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How does underlying Cirrhosis influence Covid-19?

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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 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/(COVID-19) leads to the infection of many patients with underlying chronic liver diseases. To discuss about the same, we interviewed Dr. Shiv Kumar Sarin, Director of Institute of Liver and Biliary Sciences (ILBS); Dr. Anil Arora, Chairman, Institute Of Liver Gastroenterology & Pancreatico Biliary Sciences Sir Ganga Ram Hospital and Dr. Kaushal Madaan, principal director and head of Hepatology from Max chain of hospitals.

Question: Since there is a lot fear among people as far as Covid is concerned, how should a liver patient, someone who perhaps has fatty liver, liver cirrhosis, how should they go about their regular checkups? Should they visit hospitals? Should they consult you all over? What are they supposed to do?

Dr. Sarin: First of all we should know that liver is located on the right side of the body and weighs a kilogram and a half. It is one of the largest organs in the human body. If you put a lot of stuff on the liver, then it is not a healthy liver. If there is extra fat for too long, the liver will shrink and it may become fibrous, discard and late stages of cirrhosis.

Question: Those who already perhaps have these diseases, they also have a lot of apprehensions as far as their regular checkups are concerned, because that’s also extremely important for them. Should they skip it as of now, should they visit hospitals, or should they stick to video consultation? What would be your advice to those who already have liver diseases, but perhaps don’t have Covid, have an anxiety or fear of Covid in the back of their mind.

Dr. Sarin: Those who have fatty liver certainly are not having the disease. Fatty liver itself is just extra fat. But if somebody has cirrhosis and he knows somebody who has got alcohol liver injury or has 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 use a teleconsult or go to the hospital. What you can do at home is, of course, continue your own diet and the prescription that the doctor has given.

Question: We all know that because of the fear of Covid, there is a lot of concoction of medicines which many of us are consuming already. There are alternate medications that many people are taking. There were reports that Giloy could cause some liver damage, then later there were reports no it doesn’t do that.

What would be your stand on this alternative medication when it comes to avoiding Coronavirus or just taking these medications as a precaution?

Dr. Arora: Liver is an organ that does not require any servicing, does not require any maintenance till you intentionally or accidentally try to injure it. You do not need any medication. You do not need a specific diet. You do not need any type of maintenance, but do everything to prevent the damage.

Two major reasons why the liver gets damaged is, if you are having too much 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 integrated metabolism of fat, carbohydrates as well as proteins. It also is known to produce a number of coagulation and anticoagulation factors.

In fact, there have been excellent guidelines from CDC, from our own ICMR and the Government of India and AIIMS, which tell us that we need 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 metabolized 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.

Question: But I specifically mentioned giloy because there is a lot of debate around it. And also it’s not just giloy, but a lot of as I said ayurvedic, alternative medication which people are taking. Dr. Kaushal, would you also perhaps tell your patients to stay off this concoction of alternative medicine, medicine that claim to be herbal and perhaps give you better immunity against Coronavirus?

Dr. Kaushal: These herbal and alternative medicines, even before this pandemic of Covid started, we have been advising our patients, whether or not they have underlying liver disease, to avoid taking herbal medicines of whose ingredients we are not sure of. When this pandemic came, we realised that there were many patients who were coming into 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. In fact, you would have recently seen a publication published in an indexed journal that presented about five or six cases similar to what I have been talking about and I think all of us would have seen such cases. See, how we make a diagnosis is by the exclusion of all other possibilities. We could not find any cause and only this thing stood apart, as patients were using kadhas… I don’t know what kind of mixtures they were having, what kind of concoctions… Two times a day, three times a day, for almost a year they were having it and they landed up with liver injuries. So I definitely think that these are the culprits in such cases.

Question: Could it also affect a healthy patient, someone who has a healthy liver and they start to take alternate medication? What would be your advice to them?

