Once again: TB vaccine linked to lower risk of contracting COVID-19

 A widely used tuberculosis vaccine is associated with reduced likelihood of contracting COVID-19 (coronavirus), according to a new study by Cedars-Sinai. The findings raise the possibility that a vaccine already approved by the U.S. Food and Drug Administration may help prevent coronavirus infections or reduce severity of the disease.

The vaccine, known as Bacillus Calmette-Guérin (BCG), was developed between1908 and 1921 and is administered to more than 100 million children around the world every year. In the U.S., it is FDA-approved as a drug to treat bladder cancer and as a vaccine for people at high risk of contracting TB. The BCG vaccine is currently being tested in multiple clinical trials worldwide for effectiveness against COVID-19.

In the new study, published online Nov. 19 in The Journal of Clinical Investigation, investigators tested the blood of more than 6,000 healthcare workers in the Cedars-Sinai Health System for evidence of antibodies to SARS-CoV-2, the virus that causes COVID-19, and also asked them about their medical and vaccination histories.

They found that workers who had received BCG vaccinations in the past-nearly 30% of those studied-were significantly less likely to test positive for SARS-CoV-2 antibodies in their blood or to report having had infections with coronavirus or coronavirus-associated symptoms over the prior six months than those who had not received BCG. These effects were not related to whether workers had received meningococcal, pneumococcal or influenza vaccinations.

The reasons for the lower SARS-CoV-2 antibody levels in the BCG group were not clear, according to Moshe Arditi, MD, director of the Pediatric and Infectious Diseases and Immunology Division at Cedars-Sinai and co-senior author of the study.

"It appears that BCG-vaccinated individuals either may have been less sick and therefore produced fewer anti-SARS-CoV-2 antibodies, or they may have mounted a more efficient cellular immune response against the virus," said Arditi, professor of Pediatrics and Biomedical Sciences. "We were interested in studying the BCG vaccine because it has long been known to have a general protective effect against a range of bacterial and viral diseases other than TB, including neonatal sepsis and respiratory infections."

In the new study, the lower antibody levels in the BCG group persisted despite the fact that these individuals had higher frequencies of hypertension, diabetes, cardiovascular diseases and COPD, which are known risk factors for being more susceptible to SARS-CoV-2 and developing the more severe forms of COVID-19 illness.

While noting that no one believes BCG will be more effective than a specific vaccine for COVID-19, Arditi explained that it could be more quickly approved and made available, given that it has a strong safety profile demonstrated by many years of use. "It is a potentially important bridge that could offer some benefit until we have the most effective and safe COVID19 vaccines made widely available," he said.

"Given our findings, we believe that large, randomized clinical trials are urgently needed to confirm whether BCG vaccination can induce a protective effect against SARS-CoV2 infection," said Susan Cheng, MD, MPH, MMSc, associate professor of Cardiology and director of Public Health Research at the Smidt Heart Institute at Cedars-Sinai. She was the other co-senior author of the study. The first author was Magali Noval Rivas, Ph.D., assistant professor of Pediatrics at Cedars-Sinai.

In fact, a number of randomized clinical trials have been launched to study the potential protective effects of BCG vaccination against COVID-19. Along with Texas A&M University, Baylor College of Medicine, and the University of Texas MD Anderson Cancer Center, Cedars Sinai is a site for the U.S. arm of this ongoing trial, which is recruiting hundreds of healthcare workers. Arditi serves as the principal investigator of this clinical trial at Cedars-Sinai.

"It would it be wonderful if one of the oldest vaccines that we have could help defeat the world's newest pandemic," Arditi said.

More information: Magali Noval Rivas et al. BCG vaccination history associates with decreased SARS-CoV-2 seroprevalence across a diverse cohort of healthcare workers, Journal of Clinical Investigation (2020). DOI: 10.1172/JCI145157

https://medicalxpress.com/news/2020-11-tuberculosis-vaccine-linked-covid-.html

Which approaches are most effective at reducing COVID-19 spread

 Simon Fraser University professors Paul Tupper and Caroline Colijn have found that physical distancing is universally effective at reducing the spread of COVID-19, while social bubbles and masks are more situation-dependent.

