Early in the COVID-19 pandemic, scientists identified how SARS-CoV-2, the virus that causes COVID-19, gets inside cells to cause infection. All current COVID-19 vaccines and antibody-based therapeutics were designed to disrupt this route into cells, which requires a receptor called ACE2.
Now, researchers at Washington University School of Medicine in St. Louis have found that a single mutation gives SARS-CoV-2 the ability to enter cells through another route – one that does not require ACE2. The ability to use an alternative entry pathway opens up the possibility of evading COVID-19 antibodies or vaccines, but the researchers did not find evidence of such evasion. However, the discovery does show that the virus can change in unexpected ways and find new ways to cause infection. The study is published in the journal Cell Reports. “This mutation occurred at one of the spots that change a lot as the virus circulates in the human population,” said co-senior author Sebla Kutluay, PhD, an assistant professor of molecular microbiology.
“Most of the time, alternative receptors and attachment factors simply enhance ACE2-dependent entry. But in this case, we have discovered an alternative way to infect a key cell type —a human lung cell —and that the virus acquired this ability via a mutation that we know arises in the population. This is something we definitely need to know more about.”
The finding was serendipitous. Last year, Kutluay and co-senior author M. Ben Major, PhD, the Alan A. and Edith L. Wolff Distinguished Professor of Cell Biology & Physiology, planned to study the molecular changes that occur inside cells infected with SARS-CoV-2.
Most researchers study SARS-CoV-2 in primate kidney cells because the virus grows well in them, but Kutluay and Major felt it was important to do the study in the lung or other cells similar to the ones that are naturally infected. To find more relevant cells capable of growing SARS-CoV-2, Kutluay and Major screened a panel of 10 lung and head-and-neck cell lines.
“The only one that was able to be infected was the one I had included as a negative control,” Major said. “It was a human lung cancer cell line with no detectable ACE2. So that was a crazy surprise.”
Kutluay, Major and colleagues —including co-first authors and postdoctoral researchers Maritza Puray-Chavez, PhD, and Kyle LaPak, PhD, as well as co-authors Dennis Goldfarb, PhD, an assistant professor of cell biology & physiology and of medicine, and Steven L. Brody, MD, the Dorothy R. and Hubert C. Moog Professor of Pulmonary Diseases in Medicine, and a professor of radiology —discovered that the virus they were using for experiments had picked up a mutation.
The virus had originally been obtained from a person in Washington state with COVID-19, but as it was grown over time in the laboratory, it had acquired a mutation that led to a change of a single amino acid at position 484 in the virus’s spike protein. SARS-CoV-2 uses spike to attach to ACE2, and position 484 is a hot spot for mutations. A variety of mutations at the same position have been found in viral variants from people and mice, and in virus grown in the lab. Some of the mutations found in virus samples taken from people are identical to the one Kutluay and Major found in their variant. The Alpha and Beta variants of concern have mutations at position 484, although those mutations are different.
“This position is evolving over time within the human population and in the lab,” Major said. “Given our data and those of others, it is possible that the virus is under selective pressure to get into cells without using ACE2. In so many ways, it is scary to think of the world’s population fighting a virus that is diversifying the mechanisms by which it can infect cells.”
To determine whether the ability to use an alternative entry pathway allowed the virus to escape COVID-19 antibodies or vaccines, the researchers screened panels of antibodies and blood serum with antibodies from people who have been vaccinated for COVID-19 or recovered from COVID-19 infection. There was some variation, but in general, the antibodies and blood sera were effective against the virus with the mutation.
It is not yet clear whether the alternative pathway comes into play under real-world conditions when people are infected with SARS-CoV-2. Before the researchers can begin to address that question, they must find the alternative receptor that the virus is using to get into cells. “It is possible that the virus uses ACE2 until it runs out of cells with ACE2, and then it switches over to using this alternative pathway,” Kutluay said. “This might have relevance in the body, but without knowing the receptor, we cannot say what the relevance is going to be.”
