Category: COVID

Categories : COVIDTags :

Scientist Identify the Gene Responsible for Doubling Severe COVID Risk

On By ModernMedia
Image source: Pixabay

Scientists at Oxford University have identified the gene responsible for doubling the risk of respiratory failure from COVID. Some 60% of people of South Asian descent carry the high-risk genetic signal, partly explaining the impact of COVID in the Indian subcontinent and the excess deaths seen in some UK communities.

Prior research already identified a stretch of DNA on chromosome 3 which doubled the COVID mortality risk of adults under 65. However, scientists did not know how this genetic signal worked to increase the risk, nor the exact genetic change that was responsible.

In a study published in Nature Genetics, an Oxford University team used cutting edge technology to work out which gene was causing the effect, and how it was doing so.

Study co-lead Jim Hughes, Professor of Gene Regulation, said: “The reason this has proved so difficult to work out, is that the previously identified genetic signal affects the ‘dark matter’ of the genome. We found that the increased risk is not because of a difference in gene coding for a protein, but because of a difference in the DNA that makes a switch to turn a gene on. It’s much harder to detect the gene which is affected by this kind of indirect switch effect.”

The team trained an artificial intelligence algorithm to analyse huge quantities of genetic data from hundreds of types of cells from all parts of the body, to show that the genetic signal is likely to affect cells in the lung. Then the researchers used a newly developed precision technique to zero in on the DNA at the genetic signal. This examines the way that the billions of DNA letters fold up to fit inside a cell to locate the specific gene that was being controlled by the sequence that increases severe COVID risk.

Dr Damien Downes, who led laboratory work, said: “Surprisingly, as several other genes were suspected, the data showed that a relatively unstudied gene called LZTFL1 causes the effect.”

The researchers found that the higher risk version of the gene probably prevents the cells lining airways and the lungs from responding to the virus properly. But importantly it doesn’t affect the immune system, so the researchers expect people carrying this version of the gene to respond normally to vaccines.

The researchers are also hopeful that drugs and other therapies could target the pathway preventing the lung lining from transforming to less specialised cells, raising the possibility of new treatments customised for those most likely to develop severe symptoms.

Study co-lead Professor James Davies, Associate Professor of Genomics at Oxford University, said: “The genetic factor we have found explains why some people get very seriously ill after coronavirus infection. It shows that the way in which the lung responds to the infection is critical. This is important because most treatments have focussed on changing the way in which the immune system reacts to the virus.”

About 60% of people with South Asian ancestry carried this higher-risk version of the gene compared to 15% of those with European ancestry – explaining in part the higher death rates and hospitalisations in the former group. The study also found that 2% of people with Afro-Caribbean ancestry carried the higher risk genotype, meaning that this genetic factor does not completely explain the higher death rates reported for black and minority ethnic communities.

Prof Davies explained: “The higher risk DNA code is found more commonly in some black and minority ethnic communities but not in others. Socioeconomic factors are also likely to be important in explaining why some communities have been particularly badly affected by the COVID pandemic.

“Although we cannot change our genetics, our results show that the people with the higher risk gene are likely to particularly benefit from vaccination. Since the genetic signal affects the lung rather than the immune system, it means that the increased risk should be cancelled out by the vaccine.”

Source: Oxford University

Categories : COVID General InterestTags :

Cats and Dogs Develop Myocarditis from COVID

On By ModernMedia
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A new study reveals that pets can be infected with the Alpha variant of SARS-CoV-2. Due to its increased transmissibility and infectivity, this variant rapidly outcompeted pre-existing variants in England, before being replaced by the Delta variant.

The study, which was published in Veterinary Record, describes the first identification of the SARS-CoV-2 Alpha variant in domestic pets; two cats and one dog were positive on PCR test, while two additional cats and one dog displayed antibodies two to six weeks after they developed signs of cardiac disease. Many owners of these pets had themselves developed respiratory symptoms several weeks before their pets became ill and had also tested positive for COVID.  

These pets all had experienced an acute onset of cardiac disease, including severe myocarditis. Humans also have a slight risk for myocarditis from COVID, particularly in children, for whom the risk is 37 times higher than without having contracted COVID, according to the US Centers for Disease Control.

