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Friday, April 26, 2024
Coronavirus

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The genetically altered yellow fever vaccine was highly effective in animals. If it passes clinical trials, the new vaccine would have some advantages over other SARS-CoV-2 vaccines.

The research suggests that the newly developed vaccine would not only protect against COVID-19 but also against yellow fever.

In addition, it appears to provide protection after a single shot, whereas SARS-CoV-2 vaccines such as the one that Pfizer and BioNTech have developed require two doses 1 month apart.

“This has important logistical implications, in particular for countries with a less advanced medical system,” explains Prof. Johan Neyts, from the Rega Institute at KU Leuven in Belgium. Prof. Neyts is one of the virologists who led the research.

Prof. Neyts also believes that the vaccine may offer long lasting immunity against COVID-19.

“It could therefore be an ideal candidate for repeat vaccinations when immunity decreases in people who have received one of the first-generation vaccines,” he says.

The study, which appears in the journal Nature and as a preprint, suggests that a single shot of the vaccine protected hamsters against SARS-CoV-2, which is the virus that causes COVID-19. It also protected mice and monkeys.

The team is now preparing to conduct clinical trials of the new vaccine, which is provisionally called RegaVax, in 2021.

Established vaccine

The standard yellow fever vaccine, known as YF17D, has been in use for 80 years and has a good safety record. It delivers a live, “attenuated” (weakened) strain of the yellow fever virus.

The team at KU Leuven had previously used the same virus as the basis of candidate vaccines against the Zika, Ebola, and rabies viruses.

The scientists use the yellow fever virus as a “vector” to deliver fragments of genetic material from other viruses. The fragments provoke a targeted immune response and long-term immunity to future infections.

Vaccines that employ the yellow fever virus as a vector are already licensed for use against Japanese encephalitis and dengue viruses.

To create their SARS-CoV-2 vaccine, the virologists at KU Leuven inserted a genetic sequence from SARS-CoV-2 into the yellow fever virus.

The sequence is a blueprint for SARS-CoV-2 spike proteins, which give the virus its characteristic crown-like appearance. When host cells become infected with the weakened yellow fever virus, they make copies of the spike, which, in turn, provoke an immune response.

Hamster model of COVID-19

To test the vaccine, the researchers gave a single dose to hamsters, which are an established model of SARS-CoV-2 infection.

When they dripped a solution of SARS-CoV-2 into some of the animals’ noses 10 days later, most were immune to infection.

Around 3 weeks after vaccination, all the animals the researchers tested were immune.

None of the vaccinated hamsters developed any signs of lung infection, whereas hamsters that received the inactive control vaccine showed clear signs of lung disease.

The researchers also tested the vaccine in monkeys. They detected low blood levels of “neutralizing” antibodies, which disable the virus, 7 days after vaccination. After 14 days, however, there were high concentrations in the animals’ blood.

“This is very fast,” says Prof. Neyts. “Moreover, in the vaccinated animals, the virus was completely or nearly completely gone from their throats.”

Lifelong protection?

More than 500 million people worldwide have received the original yellow fever vaccine, which usually provides lifelong protection.

“A vaccine that works against COVID-19 and yellow fever could offer an important contribution to the WHO’s campaign to eradicate yellow fever by 2026,” says Prof. Neyts. “Especially now that we know there are mosquito species present in Asia that can transmit the yellow fever virus.”

Another important advantage of the newly developed vaccine is that it can be stored at 36–46°F (2–8°C). By contrast, Pfizer and BioNTech’s SARS-CoV-2 vaccine must be stored at -94°F (-70°C).

“That’s already challenging in the Western world, but it may be nearly impossible to vaccinate large populations in remote tropical and subtropical regions,” says Prof. Neyts.

Only clinical trials can reveal whether or not the vaccine is safe and effective in humans. However, the researchers are optimistic that it will provide rapid, strong immunity after a single dose.

In the preprint of their paper, they conclude:

“In light of the threat [that] SARS-CoV-2 will remain endemic with spikes of reinfection, as a recurring plague, vaccines with this profile may be ideally suited for population-wide immunization programs.”

They note that a limitation of the original yellow fever vaccine is its unsuitability for people over 60 years of age and anyone with reduced immunity. These two groups are particularly vulnerable to COVID-19.

However, the study authors report that their new candidate vaccine appeared to be safer, at least in mice, than the older vaccine on which they based it.

“These preliminary, though encouraging, data suggest that [the new vaccine] might also be safe in those persons most vulnerable to COVID-19,” they write.

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A recent study found an association between metformin and a significantly reduced mortality risk in women with type 2 diabetes or obesity who were hospitalized with COVID-19.

Metformin is a first-line medication for treating type 2 diabetes, and many in the United States use the branded version Glucophage.

The results of the recent investigation into metformin use, obesity, diabetes risk, and COVID-19 mortality appear in The Lancet Healthy Longevity.

In the week ending November 28, 2020, the cumulative COVID-19 hospitalization rate in the United States reached a new peak.

The reported mortality rate due to pneumonia, influenza, and COVID-19 was 12.8%, though the receipt of additional data is likely to increase this figure.

People with certain medical conditions, including obesity and type 2 diabetes, have an increased risk of severe COVID-19, and may require hospitalization, intensive care, or mechanical ventilation. The risk of death from the illness is also higher for these groups.