Dr. Sarin: Any medicine whether allopathic, homoeopathic or ayurvedic or preparation can be harmful or beneficial. I do not know much about the homeopathic or allopathic medicines. I can certainly say that there are certain herbs that can be harmful. No medicine should be consumed without a scientifically proven safety.

Secondly, a healthy liver is a necessity for better immunity. As far as covid is concerned, the infection initially transits to the lungs and then to the liver where it finally settles. This is called bystander hepatitis. Bystander implies that whatever Corona does, harm to the liver is possible.  has severe Covid, he will have something like 70% of them will have liver enzymes being normal. In mild Covid, 10-20% will be having liver enzymes normal. Food can injure the liver, drugs which are taken, preparations that are taken, all can cause injury to the liver.

Question: Talking of drugs, there were reports that azithromycin, remdesivir, those drugs could also affect the liver, but they were widely prescribed by physicians. What would you say to liver patients? Should they stay off these drugs? And those who get serious, perhaps their families are told to administer remdesivir. What are they supposed to do then?

Dr. Sarin: So, remdesiver 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. If you have read some very interesting Lancet papers, Corona 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. Secondly, if somebody is also mixing alcohol with Corona pills and ppl were staying home, they were drinking.

Question: Dr. Arora, I know a lot of patients, not liver patients but younger ones who are comorbid, have diabetes etc. The day they recovered, the first question they have in mind is that can I have a drink now? What would you say to those who have liver diseases, perhaps got Corona, have recovered and are craving a drink?


Dr. Arora: See 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, socializing 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 something that 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.

Question: Does Covid affect them more severely if they have liver cirrhosis? And what about those who have had a liver transplant?

Dr. Kaushal: There is ample data to suggest that patients who have fatty liver disease have a very severe lung disease when they acquire Covid. They have very poor outcomes and more of them end up in the ICU, end up with ventilatory support. Patients who are just at the stage of waiting for a transplant, are the ones who have advanced liver diseases. So, obviously, if they acquire 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 immunossuppressed, they’re not able to mount an immunoinflammatory response to Covid so they may have mild disease. But this is a controversial issue and more and more data is coming in.

Question: Is the severity or risk of Covid a lot more once they catch it? Secondly, is the treatment for them different? Is it special treatment or they take the same medication as the general population who catches the virus? And if someone has liver disease, generally when people catch Covid, they go to general physicians. Should they also consult their liver doctor in the loop about the medications they are taking?

Dr, Sarin: If the transplant was done within the last three months, corona 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 corona infection, there is a problem again. Corona does not make people worse, but they are already predisposed to other illnesses.

Liver is the root cause of diabetes and blood pressure and high triglycerides. If you have fatty liver or is obese, diabetic, is comorbid, he must look at the liver enzymes. Covid 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.

Question: What about liver patients? Once they recover, what is the post-Covid care that they need? What are the tests which are required and why would you say they shouldn’t throw caution to the wind? Perhaps why would you say that those who have liver diseases have recovered from Covid should still be cautious and should still measure their parameters? 

Dr. Arora: All those who suffer from Covid are likely to come down with something called ‘Long Covid’ There is a multitude of reasons for that. You may have a bit of virus or the immune process which may still be simmering around the body. Or you may have an immune complex disease that may be present or activation of the immune system. Now coming back to the liver, in patients with liver disease, if you have a concomitant Covid, you may have multiple reasons why the liver can get affected. It may occur because of 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.

A number of drugs that are given to treat Covid have indirect toxicity on the liver. If you have had a recent infection, you are likely to come down with more complications. You have to regularly follow up with a liver specialist if you have underlying liver disease.

Question: what would you tell all your patients, should they go, and get vaccinated at the earliest? Perhaps it is these patients who already are susceptible, who already have compromised immunity, who need to get vaccinated at the earliest.

