Ontario health unit partially closes 2 Amazon fulfilment centres to control COVID-19

 Peel Public Health announced on Saturday that it has partially closed two Amazon fulfilment centres to control COVID-19 outbreaks in those workplaces.

The centres are located in Brampton, Ont., at 8050 Heritage Rd., and in Bolton, Ont., at 12724 Coleraine Dr. The businesses were required to close at midnight on Friday. Peel Region is located northwest of Toronto.

Peel Public Health said the businesses and employees have been notified.

The public health unit said the centres have been closed under Section 22 of Ontario's Health Protection and Promotion Act. On its website, it said a partial closure may mean the mass dismissal of a shift or work area.

Peel Public Health added that its closures would apply to businesses that have had five or more COVID-19 cases that were acquired in the workplace over a span of two weeks.

Dr. Lawrence Loh, Peel Region's medical officer of health, said on Saturday that the public health unit identified 11 workplaces in total on Friday for "priority review" to stop the spread of the virus. The closures are an attempt to protect the community, he said.

Of the 11, the public health unit partially closed the two Amazon workplaces, it found out that three other workplaces have already been closed by their employers and it is reviewing six additional workplaces to determine if closure is necessary.

"I think you can anticipate that there will be other closures once we've had a chance to review," Loh told CBC News. "This is the first day, starting out, of our new policy."

Loh noted that Peel has a number of workplaces where workers cannot work from home and where they are precariously or temporarily employed.

"It's just a reflection of the unique makeup of the Region of Peel that we have taken this step."

In a statement to CBC News on Saturday, Amazon said three shifts at the Brampton facility and one shift in Bolton are being temporarily suspended.

"Our most recent round of mandatory testing confirmed a positivity rate of approximately one per cent, and there appears to be little risk of spread within our facility. However, following the direction of Peel Public Health, we are temporarily suspending a number of shifts at our Heritage Road and Bolton facilities," it said in a statement.

"We have 18 shifts operating at our Heritage Road facility and 18 shifts at our Bolton facility. All employees will receive full pay and benefits."

According to Amazon, five or more cases were identified on the suspended shifts in the past two weeks, but it declined to say how many. It also declined to say how many workers are affected overall.

A person walks outside the Amazon fulfilment centre in Brampton, Ont., on April 20. In a statement to CBC News on Saturday, Amazon said three shifts at its Brampton facility and one shift at its centre in Bolton, Ont., are being temporarily suspended due to COVID-19 outbreaks. (Nathan Denette/The Canadian Press)

The company said it would provide full pay and benefits to workers who are isolating and that all employees on the suspended shifts will be tested.

"Nothing's more important than the health and safety of our employees and the communities we serve," it added.

Amazon said the closure will have a "short-term impact" on its customers, but it will work to restore full service as soon as possible.

Companies urged to pay sick leave when closed

Peel Public Health said it would review the closures on a daily basis to determine the best course of action, adding that "modified closure criteria" would apply to large businesses.

"Based on risk assessment, it will be determined if full or partial closure is warranted," Peel Public Health said in a news release on Friday.

Any closures could last up to 10 days, and all affected employees must go into isolation during that time. They are not allowed to work in any other workplace.

"Absent legislated paid sick days, employers required to close under these provisions are strongly recommended to provide paid leave for impacted employees," the public health unit said.

The 10-day period will allow public health officials to investigate the outbreaks without the risk of spread of infection and to provide recommendations to the workplaces, the public health unit said.

Premier Doug Ford said on Thursday that his government has started work on a paid sick leave program after months of insisting that the program offered by the federal government was sufficient. The provincial government recently voted down a bill by the NDP that would have granted all workers access to paid sick days provided by their employers. 

Dr. Lawrence Loh, medical officer of health for Peel Region, said on Tuesday: 'Workplaces that remain open continue to be a major driver of COVID-19 cases in Peel, as they have been throughout the course of our emergency response.' (CBC)

Loh, for his part, has said: "Workplaces that remain open continue to be a major driver of COVID-19 cases in Peel, as they have been throughout the course of our emergency response."