Visceral fat accumulating around organs may lead to insulin resistance, increasing the risk of developing type 2 diabetes. Meanwhile, visceral fat cells secrete inflammatory substances, such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and D-dimer, which may be associated with severe COVID-19.

People with type 2 diabetes also have increased levels of TNF-α, which contributes to insulin resistance. In addition, the anti-inflammatory cytokine IL-10 is present in lower levels in people with obesity and type 2 diabetes.

Anti-inflammatory effects

Metformin, a safe, effective, relatively inexpensive drug, elevates anti-inflammatory IL-10 levels while decreasing the inflammatory markers TNF-α and IL-6 in people with or without diabetes.

Due to metformin’s anti-inflammatory effects and early reports of decreased COVID-19 mortality rates in people taking the drug, researchers at the University of Minnesota Medical School, in Minneapolis, and UnitedHealth Group (UHG), in Miami, FL, decided to investigate whether metformin decreased COVID-19 death risk — and whether any reduction would be sex-specific.

They refer, in their study paper, to previous findings that metformin reduced inflammation to a greater extent in women than in men.

“While effective therapies to mitigate the harm of the SARS-CoV-2 virus are being developed, it is important that we also look to and evaluate commonly used medications with good safety profiles for their potential to combat the virus,” stated Dr. Deneen Vojta, co-senior study author and executive vice president of research and development at UHG.

The researchers conducted a retrospective analysis of claims data from January 1 through June 7, 2020, from UHG’s Clinical Discovery Claims Database. This contains enrollment records, medical claims, laboratory results, and pharmacy claims for individuals of diverse ages, races, and ethnicities who had been admitted to hospitals with COVID-19 throughout the 50 states.

People included in the study were 18 years or older, had a diagnosis of obesity or type 2 diabetes, and had at least 6 months of continuous enrollment in UHG during 2019. Each had also been admitted to a hospital for COVID-19.

In total, the study analyzed the claims data of 6,256 individuals, with 3,923 in the non-metformin group and 2,333 in the metformin group.

In the non-metformin group, the average age was 76 years, approximately 55% were female, and 95% had type 2 diabetes. In the metformin group, the average age was 73 years, approximately 48% were female, and 99% had type 2 diabetes.

In all, 20.2% of those in the non-metformin group died of COVID-19 during hospitalization, compared with 16.9% of the metformin group.

The study did not show that metformin use significantly decreased COVID-19-related mortality in the overall group of men and women. However, the subgroup analysis of data by sex demonstrated a significant association between metformin use and decreased mortality in women.

Among people with type 2 diabetes or obesity, the study found a 21–24% reduction in mortality among women who had filled a metformin prescription before hospitalization, compared with women who had not.

There are certain limitations to the study. For instance, retrospective analyses are often affected by biases and unmeasured confounders. Also, claims data do not provide information about adherence to metformin treatment, account for patients who paid cash for metformin, or differentiate among people with different classes of obesity.

Wide-reaching consequences

In the U.S., more than 42% of women have obesity, and 16.2 million women have diabetes. The use of a medication that is relatively inexpensive, is readily available, and has a good safety profile might significantly reduce COVID-19-related mortality in this at-risk population.

“Observational studies like this cannot be conclusive but contribute to growing bodies of evidence. Seeing a bigger association with protection in women over men may point toward inflammation reduction as a key way that metformin reduces risk from COVID-19.” – Principal investigator Dr. Carolyn Bramante

Dr. Bramante and Dr. Christopher Tignanelli, a co-senior author of the study, plan to conduct a multi-site, prospective, randomized pilot study with Dr. Ken Cohen, executive director of clinical research at UHG Research and Development, to understand how metformin may decrease mortality, plus the optimal duration and timing of the treatment.

This upcoming study may provide the data needed to discern the true impact of metformin on COVID-19-related mortality.

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A recent article in JAMA discusses why older adults appear to be coping better with loneliness and social isolation than younger adults during the COVID-19 pandemic.

Pandemics are stressful, and the loneliness that comes with isolation takes a toll on mental health.

Surveys from the Centers for Disease Control and Prevention (CDC) conducted between June 24 and June 30, 2020, found that 40.9% of respondents experienced at least one mental or behavioral health condition. These ranged from symptoms of anxiety, depression, and trauma to starting or increasing substance use.

While all humans need social contact, some cope better with less contact than others.

Young and old

Social deprivation, the reduction or prevention of levels of social interaction considered normal depending on culture, is particularly harmful for adolescents.

A 2020 review of studies investigating social isolation and loneliness, published between January 1, 1946, and March 29, 2020, found that these factors strongly predicted later depression in children, adolescents, and young adults.

Additionally, loneliness correlated with an increased risk of mental health problems up to 9 years later in life.

An April 2020 article from the European Paediatric Association investigated adolescent mental health during the COVID-19 pandemic. The researchers reviewed data from preliminary studies in China and found that those aged 3–18 were more clingy, distracted, irritable, and fearful of asking coronavirus-related questions. They also had trouble sleeping, poor appetites, and separation problems.

Young adults are also vulnerable to the psychological effects of social isolation. An October 2020 studyfound that in a group of 564 adults aged 22–29 years, 60.7% of whom were female, loneliness increased between January and April–May. This effect was more prevalent in females, as were increased symptoms of depression.

Social isolation can also cause physical symptoms, such as a weakened immune system, an increased risk of diabetes, and an increased risk of death.

