Pfizer, BioNTech experimental COVID-19 vaccine shows promise in early trial: Study

Agencies
July 2, 2020

The American pharmaceutical giant Pfizer Inc. and the European biotechnology company BioNTech SE have conducted an experimental trial of a COVID-19 vaccine candidate and found it to be safe, well-tolerated, and capable of generating antibodies in the patients.

The study, which is yet to be peer-reviewed, describes the preliminary clinical data for the candidate vaccine -- nucleoside-modified messenger RNA (modRNA), BNT162b1.

It said the amount of antibodies produced in participants after they received two shots of the vaccine candidate was greater than that reported in patients receiving convalescent plasma from recovered COVID-19 patients.

"I was glad to see Pfizer put up their phase 1 trial data today. Virus neutralizing antibody titers achieved after two doses are greater than convalescent antibody titers," tweeted Peter Hotez, a vaccine scientist from Baylor College of Medicine in the US, who was unrelated to the study.

Researchers, including those from New York University in the US, who were involved in the study, said the candidate vaccine enables human cells to produce an optimised version of the receptor binding domain (RBD) antigen -- a part of the spike (S) protein of SARS-CoV-2 which it uses to gain entry into human cells.

"Robust immunogenicity was observed after vaccination with BNT162b1," the scientists noted in the study.

They said the program is evaluating at least four experimental vaccines, each of which represents a unique combination of mRNA format and target component of the novel coronavirus, SARS-CoV-2.

Based on the study's findings, they said BNT162b1 could be administered in a quantity that was well tolerated, potentially generating a dose dependent production of immune system molecules in the patients.

The research noted that patients treated with the vaccine candidate produced nearly 1.8 to 2.8 fold greater levels of RBD-binding antibodies that could neutralise SARS-CoV-2.

"We are encouraged by the clinical data of BNT162b1, one of four mRNA constructs we are evaluating clinically, and for which we have positive, preliminary, topline findings," said Kathrin U. Jansen, study co-author and Senior Vice President and Head of Vaccine Research & Development, Pfizer.

"We look forward to publishing our clinical data in a peer-reviewed journal as quickly as possible," Jansen said.

According to Ugur Sahin, CEO and Co-founder of BioNTech, and another co-author of the study, the preliminary data are encouraging as they provide an initial signal that BNT162b1 is able to produce neutralising antibody responses in humans.

He said the immune response observed in the patients treated with the experimental vaccine are at, or above, the levels observed from convalescent sera, adding that it does so at "relatively low dose levels."

"We look forward to providing further data updates on BNT162b1," Sahin said.

According to a statement from Pfizer, the initial part of the study included 45 healthy adults 18 to 55 years of age.

It said the priliminary data for BNT162b1 was evaluated in 24 subjects who received two injections of 10 microgrammes ( g) and 30 g -- 12 subjects who received a single injection of 100 g, and 9 subjects who received two doses of a dummy vaccine.

The study noted that participants received two doses, 21 days apart, of placebo, 10 g or 30 g of BNT162b1, or received a single dose of 100 g of the vaccine candidate.

According to the scientists, the highest neutralising concentrations of antibodies were observed seven days after the second dose of 10 g, or 30 g on day 28 after vaccination.

They said the neutralising concentrations were 1.8- and 2.8-times that observed in a panel of 38 blood samples from people who had contracted the virus.

In all 24 subjects who received two vaccinations at 10 g and 30 g dose levels, elevation of RBD-binding antibody concentrations was observed after the second injection, the study noted.

It said these concentrations are 8- and 46.3-times the concentration seen in a panel of 38 blood samples from those infected with the novel coronavirus.

At the 10 g or 30 g dose levels, the scientists said adverse reactions, including low grade fever, were more common after the second dose than the first dose.

According to Pfizer, local reactions and systemic events after injection with 10 g and 30 g of BNT162b1 were "dose-dependent, generally mild to moderate, and transient."

It said the most commonly reported local reaction was injection site pain, which was mild to moderate, except in one of 12 subjects who received a 100 g dose, which was severe.

The study noted that there was no serious adverse events reported by the patients.

Citing the limitations of the research, the scientists said the immunity generated in the participants in the form of the T cells and B cells of their immune system, and the level of immunity needed to protect one from COVID-19 are unknown.

With these preliminary data, along with additional data being generated, Pfizer noted in the statement that the two companies will determine a dose level, and select among multiple vaccine candidates to seek to progress to a large, global safety and efficacy trial, which may involve up to 30,000 healthy participants if regulatory approval to proceed is received.

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Agencies
February 6,2020

Researchers have found the rates of lung cancer are higher in young women than men.

The study, published in the journal Pediatrics, examined lung cancer rates in young adults in 40 countries across five continents and uncovered a trend of higher lung cancer rates in women compared with men in recent years.

The emerging trend was widespread, affecting countries across varied geographic locations and income levels.

