Online COVID mortality risk calculator may help determine who should get vaccines first

 A new online calculator for estimating individual and community-level risk of dying from COVID-19 has been developed by researchers at the Johns Hopkins Bloomberg School of Public Health. The researchers who developed the calculator expect it to be useful to public health authorities for assessing mortality risks in different communities, and for prioritizing certain groups for vaccination as COVID-19 vaccines become available.

The algorithm underlying the calculator uses information from existing large studies to estimate risk of COVID-19 mortality for individuals based on age, gender, sociodemographic factors and a variety of different health conditions. The risk estimates apply to individuals in the general population who are currently uninfected, and captures factors associated with both risk of future infection and complications after infection.

"Our calculator represents a more quantitative approach and should complement other proposed qualitative guidelines, such as those by the National Academy of Sciences and Medicine, for determining individual and community risks and allocating vaccines," says study senior author Nilanjan Chatterjee, Ph.D., Bloomberg Distinguished Professor in the departments of Biostatistics and Epidemiology at the Bloomberg School.

The new risk calculator is presented in a paper that appears in the journal Nature Medicine.

The researchers also collaborated with PolicyMap, Inc. to develop interactive maps for viewing numbers and the proportion of individuals at various levels of risks across U.S. cities, counties and states. These maps will allow local policymakers to plan for vaccination, shielding high-risk individuals, and other targeted intervention efforts.

COVID-19, the pandemic infectious disease that has swept the world over the past ten months, afflicting nearly 70 million people and killing more than 1.5 million worldwide, can affect different people in starkly different ways. Children and young adults may suffer very mild disease or no symptoms at all, whereas the elderly have infection mortality rates of at least several percent. There are also clear ethnic and racial differences—Black and Latinx patients in the U.S., for example, have died of COVID-19 infections at much higher rates than white patients—as well as differences linked to preexisting medical conditions such as diabetes.

"Although we have long known about factors associated with greater mortality, there has been limited effort to incorporate these factors into prevention strategies and forecasting models," Chatterjee says.

He and his team developed their risk model using several COVID-19-related datasets, including from a large U.K.-based study and state-level death rates published by the Centers for Disease Control and Prevention, and then validated the model for predicting community-level mortality rates using recent deaths across U.S. cities and counties.

The calculator based on the model is available online for public health officials and interested individuals alike. It enables a user to determine individual risk based on factors such as age, sex, race/ethnicity, and medical history and can be used to define risk for a group, such as for a particular community, corporation, or university, based on the mix of relevant factors that define the group.

In their paper, Chatterjee and colleagues used their calculator to describe the risk distribution for the whole U.S. population, showing, for example, that only about four percent of the population at high risk—defined as five times greater risk than the U.S. average—is expected to contribute close to 50 percent of the total deaths. The researchers also showed that population-level risk varies considerably from city to city and county to county. "For example, the percentage of the adult population exceeding the fivefold risk threshold varies from 0.4 percent in Layton, Utah, to 10.7 percent in Detroit, Michigan," Chatterjee says.

The calculator allows users to calculate mortality risk of individuals by combining information on individual-level factors with community-level pandemic dynamics, as available from a large variety of forecasting models. Thus, when a big wave of infections hits a population, the risk estimates for individuals will rise in that community. Currently, the tool is updated on a weekly basis to incorporate information on state-level pandemic dynamics.

Chatterjee and his colleagues expect that their calculator will be useful in setting priorities for allocating early COVID-19 vaccines and other scarce preventive resources such as N95 masks. Proposed guidelines from the U.S. National Academy of Sciences, Engineering and Medicine put frontline medical workers in the top-priority category to maximize societal benefits and minimize the chance that they will infect others, but most other priority categories are based broadly on estimated risks for infection and disease severity and, for example, give higher priority to the elderly and to people with conditions such as diabetes.

"People may understand broadly that with a preexisting condition such as obesity or diabetes, for example, they are at higher risk, but with our calculator they should be able to understand their risk in a way that takes multiple factors into account," Chatterjee says.