A 2016 study found a strong link between a poor social life and an elevated risk of inflammation during adolescence.

In older adults, a lack of social interaction is linked to a greater risk of hypertension, compared with diabetes.

The CDC cite 2020 estimates that one-third of adults aged 45 or older feel lonely, and almost 1 in 4 adults 65 or older are socially isolated. This is associated, they report, with health risks, including higher rates of depression, anxiety, and suicide.

However, while older adults may be experiencing significant social isolation from loved ones, this may not necessarily translate into worsening mental health, according to a recent Viewpoint article in JAMA.

Older adults less severely affected

A group of researchers at institutions in Massachusetts, California, and Pennsylvania looked at early data from several global studies on older adults and mental health during the pandemic.

While older adults are considered a vulnerable population for severe COVID-19 and related mortality, the researchers found that these adults were less negatively affected by mental health strain than younger adults.

One report from the CDC, for example, concluded that older adults were less likely to start or increase substance use and less likely to think about suicide.

Of course, these findings do not apply to every older adult. In the same report, the CDC acknowledge that adults from marginalized groups or low-income households, and those who provided unpaid caregiving services were more likely to experience adverse health effects.

This is consistent with other evidence of higher levels of anxiety, depression, stress, and post-traumatic stress disorder in people of color, compared with white people, during the COVID-19 pandemic.

Factors affecting resiliency in older adults

Based on the evidence, the authors suggest that older adults better withstand the mental health strains of the pandemic thanks to increased resilience and a drive to stay connected with others.

They explain that some global studies have shown that resilience is linked to maintaining meaningful relationships with others and access to mental health care.

“However, despite this early resilience, older adults expressed concerns about their longer-term physical and financial well-being,” the authors caution.

Resilience might also be linked with wisdom. The analysis found that having wisdom is associated with higher levels of compassion and less loneliness.

Improving resiliency

The researchers observe that increased access to technology could improve resiliency in some older adults who do not have smartphones, for example.

“Many older adults do not have the resources required to deal with the stress of COVID-19. This may include material (e.g., lack of access to smart technology), social (e.g., few family members or friends), or cognitive or biological (e.g., inability to engage in physical exercise or participate in activities or routines) resources.”

Increasing access to technology and related education may help older adults maintain social relationships and boost their engagement with mental health services.

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For the first time, researchers have demonstrated how the gut microbiome — the community of microorganisms living in the gut — can influence the immune system in humans. Their work could lead to new treatments for immune-related conditions.

The researchers at Memorial Sloan Kettering Cancer Center in New York, NY, tracked the recovery of patients’ gut microbiota and immune system after bone marrow transplants (BMTs) following treatment for blood cancers.

Healthcare professionals use chemotherapy and radiation therapy to destroy cancerous blood cells in conditions such as leukemia and lymphoma. After completion of the treatment, which also kills healthy immune cells, specialists inject patients with stem cells from a donor’s blood or bone marrow.

These donated cells slowly restore patients’ ability to make their own blood cells.

However, patients have to take antibiotics in the first few weeks after the transplant because they are still vulnerable to infections. These upset the balance of their gut microbiota, killing “friendly bacteria” and allowing dangerous strains to thrive.

Unique opportunity

Once patients’ immune systems are strong enough, they can stop taking the antibiotics, which allows their gut microbiota to recover.

The researchers at Sloan Kettering used this unique opportunity to study how the microbiota affects the immune system.

“The scientific community had already accepted the idea that the gut microbiota was important for the health of the human immune system, but the data they used to make that assumption came from animal studies,” explains systems biologist Joao Xavier, who is co-senior author of the paper with his former postdoc Jonas Schluter.

“The parallel recoveries of the immune system and the microbiota, both of which are damaged and then restored, gives us a unique opportunity to analyze the associations between these two systems,” says Dr. Schluter, who is now an assistant professor at NYU Langone Health in New York, NY.

Using blood and fecal samples from more than 2,000 patients treated at the cancer center between 2003–2019, the researchers were able to track daily changes in their gut microbiota and the number of immune cells in their blood.

Thousands of data points

“Our study shows that we can learn a lot from stool — biological samples that literally would be flushed down the toilet,” says Dr. Xavier. “The result of collecting them is that we have a unique dataset with thousands of data points that we can use to ask questions about the dynamics of this relationship.”

The researchers used a machine-learning algorithm to identify patterns in the data, which included information about patients’ medications and the side effects they experienced.

One of the findings was that the presence of three types of gut bacteria — called Faecalibacterium, Ruminococcus 2, and Akkermansia — was associated with increased blood concentrations of immune cells called neutrophils.

By contrast, two types called Rothia and Clostridium sensu stricto 1, were associated with reduced numbers of these immune cells.

Computer simulations by the researchers predicted that enriching microbiota with the three “friendly” genera would speed up the recovery of patients’ immune systems.

“This research could eventually suggest ways to make BMTs safer by more closely regulating the microbiota,” says co-author Marcel van den Brink.

The study appears in Nature.

Improved treatments

Concluding their paper, the authors write:

“Our demonstration that the microbiota influences systemic immunity in humans opens the door toward an exploration of potential microbiota-targeted interventions to improve immunotherapy and treatments for immune-mediated and inflammatory diseases.”

A previous study found that having a greater diversity of bacterial species in the gut is associated with a better chance of survival after a stem cell transplant. This research also found that a low diversity of bacteria increased the likelihood of potentially fatal graft-versus-host disease, when the donor immune cells attack the recipient’s tissues.