The researchers developed a model to test the effectiveness of measures such as physical distancing, masks or social bubbles when used in various settings.

Their paper was published Nov. 19 in the journal Proceedings of the National Academy of Sciences of the United States of America (PNAS).

They introduce the concept of "event R," which is the expected number of people who become infected with COVID-19 from one individual at an event.

Tupper and Colijn look at factors such as transmission intensity, duration of exposure, the proximity of individuals and degree of mixing—then examine what methods are most effective at preventing transmission in each circumstance.

The researchers incorporated data from reports of outbreaks at a range of events, such as parties, meals, nightclubs, public transit and restaurants. The researchers say that an individual's chances of becoming infected with COVID-19 depend heavily on the transmission rate and the duration—the amount of time spent in a particular setting.

Events were categorized as saturating (high transmission probability) or linear (low transmission probability). Examples of high transmission settings include bars, nightclubs and overcrowded workplaces while low transmission settings include public transit with masks, distancing in restaurants and outdoor activities.

The model suggests that physical distancing was effective at reducing COVID-19 transmission in all settings but the effectiveness of social bubbles depends on whether chances of transmission are high or low.

In settings where there is mixing and the probability of transmission is high, such as crowded indoor workplaces, bars and nightclubs and high schools, having strict social bubbles can help reduce the spread of COVID-19.

The researchers found that social bubbles are less effective in low transmission settings or activities where there is mixing, such as engaging in outdoor activities, working in spaced offices or travelling on public transportation wearing masks.

They note that masks and other physical barriers may be less effective in saturating, high transmission settings (parties, choirs, restaurant kitchens, crowded offices, nightclubs and bars) because even if masks halve the transmission rates that may not have much impact on the transmission probability (and so on the number of infections).

The novel coronavirus is relatively new but the science continues to evolve and increase our knowledge of how to effectively treat and prevent this highly contagious virus. There is still much that we do not know and many areas requiring further study.

"It would be great to start collecting information from exposures and outbreaks: the number of attendees, the amount of mixing, the levels of crowding, the noise level and the duration of the event," says Colijn, who holds a Canada Research Chair in Mathematics for Evolution, Infection and Public Health.

More information: Paul Tupper et al, Event-specific interventions to minimize COVID-19 transmission, Proceedings of the National Academy of Sciences (2020). DOI: 10.1073/pnas.2019324117

https://medicalxpress.com/news/2020-11-approaches-effective-covid-.html

Frequent, rapid testing could cripple COVID within weeks: study

 Testing half the population weekly with inexpensive, rapid-turnaround COVID-19 tests would drive the virus toward elimination within weeks— even if those tests are significantly less sensitive than gold-standard clinical tests, according to a new study published today by University of Colorado Boulder and Harvard University researchers.

Such a strategy could lead to "personalized stay-at-home orders" without shutting down restaurants, bars, retail stores and schools, the authors said.

"Our big picture finding is that, when it comes to public health, it's better to have a less sensitive test with results today than a more sensitive one with results tomorrow," said lead author Daniel Larremore, an assistant professor of computer science at CU Boulder. "Rather than telling everyone to stay home so you can be sure that one person who is sick doesn't spread it, we could give only the contagious people stay-at-home orders so everyone else can go about their lives."

For the study, published in the journal Science Advances, Larremore teamed up with collaborators at CU's BioFrontiers Institute and the Harvard T.H. Chan School of Public Health to explore whether test sensitivity, frequency, or turnaround time is most important to curb the spread of COVID-19.

The researchers scoured available literature on how viral load climbs and falls inside the body during infection, when people tend to experience symptoms, and when they become contagious.

They then used mathematical modeling to forecast the impact of screening with different kinds of tests on three hypothetical scenarios: in 10,000 individuals; in a university-type setting of 20,000 people; and in a city of 8.4 million.

When it came to curbing spread, they found that frequency and turnaround time are much more important than test sensitivity.