Dr. Kaushal: I totally agree. I feel that there is a lot of vaccine hesitancy, especially in patients who have comorbidities. Since they have an underlying disease, they have anxiety that whether the vaccine will suit them or not or whether it is going to cause harm to them. So we keep getting phone calls and patients want to ask one thing that should we get vaccinated? So answer for all of that is whether they have early liver disease or advanced liver disease, they are best in a vaccinated state. So they should all get vaccinated, whichever stage of liver they are in. Because if they don’t take and if they have advanced liver disease and if they catch the infection then definitely the outcomes are going to be worse. So one-line answer is that any patient who has any kind of liver disease must take a vaccine.

Question:  What is the post-Covid care? I would like to ask you also this question because a lot of people seem to be ignoring that.

Dr. Sarin: First, patients with liver disease have weak muscles. We call it sarcopenia. Even if they are obese, they have very limited muscle power. If your liver is weak, your muscles are also weak and after Covid there is extreme fatigue, loss of appetite. You have to work extra, be more careful about this, and get your antibodies done if you need them.

The second important thing for a patient with cirrhosis after Covid is gone is to remember that the liver can digest more fats than it can digest pure carbohydrates. So just avoid carbs. Your main diet should remain protein-based, good whey protein or something and then next, the energy source can be fat. But yes exercises are very essential. It’s very difficult for patients who have got cirrhosis and Covid.

Question: A question that comes to the mind of liver patients is that they already have compromised immunity, they may not have enough antibodies. So, is the vaccine even good enough for me? What if I don’t end up making antibodies?

Dr. Arora: If you look at the various registration trial which was conducted in both US and UK, the initial registration trial excluded patients who had chronic liver diseases or those with an immunocompromised state. In fact, there is data published on Pfizer’s registration trial which has shown that in patients who have advanced liver disease and those who had undergone liver transplantation, the chance of development of antibodies is only 20%. So 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 you can be more confident that you won’t have the viral infection, do not be under the wrong impression that you have been protected. If you do not have antibodies even after vaccination, you have to be extra careful. You have to use double the precaution which a normal person uses. You just cannot move out to public places. You must be extra cautious.

Question: As we conclude what will be your one message to all the liver patients, all those who are suffering from liver diseases, one as far as prevention is concerned and two, in case they get Covid?

Dr. Kaushal: So I think in terms of prevention, I think everyone knows in the last one and a half years what they have to do in order to prevent getting Covid, that is masking, social distancing and washing hands. So that is one message which is true even for patients who have underlying liver disease. Second, they should not fear. Patients who have the early liver disease may not fear. They will have outcomes that are similar to the normal population. Only, those patients who have advanced liver disease, advanced fatty liver, obese, diabetic and post-transplant patients are the ones who need to fear and therefore need to take more precautions and they should get vaccinated as early as possible. And they should avoid like we said the herbal and these kinds of concoctions which contain unscientific mixtures of medicines that might harm the liver. So these are my messages.

Question: What would you say to assuage the fear of perhaps those who already have liver diseases and generally have a fear of Covid? We were speaking earlier of transplant as well, should perhaps people keep such procedures at bay or go ahead with them?

Dr. Sarin: Well the first message for those who do not have liver diseases is to reboot yourself. Lose weight, be careful. Only a healthy body will sustain the onslaught of any Covid infection. So be ready and be healthy. For those who have liver disease, be extra cautious. Transplants are going on and in fact, nearly a hundred have been done during the Covid era at ILBS and I’m sure at many many other centres. So please if you need a transplant, you should go, get yourself transplanted. But yes those who are not… one in a hundred gets a transplant, all other patients, 99 out 100 please be careful. Be in touch with your doctors and specialists. Do not miss your drugs and get your regular screening done. Must get vaccinated for Covid and do not let your guards down. Have Covid appropriate behaviour. You will live normally and you will pass through this Covid. Don’t be worried. But be careful, don’t make a mistake. 

Question: as far as Covid is concerned, we were speaking of course in extensive detail about managing your liver diseases, preventing Covid. Final question for those who have liver diseases, should they continue the medication which they were taking earlier or should they halt at a time when they have Covid and perhaps are taking Covid medication coz there is a lot of confusion amongst the laymen on the same?