“Our study reports the first cases of cats and dogs affected by the COVID alpha variant and highlights, more than ever, the risk that companion animals can become infected with SARS-CoV-2,” said lead author Luca Ferasin, DVM, PhD, of The Ralph Veterinary Referral Centre, in the UK. “We also reported the atypical clinical manifestations characterised by severe heart abnormalities, which is a well-recognised complication in people affected by COVID but has never described in pets before. However, COVID infection in pets remains a relatively rare condition and, based on our observations, it seems that the transmission occurs from humans to pets, rather than vice versa.”

Source: Wiley

Categories : COVIDTags :

Pfizer’s Paxlovid Could Deliver Knockout Blow to COVID

On By ModernMedia
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Pharmaceutical giant Pfizer announced today that Paxlovid, its investigational novel COVID oral antiviral candidate, significantly reduced hospitalisation and death, based on an interim analysis of its phase II/III clinical trials showing an 89% reduction of risk of hospitalisation or death due to COVID. 

The phase II/III EPIC-HR (Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients) randomised, double-blind study of non-hospitalised adult patients with COVID, who are at high risk of progressing to severe illness. The scheduled interim analysis showed an 89% reduction in risk of COVID-related hospitalisation or all-cause mortality compared to placebo in patients treated within three days of symptom onset (primary endpoint). Only 0.8% of patients who received Paxlovid were hospitalised through Day 28 with zero deaths, compared to 7.0% of patients who received placebo and were hospitalised or died. Similar reductions in COVID-related hospitalisation or mortality were seen in patients treated within five days of symptom onset; 1.0% of patients in the intervention arm were hospitalised through Day 28 with zero deaths, compared to 6.7% of placebo arm patients. In the overall study population through Day 28, no deaths were reported in intervention arm patients as compared to 10 (1.6%) deaths in placebo arm patients.

The results show such an overwhelming effectiveness that Pfizer, in consultation with the US Food and Drug Administration (FDA), will cease further enrollment into the study and will apply for Emergency Use Authorization (EUA) as soon as possible.

If it gets the green light, Pfizer’s Paxlovid, would be the first oral antiviral of its kind, a specifically designed SARS-CoV-2-3CL protease inhibitor. PF-07321332 inhibits viral replication at the proteolysis stage, before viral RNA replication. Co-administration with a low dose of ritonavir helps slow the metabolism of PF-07321332 in order for it to remain active in the body for longer at higher concentrations. It has shown effectiveness against multiple variants, and could have broad general effectiveness against coronaviruses.

“All of us at Pfizer are incredibly proud of our scientists, who designed and developed this molecule, working with the utmost urgency to help lessen the impact of this devastating disease on patients and their communities,” said Mikael Dolsten, MD, PhD, Chief Scientific Officer and President, Worldwide Research, Development and Medical of Pfizer. “We’re thankful to all of the patients, investigators, and sites around the world who participated in this clinical trial, all with the common goal of bringing forth a breakthrough oral therapy to help combat COVID.”

The review of safety data included a larger cohort of 1881 patients in EPIC-HR, whose data were available at the time of the analysis. Adverse events were comparable between paxlovid (19%) and placebo (21%), which were mostly mild.

Pfizer kicked off the EPIC-HR study in July 2021 after positive results from Phase I clinical trials, followed in August by the Phase II/III EPIC-SR (Evaluation of Protease Inhibition for COVID-19 in Standard-Risk Patients), to evaluate efficacy and safety in patients with a confirmed diagnosis of SARS-CoV-2 infection who are at standard (low) risk. This trial includes a cohort of vaccinated at-risk patients who have an acute breakthrough COVID infection. A further trial is investigating prophylaxis among household members of patients with a COVID infection. 

Source: Pfizer

Categories : COVIDTags :

Enzymes Speed up Production of Molnupiravir for COVID

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Molnupiravir is being developed for the treatment of COVID, which has been submitted for review by the US Food and Drug Administration, but large-scale production to treat COVID is still a challenge. Now, researchers have engineered enzymes to help manufacture the pill, resulting in a much shorter synthesis with a higher yield than current methods. The details of their work are reported in ACS Central Science.