Major added, “That’s where we’re going right now. What is the receptor? If it’s not ACE2, what is it?”
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Benefits and afflictions of using Giloy
A year and a half have passed since the Covid-19 pandemic swept across the globe. While there seemed no possible cure for the disease and researchers intensified their search for effective treatment and vaccine, many clinical trials were happening around the world and herbs emerged as a possible alternative treatment. Two of them include Giloy and Ashwagandha.
Giloy is a popular ayurvedic remedy for a number of health conditions including fever, infections and diabetes. However, there have been numerous debates about its benefits. While Ayurvedic doctors have claimed that the herb is not harmful, there have also been some reports claiming that giloy can lead to liver damage. A study published in the Journal of Clinical and Experimental Hepatology claimed the herb is harmful to the liver. On the other hand, the Ministry of AYUSH argued that giloy had been scientifically proven to be an effective remedy for multiple disorders.
To comprehend the facts related to the medicinal herb, we interviewed some eminent personalities from the field of gastroenterology and hepatology. An expert from the field of liver and gastroenterology suggested that alternative medications like giloy can cause some serious liver injuries. Dr Kaushal Madaan, Head of Hepatology, Max chain of hospitals, said: “When this pandemic came, we realised that there were many patients who came to us with unexplained liver failure and liver injury and some of them had even died. Only after a few months, we realised that they were taking a concoction and the most common ingredient of that concoction in these particular patients was giloy.” He pointed out that people were consuming kadhas or concoctions, twice or thrice a day, for a year, which could have caused serious liver damage.
“Even before the pandemic started, we had been advising our patients, whether or not they have underlying liver disease, to avoid taking herbal medicines of whose ingredients we are not sure about,” Dr Kaushal added, in the context of herbal and alternative medicines.
Alluding to the fact that all medicines — allopathic, homoeopathic or ayurvedic — have their pros and cons, Dr Sarin, Director, ILBS, said, “I can certainly say that there are certain herbs that can be harmful. There are certain preparation; unless they have published data, or they have data that they are only beneficial, just don’t take them if they have no scientific evidence.”
ANALYSING IMPACT OF COVID-19 ON LIVER DISEASE PATIENTS
Health experts recommend treatment and follow-up care for people with chronic liver disease.
Chronic liver diseases are common worldwide, especially in developing countries. The rapid spread of Covid-19 leads to the infection of many patients with underlying chronic liver diseases. To discuss the same, we spoke to Dr Shiv Kumar Sarin, Director of Institute of Liver and Biliary Sciences (ILBS); Dr Anil Arora, Chairman, Institute Of Liver Gastroenterology & Pancreatic Biliary Sciences Sir Ganga Ram Hospital, and Dr Kaushal Madaan, principal director and head of Hepatology from Max chain of hospitals.
Q. What would be your advice regarding checkups to people with liver diseases and fear contracting Covid-19?
Dr Sarin: If somebody has cirrhosis, alcohol liver injury or cancer, they all require treatment and monitoring. So don’t put it away. Treatment for all liver diseases must be given and should not be delayed. Treatment is essential whether you opt for teleconsultation or go to the hospital. What you can do at home is to continue your diet and the prescription that the doctor has given.
Q. What would be your stand on alternative medication for liver diseases?
Dr Arora: Liver is an organ that does not require any servicing and maintenance till you intentionally or accidentally try to injure it. You don’t need any medication. You don’t need a specific diet. You don’t need any type of maintenance but do everything to prevent the damage.
Two major reasons why the liver gets damaged are if you are having too many of the calories in the diet, so initially, it gets deposited in the peripheral tissue that is subcutaneous tissue, and once those stores get exhausted, it tends to get into the vital organs. The liver is a central organ for the metabolism, production and synthesis of various proteins, and the integrated metabolism of fat, carbohydrates as well as proteins. It also is known to produce a number of coagulation and anticoagulation factors.