Dr. Arora: Ya. I think almost all medication that is necessary for the management of liver diseases can be continued under the supervision of a trained doctor. That goes without saying. We have very few active Covid cases now and I am sure that doctors are good enough to know what sort of combination is safe for them. Coming on to the message that I have to give. Starting with what Dr. Sarin said about the liver on the right side, I think you should always listen to your heart. The heart is always on the left side but it is always right. So if you have learnt any lesson during this devilish perfidious second wave which has killed millions of people. If you have learnt something then have some civility, behave properly, get vaccinated and do not just move out of the house. You should remember till everybody is safe, you cannot be safe. The whole world has to get vaccinated before you can lower your guard. So listen to your heart if you have understood something from this devilish virus.

One clear message coming from all the doctors collectively here is that prevention is better than cure. Stay home. It gains all the more significance considering we have those viral pictures of people holidaying in Manali. Don’t do that. We have these doctors who are working a lot for us. Let’s keep ourselves safe.

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Giloy – Benefits and afflictions

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A year and a half has 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 an effective treatment and vaccine, many clinical trials were happening around the world and herbs emerged as a possible alternate 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 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.”

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Unusual Large And Multiple Liver Abscesses in Patient Recovered From COVID-19

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During the second wave of the COVID-19, in April-May 2021, a number of COVID-19 patients presented with some unusual manifestations. We saw for the first time in last two months unusually large and multiple liver abscesses in fourteen patients after recovery from COVID-19 infection. Liver abscess (Pus formation in Liver) is commonly caused by a parasite known as Entamoeba histolytica (Picture attached) which is transmitted by contaminated food and water.

According to Prof. Anil Arora, Chairman, Institute of Liver Gastroenterology and Pancreaticobiliary Sciences, Sir Ganga Ram Hospital, New Delhi, “What we found unusual was that after recovery from Covid within 22 days in patients who were otherwise immunocompetent had large areas of both lobes of liver filled with pus at multiple locations requiring drainage and hospitalization.”

Prof. Anil Arora, further added “These patients were of age group between 28-74 yrs, ten were males and four females. All patients had fever and upper abdominal pain and 3 patients also had associated lower GI bleeding with black coloured stools. Eight of these patients received steroids for the management of COVID-19 symptoms. Six patients had multiple large abscesses in both lobes of liver of which 5 patients had unusually large abscess (>8cm) the largest being 19 cm size (Figures attached). Three patients who had blood in stools showed ulcers in large intestine which were detected by colonoscopy (large intestine were seen through a camera). Median duration between COVID-19 symptoms and diagnosis of liver abscess was 22 days. Thirteen out of Fourteen patients were successfully treated with antibiotics, Metronidazole medications and drainage of pus from the liver. While one patient with large multiple abscesses died due to massive bleeding in abdomen after rupture of abscess in the abdominal cavity. Rest are stable and have been discharged.”

Prof. Anil Arora also said that “In our patients we found multiple and large abscesses which is very unusual for an immunocompetent person. We believe that suppression of immunity by COVID-19 infection along with use of steroids to treat Covid infection per se, low index of suspicion for liver abscess and delay in treatment in patients recuperating from Covid in this pandemic probably led to development of multiple and large abscesses in Liver.”

Entamoeba histolytica is a common parasite in countries with poor sanitation services. This parasite causes amoebiasis, an intestinal infection that is also called amoebic dysentery. After an infection has occurred, the parasite may be carried by the bloodstream from the intestines to the liver and causes liver abscess. Normally these abscesses are single and not very large and picked up early on routine ultrasonography of the abdomen as a part of workup for fever and associated symptoms in immunocompetent patients. Poor nutrition, immunocompromised status (like in HIV and cancer patients) and steroid use predisposes patients to these infections by amoeba causing liver abscesses.