More information: Jin Jin et al. Individual and community-level risk for COVID-19 mortality in the United States, Nature Medicine (2020). DOI: 10.1038/s41591-020-01191-8

https://medicalxpress.com/news/2020-12-online-covid-mortality-vaccines.html

Unexpectedly, data show anaesthetists, intensive care doctors at lower risk of SARS-CoV-2

 Following the first recorded death of an anaesthetist from COVID-19 in the UK in November 2020, a review of available data published in Anaesthesia (a journal of the Association of Anaesthetists) shows that unexpectedly, despite their perceived increased exposure to COVID-19 patients and high-risk procedures, anaesthetists and intensive care doctors appear to be at lower risk of being infected with SARS-CoV-2 and developing COVID-19.

The analysis was carried out by Professor Tim Cook, Consultant in Anaesthesia and Intensive Care Medicine, Royal United Hospitals Bath NHS Foundation Trust, Bath, UK, and School of Medicine, University of Bristol, UK, and Dr. Simon Lenanne, General Practitioner, Ross-on-Wye, Herefordshire, UK. The authors undertook the review following the death on November 12, 2020, of anaesthetist Dr. Krishnan Subramanian, who was aged 46 years and worked at the Royal Derby Hospital, UK.

"This very sad event is a moment for pause and reflection. Every death is a tragedy, and our first thoughts should be with Dr. Subramanian's family, friends and colleagues," say the authors.

Reviewing numerous studies, the authors say that overall, healthcare workers in patient-facing roles are at two- to four-fold increased risk of infection and harm from COVID-19. Household members of healthcare staff are also at increased risk. However, it remains uncertain whether working in a patient-facing healthcare role significantly increases the risk of death from COVID-19.

"Three separate studies from Oxford, Leicester and Birmingham and including more than 20,000 healthcare staff indicate that those working in anaesthesia and intensive care had less than half the risk of infection than physicians dealing with COVID-19 patients on the wards. These studies also found significantly higher rates of infection in both front-line nurses and housekeeping staff compared to anaesthetists and intensivists," say the authors. "And in a study of Scottish of hospital admission of healthcare workers, working in ICU was again associated with approximately half the risk of working in 'front door' roles. Even household contacts of 'front door' healthcare workers had a higher risk of hospital admission than those working in ICU."

The authors also conducted an analysis to explore whether deaths of anaesthetists were lower than expected amongst the general population and amongst healthcare workers. Using data from The Royal College of Anaesthetists census, NHS Digital, the Office of National Statistics, and their own database of healthcare worker deaths the authors compared the expected and observed number of deaths amongst UK anaesthetists/ intensivists with various comparator groups.

Overall deaths amongst anaesthetists and intensivists were disproportionately low—ranging between less than a half to a quarter of expected deaths based on the numbers working in this speciality. The number of deaths expected among anaesthetists, based on representation of anaesthetists among doctors, and COVID-19 related deaths among the general population would be several times higher than the single death recorded so far (3 or 4 in total).

The authors explain: "This analysis indicates that, irrespective of the comparator group used, deaths among anaesthetists and intensivists are notably lower than expected and certainly not high, as some would have predicted."

The authors offer several possible explanations for the lower risk observed. These include better personal protective equipment or better use of it, working in well-ventilated environments and the possibilities that both the patients who are admitted to ICU are less infectious than those on the wards, and that the high risk procedures such as establishing a patient on a ventilator (including intubation) are not as high risk as has been assumed.

The authors say: "This analysis highlights both the relative safety of anaesthetists and intensivists from occupational harm from SARS-CoV-2 and the increased risks for others working on the wards, both in clinical and non-clinical roles."

They conclude: "It is our opinion that those working in anaesthesia and critical care should continue with current practices to maintain their own safety and that of their working environment. A more challenging question is whether some of the procedures that appear to keep anaesthetists and intensivists safe such as high level protective respirators should be extended to general practice and the wards where other healthcare workers are more at risk."