For instance, in one scenario in a large city, widespread twice-weekly testing with a rapid but less sensitive test reduced the degree of infectiousness, or R0 ("R naught"), of the virus by 80%. But twice-weekly testing with a more sensitive PCR (polymerase chain reaction) test, which takes up to 48 hours to return results, reduced infectiousness by only 58%. When the amount of testing was the same, the rapid test always reduced infectiousness better than the slower, more sensitive PCR test.

That's because about two-thirds of infected people have no symptoms and as they await their results, they continue to spread the virus.

"This paper is one of the first to show we should worry less about test sensitivity and, when it comes to public health, prioritize frequency and turnaround," said senior co-author Roy Parker, director of the BioFrontiers Institute and a Howard Hughes Medical Institute investigator.

The study also demonstrates the power of frequent testing in shortening the pandemic and saving lives.

In one scenario, in which 4% of individuals in a city were already infected, rapid testing three out of four people every three days reduced the number ultimately infected by 88% and was "sufficient to drive the epidemic toward extinction within six weeks."

The study comes as companies and academic research centers are developing low-cost, rapid turnaround tests that could be deployed in large public settings or commercialized for do-it-yourself use.

Sensitivity levels vary widely. Antigen tests require a relatively high viral load—about 1,000 times as much virus compared to the PCR test—to detect an infection. Another test, known as RT-lamp (reverse transcription loop-mediated isothermal amplification), can detect the virus at around 100 times as much virus compared to the PCR. The benchmark PCR test requires as little as 5,000 to 10,000 viral RNA copies per milliliter of sample, meaning it can catch the virus very early or very late.

In the past, federal regulators and the public have been reluctant to embrace rapid tests out of concern that they may miss cases early in infection. But, in reality, an infected person can go from 5,000 particles to 1 million viral RNA copies in 18 to 24 hours, said Parker.

"There is a very short window, early in infection, in which the PCR will detect the virus but something like an antigen or LAMP test won't," Parker said.

And during that time, the person often isn't contagious, he said.

"These rapid tests are contagiousness tests," said senior co-author Dr. Michael Mina, an assistant professor of epidemiology at the Harvard T.H. Chan School of Public Health. "They are extremely effective in detecting COVID-19 when people are contagious."

They are also affordable, he added. The rapid tests can cost as little as $1 each and return results in 15 minutes. Some PCR tests can take several days.

Mina envisions a day when the government sends simple, cheap DIY tests to every home. Even if half of Americans tested themselves weekly and self-isolated if positive, the result would be profound, he said.

"Within a few weeks we could see this outbreak going from huge numbers of cases to very manageable levels," Mina said.

Rapid testing could also be the key to breathing life back into former super spreader threats like football stadiums, concert venues and airports, with patrons testing themselves on the way in and still wearing masks as a precautionary measure, Larremore said.

"Less than .1% of the current cost of this virus would enable frequent testing for the whole of the U.S. population for a year," said Mina, referencing a recent Harvard economic analysis.

The authors say they are heartened to see that several countries have already begun testing all of their citizens, and hopeful that the new U.S. administration has named rapid testing as a priority.

"It's time to shift the mentality around testing from thinking of a COVID test as something you get when you think you are sick to thinking of it as a vital tool to break transmission chains and keep the economy open," Larremore said.

More information: Test sensitivity is secondary to frequency and turnaround time for COVID-19 screening, Science Advances (2020). DOI: 10.1126/sciadv.abd5393 , advances.sciencemag.org/conten … 11/20/sciadv.abd5393

https://medicalxpress.com/news/2020-11-frequent-rapid-cripple-covid-weeks.html

FDA sets Dec. 10 meeting to weigh Pfizer/BioNTech vaccine authorization

 