He said the closures would apply to businesses where those infected "could have reasonably acquired their infection at work" or if "no obvious source" for transmission is identified outside of the workplace.

Peel Region includes Brampton, Mississauga and Caledon. Bolton is a community in the town of Caledon.

Earlier this week, Peel Public Health and Toronto Public Health (TPH) announced that they would issue orders to force businesses with five or more cases of COVID-19 in the past two weeks to close.

Peel has 100 active workplace outbreaks

Mississauga Mayor Bonnie Crombie told reporters at a weekly news briefing on Wednesday that there are about 100 active workplace outbreaks in Peel Region. A total of 402 workplaces in Peel have had outbreaks since the pandemic began. She said workplace outbreaks lead to wider household and community spread.

"The reality is things have never been more serious," she said.

A study by Peel Public Health has found that out of 8,000 workers who contracted COVID-19, nearly 2,000 of them, or one in four, went to work with COVID-19 symptoms, Crombie said.

A total of 80 of the workers went to work after receiving a positive COVID-19 test, she said.

"The action that Dr. Lawrence Loh has taken is necessary and addresses where the transmission is occurring," she added.

Crombie acknowledged that Section 22 orders would be "very difficult" on businesses and employees.

TPH says identifying workplaces to be done 'carefully'

Toronto Public Health, for its part, said on Saturday it is investigating 10 workplaces, and if there are any actions required under Section 22, it expects to notify the businesses starting on Monday.

TPH will notify the media at the city's news briefing on Monday about when it will publicly disclose the names of the businesses.

"The primary objective and principal public health benefit of the order is to separate employees from one another in workplaces where transmission of COVID-19 is identified and linked to the location," Dr. Eileen de Villa, the city's medical officer of health, said in a news release.

"These workplaces generally do not see high traffic from the general public. This is especially so given the province's stay-at-home order and provincial regulation of public-facing business activity."

TPH said it will notify the owner or operator of a workplace about whether a closure is full or partial and which employees need to be sent home to isolate for 10 days. It said it would posts signs at all entrances to a workplace subject to an order.

https://www.cbc.ca/news/canada/toronto/peel-public-health-workplace-closures-1.6001128

Gout med in Phase 3 trial for Covid-19 treatment

 

ClinicalTrials.gov Identifier: NCT04504734

Recruitment Status  : Enrolling by invitation First Posted  : August 7, 2020 Last Update Posted  : April 23, 2021

Brief Summary:

This is a Phase 3, multi-center, randomized, double blind, placebo controlled, clinical study of bucillamine (2 dosage levels) in patients with mild-moderate COVID-19. Patients will be randomized 1:1:1 to receive bucillamine 100 mg 3 times a day (TID), bucillamine 200 mg TID or placebo TID for up to 14 days. After the first interim analysis when a single dose is selected, patients will then be randomized 2:1 to the selected bucillamine dose or placebo The study will be overseen by an independent Data and Safety Monitoring Board (DSMB). Up to 10 centers in the United States will conduct this study. Up to 1000 patients will be enrolled in this study. Patients will participate in the study approximately 45 days.

Condition or disease	Intervention/treatment	Phase
Covid19	Drug: BucillamineDrug: Placebo	Phase 3

Detailed Description:

This is a Phase 3, multi-center, randomized, double blind, placebo controlled, clinical study of bucillamine (2 dosage levels) in patients with mild-moderate COVID-19. Patients will be randomized 1:1:1 to receive bucillamine 100 mg 3 times a day (TID), bucillamine 200 mg TID or placebo TID for up to 14 days. After the first interim analysis when a single dose is selected, patients will then be randomized 2:1 to the selected bucillamine dose or placebo The study will be overseen by an independent Data and Safety Monitoring Board (DSMB). Up to 10 centers in the United States will conduct this study.