Dr. Mike Nathanson, President of the Association of Anaesthetists, said: "The whole profession was saddened to hear of the tragic death of Dr. Krishnan Subramanian. It is reassuring to see that, to date, we have lost no further anaesthestists or intensivists to COVID-19 despite their involvement on the front line of battling this pandemic. The death of each healthcare worker has been in our minds, however. This analysis reminds us of the risks, and of factors that may explain why anaesthetists and intensivists appear to have so far largely escaped the worst of this illness. We are not complacent, and we will continue to work for the wellbeing of the anaesthetists and intensivists we represent."

https://medicalxpress.com/news/2020-12-unexpectedly-anaesthetists-intensive-doctors-sars-cov-.html

Peru Halts Trial for Chinese Sinopharm Covid-19 Vaccine

 Peru's Health Ministry said Saturday it has suspended a trial for a Chinese Covid-19 vaccine after a participant presented health problems.

The Healthy Ministry said a trial with 12,000 volunteers for China's Sinopharm vaccine has been temporarily put on hold as it investigates whether the vaccine caused what it described as a "serious adverse event" in one of the participants. The trial was expected to finish in the coming days.

Germán Málaga, a health researcher at the Cayetano Heredia University in Lima, where the trial is taking place, said a volunteer presented neurological problems, resulting in difficulty moving his legs. Dr. Málaga told radio station RPP Noticias that he didn't believe the health problem was due to the vaccine, but more information was needed.

"We are concerned about the situation, and we are providing all of our help and support to ensure that it is cleared up," he said.

The United Arab Emirates said this week that its own trial for the Sinopharm vaccine had shown that it was 86% effective in protecting people from Covid-19.

The U.A.E.'s trial included 31,000 people. The analysis of its effectiveness against Covid-19 was based on a strain of the vaccine developed in Beijing. Another strain has been developed in Wuhan.

In Peru, it isn't clear which Sinopharm strain was used in the country's trial. A spokesman for the Health Ministry didn't respond to requests for comment.

Peru has confirmed more than 36,500 deaths from Covid-19, giving it one of the highest per capita mortality rates in the world.

The country of 32 million people has signed a deal with Pfizer Inc. to receive some 9.9 million doses of its Covid-19 vaccine. Government officials here hope the first batch of that vaccine will be delivered around March or April.

Peru also has signed an agreement to receive vaccines from a World Health Organization-backed initiative, called Covax. That program aims to distribute some 2 billion vaccines to poorer countries by the end of 2021.

https://www.marketscreener.com/quote/stock/SINOPHARM-GROUP-CO-LTD-5774274/news/Sinopharm-Peru-Halts-Trial-for-Chinese-Covid-19-Vaccine-32000384/

Over 73% of U.S. Adults Overweight or Obese

 About 42% of American adults had obesity in 2017-2018, National Health and Nutrition Examination Survey (NHANES) data showed.

Among adults ages 20 and older, 42.4% were identified as having a body mass index (BMI) of 30 or higher, while 9.2% had severe obesity, defined as a BMI of 40 or higher, reported Cheryl Fryar, MSPH, of the National Center for Health Statistics in Hyattsville, Maryland, and colleagues.

Another 30.7% of American adults were overweight, with a BMI of 25 to 29.9.

When the results were stratified by age, adults 40 to 59 saw the highest rates of obesity, with 45% of this age group with a BMI of 30 or higher. Middle-aged men had the highest prevalence of obesity, at a rate of 46%.

Not surprisingly, the rates of obesity also varied according to ethnicity.

Most notably, non-Hispanic Asian Americans consistently and overwhelmingly had the lowest rates of obesity, with only 18% and 17% of Asian men and women having a BMI over 30 in the most recent survey period.

On the other hand, Mexican American adults had some of the highest rates, with 51% of men and 50% of women with obesity. Similarly, 41% of non-Hispanic Black men had obesity, as did 57% of Black adult women.

"Although BMI is widely used as a measure of body fat, at a given BMI level, body fat may vary by sex, age, and race and Hispanic origin," Fryar's group wrote. "In particular, research suggests that health risks may begin at a lower BMI among Asian persons compared with others."

The current prevalence of obesity in the U.S. is in stark contrast to what the nation looked like several decades ago.

In national data from the survey period of 1960-1962, only about 13.4% of adults had obesity and less than 1% had severe obesity. And during that same survey period, about 31.5% of American adults were considered overweight.