The changes appeared to be driven by a rising rate of adenocarcinoma lung cancer among women, said the study researchers from University of Calgary in Canada.

Lung cancer rates have been higher among men than women because men started smoking in large numbers earlier and smoked at higher rates; however, recent studies have reported converging lung cancer incidence rates between sexes.

Among men, age specific lung cancer incidence rates generally decreased in all countries, while in women the rates varied across countries with the trends in most countries stable or declining, albeit at a slower pace compared to those in men.

For the findings, lung and bronchial cancer cases between 30-64 age group from 1993-2012 were extracted from cancer incidence in five continents.

The study found the higher emerging rates of lung cancer in young women compared to young men.

According to the researchers, future studies are needed to identify reasons for the elevated incidence of lung cancer among young women.

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Agencies
July 15,2020

The first COVID-19 vaccine tested in the US revved up people's immune systems just the way scientists had hoped, researchers reported Tuesday -- as the shots are poised to begin key final testing.

No matter how you slice this, this is good news, Dr. Anthony Fauci, the U.S. government's top infectious disease expert, told The Associated Press.

The experimental vaccine, developed by Fauci's colleagues at the National Institutes of Health and Moderna Inc., will start its most important step around July 27: A 30,000-person study to prove if the shots really are strong enough to protect against the coronavirus.

But Tuesday, researchers reported anxiously awaited findings from the first 45 volunteers who rolled up their sleeves back in March. Sure enough, the vaccine provided a hoped-for immune boost.

Those early volunteers developed what are called neutralizing antibodies in their bloodstream -- molecules key to blocking infection -- at levels comparable to those found in people who survived COVID-19, the research team reported in the New England Journal of Medicine.

This is an essential building block that is needed to move forward with the trials that could actually determine whether the vaccine does protect against infection, said Dr. Lisa Jackson of the Kaiser Permanente Washington Research Institute in Seattle, who led the study.

There's no guarantee but the government hopes to have results around the end of the year -- record-setting speed for developing a vaccine.

The vaccine requires two doses, a month apart.

There were no serious side effects. But more than half the study participants reported flu-like reactions to the shots that aren't uncommon with other vaccines -- fatigue, headache, chills, fever and pain at the injection site. For three participants given the highest dose, those reactions were more severe; that dose isn't being pursued.

Some of those reactions are similar to coronavirus symptoms but they're temporary, lasting about a day and occur right after vaccination, researchers noted.

Small price to pay for protection against COVID, said Dr. William Schaffner of Vanderbilt University Medical Center, a vaccine expert who wasn't involved with the study.

He called the early results a good first step, and is optimistic that final testing could deliver answers about whether it's really safe and effective by the beginning of next year.

It would be wonderful. But that assumes everything's working right on schedule, Schaffner cautioned.

Moderna's share price jumped nearly 15 percent in trading after US markets closed. Shares of the company, based in Cambridge, Massachusetts, have nearly quadrupled this year.

Tuesday's results only included younger adults. The first-step testing later was expanded to include dozens of older adults, the age group most at risk from COVID-19.

Those results aren't public yet but regulators are evaluating them. Fauci said final testing will include older adults, as well as people with chronic health conditions that make them more vulnerable to the virus and Black and Latino populations likewise affected.

Nearly two dozen possible COVID-19 vaccines are in various stages of testing around the world. Candidates from China and Britain's Oxford University also are entering final testing stages.

The 30,000-person study will mark the world's largest study of a potential COVID-19 vaccine so far. And the NIH-developed shot isn't the only one set for such massive U.S. testing, crucial to spot rare side effects. The government plans similar large studies of the Oxford candidate and another by Johnson & Johnson; separately, Pfizer Inc. is planning its own huge study.

Already, people can start signing up to volunteer for the different studies.

People think this is a race for one winner. Me, I'm cheering every one of them on, said Fauci, who directs NIH's National Institute of Allergy and Infectious Diseases.

We need multiple vaccines. We need vaccines for the world, not only for our own country. Around the world, governments are investing in stockpiles of hundreds of millions of doses of the different candidates, in hopes of speedily starting inoculations if any are proven to work.

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Agencies
June 30,2020

Between 30-40 per cent of deaths from studies in intensive care units from different countries are people with diabetes, said Paul Zimmet, Professor of Diabetes, Monash University, Australia.

Zimmet, who is President International Diabetes Federation, added that the actual mechanism as to why COVID-19 may cause diabetes is as yet unknown, however, several possibilities exist. "COVID-19 is a very destructive and cunning virus and causes terrible damage to tissues including the lungs and pancreas," said Zimmet. Below are excerpts from an exclusive chat with IANS.

Why do you say Diabetes is dynamite if a person has been infected with COVID-19?

There have been many deaths in many countries, e.g. Italy, China, the UK and US among people with diabetes after infection with COVID-19 (SARS-Cov-2).

