COVID-19 may trigger new diabetes

Emerging evidence suggests that COVID-19 may actually trigger the onset of diabetes in healthy people and also cause severe complications of pre-existing diabetes.

A letter published today in the New England Journal of Medicine and signed by an international group of 17 leading diabetes experts involved in the CoviDiab Registry project, a collaborative international research initiative, announces the establishment of a Global Registry of new cases of diabetes in patients with COVID-19.
The Registry aims to understand the extent and the characteristics of the manifestations of diabetes in patients with COVID-19, and the best strategies for the treatment and monitoring of affected patients, during and after the pandemic.
Clinical observations so far show a bi-directional relationship between COVID-19 and diabetes. On the one hand, diabetes is associated with increased risk of COVID-19 severity and mortality. Between 20 and 30% of patients who died with COVID-19 have been reported to have diabetes. On the other hand, new-onset diabetes and atypical metabolic complications of pre-existing diabetes, including life-threatening ones, have been observed in people with COVID-19.
It is still unclear how SARS-Cov-2, the virus that causes COVID-19, impacts diabetes. Previous research has shown that ACE-2, the protein that binds to SARS-Cov-2 allowing the virus to enter human cells, is not only located in the lungs but also in organs and tissues involved in glucose metabolism such as the pancreas, the small intestine, the fat tissue, the liver and the kidney. Researchers hypothesize that by entering these tissues, the virus may cause multiple and complex dysfunctions of glucose metabolism. It has also been known for many years that virus infections can precipitate type 1 diabetes.
Francesco Rubino, Professor of Metabolic Surgery at King’s College London and co-lead investigator of the CoviDiab Registry project, said: “Diabetes is one of the most prevalent chronic diseases and we are now realizing the consequences of the inevitable clash between two pandemics. Given the short period of human contact with this new coronavirus, the exact mechanism by which the virus influences glucose metabolism is still unclear and we don’t know whether the acute manifestation of diabetes in these patients represent classic type 1, type 2 or possibly a new form of diabetes”.
Paul Zimmet, Professor of Diabetes at Monash University in Melbourne, Honorary President of the International Diabetes Federation and co-lead investigator in the CoviDiab Registry project said: “We don’t yet know the magnitude of the new onset diabetes in COVID-19 and if it will persist or resolve after the infection; and if so, whether or not or COVID-19 increases risk of future diabetes. By establishing this Global Registry, we are calling on the international medical community to rapidly share relevant clinical observations that can help answer these questions”.
Stephanie Amiel, Professor of Diabetes Research at King’s College London and a co-investigator of the CoviDiab Registry project said: “The registry focuses on routinely collected clinical data that will help us examine insulin secretory capacity, insulin resistance and autoimmune antibody status to understand how COVID-19 related diabetes develops, its natural history and best management. Studying COVID-19-related diabetes may uncover novel mechanisms of disease.”

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More information: New England Journal of Medicine (2020). DOI: 10.1056/NEJMc2018688

https://medicalxpress.com/news/2020-06-covid-trigger-diabetes-experts.html

Up to 45 percent of SARS-CoV-2 infections may be asymptomatic

An extraordinary percentage of people infected by the virus behind the ongoing deadly COVID-19 pandemic never show symptoms of the disease, according to the results of a Scripps Research analysis of public datasets on asymptomatic infections.