From the early 1960s to today, however, the rates of obesity steadily increased each decade, doubling from 15% in 1976-1980 to 30.9% in 1999-2000.

But since the turn of the century, the rise in obesity rates seemed to slow down a bit despite still increasing. For example, the only times that obesity rates actually fell in the past 60 years was in 2007-2008 and again in 2011-2012.

Regarding children, the researchers found that 19.3% of Americans ages 2-19 had obesity, defined as a BMI at or above the 95th percentile on the growth chart. This included about 6.1% of kids who were identified as having severe obesity, measured as a BMI at or above 120% of the 95th percentile.

In addition to this, another 16.1% of U.S. children were overweight during the 2017-2018 survey period, defined as at or above the 85th percentile on the sex-specific BMI-for-age growth chart.

At this time, the rates of obesity were highest among teens: 21% of those ages 12-19 had obesity, with the rates for teen boys slightly higher than for teen girls (23% vs 20%).

Similar to in adults, the obesity rates followed similar ethnic patterns among kids. As for boys, the highest rates of obesity were seen among those of Mexican American (29%) and Hispanic (28%) descent, whereas for girls, the highest rates of obesity were among Black (29%) and Mexican American (25%) children and adolescents.

Again similar to the situation in adults, obesity in American kids followed a trajectory over the past several decades. In the 1971-1974 survey period, only 5% of U.S. kids had obesity, with only 1% of this subset having severe obesity; only 10% of kids were then overweight.

Primary Source

NCHS Health E-Stat

Source Reference: Fryar C, et al "Prevalence of overweight, obesity, and severe obesity among adults aged 20 and over: United States, 1960–1962 through 2017–2018" NCHS Health E-Stats; 2020.

Secondary Source

NCHS Health E-Stat

Source Reference: Fryar C, et al "Prevalence of overweight, obesity, and severe obesity among children and adolescents aged 2-19 years: United States, 1963–1965 through 2017–2018" NCHS Health E-Stats; 2020.

https://www.medpagetoday.com/primarycare/obesity/90142

Pfizer Analyst Breaks Down The FDA Process For Coronavirus Vaccine Candidate

 Pfizer Inc. 

PFE 1.5% and BioNTech SE's – ADR BNTX 1.73% coronavirus vaccine candidate passed the Adcom test, with the FDA panel voting 17-4 in favor of its risk-benefit profile in individuals 16 and older. 

Here's SVB Leerink analyst Geoffrey Porges' take on the dynamics of the Adcom vote. 

FDA Approval Imminent: The 17-4 vote favoring the vaccine candidate, with one abstention, should support emergency use authorization within days, Porges said in a note. 

"It is possible that the 16-17-year-old cohort is excluded from the initial EUA, which practically won't make much difference anyway, given the tiering of access proposed by the CDC's ACIP," the analyst said.

The Panel's Concerns: The vaccine committee expressed concerns regarding the trial integrity after a potential emergency use authorization, as well as long-term follow-up on trial participants and safety, especially against the backdrop of anaphylaxis reported from the U.K. following vaccination, Porges said.

The members debated whether the 16-17 age group should be included in an emergency use authorization, the analyst said. 

The most important reason for the "no" and "abstain" votes is the inclusion of the 16-17-year olds, he said. 

"Had the voting question excluded this cohort, the vote in favor of approval may have been unanimous."

The committee voiced concerns regarding the loss of blinded follow-up and randomized data when a vaccine becomes available under emergency use, Porges said.

Some members were worried about the impact of unblinding on data, which is required for the full Biologics License Application, the analyst said. 

The FDA proposed an alternative: a "blinded crossover' design, in which participants in the active vaccine arm will receive placebo shots, while placebo participants will receive active vaccine without unblinding, he said. 

Pfizer highlighted the logistical difficulties associated with this "blinded crossover" design, which would require bringing the 44,000 trial participants back to the trial sites two additional times for vaccination.

The FDA suggested other approaches may be utilized to assess long-term safety after unblinding, Porges said.

One potential way to assess the durability of response would be to compare the number of COVID-19 cases seen in the newly vaccinated individuals versus previously vaccinated individuals, the analyst said. 