In this present pandemic, a high index of suspicion of such infections in the form of fever and pain in right abdomen merits a timely intervention in the form of an early diagnosis and effective medical therapy can effectively save uncalled misery and avoidable hospitalization in these patients, said Dr. Praveen Sharma, Senior Consultant Gastroenterology, Sir Ganga Ram hospital.

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CHEMICALS FOUND IN CONSUMER PRODUCTS COULD INCREASE BREAST CANCER RISK

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A new study has shown that several common chemicals, including ingredients in consumer products and drinking water contaminants, could increase the risk of breast cancer by causing cells in breast tissue to produce more of the hormones estrogen or progesterone. The findings of the study appeared in the journal ‘Environmental Health Perspectives’. Every day, people are exposed to synthetic chemicals through the products they use. For many of these chemicals, the health effects are unknown.

However, this study has found the adverse effects of these chemicals and how it may increase the risk of breast cancer. “The connection between estrogen and progesterone and breast cancer is well established,” said co-author Ruthann Rudel, a toxicologist and research director at Silent Spring Institute. “So, we should be extremely cautious about chemicals in products that increase levels of these hormones in the body,” added Rudel. For instance, in 2002, when the Women’s Health Initiative study found combination hormone replacement therapy to be associated with an increased risk of breast cancer, women stopped taking the drugs and incidence rates went down.

“Not surprisingly, one of the most common therapies for treating breast cancer is a class of drugs called aromatase inhibitors that lower levels of estrogen in the body, depriving breast cancer cells of the hormones they need to grow,” said Rudel. To identify these chemical risk factors, Rudel and Silent Spring scientist Bethsaida Cardona combed through data on more than 2000 chemicals generated by the US Environmental Protection Agency (EPA)’s ToxCast program.

The goal of ToxCast is to improve the ability of scientists to predict whether a chemical will be harmful or not. The program uses automated chemical screening technologies to expose living cells to chemicals and then examine the different biological changes they cause.

Reporting in the journal Environmental Health Perspectives, Rudel and Cardona identified 296 chemicals that were found to increase estradiol or progesterone in cells in the laboratory. 71 chemicals were found to increase levels of both hormones. The chemicals included ingredients in personal care products, chemical flame retardants in building materials and furnishings, and a number of pesticides.

The researchers don’t yet know how these chemicals are causing cells to produce more hormones. It could be the chemicals are acting as aromatase activators, for instance, which would lead to higher levels of estrogen, said Cardona. “What we do know is that women are exposed to multiple chemicals from multiple sources on a daily basis, and that these exposures add up.” The Silent Spring researchers hope this study will be a wake-up call for regulators and manufacturers in how they test chemicals for safety.

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Covid-19 antibodies persist at least nine months after infection

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A new study led by researchers at Imperial College London and University of Padua shows antibody levels remain high nine months after SARS-CoV-2 infection, whether symptomatic or asymptomatic. The results of the study were published in the journal Nature Communications. Researchers tested more than 85 per cent of the 3,000 residents of Vo’, Italy, in February/March 2020 for infection with SARS-CoV-2, the virus that causes COVID-19, and tested them again in May and November 2020 for antibodies against the virus.

The team found that 98.8 per cent of people infected in February/March showed detectable levels of antibodies in November, and there was no difference between people who had suffered symptoms of COVID-19 and those that had been symptom-free. Antibody levels were tracked using three ‘assays’ – tests that detect different types of antibodies that respond to different parts of the virus. The results showed that while all antibody types showed some decline between May and November, the rate of decay was different depending on the assay.

The team also found cases of antibody levels increasing in some people, suggesting potential re-infection with the virus, providing a boost to the immune system.

Lead author Dr Ilaria Dorigatti, from the MRC Centre for Global Infectious Disease Analysis and the Abdul Latif Jameel Institute for Disease and Emergency Analytics (J-IDEA) at Imperial, said: “We found no evidence that antibody levels between symptomatic and asymptomatic infections differ significantly, suggesting that the strength of the immune response does not depend on the symptoms and the severity of the infection. “However, our study does show that antibody levels vary, sometimes markedly, depending on the test used. This means that caution is needed when comparing estimates of infection levels in a population obtained in different parts of the world with different tests and at different times.”