In 2018, the Sloan Kettering researchers published results from a clinical trial in which they used fecal transplants to restore patients’ microbiota after treatment for blood cancer.

They used the patients’ own fecal matter, which had been collected and frozen before the bone marrow transplant and antibiotic treatment disrupted their gut microbiota.

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“The lockdown affected my access to care because I cannot get to the clinic for my drugs and I was also scared of going to the hospital because of the pandemic.”

These were the words of Mrs. Patience, a person living with Human Immuno-deficiency Virus (HIV). Patience, mother of three, who discovered her status in 2011.

According to her, the first time she found out, it was something else but she summoned the courage and with help from the family, especially the husband.

She continued: “When we found out about my status, it was towards our wedding. There was an overnight meeting in the church asking my husband not to marry me because he was negative and if he married me that he was going to die but he stood by me. Where will I start? The stigmatisation at the meetings, they said a lot of things. When I gave birth, my baby was negative, they started arguing whether I was truly positive. All my children are negative and my husband too.”

The mother of three said, HIV is not a death sentence, rather people should endevour to know their status and access care immediately to avoid complications.

Meanwhile, another patient, Christopher Lee said he discovered his status in 2000 when HIV came newly to the country.He lamented on the high-level stigma associated with HIV as at that time.

Lee said: “When I discovered my status, I started going to the hospital for treatment and monitoring, before then, I was having loss of appetite, I lost weight, I was having catarrh and my CD4 as at then was around 200. I have been taking drugs since then and I am okay.”

Lee disclosed that he got the infection from the wife. However, during the lockdown, Lee travelled to his village in Kaduna State where he visited the general hospital to access care.

He said: “I went to the clinic because of the lockdown my drugs were about to finish. They asked me the name of my drugs, I told them, and they now gave me drugs for three months. I called my clinic and told them that I have picked my drugs from another hospital.”

Lee said that presently, the stigma still persists, though he has disclosed his status with some of the church members, family and a lot of people know about it but many are dying because of ignorance. He admitted that the lockdown did not affect his access to care to care and treatment.

Professor of Haematology and Blood Transfusion, Lagos University Teaching Hospital (LUTH) Idi-Araba, Alani Akanmu, said there was the disruption of services during lockdown because it was not convenient at all for patients to access the services that were available due to the issue of transportation. He said that as a foremost institute, they had to keep in contact with patients through phone conversations and zoom and with support of a Non Governmental Organisation (NGO) that established a drug collection centre for the members of the community.

Deputy Director of Prevention, Care and Treatment, Institute of Human Virology Nigeria (IHVN), Dr. Helen Omuh, said due to the initial mitigation measures instituted by the government, access to HIV services by people living with HIV (PLHIV) was affected and most patients could not visit the health facilities for their drugs and laboratory tests due to movement restriction and fear of COVID 19.

She said that poor quality data and low capacity for data management had persisted despite improvement observed with the electronic medical records system. Good quality data is required to guide decisions, policies and research. Though the drugs are free, there may be some out of pocket expenses with the national health insurance system covering less than 10 per cent of the eligible population. Political commitment for sustained funding and effective co-ordination is also a crucial challenge in managing HIV,” she said.

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A retrospective, observational study has found that people who received the BCG vaccination — which prevents tuberculosis — were less likely to report symptoms of COVID-19 and less likely to have antibodies against the infection in their blood.

Scientists developed the BCG (bacillus Calmette-Guérin) vaccine more than 100 years ago to protect against the bacterial infection tuberculosis (TB).

According to the World Health Organization (WHO), by 2004, around 100 million children a year were receiving the vaccine.

In the United States, BCG is approved for people at high risk of developing TB and for treating some forms of bladder cancer.

But research also suggests that BCG vaccination early in life can reduce child mortality by up to 45%, mainly through reduced susceptibility to sepsis (blood poisoning) in babies, respiratory infections, and fever.

In adolescents and older people, there is also some evidence that BCG protects against viral respiratory infections.

Scientists believe the vaccine primes the “innate” immune system, the body’s first line of defense against viruses and other invading organisms. Unlike adaptive immunity, innate immunity rarely targets specific pathogens that the body has encountered in the past.

Researchers at the Cedars-Sinai Medical Center in Los Angeles, CA, wondered whether BCG might reduce susceptibility to SARS-CoV-2, the virus that causes COVID-19.

“We were interested in studying the BCG vaccine because it has long been known to have a general protective effect against a range of bacterial and viral diseases other than TB, including neonatal sepsis and respiratory infections,” says co-senior author Dr. Moshe Arditi, director of the Pediatric and Infectious Diseases and Immunology Division at Cedars-Sinai.

The team has reported their results online in The Journal of Clinical Investigation.

COVID-19 symptoms and antibodies

Between May 11 and June 18, 2020, 6,201 healthcare workers gave blood samples and answered questions about their medical history, including whether they had received BCG and vaccines against two other bacterial infections and influenza.

In total, 1,836 said they had received the BCG vaccination, 4,275 said they had not received it, and 90 were unsure.

Those with the vaccination were less likely to report experiencing symptoms of COVID-19 at any time in the past 6 months.

Overall, 3.5% of the entire cohort tested positive for SARS-CoV-2 antibodies.

