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A National Institutes of Health research explains the immunological response induced by COVID-19 infection, which destroys blood vessels in the brain and may result in short- and long-term neurological problems. Researchers from the National Institute of Neurological Disorders and Stroke (NINDS) analysed brain abnormalities in nine persons who died abruptly after getting the virus in a study published in Brain.

The researchers discovered evidence that antibodies, which are proteins produced by the immune system in reaction to viruses and other intruders, are engaged in an attack on the cells lining the blood arteries in the brain, causing inflammation and damage. SARS-CoV-2 was not discovered in the patients’ brains, which is consistent with a previous research by the group, indicating that the virus was not directly invading the brain.

Understanding how SARS-CoV-2 causes brain damage might aid in the development of medicines for COVID-19 individuals with persistent neurological symptoms.

“Patients often develop neurological complications with COVID-19, but the underlying pathophysiological process is not well understood,” said Avindra Nath, M.D., clinical director at NINDS and the senior author of the study. “We had previously shown blood vessel damage and inflammation in patients’ brains at autopsy, but we didn’t understand the cause of the damage. I think in this paper we’ve gained important insight into the cascade of events.”

Also Read: COVID-19: Virus spike protein flexibility improved by human cell’s own modifications

Dr. Nath and his colleagues discovered that antibodies created in response to COVID-19 may inappropriately attack blood-brain barrier cells. Tightly packed endothelial cells contribute to the formation of the blood-brain barrier, which prevents dangerous compounds from entering the brain while enabling essential molecules to flow through. Damage to endothelial cells in blood arteries in the brain might result in protein leakage. Some COVID-19 patients get bleeding and clots, increasing their risk of stroke.

Researchers discovered immunological complexes – chemicals created when antibodies bind antigens (foreign substances) – on the surface of endothelial cells in the brains of COVID-19 patients for the first time. These immune complexes can cause tissue harm by causing inflammation.

The discovery expands on their prior findings of brain injury caused by weakening and leaky blood vessels. The researchers thought that the harm was caused by the body’s normal inflammatory reaction to the infection.

Dr. Nath and his colleagues analysed brain tissue from a subgroup of patients in the prior study to further investigate this immune response. The nine people, ranging in age from 24 to 73, were chosen because structural brain scans revealed symptoms of blood vessel damage in the brain. The samples were compared to ten controls. The researchers used immunohistochemistry, a method that employs antibodies to detect particular marker proteins in tissues, to investigate neuroinflammation and immune responses.

Researchers discovered indicators of leaky blood vessels in their previous work, based on the presence of blood proteins that ordinarily do not pass the blood brain barrier. This shows that the blood-brain barrier’s tight connections between endothelial cells are disrupted.

Dr. Nath and his colleagues discovered deposits of immune complexes on the surface of endothelial cells, indicating that the damage was most likely caused by an immunological response.

These findings point to an antibody-mediated assault on endothelial cells. When endothelial cells are active, they produce proteins known as adhesion molecules, which induce platelets to adhere to one another. Endothelial cells in brain tissue samples were discovered to have high amounts of adhesion molecules.

“Activation of the endothelial cells brings platelets that stick to the blood vessel walls, causing clots to form and leakage to occur. At the same time the tight junctions between the endothelial cells get disrupted causing them to leak,” Dr. Nath explained. “Once leakage occurs, immune cells such as macrophages may come to repair the damage, setting up inflammation. This, in turn, causes damage to neurons.”

Researchers discovered that in locations with endothelial cell injury, more than 300 genes exhibited decreased expression, whereas six genes showed elevated expression. These genes have been linked to oxidative stress, DNA damage, and metabolic dysfunction. This might lead to a better understanding of the molecular basis of COVID-19-related neurological symptoms, as well as novel treatment targets.

These findings provide insight into the immune response that damages the brain following COVID-19 infection. However, because the virus was not found in the brain, it is unclear which antigen the immune response is targeting. Antibodies against the SARS-CoV-2 spike protein may attach to the ACE2 receptor, which the virus uses to enter cells. More study is required to investigate this theory.