The oral antiviral molnupiravir was originally developed to treat influenza, and works by causing viruses to make errors when copying their own RNA, introducing mutations that inhibit replication. Recently, interim phase 3 clinical trial findings indicated that molnupiravir reduced the risk of hospitalisation and death from COVID for newly diagnosed, at-risk patients, and that it had equal effectiveness against different SARS-CoV-2 variants. Researchers set out to develop a shorter, higher-yielding and sustainable way to synthesise the molecule.

The team came up with a three-step synthesis of molnupiravir from ribose, a sugar molecule. They identified enzymes or chemical treatments to sequentially add the appropriate chemical groups to ribose to generate the molecule. For the second step of the synthesis, the team identified bacterial enzymes that weakly catalysed the desired reactions. Using in vitro evolution, they greatly enhanced these enzymes’ activities. The new synthetic route, which also included a phosphate recycling strategy, was 70% shorter and had a seven-fold higher overall yield than the original route.

Source: American Chemical Society

Categories : COVIDTags :

Over 28 Million More Years of Life Lost in 2020

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Over 28 million more years of life were lost than expected in 2020 in 31 upper-middle and high-income countries, according to a University of Oxford-led study published in the BMJ.

Save for a handful of exceptions, 37 countries examined including the US had more premature deaths than expected in 2020, with a higher rate in men than women.

Understanding the full impact of the COVID pandemic requires counting excess deaths, and analysing how premature those deaths are. Years of life lost (YLL) is a more detailed assessment of COVID’s impact on populations as it measures both the number of deaths and the age at which death occurs.

Researchers used this measure to estimate the changes in life expectancy and excess years of life lost from all causes in 2020. They compared the observed life expectancy and years of life lost in 2020 with historical trends in 2005-19 in 37 upper-middle and high-income countries.

Between 2005 and 2019, life expectancy at birth rose for both men and women in all the countries studied. In 2020, a drop in life expectancy was seen in both men and women in all countries save New Zealand, Taiwan, and Norway, where there was a life expectancy gain and Denmark, Iceland, and South Korea saw no change.

The biggest life expectancy drop was in Russia (−2.33 years in men and −2.14 in women), the US (−2.27 and 1.61), Bulgaria (−1.96 and −1.37), Lithuania (−1.83 and −1.21), Chile (−1.64 in men), and Spain (−1.11 in women). Years of life lost declined in most countries in both men and women between 2005 and 2019, except Canada, Greece, Scotland, Taiwan, and the US.  

In 2020, years of life lost were higher than expected in all countries except Taiwan and New Zealand, where there was a reduction in years of life lost, and Iceland, South Korea, Denmark, and Norway, where there was no evidence of a change in years of life lost. In the remaining 31 countries, more than 222 million years of life were lost in 2020, which is 28.1 million more than expected (17.3 million in men and 10.8 million in women).  

The highest excess years of life lost (per 100 000) were in Russia (7020 in men and 4760 in women), Bulgaria (7260 and 3730), Lithuania (5,430 in men and 2,640 in women), and the US (4,350 in men and 2,430 in women).

Overall, excess years of life lost in 2020 were over five times greater (2510 per 100 000) than those associated with the seasonal influenza epidemic in 2015 (458 per 100 000).

The excess years of life lost were relatively low in people under 65 years, except in Russia, Bulgaria, Lithuania, and the US where the excess years of life lost was more than 2 000 per 100 000.

Most countries in Asia, Africa, and Latin America were excluded due to insufficient data, and researchers could not account for other factors, such as socioeconomic status, regional disparities, and race or ethnicity. However, the findings are largely in line with previous studies, and the use of authoritative national mortality data, together with a validated analytical approach, suggests that the results are robust.

“Our findings of a comparable or lower than expected YLL in Taiwan, New Zealand, Denmark, Iceland, Norway, and South Korea underscore the importance of successful viral suppression and elimination policies, including targeted and population based public health policy interventions,” the researchers wrote. “As many of the effects of the pandemic might take a longer time frame to have a measurable effect on human lives, continuous and timely monitoring of excess YLL would help identify the sources of excess mortality and excess YLL in population subgroups.”