Patients qualifying for study enrollment will initiate therapy as outpatients, under home quarantine. Patients will receive continued standard care of therapy (per study site written policies or guidelines) together with bucillamine and/ or matching placebo for up to 14 days. Dosing should continue until the treatment course is completed or as medically indicated (e.g., deterioration of clinical status and alternative therapy required). If the patient requires hospitalization during the study period, treatment will be discontinued.

Following completion of the treatment course, follow up assessments will be performed by a study nurse 14, 28, 42, and 60 days following the end of treatment.

Up to 1000 patients will be enrolled in this study. Patients will participate in the study approximately 45 days.

https://clinicaltrials.gov/ct2/show/study/NCT04504734?term=bucillamine&draw=2&rank=2

Why women may see more side effects to COVID vaccine than men

 Studies show men and women react differently to COVID-19, but health officials say they react differently to the vaccine too, and it may be contributing to some of the vaccine hesitancy out there, experts say.

Dr. Maryrose Laguio-Vila is the chief of the Infectious Disease Unit at Rochester Regional Health. She says data shows men generally tend to have more severe cases of COVID-19, more end up in the ICU.

“Mens’ immune systems aren’t as robust as women’s, so men have higher risks for COVID, so there’s a higher mortality rate with men,” she said.

But the key term here is immune system.

Women have stronger ones – and that’s going to play a role in how they react to vaccines, too. She says studies have shown in vaccines for influenza and hepatitis, women generally have higher immune responses.

“It’s because of the impact of the X chromosome. Women have two X chromosomes, and men have an X and a Y, and on the X chromosome there are a lot of immune function genes that are present,” she says.

As a result of this, she says women have higher antibody levels and immune cells. This contributes to some women experiencing more extreme side effects to the COVID-19 vaccine like headache, or higher fevers. Another feature that contributes to the difference we’re seeing in genders, is the influence of sex hormones. “Estrogen and progesterone stimulate the immune system differently than testosterone,” she says.

Some women may be noticing these side effects more present in others, and it could be contributing to the vaccine hesitancy health officials have been speaking about for weeks.

That’s why Dr. Laguio-Vila says it’s important women understand what the vaccine is actually doing in your body to help fight disease.

“When someone has natural infection, your symptoms are a part of the immune system stimulated to react against it … when we get a vaccine it is mimicking that exposure.”

Some fear the six blood clot events occurring in women who took the Johnson & Johnson vaccine.

Dr. Laguio-Vila says while the risk is always there  – it’s one in ten million. And women should know that doctors all across the globe are surveilling this data closely.

“I think the increased surveillance akin with high number of people getting vaccine raises awareness for extremely rare, rare, outcomes,” she says.

Age is another impact too, says Dr. Laguio-Vila. The younger you are, the healthier your immune system, and the stronger the side effects could be.

“The immune system ages over time like other organs, so younger women have more robust responses compared to older. Younger ages in general have more robust reactions compared to older,” she said.

Dr. Laguio-Vila says she’s heard of some women expressing concerns or hearing stories of menstrual cycles being affected by the vaccine.

“I’ve seen some of that said, I will say I don’t think it makes physiological sense, because the immune system that’s stimulated by the vaccine doesn’t really interfere with the estrogen progesterone cycles of periods. I don’t think we know yet if there is any association or validity to those claims,” she said.

https://www.rochesterfirst.com/coronavirus/yes-women-are-experiencing-more-side-effects-to-covid-vaccine-than-men-and-heres-why/

Texas A&M trains over 200 employees of FUJIFILM Texas unit in COVID-19 vaccine making

 The Texas A&M University System is collaborating with FUJIFILM Diosynth Biotechnologies Texas to train their workforce that is mass-producing two COVID-19 vaccine candidates for the federal government.

For the past nine months, a dedicated team of Texas A&M University scientists at the National Center for Therapeutics Manufacturing (NCTM) has been training workers on the biomanufacturing basics needed to produce the COVID-19 vaccine candidates.

The NCTM is a joint research center of the Texas A&M Engineering Experiment Station and Texas A&M.