Among those who reported receiving the BCG vaccine, 2.7% tested positive, while among those who said they hadn’t received it, 3.8% tested positive.

“It appears that BCG-vaccinated individuals either may have been less sick and therefore produced fewer anti-SARS-CoV-2 antibodies, or they may have mounted a more efficient cellular immune response against the virus,” says Dr. Arditi.

After adjusting for age and sex, BCG vaccination — but none of the other vaccinations — was still associated with a reduced likelihood of testing positive for SARS-CoV-2 antibodies.

In their paper, the researchers write:

“Taken together, these results indicate that a history of BCG vaccination confers a nonspecific protective effect against infection with SARS-CoV-2 and decreases the presence of self-reported COVID-19 symptoms. This appears to be specific to BCG, as [other vaccinations] […] are not associated with similar protection against infection with SARS-CoV-2.”

Self-reported vaccination history

One of the study’s limitations was that it relied on participants’ recollection of which vaccines they had received, and whether they had experienced typical COVID-19 symptoms in the previous 6 months.

In addition, the numbers in each group who developed symptoms or tested positive were relatively small, which limited the statistical power of the study and the reliability of its findings.

However, it is interesting to note that those who reported receiving the BCG vaccination were older on average. They were also more likely to have diabetes, hypertension, cardiovascular disease, and chronic obstructive pulmonary disease.

These are all factors that increase a person’s chances of developing a severe COVID-19 infection.

In August 2020, Medical News Today reported another observational study, which suggested countries with mandatory BCG vaccination had a degree of “herd immunity” against the disease.

There are 22 clinical trials currently investigating BCG’s potential to prevent or treat COVID-19, which should provide more definitive evidence. Dr. Arditi and Cedars-Sinai are involved in one of the studies.

No-one believes BCG will be more effective than specific vaccines for COVID-19, Dr. Arditi explains. But if the trials prove its worth, as a well-established vaccine, BCG could be quickly approved and rolled out for this application.

“It is a potentially important bridge that could offer some benefit until we have the most effective and safe COVID-19 vaccines made widely available,” he says.

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Scientists have recorded more breakthroughs in the search for natural cures for COVID-19. They found that Xylitol and grapefruit seed extract nasal spray helps COVID-19 patients to recover faster and that pomegranate peel and Cat’s claw extracts inhibited replication of the Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV-2), which causes COVID-19. Researchers have also identified compounds in traditional Chinese medicine herbs that could prevent SARS-CoV-2 infection.

Until now, no effective and safe therapeutic medications for COVID-19 or preventative vaccines against SARS-CoV-2 infection have been developed and rolled out for general usage. Therefore, the search continues to develop effective therapeutic options to treat COVID-19, while vaccines against its causative pathogen undergo clinical trials and await regulatory body approval.

United States-based researchers Camille Celeste Go, Krunal Pandav, Marcos A. Sanchez-Gonzalez, and Gustavo Ferrer have published a report exploring the potential role of Xylitol and Grapefruit seed extract (in the form of a nasal spray) in treating COVID-19. Their study titled, “Potential Role of Xylitol Plus Grapefruit Seed Extract Nasal Spray Solution in COVID-19: Case Series,” was released in the open-access journal Cureus.

The authors of the study explained the significant impact of COVID-19 on the healthcare systems of many countries around the world. They explained that angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) are two potential drug targets. The ACE2 receptor acts as the binding site where the virus attaches to enter into the host cells. The TMPRSS2 also plays an important role in viral entry into the cells. These are both present abundantly in the bronchial epithelium and alveolar type II epithelium cells, as well as the epithelial lining of the nose.

Earlier studies have shown that nasal sprays could be a good option in both preventing SARS-CoV-2 infection and treating it.

Prior studies have also emphasized how viral shedding occurs mostly from the nose and nasal cavity, which puts healthy individuals in contact with those infected at greater risk.

The researchers identified two agents: xylitol and grapefruit seed extract (GSE), which, when administered intranasally in the form of nasal sprays could help ameliorate COVID-19 symptoms in patients.

Xylitol has had demonstrable antiviral effects in labs against several viruses, including avian influenza virus (AIV), Newcastle disease virus (NDV), infectious bursal disease virus (IBDV), the team explains.

They used the xylitol-GSE nasal spray for a duration of seven days in COVID-19 patients and presented a case series of three different patients to chart its impact on their bouts of the disease.

The researchers concluded: “The three COVID-19 patients presented with mild-moderate risks and mild symptoms. They were given the intranasal nasal spray along with other adjuvant supportive treatments. The patients showed, ‘rapid clinical improvement and shortened time to negativization on repeat intranasal swab test via PCR.’

“The spray was found to be safe, and the authors suggest that this spray could be ‘a potential adjunct treatment option in mild-moderate COVID-19 cases.’”

Researchers led by first author Relja Suručić from the Department of Pharmacognosy, Faculty of Medicine, University of Banja Luka, Banja Luka, Bosnia, and Herzegovina, have studied the use of pomegranate peel extracts in preventing infections with SARS-CoV-2. Their study titled, “Computational study of pomegranate peel extract polyphenols as potential inhibitors of SARS-CoV-2 virus internalization,” was published in the latest issue of the journal Molecular and Cellular Biochemistry.