Source: University of Oxford

Categories : COVIDTags :

Hopes Dashed for Ciclesonide as COVID Treatment

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Despite high hopes, the first placebo controlled trial of inhaled steroids for COVID suggests that ciclesonide, an inhaled and nasal steroid drug commonly used for asthma and rhinitis, does not help young healthy people with COVID and respiratory symptoms improve earlier.

The study, published in the BMJ, was motivated by research showing that ciclesonide, which is safe, inexpensive and widely available, could decrease viral replication of SARS-Cov2 in mouse models of COVID. A randomised, double-blind, placebo-controlled trial of inhaled ciclesonide was designed to evaluate the resolution of symptoms in adults with COVID presenting with respiratory symptoms.

“Based on my experience treating asthma, I thought it made sense to see if it would decrease the lung inflammation in patients with COVID early in the disease, as lung disease has an important impact for patients and is a major effect of the virus,” explained Dr Nicole Ezer, the first and lead author of the study, who is a lung specialist and a researcher in the Translational Research in Respiratory Diseases Program at the RI-MUHC. “In addition, we felt it was important to study a drug for COVID that has a very good safety profile and could be used in high, middle and low-income countries safely to reduce respiratory symptoms. Access to affordable medications is very important to decrease disparities in health outcomes across the world.”

The importance of placebo control
From Sept. 15, 2020 to June 8, 2021, the study recruited 215 symptomatic adults and randomly assigned them to either inhaled and intranasal ciclesonide or inhaled and intranasal placebo for 14 days. Participants were asked to complete a survey online on the day of enrollment and on six other occasions until day 14, with a follow-up survey at day 29.

Based on the assumption that treatment would be most effective if given early in the disease process, participants were recruited within five days of a positive PCR test result for SARS-CoV-2 and symptom onset and received the treatment at home by commercial courier. No vaccinated participants were included in the trial.

No significant difference was seen between the intervention and control group. After seven days of treatment, 40% taking ciclesonide had no more fever and respiratory symptoms, vs 35% taking placebo. At day 14, these figures amounted to 66% in the ciclesonide group compared with 58% in the placebo group.

Those results are disappointing, especially since two recent open label studies had raised hopes in the scientific community that inhaled steroids could alleviate respiratory symptoms associated with COVID, and one study demonstrated efficacy of dexamethasone in admitted patients with COVID.

“The previously published studies had a major limitation: they were open label with no placebo. Other studies have shown that inhalers have a strong placebo effect,” explained the study’s senior author, Dr Emily McDonald, associate professor of medicine at McGill University. “Here’s a strong reminder that any study of a medication, in particular of inhalers, needs to be controlled with a placebo before we rush to recommend them.”

In spite of the study’s outcome, researchers still believe there is potential for the treatment of COVID with inhaled steroids.

“It’s still possible that inhaled steroids might be beneficial for older at-risk populations,” said Dr Ezer, who is also an assistant professor of medicine at McGill University. “We need more research focused on older adults and people who are high-risk, but those studies must have a placebo arm to make sure they aren’t coming to a false conclusion of benefit.”

Source: McGill University

Categories : COVIDTags :

Feeling of Invulnerability against COVID Leads to Vaccine Refusal

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An international survey has found that people who do not believe that being infected with COVID could seriously threaten their health are both less likely to believe in the importance of preventing spread of the disease and less willing to get vaccinated. 

To contain COVID, it may be critical for individuals to feel concern about taking action to prevent transmission within their community. However  such concerns and actions could be impacted by a number of both individual and cultural factors. Leonhardt and colleagues hypothesised that one factor influencing pandemic concerns could be people’s perceived invincibility to COVID. The findings were presented in PLOS ONE.

To test this idea, the researchers analysed responses from over 200 000 people across 51 countries from an ongoing online survey. The survey included a question about how serious it would be to get infected with COVID, as well as questions about willingness to get vaccinated and taking action to reduce spread in one’s community. The researchers also accounted for participants’ overall health, age, sex, and level of education.

