, researchers performed a retrospective analysis of each nation's guidelines (NGs) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection therapy using the Reporting Checklist for Public Versions of Guidelines (RIGHT-PVG) survey checklist and a developed comparison metric based on WHO standards.
Between September and November 2022, data for guidelines compiled by the Ministries of Health, National Infectious Disease websites, COVID-19 Clinical Research Coalition, and key opinion researchers and leaders were analyzed. The most recent national guidelines for SARS-CoV-2 infection therapy were stratified by severity while eliminating local or regional hospital guidelines, vaccination policies, infection control measures, and those without pharmacological recommendations. Any information about COVID-19 complications, such as bacterial pneumonia and thrombosis, was eliminated from the guidelines.
Eight physicians and one clinical nurse extracted information, including publication dates, language, body, illness severity rating, prescribed medications, regulatory status, and regulatory data collected by national-level authorities. Antibiotic suggestions were omitted unless intended for SARS-CoV-2 infection.
Countries were categorized into five areas based on WHO classification, which included the European Region (EUR), the African Region (AFR), the Southeast Asian Region (SEAR), the Region of the Americas (AMR), the Western Pacific, and Eastern Mediterranean Region (EMR). Data on treatment recommendations from the relevant health authorities in each nation were obtained and analyzed.
The alignment between national recommendations and the WHO's 11th iteration of recommendations was determined. To this end, positive numeric weights were assigned to suggestions that adhered to WHO criteria, whereas negative weights were assigned to those that discouraged or included non-evidence-based advice. The final score reflected the country's adherence to WHO recommendations.
Therapeutic suggestions and illness severity categories were evaluated using the World Bank's gross domestic product (GDP) per capita, Human Development Index, and Global Health Security Index.
COVID-19 treatment guidelines were obtained from 109 WHO member countries and exhibited significant variability in recommendations and illness severity categories. Therapeutic advice in some NGs deviated significantly from WHO recommendations. In late 2022, 93% of national guidelines recommended one or more medications that failed randomized trials and were unauthorized by the WHO.
Despiterobustevidence of treatment benefits, approximately 10% of NGs did not recommend corticosteroids for severe sickness. Stratifying by yearly GDP, Human Development Index (HDI), and Global Health Security Index (GHS), NGs from low-resource countries showed the highest gap.
The median population of nations with acquired recommendations was 14 million, with 70% of guidelines implemented in EUR, followed by the AFR at 53%. Moreover, 65% of guidelines were released six months before the WHO protocols, with 31% issued or revised over the same period.
About 84% of recommendations did not describe COVID-19 severity according to WHO definitions, with only 9.2% of guidelines incorporating severity criteria equivalent to those used by the WHO. The range of therapies included in the recommendations ranged from one to 22, with the median being five, regardless of severity. Comparatively, WHO guidelines prescribe ten medicines.
In late 2022, several NGs continued to advocate medications that the WHO had previously cautioned against, with some regional variance. Taken together, 105 NGs recommended at least one WHO-approved therapy, with 71% of medications appropriate for the severity of SARS-CoV-2 infection.
Corticosteroids were the most widely recommended medicine, with 92% of NGs using these therapeutics and 80% indicating their use for the same illness severity as the WHO. Moreover, 23% and 79% of the 72 NGs recommended remdesivir and tocilizumab for mild COVID-19, respectively.
Based on the study findings, COVID-19 has resulted in considerable variance in NG recommendations, with many advocating inefficient, costly, and inaccessible remedies, particularly in low-resource areas.
The study findings emphasize the importance of formalizing procedures for generating NGs for infectious diseases to ensure their development based on the best available data. Recommendations provided by NGs varied greatly, some of which did not have any national guidelines, omitted WHO-recommended medicines, proposed untested medications, or used different SARS-CoV-2 infection severity classifications.
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