Several natural products are being explored to prevent SARS-CoV-2 infection or treat it effectively. Pomegranate (Punica granatum L., Punicaceae family) consumed worldwide has been known to have beneficial health properties and useful in treating type 2 diabetes, atherosclerosis, cardiovascular diseases, inflammatory diseases, cancers, etc.

Pomegranate peel extracts are known to contain “phytobiotics such as hydrolyzable tannins (ellagitannin, punicalagin, punicalin, gallic and ellagic acid), flavonoids, anthocyanins, and other phenols,” explain the researchers. These polyphenols are known to have several properties, including anti-inflammatory effects; antioxidant effects; hypoglycaemic or blood sugar reducing effects; lipid-lowering or cholesterol-lowering effects; antihypertensive or blood pressure lowering effects; and antimicrobial effects.

Pomegranate extracts have been known to be useful against viruses such as “influenza virus, herpes virus, poxviruses, and human immunodeficiency virus,” the researchers state. Molecules in the extract called the “punicalagin, punicalin and ellagic acid”, also show effects against hepatitis C virus (HCV). Pomegranate peel extracts (PoPEx) have also shown effects against the influenza virus by preventing virus entry and transcription of the RNA.

This study targeted four major ellagitannin members present in PoPEx, “punicalagin, punicalin, ellagic acid, and gallic acid,” to see their efficacy against SARS-CoV-2 in lab models (in silico tools).

The results of this study showed that constituents of pomegranate peel extracts such as punicalagin and punicalin show significant potential in interacting with the selected protein targets and thus could possibly prevent the viral entry into the host cell. This needs to be followed up with in vitro and in vivo studies they write.

The viral entry prevention into the host cell could effectively prevent the infection. This study showed that PoPEx polyphenols could offer potential inhibitory activity against the SARS-CoV-2, especially during its host cell entry. Authors of the study write, “punicalagin and punicalin are promising candidates for further anti-SARS-CoV-2 in vitro studies”.

The team concluded, “Being the ingredients of a natural product that is used as food, these candidates also have a confirmed safety profile which is their additional and important advantage in the disease treatment.”

Also, researchers in Columbia and Peru have shown that Uncaria tomentosa – a woody vine native to South America known of as “Cat’s claw” – exerts in vitro antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the agent that causes coronavirus disease 2019 (COVID-19).

Study: The hydroalcoholic extract of Uncaria tomentosa (Cat´s claw) inhibits the replication of 2 novel coronaviruses (SARS-CoV-2) in vitro.

The study found that the hydroalcoholic extract of Uncaria tomentosa inhibited SARS-CoV-2 viral replication and reduced its cytopathic effect on Vero E6 cells.

The researchers say U. tomentosa has already been widely used as an immune-modulatory agent and that previous studies have shown the extract has a range of effects on several viruses.

However, the team – from the University of Antioquia-UdeA in Medellín, Columbia and the National University of San Marcos in Lima, Peru – say this is the first study to test the effects of U. tomentosa on SARS-CoV-2.

Now, Wildeman Zapata and colleagues report that U. tomentosa reduced the viral titer and cytopathic effect of SARS-CoV-2 in the Vero E6 cell line after just 48 hours of treatment.

“Based on our results, U. tomentosa is a promising medicinal herb to combat COVID-19, but it is necessary to continue with animal models followed by clinical trials to validate our results in the context of COVID-19 patients,” writes the team.

A pre-print version of the paper is available on the server bioRxiv*, while the article undergoes peer review.

Meanwhile, using computational methods, a team of researchers identified three compounds in traditional Chinese medicine that could be used against SARS-CoV-2: quercetin, puerarin, and kaempferol. Of the three compounds, quercetin showed the highest binding affinity to both the ACE2 receptor and the receptor-binding domain of the SARS-CoV-2 spike protein, and could thus provide a dual synergistic effect.

Traditional Chinese medicine, widely used for many diseases, showed therapeutic effects during the 2003 SARS-CoV epidemic. The RBD of the SARS-CoV-2 has significant structural homology with SARS-CoV. Although the use of Chinese herbs with modern medicine has shown benefits in COVID-19 patients, several components are present in the herbs and have complex interactions, making it challenging to uncover the molecular mechanisms responsible for its therapeutic effects.

Several computational studies have helped predict active compounds in the medicinal herbs with the potential to accelerate traditional medicine-based drug discovery.

Researchers from various institutions in China used computational analysis to discover potential molecule candidates against SARS-CoV-2 infection. Using the Traditional Chinese Medicine Pharmacology database, they screened for molecules that could target ACE2.

They identified the compound puerarin that could target ACE2. Then, they screened for Chinese herbs that have this compound in the database and found five. Furthermore, since it is thought that compounds in the same herbal medicine have synergistic properties, they expanded their search to include all the compounds in the five herbs to arrive at 41 compounds.

Upon analysing which compounds were present in the maximum number of herbs, they found puerarin was present in all the five herbs, and quercetin and kaempferol were present in three herbs. Next, they predicted potential drug targets of the selected compounds using the database, leading to 240 possible targets. Upon further analysis, they selected puerarin, quercetin, and kaempferol for further study.

Next, the authors performed molecular docking analysis to determine potential binding sites and binding affinity to ACE2. All the three compounds could bind on the same region of ACE2, which is located some distance from the binding position of SARS-CoV-2. It is likely the compounds are causing changes in conformations rather than competing with the spike protein to bind to ACE2. Quercetin had the highest binding affinity, forming both strong and weak hydrogen bonds.

