U.S. meatpackers try UV air cleaning tech after COVID-19 outbreaks

Two of the world’s largest meatpackers said on Friday they have installed ultraviolet air cleaning equipment in some U.S. plants, as pressure mounts on food companies to protect workers amid growing concerns about airborne transmission of the coronavirus.

JBS USA, owned by Brazil’s JBS SA (JBSS3.SA) and one of four major U.S. beef processors, said it installed “ultraviolet germicidal air sanitation” equipment in plant ventilation and air purification systems that use a specific frequency range of light waves to kill germs.

Tyson Foods Inc (TSN.N), which produces beef, pork and chicken, said it is doing extensive research on air flow and testing ultraviolet air treatment systems across several plants.

It is not known whether such technologies kill the new coronavirus.

The moves underscore the mounting pressure to protect workers in the U.S. meat industry, which has seen more than 16,000 plant employees in 23 states infected with COVID-19 and 86 worker deaths related to the respiratory disease.

Plant employees and their families have said processors like JBS and Tyson Foods told sick workers to show up at plants, and moved too slowly to protect them with social distancing and equipment like masks.

As worker infections grew, so have meatpackers’ legal problems. In one case, the family of a Pennsylvania man who died from COVID-19 sued JBS USA parent company JBS SA for failing to protect him at the meat plant where he worked.

Low temperatures, which generally allow viruses to survive in the air longer, and crowded working conditions have made meatpacking plants global coronavirus hotspots.

In Germany, a COVID-19 outbreak forced meatpacking plants to review infection risks posed by their cooling systems. One meatpacker had to install high-efficiency HEPA filters typically used in hospitals before being allowed to reopen on Friday.

The World Health Organization last week acknowledged “evidence emerging” of the airborne spread of the novel coronavirus.

The U.S. Centers for Disease Control and Prevention has recommended meat companies consider consulting engineers to ensure adequate ventilation in work areas, but has not required changes to air systems.

JBS told Reuters it also installed “plasma air cleaning technology” in U.S. plants that uses bipolar ionization to neutralize particulates in the air, including virus cells and bacteria.

The company said it is still collecting data on how well the air treatment system works.

Some rivals are holding off. Privately held chicken company Perdue Farms said it has not made any ventilation changes because it has not seen scientific data that shows the virus is spread through industrial air systems. Employees are wearing masks and practicing social distancing for protection, according to the company.

https://www.reuters.com/article/us-health-coronavirus-usa-meatpacking/rare-air-u-s-meatpackers-try-air-cleaning-tech-after-covid-19-outbreaks-idUSKCN24J00T

How does COVID-19 affect kids? Science has answers and gaps

What role children play in the coronavirus pandemic is the hot-button question of the summer as kids relish their free time while schools labor over how to resume classes.

Many doctors who specialize in pediatrics and infectious diseases say much of the evidence is inconclusive.

“There are still a lot of unanswered questions. That is the biggest challenge,” said Dr. Sonja Rasmussen, a pediatrics professor at the University of Florida and former scientist at the U.S. Centers of Disease Control and Prevention.

Several studies suggest, but don’t prove, that children are less likely to become infected than adults and more likely to have only mild symptoms.

An early report from Wuhan, China, where the outbreak began last winter, found that fewer than 2% of cases were in children. Later reports suggest between 5% and 8% of U.S. cases are in kids.

Through July 9, about 200,000 kids had tested positive in the U.S., according to a count based on state reports by the American Academy of Pediatrics. The number of kids who have been infected is almost certainly far higher than that though, experts say, because those with mild or no symptoms are less likely to get tested.

The CDC says that 228 children and teens through age 17 have died from the disease in the U.S. as of Thursday. More than 138,000 Americans have died in total, and there have been more than 3.6 million confirmed cases.

One early study examining infections in children comes from a Wuhan hospital. Of 171 children treated there, most had relatively mild illness. One child died, and only three needed intensive care and ventilator treatment. Perhaps more worrisome was that 12 had X-ray evidence of pneumonia, but no other symptoms.

A CDC study involving 2,500 children published that same month, in April, echoed those findings. About 1 in 5 infected children were hospitalized versus 1 in 3 adults; three children died. The study lacks complete data on all the cases, but it also suggests that many infected children have no symptoms.

“We’re trying to figure out who those kids are,” Rasmussen said. “We need to figure out the impact on kids and on the rest of the community, their parents and their grandparents. If they’re transmitting a lot to each other, and then bringing it home to their families.”

Not knowing if children are infected makes it difficult for schools to reopen safely, many experts say. Scarce data on whether infected children—including those without symptoms—easily spread the disease to others complicates the issue, said Jeffrey Shaman, a Columbia University infectious disease specialist.

A National Institutes of Health-sponsored study seeking to answer that question and others is under way.

A JAMA Pediatrics study from May, cited Thursday by White House Press Secretary Kayleigh McEnany, involved just 48 children treated in U.S. and Canadian intensive care units. As McEnany indicated, most were not critically ill. Still, she did not mention that 18, or almost 40%, needed ventilator treatment and two died.

McEnany was correct that children appear less likely to become critically ill from COVID-19 than from the flu. But the CDC says COVID-19 can be more contagious and has been linked with more “superspreading” events than the flu, meaning it can quickly spread and infect lots of people.