Professor Enrico Lavezzo, from the University of Padua, said: “The May testing demonstrated that 3.5 per cent of the Vo’ population had been exposed to the virus, even though not all of these subjects were aware of their exposure given the large fraction of asymptomatic infections. “However, at the follow-up, which was performed roughly nine months after the outbreak, we found that antibodies were less abundant, so we need to continue to monitor antibody persistence for longer time spans.”

The team also investigated the infection status of household members, to estimate how likely an infected member is to pass on the infection within the household. Their modelling suggests that there was a probability of about 1 in 4 that a person infected with SARS-CoV-2 passes the infection to a family member and that most transmission (79 per cent) is caused by 20 per cent of infections.

This finding confirms that there are large differences in the number of secondary cases generated by infected people, with the majority of infections generating no further infections and a minority of the infections generating a large number of infections.

The large differences in how one infected person may infect others in the population suggest that behavioural factors are key for epidemic control, and physical distancing, as well as limiting the number of contacts and mask-wearing, continue to be important to reduce the risk of transmitting the disease, even in highly vaccinated populations. The team’s dataset, which includes the results of the two mass PCR testing campaigns conducted in February and March and the antibody survey conducted in May and then again in November, also allowed them to tease apart the impact of various control measures.

They showed that, in the absence of case isolation and short lockdowns, manual contact tracing alone would not have been enough to suppress the epidemic.

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STUDY SHOWS WHY SECOND DOSE OF COVID-19 VACCINE SHOULD NOT BE SKIPPED

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The second dose of a COVID-19 vaccine induces a powerful boost to a part of the immune system that provides broad antiviral protection, according to a study led by investigators at the Stanford University School of Medicine.

The findings published in the journal Nature strongly supports the view that the second shot should not be skipped. “Despite their outstanding efficacy, little is known about how exactly RNA vaccines work,” said Bali Pulendran, PhD, professor of pathology and of microbiology and immunology. “So we probed the immune response induced by one of them in exquisite detail.”

The study was designed to find out exactly what effects the vaccine, marketed by Pfizer Inc., has on the numerous components of the immune response.

The researchers analyzed blood samples from individuals inoculated with the vaccine. They counted antibodies, measured levels of immune-signalling proteins and characterized the expression of every single gene in the genome of 242,479 separate immune cells’ type and status. “The world’s attention has recently been fixed on COVID-19 vaccines, particularly on the new RNA vaccines,” said Pulendran, the Violetta L. Horton Professor II.

He shares senior authorship of the study with Kari Nadeau, MD, PhD, the Naddisy Foundation Professor of Pediatric Food, Allergy, Immunology, and Asthma and professor of paediatrics, and Purvesh Khatri, PhD, associate professor of biomedical informatics and of biomedical data science. The study’s lead authors are Prabhu Arunachalam, PhD, a senior research scientist in Pulendran’s lab; medical student Madeleine Scott, PhD, a former graduate student in Khatri’s lab; and Thomas Hagan, PhD, a former postdoctoral scholar in Pulendran’s Stanford lab and now an assistant professor at the Yerkes National Primate Research Center in Atlanta. “This is the first time RNA vaccines have ever been given to humans, and we have no clue as to how they do what they do: offer 95% protection against COVID-19,” said Pulendran.

Traditionally, the chief immunological basis for approval of new vaccines has been their ability to induce neutralizing antibodies: individualized proteins, created by immune cells called B cells, that can tack themselves to a virus and block it from infecting cells. “Antibodies are easy to measure,” Pulendran said. “But the immune system is much more complicated than that. Antibodies alone don’t come close to fully reflecting its complexity and potential range of protection.”

Pulendran and his colleagues assessed goings-on among all the immune cell types influenced by the vaccine: their numbers, their activation levels, the genes they express and the proteins and metabolites they manufacture and secrete upon inoculation.