All the three compounds tested were found in the herb Radix Bupleuri confirming that compounds in a single herb have synergistic pharmacological properties. The herb is popular in China and has been used to treat flu, inflammation, malaria, and hepatitis B. It is also one of 26 Chinese herbal medicines advised by traditional Chinese medicine practitioners to combat COVID-19.

Puerarin has been approved for use in China for decades and could be an ideal drug repurposed for its antiviral properties. Although its binding affinity is lower than quercetin, it has a safe dose limit of about 0.5 gram, so it could be used at a high dose to achieve a suitable antiviral effect. It also has beneficial effects on fever, cardiovascular disease, and neurological dysfunction, so it can also be used as an adjuvant to help improve COVID-19 symptoms.

Quercetin showed a higher binding affinity to both ACE2 and the RBD of the spike protein. The dual binding effect of quercetin could therefore be synergistic and provide a strong antiviral effect against SARS-CoV-2. Furthermore, since analysis suggested that quercetin could affect immunomodulation and because studies have shown patients with severe COVID-19 disease tend to experience cytokine storms, quercetin could help alleviate symptoms in such cases.

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Individuals infected with coronavirus are unlikely to catch the illness again for at least six months, researchers at the University of Oxford said Friday.

The finding comes as part of a large-scale study into Covid-19 reinfection after observations from healthcare professionals that the phenomenon was relatively rare.

Oxford University Professor David Eyre, one of the authors of the study, said the findings were “really good news”.

“We can be confident that, at least in the short term, most people who get Covid-19 won’t get it again,” he said.

The authors highlighted they had not yet gathered enough data to make a judgement on reinfection after six months.

However, the ongoing study has an end goal of verifying how long protection from reinfection lasts in total.

The director of infection prevention and control at study partners Oxford University Hospitals (OUH), Katie Jeffery, called the finding “exciting”.

It indicated “that infection with the virus provides at least short-term protection from re-infection”, she added.

US biotech firm Moderna announced this week its vaccine candidate was nearly 95 percent effective in a trial — a week after similar results were announced by pharma giant Pfizer and its German partner BioNTech.

The Oxford study into reinfection drew on data from regular coronavirus testing of 12,180 health care workers at OUH over a period of 30 weeks.

It found that none of the 1,246 staff with coronavirus antibodies developed a symptomatic infection.

Three members of staff with antibodies did test positive for the virus that causes Covid-19 but were all well and did not develop symptoms.

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Scientists discover that a drug used to treat arthritis shows promising initial results for treating COVID-19 in older adults.

An international team of scientists has found that the arthritis drug baricitinib shows promise for increasing the survival of older adults with COVID-19.

The new research, appearing in the journal Science Advances, lays the groundwork for larger, randomized controlled trials to confirm the initial findings.

Repurposed drugs

Alongside developing an effective and safe vaccine for SARS-CoV-2, scientists are also identifying potential treatments that may help increase the survival chances of people who develop COVID-19.

To do this quickly, scientists have turned to previously available drugs, looking to repurpose them as COVID-19 treatments. Since these medicines already have approval for use, many of the safety tests involved in the development of a novel drug are not required.

However, this is still no small task. There are thousands of potential drugs to search through when identifying those that may be worth testing.

To speed up the process, scientists used artificial intelligence (AI) systems that can rapidly analyze these medicines and determine if they could be effective COVID-19 treatments.

One such drug that artificial intelligence software identified in February 2020 was baricitinib, a medication for adult rheumatoid arthritis.

The software identified this drug because it had two potential mechanisms of action. The first might reduce inflammation, while the second might make it more difficult for the virus to access a person’s cells.

Since these initial findings, baricitinib has been used in clinical settings to treat COVID-19. The scientists behind the present study drew on this initial clinical data and conducted laboratory tests to determine how effective the drug may be as a treatment.

Increased survival

The scientists looked at 83 patients from the University of Pisa, Italy, and the Albacete Hospital, Spain. The participants had an average age of 81 years, with moderate to severe COVID-19, and were given baricitinib as treatment. The research team compared this group to a control group of patients from Italy and Spain, who did not take the drug.

The scientists found that the group who received baricitinib was less likely to need mechanical ventilation, while the patients were less likely to die compared with the control group.

Specifically, 34.9% of the control group either died or needed mechanical ventilation, compared with 16.9% of the patients treated with baricitinib.

Two mechanisms of action

To better understand how baricitinib may causing this beneficial effect, the scientists studied its impact on miniature human organs grown in a laboratory.

This confirmed the initial findings of the AI software: that baricitinib reduces inflammation and makes it more difficult for the virus to access a person’s cells.

A leading cause of death for people with COVID-19 has been acute respiratory distress syndrome. This occurs when a person’s inflammatory response to SARS-CoV-2 goes out of control, damaging respiratory system cells and potentially affecting many other organs in their body.

The scientists found that this inflammatory response can also make it easier for the virus to enter a person’s cells as it replicates itself within their body.

Baricitinib seems to work by reducing both of these reactions, significantly increasing the chances of survival.

According to the study’s co-lead author Prof. Volker Lauschke, associate professor in Personalized Medicine and Drug Development at the Karolinska Institutet in Stockholm, Sweden, “[t]his study confirms what AI predicted, and what we were hearing from patient case reports.”