With just four instructors and a handful of support staff, the team has trained more than 200 new employees of FUJIFILM Diosynth Biotechnologies Texas. The company is the Texas A&M System’s biomanufacturing subcontracting partner in the national emergency manufacturing program.

“Texas A&M is doing a great public service,” said John Sharp, Chancellor of the Texas A&M System. “By collaborating with FUJIFILM Diosynth Biotechnologies Texas to increase the vaccine supply, our team is helping save a bunch of lives.”

The training is a customized, intensive seven-day, hands-on curricula of various aspects of cell culture and basic molecular biology, aseptic processes and microbiology, and upstream and downstream processing of biological materials.

The team worked quickly to build the program within weeks of the federal request last July. The training began almost immediately and has continued ever since.

“The ability to respond rapidly to an emergency is the main original goal of the CIADM program,” said Dr. William Jay Treat, Director of CIADM and Chief Manufacturing Officer for Texas A&M Health Science Center. “Since its creation, NCTM has been critical to developing training programs to meet the manpower required for an emergency such as this pandemic.”

The NCTM has more than 25,000 square feet of dedicated instructional space with several million dollars worth of traditional stainless and single-use systems for upstream and downstream bioprocessing. It has contracted with more than 80 subject matter experts to build a catalog of training programs that serve the industry, government, and academia.

In the past eight years, NCTM has trained nearly 1,600 students, including new hires and employed professionals, undergraduate/graduate students, military veterans and others transitioning careers, and even high school students interested in STEM careers.

“We have never been more proud of our work than in the past nine months,” said Jenny Ligon, NCTM Assistant Director for Workforce Development, who has been with NCTM since its creation in 2012. “I’m so proud of our small but mighty team. We are happy to do our part in getting everyone vaccinated.”

https://www.kxxv.com/brazos/texas-a-m-trains-over-200-employees-of-fujifilm-diosynth-biotechnologies-in-covid-19-vaccine-making

Every second person getting tested in Kolkata is positive

 One of two persons undergoing RT-PCR tests in Kolkata and its suburbs is turning out to be Covid-positive. In the rest of the state, one of four RT-PCR report is Covid positive. That is a five-fold jump from the beginning of the month, when only one of 20 tests was positive.

“Laboratories in Kolkata and surrounding areas are reporting a positivity rate of 45%-55% while in other parts of the state the positivity rate is around 24%, up from 5% at the beginning of this month,” said a doctor attached to one of the largest laboratories conducting RT-PCR tests in the state.

This, a senior doctor at a state-run hospital said, is only the tip of the iceberg. “The actual positivity rate will be much higher. There would be so many asymptomatic or mildly symptomatic patients who are not getting themselves tested. We are not testing enough. We must not be deterred from testing more as this is one major tool to contain this wave,” he said.

Of the 25,766 samples tested in the state on April 1, only 1,274 samples were positive, a positivity of 4.9%. On Saturday, 55,060 samples were tested across the state and 25.9% samples or 14,281 persons were positive.

“One reason is the high transmissibility of the mutant virus which is infecting a large number of people in a short span of time. In most cases, entire families are getting infected. Another reason for the high positivity is that only those who are symptomatic are going in for the tests,” said Bhaskar Narayan Chaudhuri, microbiologist at Peerless Hospital.

https://timesofindia.indiatimes.com/city/kolkata/every-second-person-getting-tested-in-kolkata-is-positive/articleshow/82236519.cms

Op-Ed: Who's Really at Risk of Fragility Fractures?

 In 1994, a World Health Organization (WHO) study group published an attempt at predicting the risk of fragility fractures based on bone mineral density (BMD). Before this report, the diagnosis of "osteoporosis" was clinical -- that is, following the occurrence of a low-impact (fragility) fracture, and, depending on clinical sagacity, other related factors that can be discovered in the personal history.