• The Food & Drug Administration has set Dec. 10 as the meeting of an advisory committee to discuss the request for Emergency Use Authorization by Pfizer (NYSE:PFE) and BioNTech (NASDAQ:BNTX) for their COVID-19 vaccine.
• That's when the Vaccines and Related Biological Products Advisory Committee will gather to discuss advice it will provide to the FDA on the EUA request. That meeting will be live-streamed on the FDA's YouTube, Facebook and Twitter channels, as well as from its website.
• It will also make background materials available to the public no later than two business days before the meeting.
• Injections of the vaccine could follow almost immediately upon full FDA approval of the EUA.
• “The FDA recognizes that transparency and dialogue are critical for the public to have confidence in COVID-19 vaccines," says FDA Commissioner Stephen Hahn. "I want to assure the American people that the FDA’s process and evaluation of the data for a potential COVID-19 vaccine will be as open and transparent as possible."
• He couldn't predict how long the process would take but "A discussion about the safety and effectiveness of Pfizer and BioNTech’s vaccine with this committee, made up of outside scientific and public health experts from around the country, will help ensure clear public understanding of the scientific data and information that the FDA will evaluate."
• https://seekingalpha.com/news/3638503-fda-sets-dec-10-meeting-to-weigh-pfizer-biontech-vaccine-authorization

Gottlieb: Schools should be ‘last thing’ shut due to rising Covid cases

 

• Dr. Scott Gottlieb told CNBC that places such as New York City that stop in-person learning before limiting indoor dining have it “backwards.”
• “We should be trying to curtail whatever activities we know are sources of community spread long before we close schools,” the former FDA chief said
• Schools should be the “last thing” shut down as governors and local officials around the U.S. weigh further public health restrictions in response to surging coronavirus cases, Dr. Scott Gottlieb told CNBC on Friday.

• “We should be trying to curtail whatever activities we know are sources of community spread long before we close schools,” the former Food and Drug Administration commissioner said on “Squawk Box.” “So, some of these jurisdictions, including New York City, have it backwards where they close the schools and leave other things open where the spread is occurring.”

  New York City public schools, the nation’s largest education system, switched to fully remote learning on Thursday after the percentage of positive coronavirus tests across the city hit 3% — a metric Democratic Mayor Bill de Blasio had indicated would, at least temporarily, put an end to in-person classes. However, critics lamented that fitness centers and indoor dining at restaurants were still allowed while school buildings had to shutter.

  A better public-health approach is to place heavier restrictions on activities that present higher risk for transmission than schools, Gottlieb said. He pointed to the recent set of actions from Democratic Rhode Island Gov. Gina Raimondo, where in-person class from pre-kindergarten to eighth grade will continue. High schools will proceed with limited in-person learning, while gyms, organized sports and “bar areas” will close.

• “High schools are a bigger risk. There’s more spread in the high schools. They are a source of community spread because the older kids tend to get the virus more readily and they can spread it,” said Gottlieb, who led the FDA in the Trump administration for two years. “But we should do everything possible to preserve schools, and especially elementary schools where the educational opportunity of being in the classroom and the socialization is more important.”

  Schools had become a flashpoint over the summer, with President Donald Trump urging districts to reopen for in-person learning. Some large public districts, such as in San Francisco and Chicago, went entirely remote for the fall. Others, including New York City, employed a hybrid approach that had students in the building only a few days per week. Proponents of in-person learning, even with modifications, stressed the importance for children to be in the classroom, especially compared with online classes.

  But as the U.S. coronavirus outbreak intensifies this fall, with hospitalizations and daily new infections at record levels, governors and local officials are faced with the prospect of imposing restrictions to curb transmission and prevent health systems from becoming strained.

  In Europe, where various countries have reimposed partial lockdowns to tamp down on surging coronavirus cases, schools were prioritized, Gottlieb noted. Germany and France both shut down bars and restaurants while keeping schools open as they tried to tamp down on Covid-19 spread.

  For New York City, in particular, Gottlieb acknowledged there could be risks associated with bringing teachers to schools against the backdrop of rising infections — possibly because they might be more reliant on public transportation. But, Gottlieb stressed, “if they had better control of over their spread and were taking more stringent measures in other venues, they probably could keep the schools open longer. That should be the last thing we close, especially elementary schools.”

• https://www.cnbc.com/2020/11/20/dr-scott-gottlieb-schools-need-to-be-the-last-thing-shut-down.html

Early Short-Course Corticosteroids in Hospitalized Patients With COVID-19

 Raef Fadel, Austin R Morrison, Amit Vahia, Zachary R Smith, Zohra Chaudhry, Pallavi Bhargava, Joseph Miller, Rachel M Kenney, George Alangaden, Mayur S Ramesh ...

