Food-borne bacteria up miscarriage risk early in pregnancy

Leading physicians are celebrating a small dose of good news that arrived Tuesday about dexamethasone, a cheap and widely used steroid shown to be able to save lives among COVID-19 patients, but also cautioning against releasing study results by press release during a global health emergency, like in the case of the latest dexamethasone study by University of Oxford.

"It will be great news if dexamethasone, a cheap steroid, really does cut deaths by one-third in ventilated patients with COVID19, but after all the retractions and walk backs, it is unacceptable to tout study results by press release without releasing the paper", Atul Gawande, surgeon and CEO of Haven Healthcare, tweeted.

"Bottom line is, good news," Dr. Fauci, America's foremost infectious diseases expert told a US newswire on Tuesday, soon after the dexamethasone results were announced in the UK.

Fauci, who has long championed the therapeutics-first view said that dexamethasone is a "significant improvement" in the available therapeutic options currently available.

On Medical Twitter and Facebook, doctors broadly agree that dexamethasone use aligns well with the way COVID19 attacks the body's immune system. Fauci said the results in the Oxford study make "perfect sense" in that context.

"We should see the number of people who actually survive go up, if the study holds up," virologist and epidemiologist Dr. Joseph Fair told a television network.

Global coronavirus cases crossed 8 million on Tuesday. In the US, Texas and Florida are facing a new wave of cases after lifting lockdown orders earlier than medical experts recommended. Amidst the relentless graph upwards, the dexamethasone study results injected hope for better survival rates among those most seriously ill.

World Health Organization chief scientist Soumya Swaminathan welcomed the results from the randomised control trial.

Dr Eugene Gu, Founder and CEO of CoolQuit tweeted that he is "genuinely impressed" with the UK dexamethasone trial. This may be a "game changer", he wrote.

"There's no conflict of interest as dexamethasone is a generic steroid. The mechanism of action makes sense because steroids can reduce cytokine storms and overactive immune systems that makes COVID-19 so deadly. The number needed to treat is 8 ventilated patients which is great."

The Oxford study found that dexamethasone reduced deaths by 35 percent in patients who needed treatment with breathing machines and by 20 percent in those only needing supplemental oxygen. Dexamethasone was one of 5 drugs studied in a large clinical trial in the United Kingdom named RECOVERY, short for Randomised Evaluation of COVID-19 Therapy.

Peter Horby, chief investigator of the University of Oxford clinical trial, said dexamethasone is the first drug to be shown to improve survival in COVID-19. Details of the study have not been released. The trial organisers said they made their announcement via a news release because of "the public health importance of these results." According to Horby's public comments, there was a lot of initial resistance to studying steroids.

During the study, 2,104 patients were randomly selected to be given 6 milligrams of dexamethasone once a day (either by mouth or by intravenous injection) for 10 days. That group was compared with 4,321 patients who received the usual care alone.

Researchers estimated that dexamethasone would prevent one death for every eight patients treated while on ventilators and one for every 25 patients on extra oxygen alone.

UK experts have called the study results a breakthrough in the fight against the virus. The researchers have promised they would publish the results soon.

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.

Washington D.C., Apr 4: While consuming a high-diet salt can result in high blood pressure, a recent study has revealed a link between salt-rich diet and weaker immune system.

The study was conducted under the leadership of the University Hospital Bonn, and the results were published in the journal Science Translational Medicine.

The research was conducted on mice that were fed a high-salt diet. Later, they were found to suffer from much more severe bacterial infections.

Human volunteers who consumed an additional six grams of salt per day also showed pronounced immune deficiencies.

The World Health Organization (WHO) has recommended a maximum amount of five grams of salt a day.

It corresponds approximately to one level teaspoon. In reality, however, many Germans exceed this limit considerably. 

Figures from the Robert Koch Institute suggest that on average men consume ten, and women more than eight grams a day.

This means that we reach for the salt shaker much more than is good for us. After all, sodium chloride, which is its chemical name, raises blood pressure and thereby increases the risk of heart attack or stroke.

"We have now been able to prove for the first time that excessive salt intake also significantly weakens an important arm of the immune system," said Prof. Dr. Christian Kurts from the Institute of Experimental Immunology at the University of Bonn.

This finding is unexpected, as some studies point in the opposite direction. For example, infections with certain skin parasites in laboratory animals heal significantly faster if these consume a high-salt diet.

The study also sheds light on the fact that the skin serves as a salt reservoir.

"Our results show that this generalization is not accurate," emphasized Katarzyna Jobin, lead author of the study.

The body keeps the salt concentration in the blood and in the various organs largely constant. Otherwise important biological processes would be impaired. The only major exception is the skin which functions as a salt reservoir of the body. This is why the additional intake of sodium chloride works so well for some skin diseases.

However, other parts of the body are not exposed to the additional salt consumed with food. Instead, it is filtered out by the kidneys and excreted in the urine.

"We examined volunteers who consumed six grams of salt in addition to their daily intake," said Prof. Kurts. This is roughly the amount contained in two fast-food meals, i.e. two burgers and two portions of French fries.

After one week, from the results, it showed that the immune cells coped much worse with bacteria after the test subjects had started to eat a high-salt diet.

In human volunteers, excessive salt intake also resulted in increased glucocorticoid levels.