Respondents who reported feeling more  invincibile to COVID were less willing to get vaccinated, the researchers found, and also less likely to believe in the importance of individual actions to reduce transmission.

The strength of this link varied between countries. Individuals with high perceived invincibility living in countries with a greater emphasis on individual freedoms and autonomy, such as the US, were less willing to get vaccinated and less willing to take action than individuals with high perceived invincibility living in cultures with greater emphasis on collective action.

The authors say their findings highlight the importance of considering both individual and cultural factors when addressing pandemics. They suggest that suppression efforts employ messaging underscoring the importance of collective action, especially in individualistic cultures. Meanwhile, future research could further explore the impact of cultural factors on health beliefs and behaviours.

The authors added: “While feeling invincible may be beneficial in overcoming economic hardships or during periods of war, the results of our study suggest that it threatens the likelihood that people get vaccinated against COVID, and this is especially the case in individualistic countries, such as the USA, where people tend to focus on their own health rather than the collective health of their community.”

Source: EurekaAlert!

Categories : COVIDTags :

Mask-wearing Protects Wearers Too

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People who adhered to masking outside of the home, but were more exposed to infection due to their circumstances, still had “significantly” lower COVID infection rates, according to research published in BMJ Open.

Although it has been widely asserted that face coverings serve to protect others, rather than the wearer, this large-scale study established a clear link between wearing a face covering outside the home and infection.

The Oxford-led study links individuals’ and households’ ability to follow non-pharmaceutical interventions (NPIs) often known as COVID behavioural interventions, using the largest and most representative dataset to date in the UK, including people from different ethnic and age groups.

Using the COVID Infection Study (CIS), study participants were asked to complete a short questionnaire, as well as taking regular COVID tests. Respondents were asked to share how often they worked outside the home, how easy it was to keep social distance in their workplace, whether they took public transport and whether they had direct contact with others on a day-to-day basis.

According to the study, “Wearing a face covering outside was a significant predictor of a lower chance of infection before mid-December 2020 in the UK, when a stricter second lockdown was implemented.”

There was a higher rate of infections among those who lacked autonomy to follow COVID behavioural measures and did not comply with masking.

Author Professor Melinda Mills said, “Lack  of  compliance  to  COVID behavioural measures  has  often been  positioned  as  an  attitude  or  choice. Yet there are large groups of people who, due to their household or employment circumstances, cannot follow measures to work from home, engage in physical distancing at the workplace or avoid public transportation. This, in turn, means that they have a higher exposure to becoming infected.

“The inability for some groups of people to follow behavioural interventions exacerbates existing health inequalities and we showed that face coverings are one measure that can mitigate this unequal exposure.”

The team found, “The  level  of  autonomy  to  adhere  to  behavioural interventions does not  predict  COVID infection  alone,  but  rather the risk of infection is diminished when individuals wear face  covering/masks.”

The study concluded that masking reduces the effects of unequal COVID exposure.
Professor Mills added, “Using a very large individual and household sample and COVID swab tests, we showed that the inability for certain groups such as women in large households or those working in occupations where it is hard to maintain physical distancing were protected from infection during key periods in 2020 in the UK”.

Source: Oxford University

Categories : COVIDTags :

US Health Body Admits Funding Coronavirus Enhancement Study

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SARS-CoV-2 virus. Source: Fusion Medical Animation on Unsplash

In an unexpected turn of events, the US National Institutes of Health (NIH) has acknowledged that it funded research into enhancing coronavirus infectivity, Vanity Fair reported.

The agency had last week sent a letter to the US House Committee on Energy and Commerce stating that its grant recipient, EcoHealth Alliance, enhanced a bat coronavirus to become potentially more infectious to humans. This was an “unexpected result” of the research, done in collaboration with Wuhan Institute of Virology.

The NIH letter also noted that EcoHealth Alliance violated terms of its grant conditions, which had stipulated that it was supposed to report to the agency if its work boosted viral growth by a factor of 10.

EcoHealth Alliance was supposed to submit a progress report at the end of the grant period in 2019 but it didn’t arrive at the NIH until August 2021, according to Vanity Fair. However, in a statement to Vanity Fair, EcoHealth Alliance said that it had reported the relevant information “as soon as we were made aware, in our four year report in April 2018.”