The safety concerns centered around anaphylaxis and pregnant women, according to SVB Leerink.

The FDA said they already include warning language in the prescribing information, and will finalize the language in the following days, Porges said. 

On the potential impact of vaccination on pregnant women, Pfizer said it is conducting a pre-clinical study in rats which should report data later this month, the analyst said.

https://www.benzinga.com/analyst-ratings/analyst-color/20/12/18754175/pfizer-analyst-breaks-down-the-fda-process-for-coronavirus-vaccine-candidate

Sanofi delays hemophilia filing 18 months amid safety concerns

 Sanofi’s response to nonfatal thrombotic events in a phase 3 hemophilia program has delayed its plans to seek approval for RNAi drug fitusiran by 18 months. The delay will “allow for the appropriate collection and assessment of safety and efficacy data under the amended protocols.”

Thrombotic events emerged as a significant concern for the fitusiran program in 2017 when dosing in a phase 2 trial was paused after a hemophilia A patient died from a blood clot. Alnylam, which ceded control of fitusiran to Sanofi early in 2018, responded to the original clinical hold by introducing new risk-mitigation measures.

Those measures, which included efforts to educate patients and physicians about reduced doses to treat breakthrough bleeds, helped Sanofi wrap up phase 2 and move into pivotal studies in 2018.

Sanofi ran into trouble again in late October when nonfatal thrombotic events in the phase 3 led it to pause dosing. Sanofi is now set to resume dosing in adolescents and adults, but a clinical trial that was giving fitusiran to children aged one to 12 years remains paused. Researchers are continuing to evaluate dosing in the pediatric study.

The resumption of the other trials follows the decision to change the dose and dosing regimen to improve the benefit-risk profile of the treatment for hemophilia A and B. Sanofi’s actions have had a significant impact on the timeline for getting fitusiran to market. 

Sanofi held the primary completion for one phase 3 trial late last month. The primary completion for a second phase 3 is set for February. Sanofi designed the trials to show the effect of fitusiran on the annualized bleeding rates of patients with severe hemophilia A and B over an eight-month period. 

The change in dose and dosing regimen means Sanofi will need to collect safety and efficacy data under the amended protocols before being in a position to seek approval for fitusiran. A delay of 18 months or so is expected.

Fitusiran was one of the drugs that survived the cull overseen by Paul Hudson when he took over as CEO of Sanofi. The RNAi therapy targets a protein that inhibits blood clotting. Phase 2 data suggested the approach may work in patients with hemophilia A and B, with or without inhibitors, providing a point of differentiation in a competitive space, but safety worries have hung over the program.  

https://www.fiercebiotech.com/biotech/sanofi-delays-hemophilia-filing-18-months-amid-safety-concerns

CDC advisory panel expected to recommend COVID-19 vaccine for widespread use

 A U.S. Centers for Disease Control and Prevention advisory panel convened on Saturday to consider whether to recommend the nation’s first COVID-19 vaccine. A vote would clear one of the final hurdles for public health authorities to begin the largest vaccination campaign in U.S. history.

The Advisory Committee on Immunization Practices (ACIP) met on Saturday morning and are expected to recommend the vaccine from Pfizer Inc and BioNTech SE as appropriate for adult Americans. ACIP is also expected to discuss whether pregnant women and teens as young as 16 should take it.

The Food and Drug Administration on Friday issued an emergency use authorization for the vaccine, clearing it for use by the general public.

After the advisory group votes, the CDC is expected to consider and approve the recommendations.

State and local public health authorities will use FDA and CDC guidance as they administer the first 2.9 million doses of the vaccine released to state, cities, and territories by the federal government.

ACIP already recommended that authorities should prioritize healthcare workers and nursing home residents for the first doses that become available.

It then falls on states and certain large cities to start administering the vaccine to local hospitals and nursing homes. Hospitals are expected to start vaccinating their employees as early as Monday.

https://www.reuters.com/article/health-coronavirus-vaccines-acip/cdc-advisory-panel-expected-to-recommend-covid-19-vaccine-for-widespread-use-idUSKBN28M0TF