PDF: https://academic.oup.com/cid/article-pdf/71/16/2114/34393325/ciaa601.pdf

Abstract

Background

There is no proven antiviral or immunomodulatory therapy for coronavirus disease 2019 (COVID-19). The disease progression associated with the proinflammatory host response prompted us to examine the role of early corticosteroid therapy in patients with moderate to severe COVID-19.

Methods

We conducted a single pretest, single posttest quasi-experiment in a multicenter health system in Michigan from 12 March to 27 March 2020. Adult patients with confirmed moderate to severe COVID were included. A protocol was implemented on 20 March 2020 using early, short-course, methylprednisolone 0.5 to 1 mg/kg/day divided in 2 intravenous doses for 3 days. Outcomes of standard of care (SOC) and early corticosteroid groups were evaluated, with a primary composite endpoint of escalation of care from ward to intensive care unit (ICU), new requirement for mechanical ventilation, and mortality. All patients had at least 14 days of follow-up.

Results

We analyzed 213 eligible subjects, 81 (38%) and 132 (62%) in SOC and early corticosteroid groups, respectively. The composite endpoint occurred at a significantly lower rate in the early corticosteroid group (34.9% vs 54.3%, P = .005). This treatment effect was observed within each individual component of the composite endpoint. Significant reduction in median hospital length of stay was also observed in the early corticosteroid group (5 vs 8 days, P < .001). Multivariate regression analysis demonstrated an independent reduction in the composite endpoint at 14-days controlling for other factors (adjusted odds ratio: 0.41; 95% confidence interval, .22 – .77).

Conclusions

An early short course of methylprednisolone in patients with moderate to severe COVID-19 reduced escalation of care and improved clinical outcomes.

Clinical Trials Registration

NCT04374071.

https://academic.oup.com/cid/article/71/16/2114/5840526

Wealthy countries block COVID-19 drugs rights waiver at WTO

 Wealthy nations on Friday reiterated their opposition to a proposal to waive intellectual property rules for COVID-19 drugs, three trade sources said, despite pressure to make an exception to improve access to drugs for poorer countries.

Supporters of the waiver say existing intellectual property (IP) rules create barriers on access to affordable medicines and vaccines and they want restrictions to be eased, as they were during the AIDS epidemic.

But opposition from the European Union, the United States and some other wealthy nations at a meeting on Friday, means the proposal set to go before the World Trade Organization’s (WTO) General Council next month is likely to fail.

“If rich countries prefer profits to life, they will kill it by tying it down in technicalities.” said a delegate supporting the motion who attended the closed-door meeting.

The 164-member WTO body usually has to agree by consensus unless members agree to proceed to a vote, which is exceptional.

A second trade source said developing countries denied that IP rights were creating barriers, saying their suspension, “was not only unnecessary but would also undermine the collaborative efforts to fight the pandemic that are already under way”.

Diplomatic missions for the United States and the EU in Geneva did not immediately provide a comment.

The proposal was first raised by India and South Africa in October. Since then, China, which has five COVID-19 vaccine candidates in late-stage trials, has voiced its support, as have dozens of other WTO members, mostly from developing countries.

The World Health Organization says it supports tackling barriers to access to COVID-19 medicines, as does Nigeria’s Ngozi Okonjo-Iweala, selected by a panel to be the WTO’s next director-general.

Lobbying outside the global trade body has also intensified.

This week, more than 100 civil society organisations wrote to EU lawmakers urging them to back the waiver.

French medical charity MSF’s senior legal and policy officer Yuanquiong Hu said recent positive data from COVID-19 vaccine trials by U.S. pharmaceutical firms added to the urgency of the waiver proposal.

“There is a hierarchical model and the poorer countries are being asked to take the leftovers,” she said.

https://www.reuters.com/article/us-health-coronavirus-wto/wealthy-countries-block-covid-19-drugs-rights-waiver-at-wto-sources-idUSKBN280211