The findings, published in Annals of Internal Medicine, suggest that asymptomatic infections may account for as much as 45 percent of all COVID-19 cases, playing a significant role in the early and ongoing spread of COVID-19. The report highlights the need for expansive testing and contact tracing to mitigate the pandemic.
“The silent spread of the virus makes it all the more challenging to control,” says Eric Topol, MD, founder and director of the Scripps Research Translational Institute and professor of Molecular Medicine at Scripps Research. “Our review really highlights the importance of testing. It’s clear that with such a high asymptomatic rate, we need to cast a very wide net, otherwise the virus will continue to evade us.”
Together with behavioral scientist Daniel Oran, Topol collected information from testing studies on 16 diverse cohorts from around the world. These datasets—gathered via keyword searches of PubMed, bioRxiv and medRxiv, as well as Google searches of relevant news reports—included data on nursing home residents, cruise ship passengers, prison inmates and various other groups.
“What virtually all of them had in common was that a very large proportion of infected individuals had no symptoms,” says Oran. “Among more than 3,000 prison inmates in four states who tested positive for the coronavirus, the figure was astronomical: 96 percent asymptomatic.”
The review further suggests that asymptomatic individuals are able to transmit the virus for an extended period of time, perhaps longer than 14 days. The viral loads are very similar in people with or without symptoms, but it remains unclear whether their infectiousness is of the same magnitude. To resolve that issue, we’ll need large-scale studies that include sufficient numbers of asymptomatic people.
The authors also conclude that the absence of symptoms may not imply an absence of harm. CT scans conducted on 54 percent of 76 asymptomatic individuals on the Diamond Princess cruise ship, appear to show significant subclinical lung abnormalities raising the possibility of SARS-CoV-2 infection impacting lung function that might not be immediately apparent. The scientists say further research is needed to confirm the potential significance of this finding.
The authors also acknowledge that the lack of longitudinal data makes distinguishing between asymptomatic and presymptomatic individuals difficult. An asymptomatic individual is someone who is infected with SARS-CoV-2, but never develops symptoms of COVID-19, while a presymptomatic person is similarly infected, but will eventually develop symptoms. Longitudinal testing, which refers to repeated testing of individuals over time, would help differentiate between the two.
“Our estimate of 40 to 45 percent asymptomatic means that, if you’re unlucky enough to get infected, the probability is almost a flip of a coin on whether you’re going to have symptoms. So to protect others, we think that wearing a mask makes a lot of sense,” Oran concludes.
More information: Daniel P. Oran et al, Prevalence of Asymptomatic SARS-CoV-2 Infection, Annals of Internal Medicine (2020). DOI: 10.7326/M20-3012
https://medicalxpress.com/news/2020-06-percent-sars-cov-infections-asymptomatic.html

Should oral polio vaccine be tested to see if it helps against Covid?

In a Perspective piece published in the journal Science, a small international team of researchers is suggesting that the oral polio vaccine be tested to see if it might protect people from infection by the SARS-CoV-2 virus. In their paper, Konstantin Chumakov, Christine Benn, Peter Aaby, Shyamasundaran Kottili and Robert Gallo suggest the vaccine has been found to provide some protection against other viral infections, and point out that it has been proven to be safe over many years.

Polio vaccines are, of course, vaccines that are used to prevent poliomyelitis infections. They have been in use since the 1950s. Polio vaccines come in two varieties: inactivated (administered by injection) and weakened (administered orally). Together, the two vaccines have nearly eradicated polio. They have also been found to confer some degree of immunity against other types of infections, both bacterial and viral. In their paper, the researchers argue for testing to see if the oral (weakened) vaccine might prove effective in preventing COVID-19 infections.
They confer some degree of immunity against other infections because they activate an innate immune response, known as the first line of defense response. In contrast, immunity is conferred against certain viruses when a person is infected with it specifically, because the body produces antibodies specifically geared towards fighting it. The authors of the Perspective piece suggest that activating the first line of defense via the oral vaccine may be all some people need to ward off COVID-19 infections. They note also that recent research has shown that the SARS-CoV-2 virus can suppress the innate immune response in patients with more serious symptoms.
The authors suggest the oral vaccine as opposed to the injectable kind be tested because the injectable vaccine does not activate an innate immune response, and because it is already licensed for use in the United States, the country that has thus far been hit hardest by the pandemic. They acknowledge that there is some small risk of using the oral vaccine, as it has been found to generate circulating vaccine-derived polioviruses, a type of polio that is vaccine derived in a very small number of people, mostly children with compromised or underdeveloped immune systems. But they suggest that if it does prove to ward off coronavirus infections, the good that could come from its use would far outweigh the bad.
More information: Konstantin Chumakov et al. Can existing live vaccines prevent COVID-19?, Science (2020). DOI: 10.1126/science.abc4262
https://medicalxpress.com/news/2020-06-oral-polio-vaccine-sars-cov-.html

Medtronic to ramp up diabetes R&D on $337M Blackstone investment

Medtronic (NYSE:MDT) announces a $337M investment from funds managed by Blackstone Life Sciences (and other co-investors) aimed at supporting R&D programs in its Diabetes Group.