Findings might help in brain treatment

The findings might help researchers better understand and treat long-term neurological symptoms caused by COVID-19, such as headaches, exhaustion, loss of taste and smell, sleep issues, and “brain fog.” The researchers believe that if the individuals in the trial had lived, they would have acquired Long COVID.

“It is quite possible that this same immune response persists in Long COVID patients resulting in neuronal injury,” said Dr. Nath. “There could be a small indolent immune response that is continuing, which means that immune-modulating therapies might help these patients. So these findings have very important therapeutic implications.”

When the coronavirus that causes COVID-19 infects human cells, the cell’s protein-processing machinery modifies the spike protein, making it more flexible and mobile, potentially increasing its ability to infect other cells and evade antibodies, according to a new study from the University of Illinois Urbana-Champaign.

The researchers developed an atomic-level computer model of the spike protein and performed several simulations to investigate the protein’s dynamics and how cell changes altered those dynamics. According to the researchers, this is the first study to offer such a thorough image of the protein that plays a major role in COVID-19 infection and immunity.

Biochemistry professor Emad Tajkhorshid, postdoctoral researcher Karan Kapoor and graduate student Tianle Chen published their findings in the Proceedings of the National Academy of Sciences.

“The dynamics of a spike are very important — how much it moves and how flexible it is to search for and bind to receptors on the host cell,” said Tajkhorshid, who also is a member of the Beckman Institute for Advanced Science and Technology. “In order to have a realistic representation, you have to look at the protein at the atomic level. We hope that the results of our simulations can be used for developing new treatments. Instead of using one static structure of the protein to search for drug-binding pockets, we want to reproduce its movements and use all of the relevant shapes it adopts to provide a more complete platform for screening drug candidates instead of just one structure.”

Also Read: Daily avocados improve diet quality, help lower cholesterol levels: Study

The spike protein of SARS-CoV-2, the virus that causes COVID-19, is the protein that juts out from the surface of the virus and binds to receptors on the surface of human cells to infect them. It also is the target of antibodies in those who have been vaccinated or recovered from infection.

Many studies have looked at the spike protein and its amino acid sequence, but knowledge of its structure has largely relied on static images, Tajkhorshid said. The atomistic simulations give researchers a glimpse of dynamics that affect how the protein interacts with receptors on cells it seeks to infect and with antibodies that seek to bind to it.

They found that the protein has several “hinges” or moving parts, allowing the head of the protein to swivel on the stalk that sticks out from the virus. The researchers documented several different conformations, including active and inactive forms, and mapped how the protein shifts from one form to another. The conformations seen in their computational simulations lined up with the types and frequencies of angles observed in experimental structural studies, the researchers said, lending support to the validity of the simulations.

Changes in Covid Spike Protein

The researchers also found that processing by the host cell changed the viral protein’s dynamics. Much research has focused on the virus’s genetic code and the mutations it has acquired as new variants emerge. However, the spike protein goes through a number of changes as it is folded and “packaged” for shipping throughout the cell. One of the most common modifications, glycosylation, is the addition of sugars called glycans at specific points.

“Little is known about these post-translational modifications. The main role that has been noted is that glycans shield the protein from the targeting of antibodies,” Chen said. “We compared glycosylated and nonglycosylated forms of the spike protein and found significant dynamic differences between the two.”

The researchers noticed enhanced range of motion in the spike protein, making it more able to flex and interact with cell surface receptors. The glycans themselves also interacted with the cell membrane, allowing the spike protein to move and search along the membrane for the receptor.

“Glycosylations not only provide an immune shield but also mediate and enhance the mobility of the spikes, increasing the chances of the virus to successfully attach to and infect the human cells. Thus, the functions of these post-translational modifications are much wider than what was initially thought,” Kapoor said. “This understanding can now provide additional opportunities for targeting the function of this virus.”