One key immune-system component examined by Pulendran and his colleagues were T cells: search-and-destroy immune cells that don’t attach themselves to viral particles as antibodies do but rather probe the body’s tissues for cells bearing telltale signs of viral infections. On finding them, they tear those cells up.

In addition, the innate immune system, an assortment of first-responder cells, is now understood to be of immense importance.

It’s the body’s sixth sense, Pulendran said, whose constituent cells are the first to become aware of a pathogen’s presence. Although they’re not good at distinguishing among separate pathogens, they secrete “starting gun” signalling proteins that launch the response of the adaptive immune system- the B and T cells that attack specific viral or bacterial species or strains. During the week or so it takes for the adaptive immune system to rev up, innate immune cells perform the mission-critical task of holding incipient infections at bay by gobbling up — or firing noxious substances, albeit somewhat indiscriminately, at — whatever looks like a pathogen to them.

The Pfizer vaccine, like the one made by Moderna Inc., works quite differently from the classic vaccines composed of live or dead pathogens, individual proteins or carbohydrates that train the immune system to zero in on a particular microbe and wipe it out. The Pfizer and Moderna vaccines instead contain genetic recipes for manufacturing the spike protein that SARS-CoV-2, the virus that causes COVID-19, uses to latch on to cells it infects.

In December 2020, Stanford Medicine began inoculating people with the Pfizer vaccine. This spurred Pulendran’s desire to assemble a complete report card on the immune response to it. The team selected 56 healthy volunteers and drew blood samples from them at multiple time points preceding and following the first and second shots. The researchers found that the first shot increases SARS-CoV-2-specific antibody levels, as expected, but not nearly as much as the second shot does. The second shot also does things the first shot doesn’t do, or barely does.

“The second shot has powerful beneficial effects that far exceed those of the first shot,” Pulendran said. “It stimulated a manifold increase in antibody levels, a terrific T-cell response that was absent after the first shot alone, and a strikingly enhanced innate immune response.”

Unexpectedly, Pulendran said, the vaccine — particularly the second dose — caused the massive mobilization of a newly discovered group of first-responder cells that are normally scarce and quiescent. First identified in a recent vaccine study led by Pulendran, these cells- a small subset of generally abundant cells called monocytes that express high levels of antiviral genes — barely budge in response to actual COVID-19 infection. But Pfizer vaccine-induced them.

This special group of monocytes, which are part of the innate museum, constituted only 0.01 per cent of all circulating blood cells prior to vaccination. But after the second Pfizer vaccine shot, their numbers expanded 100-fold to account for a full 1 per cent of all blood cells.

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COGNITIVE DEFICITS IN CHILDREN BORN PRETERM LINKED TO HIGH DAILY SCREEN TIME

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During a recent study, researchers found that among six and seven-year-olds who were born before the 28th week of pregnancy and those who had more than two hours of screen time a day were more likely to have deficits in overall IQ, executive functioning, impulse control, and attention. The findings of the study appeared in the journal ‘JAMA Pediatrics’. According to the study, those who had a television or computer in their bedrooms were more likely to have problems with impulse control and paying attention.

The findings suggested that high amounts of screen time may exacerbate the cognitive deficits and behavioural problems common to children born extremely preterm.

The study was conducted by Betty R. Vohr, M.D., and colleagues. Funding was provided by NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Heart, Lung, and Blood Institute; and National Center for Advancing Translational Sciences.

Previous studies have linked high amounts of screen time among children born full-term to language and developmental, behavioral and other problems.

In the current study, researchers analysed data from a study of children born at 28 weeks or earlier. Of 414 children, 238 had more than two hours of screen time per day and 266 had a television or computer in their bedrooms. Compared to children with less screen time per day, those with high amounts of screen time scored an average deficit of nearly 8 points on global executive function percentile scores, roughly 0.8 points lower on impulse control (inhibition) and more than 3 points higher on inatten

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