There have been guidelines from CDC, from our own ICMR and the Government of India and AIIMS, that stress on minimum medication. Even allopathic medicines are needed in minimum doses for a minimum duration of time. They will do more harm than good. Especially all chemicals, all ingestions, all food has to be metabolised through the liver. So anything and everything that you are taking for any purpose you have to take under the guidance of a registered medical practitioner, take it for a minimum period of time, at a minimum dose, for a minimum duration. Never self-medicate yourself.
Q. There were reports that drugs like azithromycin and remdesivir could affect the liver but they were widely prescribed by physicians. What would you say to liver patients?
Dr Sarin: Remdesivir cannot be given to patients with liver disease. Secondly, it is not proven beneficial. So I would be very hesitant to give. Azithromycin can also give liver injury. In fact, there is no reason to give these drugs if the patient has pre-existing liver diseases. Some Lancet papers stated that Covid-19 was more serious in those patients who had a BMI of about 25. In India, nearly 30%, one in three people, have a high BMI, they all have fatty liver. So, the disease is more common, more susceptible, injury is more progressive, and liver injury enzymes being abnormal or very high. Also, some people were mixing alcohol with Covid-19 pills as people were staying home and they were drinking.
Q. What would you say to those who have liver diseases, perhaps got Covid-19, have recovered and are craving alcohol?
Dr Arora: Drinking as a habit, when it is harmful for you, it is not recommended. If you look at our baseline population, which has non-alcoholic fatty liver disease coupled with so many metabolic abnormalities like diabetes, hypertension, these are all the risk factors that will aggravate the injury related to alcohol. Once in a while, socialising is understandable, but the problem is that alcohol is an addictive agent. If you look at the data from the US, the maximum number of cases that are being reported after cure from hepatitis is related to alcohol.
This is absolutely preventable. Not only on its own it causes problems, but in patients with underlying fatty liver or those with hepatitis B or C, this alcohol is an added synergistic effect to cause further liver damage. So, unless you are sure that there is nothing wrong, you should avoid alcohol.
Q. Does Covid affect more severely to liver cirrhosis and liver transplant patients?
Dr Madaan: There is ample data to suggest that patients who have the fatty liver disease will have a severe lung disease when they get Covid-19. They have very poor outcomes and more of them end up in the ICU. Patients, who are just at the stage of waiting for a transplant, are the ones with advanced liver diseases. So, if they get Covid-19, they are at high risk of dying. If they have a new liver, they already are immunosuppressed. Some schools of thought say that since they are already immunosuppressed, they’re not able to mount an immunoinflammatory response to Covid-19 so they may have mild disease. But this is a controversial issue.
Dr Sarin: If the transplant was done within the last three months, Covid-19 can be very severe, and you should act quickly. People who are on heavy immunosuppressants have rejections even after a year, and if they get a Covid infection, there is a problem again. Covid-19 does not make people’s health condition worse but they are already predisposed to other illnesses.
The liver is the root cause of diabetes and blood pressure and high triglycerides. If you have fatty liver or are obese, diabetic, comorbid, then you must look at the liver enzymes. Covid-19 gives you all a chance to lose weight. Become healthy, lean, and thin, so that unfortunately, if the third wave comes, you are strong, your liver is strong, and your body is strong.
Q. Tell us about the post-Covid care for liver patients?
Dr Sarin: Patients with liver disease have weak muscles. We call it sarcopenia. Even if they are obese, they have limited muscle power. If your liver is weak, your muscles are also weak and after Covid-19, there is extreme fatigue and loss of appetite. You have to be more careful about this and get your antibodies done if you need them. For a patient with cirrhosis after recovering from Covid-19, he needs to remember that the liver can digest more fats than pure carbohydrates. So avoid carbs. Your main diet should be protein-based and the energy source can be fat. Exercises are essential.