The researchers said their findings highlight the importance of understanding not only genetic mutations in the spike protein of new virus variants, but also modifications such as glycosylation and how those modifications can add to virus infectivity and immune avoidance. They also anticipate other researchers using their models to develop new diagnostics, vaccines and antiviral drugs.

“The hope is that down the road, this new understanding of the spike protein is going to be useful for therapeutic efforts. I imagine we can target the dynamics of the spike protein with compounds that bind to the hinges and make them inflexible, and therefore in principle, make the virus less effective,” Tajkhorshid said.

Source: University of Illinois at Urbana-Champaign, News Bureau

According to a new study, eating one avocado every day for six months had no effect on belly fat, liver fat, or waist circumference in those who were overweight or obese. It did, however, result in a small drop in harmful cholesterol levels.

The team, which included Penn State researchers, discovered that those who ate avocados had higher quality diets over the study time.

While previous, smaller studies indicated a relationship between consuming avocados and decreased body weight, BMI, and waist circumferences, this was the largest, most comprehensive study on the health benefits of avocados to date, due to the vast number of participants and duration of the study period.

“While the avocados did not affect belly fat or weight gain, the study still provides evidence that avocados can be a beneficial addition to a well-balanced diet,” said Penny Kris-Etherton, Evan Pugh University Professor of Nutritional Sciences at Penn State. “Incorporating an avocado per day in this study did not cause weight gain and also caused a slight decrease in LDL cholesterol, which are all important findings for better health.”

According to Kristina Petersen, associate professor of nutritional sciences at Texas Tech University, consuming avocados on a regular basis increased the overall quality of the participants’ diets by eight points on a 100-point scale.

“Adherence to the Dietary Guidelines for Americans is generally poor in the U.S., and our findings suggest that eating an avocado per day can substantially increase overall diet quality,” Petersen said. “This is important because we know a higher diet quality is associated with lower risk of several diseases including heart disease, type 2 diabetes and some cancers.”

Also Read: Covid case Update: India logs 16,159 new cases

The study, which was just published in the Journal of the American Heart Association, was carried out in collaboration with Loma Linda University, Tufts University, and UCLA, with coordination assistance provided by Wake Forest University.

One Avocado a day

The researchers ran a six-month trial with over 1,000 overweight or obese subjects, half of whom were directed to consume one avocado every day while the other half followed their regular diet and were encouraged to limit their avocado consumption to fewer than two per month. Fat in the belly and surrounding abdominal organs was carefully assessed using MRI before and after the trial.

“While one avocado a day did not lead to clinically significant improvements in abdominal fat and other cardiometabolic risk factors, consuming one avocado a day did not result in body weight gain,” said Joan Sabaté, professor at Loma Linda University School of Public Health. “This is positive because eating extra calories from avocados doesn’t impact body weight or abdominal fat, and it slightly decreases total and LDL-cholesterol.”

They also discovered that eating avocados on a regular basis reduced total cholesterol by 2.9 milligrammes per deciliter (mg/dL) and LDL cholesterol by 2.5 mg/dL.

The researchers stated that they will continue to evaluate data from the study in the future. For example, participants were not advised on how to consume their avocados each day, and future study might look at how people incorporated the avocados into their diet and whether there were any changes in the findings based on how they ate the avocado.

The Ministry of Health and Family Welfare (MoHFW) reported 16,159 new COVID-19 cases and 28 fatalities in India in the previous 24 hours.

Today’s new infections are 23.48 percent more than the 13,086 cases recorded on Tuesday. The overall number of COVID-19 cases in the country has now reached 4,35,47,809 people (4 crore 35 lakh 47 thousand 8 hundred and 9).

The daily positive rate for COVID-19 was 3.56 percent, up from 2.90 percent the day before, while the weekly positivity rate was 3.84 percent.

Total deaths due to COVID-19 in the country has increased to 5,25,270 (5 lakh 25 thousand 2 hundred and 70).

There are currently 1,15,212 (1 lakh 15 thousand 2 hundred and 12) active cases of COVID-19 in the country.