The mortality tends to be mainly in older Type 2 diabetics. Between 30-40 per cent of deaths from studies in intensive care units from different countries are people with diabetes. This outcome and other complications from the virus, particularly pneumonia, are more likely in people with diabetes which is poorly controlled with high blood sugars (poor metabolic control).

Diabetes is often associated with other chronic conditions, including obesity, hypertension and heart disease compounding the risk. These latter conditions all convey higher risk to COVID-19 infections.

ACE-2, which binds to SARS-Cov-2 and allows the virus to enter human cells is also located in organs and tissues involved in glucose metabolism. Is there solid evidence that virus after entering tissues may cause multiple and complex impairment of glucose metabolism?

The actual mechanism as to why COVID-19 may cause diabetes is as yet unknown.

However, several possibilities exist. Firstly, COVID-19 is a very destructive and cunning virus and causes terrible damage to tissues, including the lungs and pancreas.

A new study just published showed that in miniature lab-grown pancreas, and other cells such as liver, made using human stem cells, COVID-19 caused destruction of the pancreas beta cells that produce insulin.

It is possible that the virus causes disruption of the cells by disrupting cellular metabolism. This is possibly the way it brings about new-onset diabetes. ACE-2 exists in high concentration in the lung as this also explains the terrible lung side effects of COVID-19 infections.

Can COVID-19 lead to a new mechanism of diabetes? Probably a new form of diabetes or a new form of disease?

The COVID-19 virus has only been with us for about 5 months and there is a huge amount that we still must learn about its cunning and devastating ways. The purpose of the Global COVIDIAB Diabetes Registry, a joint initiative of Monash University in Australia, and King’s College London is to gain a much better understanding of how common is the appearance of COVID-19 related diabetes, what form does it take be it type 1 or type 2 or a new form, and how common are the complications that we already know e.g. diabetic keto-acidosis, hyperosmolar coma and high insulin requirements are causing high rates of ill health and mortality worldwide. The knowledge gained will aid our understanding for developing strategies to prevent and treat this terrible virus that has caused destruction globally.

Diabetes is one of the most prevalent chronic diseases in India. According to a recent study, sugar levels of diabetic persons increased by 20 per cent during nationwide lockdown in India to contain COVID-19 outbreak. Even after lockdown was lifted, many people are confined within their home. Do you think lack of physical activity will create more problems for diabetics?

My own major research has been on studying populations with high rates of diabetes, including ethnic Indian communities including India, Mauritius, and Fiji so I am very well aware of this. It is now well established that along with diabetes, that associated poor metabolic control of their diabetes places these people at the highest risk for COVID infection and its devastating complications and the associated morbidity and mortality. And these communities have high prevalence of heart disease as well.

Lockdown not only has deleterious effects on metabolic control of the diabetes through reduced opportunities for exercise to be protective serious consequences of SARS-CoV-2 infection, lockdown usually results in disruption of the regular medical care and the regular monitoring of metabolic control. This may also be partly due to the stress and poor compliance, or inability to afford their medications such as insulin. It may also be compounded by inability to access the care during the pandemic. Nevertheless, we now know that poor metabolic control heightens their risk as described above.

You have said diabetes is itself a pandemic just like Covid-19, and the two pandemics could be clashing. How could governments address this problem?

These are “The Times of COVID-19”. Most nations of the world were totally unprepared for a pandemic of this magnitude. They underestimated its potential impact and the destructive nature of the viral infection. This should prompt all countries to upgrade their guidelines to take into account the lessons learnt on infection control including training of staff specialising in infectious diseases and improved public education and taking their communities into their confidence about the terrible nature of COVID-19. The risks of COVID-19 infection need a much higher priority in the general community, particularly for people with chronic conditions such as diabetes, obesity, and cardiac conditions.

Governments are faced with chronic diseases (NCDs) like diabetes and communicable diseases (CDs) like viral and enteric diseases and TB. In general WHO gives the highest priority to communicable diseases and much less attention and funding to chronic diseases like diabetes (I was an adviser to WHO for many years (about 30) on diabetes and obesity and it was very frustrating to deal with this situation).

This attitude to diabetes, for example, has a flow down effect so that diabetes funding in countries by governments, rich and poor, suffered and was insufficient.

So now we have a COVID-19 pandemic and who are those at highest risk, yes people with diabetes and other NCDs, it is very important that now the two, Diabetes and COVID-19 are clashing face-to-face. This is a major issue that WHO and national governments have to face with equal priority’

Stressed people suffering from diabetes run a greater risk of poor blood glucose levels, what do you suggest to these people?

As mentioned in the answer above, stress is an important factor in upsetting the blood sugar (metabolic) control of diabetes. Additive to this is poor compliance with medications and diet. These and potential associated comorbidities due to other chronic conditions are part of the dynamic dynamite mixture.

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