Dr Arora: All those who suffer from Covid-19 are likely to come down with ‘Long Covid’. There are many reasons for that. You may have a bit of virus or the immune process which may still be simmering around the body or an immune complex disease that may be present or activation of the immune system. Coming back to the liver patients, if you have a concomitant Covid, you may have multiple reasons why the liver can get affected. It may occur due to the hyperinflammatory syndrome which comes out from the lungs and gets disseminated in the body, of which the liver gets the major share of the blood. Several drugs that are given to treat Covid-19 have indirect toxicity on the liver. If you have had a recent infection, you are likely to come down with more complications. Regularly follow up with a liver specialist if you have underlying liver disease.
Q. Liver patients have compromised immunity, they may not have enough antibodies. So, is the vaccine good for them?
Dr Arora: In the initial registration trials that were conducted in the US and UK, they excluded patients who had chronic liver diseases or those with an immunocompromised state. There is data published on Pfizer’s registration trial that has shown that the chance of development of antibodies is only 20% in patients with advanced liver disease or liver transplantation. Not all those with the immunocompromised state will develop antibodies. All patients who have an immunocompromised state will not produce antibodies. But in case you have developed antibodies and can be more confident that you won’t have the viral infection, don’t be under the wrong impression that you have been protected. If you don’t have antibodies even after vaccination, you have to be extra careful. You must be extra cautious.
How nutrition can help New Mothers regain their Immunity & safeguard themselves from Covid-19
When it comes to pregnancy, people become over cautious about health, environment, mental health, etc., and being over-anxious during a pandemic is natural.
Pregnant women are more vulnerable to viral infections due to modulation of the immune system leading to differential responses. Evidence has indicated that risks of SARS-CoV-2 in pregnancy are similar to that with general population. WHO indicates that pregnant women who are older, overweight, or have pre-existing medical conditions such as hypertension (high blood pressure) and diabetes are at particular risk of serious outcomes of COVID-19.
RCOG also mentioned that majority of pregnant women with COVID-19 were in their third trimester when admitted to the hospital. Therefore, it’s clearly indicated that women pregnant at 28 weeks or beyond are at highest risk.
Post child birth, returning to a “normal” pre-pregnant immune state is not well characterized and may take as long as an year after the birth. Most mothers are concerned about staying well as immune system is directly impacted by factors like childbirth, high level of stress, altered sleeping patterns, etc. We all can agree that during the early postpartum phase, a woman’s body works overtime to restore & repair itself; while some might take the slow & steady path, for others, it might be a complete U-turn bringing body back to the pre-pregnancy immunity.
WHO suggests that our diet can significantly impact our body’s ability to prevent, fight & recover from infections. There is no single food or dietary supplement that can cure or prevent Covid-19 infection, however, a healthy diet can support building a strong immune system. For mothers recovering from childbirth, immune system requires the support of many nutrients and several macro nutrients (protein, whole-carbohydrates, and essential fats) & micro nutrients (calcium, iron, folate, iodine, selenium, zinc, vitamin A, C, D, E,etc.) to replenish stores during postpartum phase.
Nutritional Goals for New Mothers
1. Since a year, we are witnessing thousands of people falling victim to COVID-19 on a daily basis. The biggest contributor to pre-existing heath conditions that put individuals at a far greater risk is their unhealthy diet. Unprocessed food should make up the bulk of every mother’s diet (breastfeeding or not). Due to high healing requirements, high quality nutrition will provide greater support.
2. If mother chooses to breastfeed, an additional 500 calorie (approx.) must be ingested to get adequate vitamins & minerals, otherwise body starts pulling body reserves to fulfil the nutritional requirements of the baby. Eating a diet with low nutritional value will negatively affect the mother, more than it will to the baby. Women diagnosed with COVID-19 are highly encouraged to breastfeed as these women produce specific antibodies called IgA that are believed to protect nursing infants from infection.
3. During early postpartum, if a mother has undergone a C-section or had perinealtearing, eating good proteins (a serving per meal) and variety of fruits & vegetables can promote tissue repair & healing.
4. Too much inflammation might hinder the healing process & it’s imperative to reduce and manage it in the first 24-48 hours. Consume dietary Sources like olive oil, fatty fish, nuts, fish oils, seeds, etc. that contain anti-inflammatory fats.