There has been an increase of 737 cases in the active COVID-19 caseload in a span of 24 hours. Active cases comprise 0.26 per cent of the total infections.

Maharashtra saw a 104 per cent rise in day-on-day COVID-19 cases. The state reported 3,098 fresh coronavirus infections in the last 24 hours, up from 1,515 from day ago. The state also reported six deaths due to the virus in a single day.

Of the new cases in Maharashtra, the highest, 1,313, were from Mumbai Circle, which comprises the commercial capital and adjoining metropolitan region, followed by Pune (1,196), Nashik (167), Nagpur (160), Akola (87), Aurangabad (65), Kolhapur (60) and Latur circle ( 50).

Tamil Nadu too witness surge in COVID-19 cases. As many as 2,662 people tested positive for the virus in the past 24 hours. The state also reported one coronavirus related death.

Chennai topped the list with 1,060 new cases followed by Chengalpet 373, Coimbatore 137, Tiruvallur 132 and Trichy 112.

West Bengal logged 1,973 new cases of Covid and three deaths in the last 24 hours.

Karnataka reported 839 fresh COVID-19 cases and two deaths, while national capital Delhi logged 615 fresh COVID-19 cases and three fatalities due to the viral disease in the last 24 hours.

Telangana added 552 fresh Covid cases in the last 24 hours.

According to the health ministry, 15,394 people recuperated from Covid in the last 24 hours increasing total recoveries to 4,29,07,327 (4 crore 29 lakh 7 thousand 3 hundred and 27).

The national recovery rate is currently at 98.53 per cent.

According to the Indian Council of Medical Research (ICMR), 4,54,465 (4 lakh 54 thousand 4 hundred and 65) COVID-19 tests were conducted in the country in the last 24 hours.

The Council also informed that since the start of the pandemic, 86,49,05,684 (86 crore 49 lakh 5 thousand 6 hundred and 84) Covid tests were conducted in the country.

COVID-19 vaccination

The health ministry bulletin on Wednesday said that 9,95,810 (9 lakh 95 thousand 8 hundred and 10) doses of Covid vaccines were administered in the country in the last 24 hours.

The nationwide Covid vaccination drive in India was started on 16 January, 2021, and since then, more than 198.20 crore vaccine doses were administered to the eligible beneficiaries.

The latest omicron subvariants — including the BA.4 and BA.5 forms causing new surges in infections in the United States — are even better at eluding vaccines and most antibody treatments than previous variants, finds a study by researchers at Columbia University Vagelos College of Physicians and Surgeons.

According to government sources, the highly transmissible sub-variant of Omicron, BA.2.75 has limited distribution in India.

According to ANI on Tuesday, this lineage has not been confirmed to have increased illness severity or transmission.

“So far this lineage has not been documented to have enhanced severity or disease spread. The predominant circulating VoC of SARS-COV-2 is the Omicron VoC,” sources told ANI.

“It is critical to continue to monitor the spread of this sublineage and also the other emerging sublineages of Omicron. The scale of genomic sequencing needs to be expanded and maintained for early detection of variant strains of SARS-COV-2,” sources added.

Also Read: Reverse Zoonosis is possible in transmission of Tuberculosis, ICMR claims

Globally, the BA.2 Omicron lineage has been seen to replace the BA.1 lineage. As the BA.2 lineage is evolving, many sublineages of BA.2 are now developing with a set of distinct mutations. B.2.75 is a similar sublineage of BA.2.

On Tuesday, India reported 13,086 new Covid19 cases in the last 24 hours and India’s active caseload currently stands at 1,14,475.

Researchers from Tamil Nadu’s National Institute for Research in Tuberculosis (NIRT) and the Indian Council of Medical Research (ICMR) discovered cases of reverse zoonosis (human-to-animal and animal-to-human) in tuberculosis transmission (TB).

Dr S Sriram of ICMR-NIRT told ANI in an exclusive interview that there is a potential and proof of Tuberculosis transmission from animals to people and vice versa.