The capital, to be disbursed over several years, will fund four undisclosed diabetes R&D programs. If successful, Blackstone-led investors will receive low-to-mid-single-digit royalties on net sales. Additional terms remain confidential.

Medtronic will host a briefing today at 6:00 pm ET from the ADA conference to discuss the deal.

https://seekingalpha.com/news/3582829-medtronic-to-ramp-up-diabetes-r-and-d-on-337m-blackstone-investment

AstraZeneca to supply up to 400M doses of COVID vaccine at no profit

AstraZeneca (NYSE:AZN) inks an agreement with Europe’s Inclusive Vaccines Alliance, led by Germany, France, Italy and the Netherlands, under which the company will supply up to 400M doses of Oxford University’s COVID-19 vaccine, currently dubbed ADZ1222 (originally ChAdOx1 nCoV-19), beginning in late Q4 at no profit.

AZN recently signed deals in the UK, U.S. and with CEPI and Gavi the Vaccine Alliance to supply 700M doses in addition to a deal with the Serum Institute of India to supply IB doses to low- and middle-income countries.

Manufacturing costs will be offset by government funding.

A Phase 2/3 trial in the UK launched last month.

AZN’s 2020 financial guidance remains unchanged.

https://seekingalpha.com/news/3582828-astrazeneca-to-supply-up-to-400m-doses-of-covid-vaccine-no-profit

Medtronic next-gen closed-loop insulin system successful in U.S. trial

Medtronic (NYSE:MDT) announces positive results from a U.S. pivotal study evaluating its MiniMed 780G Advanced Hybrid Closed Loop insulin pump in adolescent and adult diabetics. The results were virtually presented at the Scientific Sessions of the ADA.

The device, CE Mark’d this week, features a default target of 100 mg/dL (with an option of 120 mg/dL), programmable insulin action time from two to eight hours and automatic corrections every five minutes.

Average A1C levels of 7.0% with overall time in range (70-180 mg/dL) of 75% and overall time below range (less than 70 mg/dL) of 1.8%.

Autocorrection contributed 22% of all bolus insulin.

Participants in SmartGuard (closed loop) 95% of the time.

At the default setting, mean sensor glucose was 144 mg/dL overall and 148 mg/dL overall.

No severe hypoglycemia or diabetic ketoacidosis occurred.

Time in range at the default setting was 76% overall at the 2-3 hour active insulin time (AIT) and 79% at the 2 hour AIT.

The data will support a U.S. marketing application.

Related tickers: Abbott (NYSE:ABT), Tandem Diabetes Care (NASDAQ:TNDM), Insulet (NASDAQ:PODD)

https://seekingalpha.com/news/3582830-medtronic-next-gen-closed-loop-insulin-system-successful-in-u-s-trial

Roche/AbbVie’s Venclexta extends survival in leukemia study

Following up on their initial announcement in March, Roche (OTCQX:RHHBY) unit Genentech and U.S. commercialization partner AbbVie (NYSE:ABBV) announce positive results from a Phase 3 clinical trial, VIALE-A, evaluating Venclexta (venetoclax) and chemo agent azacitidine in previously untreated acute myeloid leukemia (AML) patients ineligible for intensive chemo.

The study met both primary endpoints, demonstrating statistically significant improvements in overall survival (OS) (sole U.S. efficacy endpoint) and the proportion of patients achieving complete remission (CR) and CR with incomplete blood count recovery (CRi) compared to azacitidine + placebo.

Specifically, OS in the Venclexta + azacitidine (V+a) arm was 14.7 months compared to 9.6 months in the azacitidine alone arm (p<0.001). 64% of patients receiving V+a achieved CR + CRi versus 28.3% of patients in the azacitidine group (p<0.001).

The companies are co-commercializing Venclexta in the U.S. while AbbVie has sole rights ex-U.S.

https://seekingalpha.com/news/3582827-roche-abbvies-venclexta-extends-survival-in-aml-study