5. Hydration is essential to promote optimal cell function, kidney function, body temperature control, mood regulation, cognitive function, gastrointestinal and heart function, and headache prevention.
6. Go low on sugar. Consuming sugary drinks increases the intake of carbohydrates & calories, thereby raising blood glucose levels aggravating obesity & other diseases.
7. Adequate intake of essential micronutrients may be attained through a daily diet that includes meat, fish, lentils and beans, dairy foods, nuts, seeds, eggs, citrus fruits, kiwi, strawberries, and vegetables.
8. ACOG recommends of at least 150 minutes of moderate intensity aerobic activity per week during the postpartum period. It can help improving the conditions that are known to increase the susceptibility to Covid-19. We recommend slowly getting into a structured exercise regime to promote optimal healing under a specialized postnatal guide.
9. Sleep deprivation is an inevitable part of motherhood. Sudden shift in hormones, accumulated fatigue & high demand of caring for an infant can mess up with recovery, hence increasing the stress level. Stress being a stimulant to immune system can gravely impact recovery process overtime.
Postpartum nutrition should emphasize on a well-balanced diet using whole foods to provide both mother & baby the best nutrition possible, especially during the pandemic period. Nutrition goals should focus on optimal recovery, quality eating & maintaining hydration. Give yourself time to heal as a well-rested body recovers better.
By Ishav Lamba
Author is Health Coach at MyHealthBuddy, an Online Health & Fitness Platform.
Vaccine hesitancy lower in poorer countries
A new study has examined vaccine acceptance and hesitancy rates in ten low and middle-income countries from Asia, Africa, and South America. The research published in Nature Medicine reveals willingness to get a COVID-19 vaccine was considerably higher in developing countries (80 per cent of respondents) than in the United States (65 per cent) and Russia (30 per cent). The study provides one of the first insights into vaccine acceptance and hesitancy in a broad selection of low- and-middle income countries (LMIC), covering over 20,000 survey respondents and bringing together researchers from over 30 institutions including the International Growth Centre (IGC), Innovations for Poverty Action (IPA), WZB Berlin Social Science Center, the Yale Institute for Global Health, the Yale Research Initiative on Innovation and Scale (Y-RISE), and HSE University (Moscow, Russia).
Personal protection against COVID-19 was the main reason given for vaccine acceptance among LMIC respondents (91 per cent), and concern about side effects (44 per cent) was the most common reason for vaccine hesitancy. Health workers were considered the most trusted sources of information about COVID-19 vaccines.
The study comes at a critical juncture when vaccine shipments are still slow to arrive to the majority of the world’s population, and COVID-19 cases are surging in many parts of Africa, Asia, and Latin America. The findings suggest that prioritizing vaccine distribution to low- and middle-income countries should yield high returns in expanding global immunization coverage.
“As COVID-19 vaccine supplies trickle into developing countries, the next few months will be key for governments and international organizations to focus on designing and implementing effective vaccine uptake programs,” said Niccolo Meriggi, Country Economist for IGC Sierra Leone and study co-author.
VACCINE IMMUNE RESPONSE LINKED TO AGE
A new laboratory study from Oregon Health and Science University suggests that older people appear to have fewer antibodies against the novel coronavirus.The study was published in the Journal of the American Medical Association. Antibodies are blood proteins that are made by the immune system to protect against infection. They are known to be key players in protection against SARS-CoV-2 infection. “Our older populations are potentially more susceptible to the variants even if they are vaccinated,” said senior author Fikadu Tafesse, Ph.D., assistant professor of molecular microbiology and immunology in the OHSU School of Medicine.
Tafesse and colleagues emphasized that even though they measured diminished antibody response in older people, the vaccine still appeared to be effective enough to prevent infection and severe illness in most people of all ages.“The good news is that our vaccines are really strong,” Tafesse said.However, with vaccine uptake slowing in Oregon and across the United States, researchers say their findings underscore the importance of promoting vaccinations in local communities.