“TB transmission happens through the aerosols that are generated from tuberculosis patients as it is an airborne disease. While our TB patient coughs or sneezes, or speaks, or sings, lots of aerosols are generated from the nose and oral cavity that aerosol gets expelled and that becomes the source of exposure for various other organisms including animals,” Dr S Sriram said.

He further explained, “So, when animals like cattle or any other domestic animals that are at exposure to these aerosols, they have a possibility of getting infected with tuberculosis and also on the parallel there are some situations where we have documented evidence of reverse transmission from animals to human beings.”

Research conducted by the ICMR-NIRT in Chennai found the presence of  mycobacterium. tuberculosis in animal handlers: and animals.

Also Read: Study by AIIMS shows booster dose gives effective results against Covid

Dr. Sriram said, “We have done studies in animal handlers in Chennai, where they have found that there is a presence of mycobacterium tuberculosis in animals and also the similar strains are found in the animal handlers who are working in those slaughterhouses. So, this gives us evidence for the transmission that happens between the human beings and animals.”

He also said that there is a possibility of mycobacterium tuberculosis infection from unpasteurized milk.

He said, “If you see those milk which is not pasteurized, and if that animal has a possibility of mycobacterium tuberculosis

infection, then there is a possibility that the mycobacterium. tuberculosis gets transmitted to the milk samples and then if it is consumed without pasteurization, they have a risk of getting exposed to mycobacterium tuberculosis.”

Dr. Sriram recommended for consumption of pasteurized milk to avoid the risk of mycobacterium transmission.

He said, “So, that is why we recommend using pasteurized milk and if in certain places due to the culture and the availability of resources, they are not following these practices, then there is a risk.of transmission of mycobacterium tuberculosis through these

samples. So in the current context, there is also a lot of much interventions going on in terms of the prevention of mycobacterium in the animal world.”

The Union Health Ministry’s goals to eradicate TB by 2025 also include research on the environment and zoonosis.

According to Dr. Sriram,”Considering the goal of TB elimination by 2025, we need to have an understanding of where are the reservoirs for tuberculosis. So it may be in the environment or it may be in animals. It can be in domestic or wild animals. So, there is a lot of evidence where we have seen mycobacterium in wildlife like elephants. These are evidence that informs us that there is a transmission going on between non-human host.”

“We need to try to see how we generate evidence on those hosts that reserve keep the reservoir of mycobacterium tuberculosis. So, once we move towards elimination, we need to be completely devoid of all these reservoirs. So that further transmission does not happen once we move towards automation,” he added.

A recent study undertaken by the All India Institute of Medical Sciences (AIIMS) found that booster injections were beneficial in reducing the frequency of Covid-19 infections. According to a study published in the medical journal Lancet, only 7% of Health Care Workers (HCWs) reported acquiring Covid-19 after taking a booster dosage during the research period.

Following an increase in instances of omicron variant reported in December 2021, a total of 11,474 HCWs from Delhi participated in the research. During the omicron transmission phase, over one-fifth of the employees were infected with SARS CoV-2, with a predominant moderate spectrum of Covid-19 illness.

Also Read: Monkeypox on Rise: WHO Reports 5,322 Lab-confirmed Cases in 53 Countries

“In our study, 1,363 (11.9%) HCWs took booster shots, out of which 96 (7.0%) got infected from Covid-19. We studied the density of infection and re-infection along with the effect of vaccine against the within the omicron transmission period from December 01, 2021 to February 25, 2022,” the report said.

It also noted waning effects of vaccine protection with increase in time intervals since vaccination. “We found a modest effect of Covid-19 vaccines after 2 months of completion of the second dose, and worthwhile benefits of doses beyond 6 months could be excluded. The finding is corroborated with neutralisation studies that have shown significant reduction in neutralising ability of immunity induced by vaccination,” the report said.

A team of skilled workers collected the data over the phone. All HCWs who took part in the initial round of data collection were called again to get information on immunisation history, Covid-19 testing, symptoms, and other factors.

According to the analysis, the omicron surge was associated with a higher likelihood of re-infections than prior pandemic times.