In that missing progress report (dated August 2021), lab mice infected with the enhanced virus became more ill than those infected with a wild one, reported Vanity Fair.

The Vanity Fair report also reveals a rather concerning detail contained in a leaked EcoHealth Alliance grant proposal submitted to the Defense Advanced Research Projects Agency in 2018. EcoHealth Alliance and the Wuhan Institute of virology proposed to engineer a furin cleavage site for the coronavirus to more easily enter humans cells. This matches a distinctive segment of SARS-CoV-2’s genetic code.

“If I applied for funding to paint Central Park purple and was denied, but then a year later we woke up to find Central Park painted purple, I’d be a prime suspect,” Jamie Metzl, a member of the WHO advisory committee on human genome editing, told Vanity Fair.

In its letter to US Congress, the NIH emphasised that the virus EcoHealth Alliance was studying could not have sparked the pandemic, as there was a vast genetic difference between it and SARS-CoV-2. NIH Director Francis Collins, MD, PhD, also issued a statement addressing the concerns raised by the letter, noting that such claims were “demonstrably false.”

“The scientific evidence to date indicates that the virus is likely the result of viral evolution in nature, potentially jumping directly to humans or through an unidentified intermediary animal host,” Dr Collins said in the statement.

Gilles Demaneuf, a data scientist in New Zealand, told Vanity Fair, “I cannot be sure that [COVID originated from] a research-related accident or infection from a sampling trip. But I am 100% sure there was a massive cover-up.”

In response to these criticisms of poor oversight and bad scientific judgment, the NIH has “circled its wagons”, Vanity Fair observed.

Source: Vanity Fair

Categories : Cardiovascular Disease COVIDTags :

Large Study Finds Statins Ineffective, Possibly Worsen COVID

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Though small studies have suggested that statins, which lower low-density lipoprotein (LDL), may also reduce COVID severity or mortality, findings from a large study suggest that it has no effect and may even worsen the disease.

In the effort to fight COVID, researchers have attempted to find existing medications that might have an effect on the outcome of the disease, and statins were one readily available candidate that appeared to have some effect. However, a new study published in the journal PLOS ONE suggests they may not be suitable.

“Despite the apparent beneficial effect of statins on the outcomes of various infectious diseases, our study revealed that their specific use to treat COVID is probably not merited,” said senior study author Petros Karakousis, MD, professor of medicine at the Johns Hopkins University School of Medicine. “Compared with earlier research, we looked at a larger and more widely varied inpatient population, and had better criteria for defining disease severity, thereby enabling our results to be more relevant for predicting the impact of statins on COVID outcomes in hospitalised patients.”

In the study, researchers reviewed the records of 4447 hospitalised patients, ages 18 years or older, who had been diagnosed with SARS-CoV-2 infection between March 1 and June 30, 2020. Of these, 594 (13%) were receiving statins at admission, with most statin users being men (57%) and older (ages 52–78 compared with ages 29–62) than the non-statin users. The highest percentage of statin users were black (47%), had hypertension (74%) or diabetes (53%), and were more likely to take medications for lowering blood pressure – along with statins to reduce their LDL cholesterol.

After accounting for confounding factors, statin use was found to have no significant effect on COVID mortality. However, they did find that patients hospitalised with COVID and taking statins had an 18% increased risk for having a more severe form of the disease.

“One plausible explanation for this finding is that statins increase cellular production of angiotensin-converting enzyme 2 [ACE2], the receptor on a cell’s surface through which SARS-CoV-2 gains entry,” said Prof Karakousis. “Therefore, statins may lower a cell’s resistance to infection and in turn, increase the odds that the patient will have a more severe case of COVID.”

Prof Karakousis said future studies should attempt to better define the relationship between statin use and COVID, noting that all previous ones were retrospective and had factors that could not be eliminated, such as many statin users being overweight.

The only way to definitively determine if statins have any benefit for patients with COVID is to conduct a randomised, placebo-controlled clinical trial.

Source: Johns Hopkins Medicine