While the science and technical capacity of dual-energy x-ray absorptiometry (DXA) were comparatively primitive at the time, early machines had been introduced into clinical use and this diagnostic capacity was probably the inspiration for this BMD-based effort. Expressed in simple terms, the devices measured the attenuation of a modulated x-ray beam per cm² of supine body area, and this attenuation was used to calculate the BMD.

Most of us are doubtless aware that density is a volume measurement, but this definition was chosen by literally ignoring one of the three dimensions of the solid bone being measured: the vertical dimension parallel to the beam. Such an assumption presumably posits that the measured subjects all have bones of the same thickness. For clarity, it should have been termed the "projectional" BMD.

In addition, different competing DXA technologies were known to yield differing "density" results for this g/cm² analysis for the same individual, so a resolution factor was introduced to permit comparisons between the platforms, permitting a "T-score" comparison to be used even in the absence of information about the specific DXA brand employed. The difficulty with this is that persons with thick bones will be awarded densities greater than they deserve and, worse, thin small persons may be declared "osteoporotic."

The veracity of the DXA result was soon challenged repeatedly. One early simplistic but convincing experiment compared the DXA-determined "BMD" of 53 human skeletal vertebrae to the actual density in g/cm³. The true densities varied from the DXA results by 24% to 139%.

But perhaps the DXA result might prove to be utilitarian enough to serve as an indicator of risk, despite being just a representative, albeit, imprecise number. After all, the need was to evaluate the risk to bones in vivo. In my opinion, this possibility was soon excluded by two studies. In 2003, a very well-conducted and impressively detailed multicenter academic study reported the relationship of "central" BMD measurements (DXA) to the incident fracture rate in 9,704 women, age 65 years or older over an interval of 8.5 years. The study also included the relationship to incident fractures of BMD measurement that used an ultrasound methodology. In this study, the average attributable risk -- the association of fracture history with an osteoporotic BMD -- was 15%. It was somewhat better for the critical hip fracture: 21%.

The second study documenting the wide discrepancy between DXA-defined osteoporosis and fracture occurrence was published the following year, authored by three pharmaceutical industry employees and three consultants. This 1-year study analyzing the ultrasound methodology reached the same conclusion. Out of a huge group of 149,524 post-menopausal women, only 18% of those in the WHO-defined "osteoporosis" zone incurred fractures. The remaining 82% of the fractures were again in women with better BMDs. As in the earlier study, the incidence of fracture was of course higher in the (smaller) "osteoporosis" portion of the cohort, but the number of fractures was much greater in the groups with T-scores better than -2.5.

So, if one is prescribing medical treatment for patients with a T-score of -2.5 or less, what are the potential consequences? The evidence reviewed above demonstrates that for approximately 82% of such patients, treatment with potentially harmful drugs provides no fracture prevention benefit.

The uncommon occurrence of the associated harms has not resulted thus far in the banning of these strongly antiresorptive drugs -- which include all of the bisphosphonates and even, apparently, the currently approved monoclonal antibody anti-osteoporosis drugs -- but the resultant disruption of the lives of individuals affected by osteonecrosis of the jaw and femur and other atypical low-impact fractures has been severe. This problem is vastly compounded when such treatment is afforded the so-called "osteopenic" patient with a T-score of -1.0 or less; despite the fact that a greater number of fractures occur in this group, the fourfold to fivefold increase in group size increases the number of useless treatments compounding the side-effect risk. In the largest published series of atypical fractures of the femur, many of the cases resulted after prescribing for demonstrably ineffective therapy for "osteopenia."

But if we abandon the WHO study group's failed advice, what can we do to identify risk more appropriately? The answer is to return to the pre-1994 clinical analysis of risk. This approach has also been rendered far less demanding due to the appearance of clinically derived fracture-risk algorithms based on long-term analysis of real clinical data. These really amount to codification of some of the pre-1994 clinical risk factors based on personal history, including the all-important therapeutic necessity of never neglecting the reason for a prevalent fragility fracture -- a neglect that is all too common after surgical repair.