Vaccinations reduce the spread of the virus and new and potentially more transmissible variants, especially for older people who appear to be more susceptible to breakthrough infections. “The more people get vaccinated, the less the virus circulates,” Tafesse said. “Older people aren’t entirely safe just because they’re vaccinated; the people around them really need to be vaccinated as well. At the end of the day, this study really means that everybody needs to be vaccinated to protect the community.”
Researchers measured the immune response in the blood of 50 people two weeks after their second dose of the Pfizer vaccine against COVID-19. They grouped participants into age groups and then exposed their blood serum in test tubes to the original “wild-type” SARS-CoV-2 virus and the P.1 variant (also known as gamma) that originated in Brazil.
The youngest group – all in their 20s – had a nearly seven-fold increase in antibody response compared with the oldest group of people between 70 and 82 years of age. In fact, the laboratory results reflected a clear linear progression from youngest to oldest: The younger a participant, the more robust the antibody response.
“Older people might be more susceptible to variants than younger individuals,” Tafesse said.
Study links cognitive decline with bone loss, fracture risk in women
A new research has found that cognitive decline is linked with accelerated bone loss and increased fracture risk in women. The results of the study were published in the ‘Journal of Bone and Mineral Research’. The study was led by researchers from the Garvan Institute of Medical Research. According to the findings of the study, the association between cognitive decline and bone loss was weaker in men.
The study of individuals aged 65 and older was carried out over 16 years and has revealed a potential new approach to help identify older people who may be at risk of fracture. “Bone loss and cognitive decline are major public health issues, but both are ‘silent diseases’ that can go undetected and untreated for long periods, often until the conditions are severely progressed,” said Professor Jacqueline Center, Head of the Clinical Studies and Epidemiology lab at Garvan, an endocrinologist at St Vincent’s Hospital and senior author of the study.“Our study has revealed a link between the two in women, which suggests that cognition should be monitored together with bone health, as a decline in one could mean a decline in the other. These findings may help refine best practice guidelines of how cognition and bone health are monitored in older age, to ensure appropriate treatment can be more effectively administered,” added Jacqueline.
New insights on major public health issues. Around the world, 200 million people are affected by osteoporosis and more than 35 million by dementia – numbers which are expected to double over the next two decades due to a global increase in life expectancy. “Cognitive decline and bone loss both result in increased disability, loss of independence and an increased risk of mortality. There is some evidence that older individuals with dementia have a higher risk of hip fractures, but whether the decline of both bone and cognitive health are linked over time has not been studied,” said Dr Dana Bliuc from the Garvan Institute, who is the first author of the paper.
“We set out to understand the long-term association, with our study the first to investigate both cognitive and bone health data over more than 15 years,” added Dr Dana. The team used data from the Canadian Multicentre Osteoporosis Study (CaMos), which documented skeletal health in people living in the community since 1995.
The researchers looked at cognitive and bone health measurements of 1741 women and 620 men aged 65 years and older, who had no symptoms of cognitive decline at the beginning of the study. Linking cognition and bone health“After adjusting for all other variables, we observed a significant link between a decline in cognitive health and bone loss in women. This association was weaker and not statistically significant in men,” said Dr Dana. “Interestingly, we also saw that cognitive decline over the first five years was associated with a 1.7-fold increase in future fracture risk in women in the subsequent 10 years. This was independent of the level of bone loss,” added Dr Dana.
“While this study could not identify a causal link – whether a decline in cognitive function leads to a decline in bone loss, or vice versa – it suggests that cognitive decline should be monitored along with bone health, as a decline in one may signal the need for increased vigilance in the other,” said Professor Jacqueline.The researchers noted that the link could potentially be mediated by a third factor, such as estrogen deficiency, which affects women after menopause and has been independently associated with both bone loss and cognitive decline.This research also opens the door for additional studies into what the link between these two common conditions may be.
“What our study highlights is that cognitive health is potentially an important factor for providing more information to individuals and their health professionals on fracture risk, and ultimately improve health outcomes for our older population,” concluded Professor Jacqueline.
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