“For instance, one case involved an 87-year-old severely unwell patient from Foggia, Italy, who showed rapid improvement after being given the drug, whereas her husband and son, who did not receive baricitinib, died.”

“This study has also shone a light on exactly how this drug may protect us at the cellular level. This helps us understand why other types of drugs are proving beneficial, or not beneficial, as we help identify other treatments which may tackle COVID-19.” – Prof. Volker Lauschke

The next step is to confirm the initial findings in larger, randomized controlled trials, which are already proceeding.

For Prof. Justin Stebbing, of the Department of Surgery and Cancer at Imperial College London, United Kingdom, and study co-lead author, “[w]e have seen the top-line results of a randomized study called the Adaptive Covid Treatment Trial-2 announced recently, showing benefits of baricitinib plus remdesivir, compared to remdesivir alone in over 1,000 patients.”

“Other very large trials occurring now include COV-BARRIER, and this will help create a fuller picture of the benefits and side effects of the oral medication (a small number of the patients in our study needed to stop the treatment due to problems with liver function).

“Further trials comparing baricitinib to other drugs in COVID-19 patients would also be helpful in improving outcomes.”

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A clinical trial has found that a monoclonal antibody reduces low-density lipoprotein (LDL) cholesterol levels by 50% in people with an inherited condition called familial hypercholesterolemia.

Individuals with high levels of low-density lipoprotein (LDL) or “bad” cholesterol in their blood are at increased risk of developing atherosclerosis (narrowed arteries) and cardiovascular disease.

Doctors define severe hypercholesterolemia as untreated LDL cholesterol levels of at least 190 milligrams per deciliter (mg/dl) of blood.

Cardiologists in the U.S. recommend that individuals who are at very high risk of cardiovascular disease due atherosclerosis aim for an LDL cholesterol level of around 70 mg/dl of blood.

Lifestyle changes can help reduce LDL, but people usually need to take cholesterol-lowering drugs to reach this goal. In addition, certain genetic differences can make achieving this objective more difficult for some people.

Worldwide, approximately 1 in 250 adults have an inherited condition called heterozygous familial hypercholesterolemia. This usually results from mutations in a gene for a receptor that removes LDL from the bloodstream.

Doctors usually prescribe a standard “triple therapy” of three types of cholesterol-lowering drugs for hypercholesterolemia:

  • A high dose of a statin, which reduces the amount of cholesterol the body produces.
  • A PCSK9 inhibitor, which boosts the number of LDL receptors in the liver.
  • Ezetimibe, which limits the absorption of cholesterol from the intestine.

For individuals whose LDL cholesterol level remains too high despite taking the maximum tolerable dose of this drug combination, a new drug called evinacumab that acts on a different target may soon be available.

A clinical trial published in The New England Journal of Medicine suggests that evinacumab could further reduce LDL levels in these individuals by around 50%.

This would be good news for people with mutations in the gene for the LDL receptor who don’t respond particularly well to PCSK9 inhibitors.

“There’s an unmet need for agents that address refractory hypercholesterolemia through a pathway that’s independent of the LDL receptor,” explains principal investigator Robert Rosenson, MD, Director of Cardiometabolic Disorders at the Icahn School of Medicine at Mount Sinai in New York, N.Y.

“If approved by the U.S. Food and Drug Administration, evinacumab may potentially fill that clinical gap for patients by reducing severely elevated LDL cholesterol,” he adds.

Breaking down lipids

Evinacumab is a monoclonal antibody that targets a protein called angiopoietin-like 3 (ANGPTL3). Normally, ANGPTL3 inhibits enzymes that break down lipids, including LDL, high-density lipoprotein (HDL), and triglycerides.

People with a faulty version of the gene that makes ANGPTL3 have abnormally low levels of these lipids in their blood. As a result, their chance of developing coronary artery disease is 41% lower than the general population.

By disabling ANGPTL3 with an antibody, drug developers hoped to recreate these beneficial effects in people with very high cholesterol levels.

In this phase II clinical trial, the researchers randomly assigned 272 people to receive either evinacumab — through intravenous or subcutaneous administration at various doses — or placebo treatments.

Most of the participants had heterozygous familial hypercholesterolemia.

After 16 weeks, LDL cholesterol had fallen by an average of 56% compared with placebo in those who received a subcutaneous dose of 450 mg of evinacumab weekly.

Among those who received a monthly intravenous injection of 15 mg evinacumab per kilogram of body weight, LDL cholesterol fell by 50.5% compared with the placebo group.

The authors note that some people prefer subcutaneous administration because they can do it themselves at home, avoiding the need to take time off work to visit a clinic.

Commenting on the findings, Dr. Rosenson concludes:

“Our study demonstrates that a regimen of either subcutaneous or intravenous evinacumab can have a significant impact on LDL cholesterol […] If approved for use in this setting, evinacumab could potentially arm cardiologists with a major new add-on therapy to bring patients with [heterozygous familial hypercholesterolemia] to or closer to their cholesterol-lowering goal.”

Racial diversity

The authors concede that their study had some limitations. For example, the numbers in each arm of the study were relatively small, and treatment lasted only 16 weeks.

In addition, the racial diversity of participants was not as broad as the researchers had hoped, so the results may not apply to all people in the wider population.

One of the people treated with subcutaneous evinacumab had difficulty breathing, and another had a mild anaphylactic reaction.

The pharmaceutical company Regeneron, which makes evinacumab, sponsored the study.

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