The DXA does provide one clinically useful datum. Serial scans at least 2 years apart, especially if done on exactly the same equipment, provide valuable evidence of stability or loss of BMD, and thus a rational basis for sequential therapeutic decisions. Such comparisons are misleading if used to assess the benefit of strong antiresorptive medications, as was specified in the original papers but now, I fear, are often ignored.

Banks Hinshaw, MD, is attending gynecologist at Markle & Hinshaw Gynecology in North Carolina. He has been in the private practice of gynecology since 1982 and has been especially interested, since 1996, in post-menopausal skeletal health and the pharmacology of estradiol.

https://www.medpagetoday.com/endocrinology/osteoporosis/92258

Molecular Partners Files $100M IPO to Advance COVID-19 and Cancers Therapies

 Swiss biotech company Molecular Partners announced last week it has filed for a $100 million initial public offering with the Securities and Exchange Commission in the U.S., funding which will go toward supporting the company's work in the development of protein-based treatments for COVID-19 and various cancers. 

The company said that Molecular will offer all security sold in the offering. However, the company has not yet determined the number of common shares represented by each American Depositary Shares (ADS), the number of ADSs to be offered, or the price range. 

In the announcement, Molecular said it is also applied to list its shares on the NASDAQ Global Market under "MOLN." Molecular's common shares are also listed on the SIX Swiss Exchange under "MOLN."

Joint lead bookrunners for the deal include JP Morgan, SVB Leerink, and Cowen & Co. Bookrunner and lead manager for the offering include RBC Capital Markets and Kempen & Co., respectively.

The company harnesses its proprietary DARPin molecular platform to develop candidates featuring multiple mechanisms of action to improve effectiveness and minimize toxicities of certain drugs. To help expand its drug candidates, Molecular has developed partnerships with several drug companies over the years, including collaborations with Amgen, Novartis and AbbVie.

Earlier this month, Molecular dosed its first patient in a Phase II trial of its DARPin® therapeutic candidate, ensovibep, which was designed to bind to the spike protein of the novel coronavirus at three different locations, thereby preventing cellular viral entry. This study is currently enrolling patients with symptomatic COVID-19, all of whom will receive investigational treatment. Researchers will look at the rates of viral clearance and the pharmacokinetics and tolerability associated with ensovibep. 

"In this first trial of ensovibep in patients, we hope to gain an early look at the viral clearance and the pharmacodynamic behavior of our lead COVID-19 candidate in the presence of the virus. Our preclinical trials with ensovibep have shown that it was able to bind and neutralize SARS-CoV-2 viruses both in vitro and in vivo, including against all currently known mutations of concern," said Molecular's Chief Executive Officer, Patrick Amstutz, Ph.D., in a statement. "As part of our development program, we aim to see if these results mechanistically translate into clinical efficacy in patients, with the current trial focused on examining viral presence in treated patients and the potential of the remaining virus to infect cells."

In March, Molecular and its partner Novartis entered ensovibep in the National Institutes of Health's (NIH) ACTIV-3 trial to investigate the antiviral's efficacy against COVID-19. Ensovibep is the first non-antibody treatment assessed in ACTIV-3. The clinical trial will report findings in an interim analysis after 300 patients have been enrolled and treated. ACTIV-3 is currently researching several treatment and vaccine candidates for COVID-19. The NIH selected ensovibep for inclusion after Molecular and Novartis provided the agency with independent preclinical data demonstrating the therapy's potential effects. 

"The NIH's ACTIV-3 trial provides a major expansion of ensovibep's clinical program and data collection, and recognizes the clinical and preclinical evidence we have delivered to-date supporting this candidate as a differentiated approach to COVID-19 treatment," said Amstutz in a statement. "Emerging variant strains and the challenges of vaccinating a global population create an ongoing need for effective antivirals to save lives. We will work closely with both our collaborator Novartis and the NIH to maximize support on this trial in parallel with the other clinical trials of ensovibep planned to initiate in the second quarter."

https://www.biospace.com/article/molecular-partners-files-100m-ipo-to-advance-covid-19-and-cancers-therapies-/