Also, blood clots and organ damage have been found in children with COVID-19, including those who develop a related inflammatory illness. The most recent count shows 342 U.S. children and teens have developed that condition, called multisystem inflammatory syndrome in children.

The condition is rare but can occur in children with current or recent COVID-19 infections. Symptoms include fever and problems in at least two organs, often including the heart. Digestive problems are common, and some cases have been mistaken with Kawasaki disease and toxic shock syndrome.

Perhaps the biggest unknown is whether permanent damage to lungs and other organs can result. The virus is too new to know for sure.

---

Explore further

CDC alerts doctors to COVID-19 linked condition in children

https://medicalxpress.com/news/2020-07-covid-affect-kids-science-gaps.html

Moderna’s Phase I Data

By Derek Lowe

Well, it’s finally here – eight weeks to the day after press-releasing some top line results, the full paper is out on the Moderna mRNA vaccine candidate’s Phase I trial. I’m very glad to see it – it’s going to be very important for the full data sets on all the vaccine candidates to be made public.

So how’s it look? As we found out back in May, we’re looking at three groups of 15 volunteers each, 18 to 55 years old, getting 25 µg, 100 µg, or 250 µg of mRBA-1273 in two doses 28 days apart. The vaccine itself is an RNA sequence for a trimer form of the S (Spike) protein of the coronavirus (similar to the Pfizer/BioNTech mRNA vaccine in that way). It comes with a transmembrane anchor and the S1-S2 cleavage site between the subunits still intact, stabilized in the “prefusion” conformation that it will present in the wild-type virus before it infects cells. That stabilization is through the substitution of two residues at the top of the S2 subunit with proline residues, the “S 2P” form, and the same trick has been used to stabilize other surface proteins of other viruses entirely. (For those who aren’t into protein engineering, proline is unique among amino acid residues in forcing a much more limited conformation in the protein chain, particularly when you have two of them back-to-back). It’s in a lipid nanoparticle (LNP) formulation

As mentioned before, all patients seroconverted within 15 days of the first dose. The antibody titers generated were dose-dependent and were much higher (several-fold) after the second round of injections. Adverse events (fever, chills, pain at the injection site) were definitely more common after the second injection, too, which is just what you’d expect. With that in mind, it’s worth noting the design of the trial, a standard one that’s quite sensible when you’re stepping in to tweak the immune system. The dosing started off with four “sentinel” patients at the lowest dose, followed by four in the middle dose. After those showed nothing serious, both of those groups were then fully enrolled. After Day 8 of the full dosing, four sentinel patients were injected in the highest-dose group, and after them, the rest of that group were enrolled. For the wrong way to try out a new immunology approach, see here.

The patients were assayed for antibody levels (in a standard ELISA format), for neutralizing antibodies (by looking for inhibition in various cell-infection assays), and for T-cell levels. As you’d expect, none of the patients’ plasma showed the ability to neutralize the coronavirus before the trial dosing began. And neutralization was still low after the first injection, although the antibody titers had gone up. By Day 43, though (post-second injection), all participants were able to neutralize the effects of the virus in the cell-infection assays by at least 80%, with those responses also being dose-dependent. A comparison showed that this activity was the same or higher than that found with the plasma of convalescent patients (samples from 38 people, collected 23 to 60 days after onset of symptoms). But one thing that you do notice as you look over the data was that day 43 was the best – there was a further evaluation at day 57, and all three groups had gone down a bit in just those two weeks. You can see this happening in the pseudovirus neutralization assays in the paper’s Table 2 and in Figure S8. These patients are no doubt continuing to be monitored, and it is of great interest to see how their neutralizing antibody titers hold up.

That said, antibody levels are not the only thing that determines immunity. T cells are a big part of this story, although we don’t know all the details – you’ll generally hear a lot more about antibody titers because they’re a lot easier to measure, and to be fair they are often a good proxy for overall immunity. But not always. As for the T-cell data here, CD4+ cell responses were noted, but there was much weaker CD8+ activity (and that only after the second dose in the 100 µg group). Those CD4+ cells can be further differentiated into Th1 and Th2 cells, which each produce a different suite of cytokines. In this case, the vaccine seemed to mostly elicit Th1. The balance between those two types is a complex subject indeed (they have different modes of action and can influence each other’s activity as well), and that also goes for the balance between the CD4+ and CD8+ T cells in general.

I’m not enough of an immunology geek to be able to tell you what profile we would be looking for, and I don’t think we even quite know yet. My impression is that CD8+ cells are more well-established as being important in clearing viral infections (especially respiratory viruses), but the CD4+ ones (and the ratio of the two) are real players as well. As for the Th1 and Th2 subsets of those CD4+ cells, there’s evidence that the Th1 type are more powerful against viral pathogens, at least for some viruses. The general belief, in fact, has been that Th1 cells are more important in fighting intracellular pathogens in general, with Th2 cells going after extracellular parasites and the like, but (like everything else in immunology) that framework has only become more complicated as we learn more about it.

So from my bozo-immunology perspective, I think at first glance that I would rather see a more robust CD8+ response than what Moderna has shown here. Others seem to feel similarly. But that said, I don’t know what the convalescent patient T-cell situation is, either: what kind of response did these people have when they cleared the virus on their own? We don’t have the figures from the set of patients in this paper (they just took plasma to evaluate antibodies). But we know from a study of 10 infected patients with respiratory distress that those patients had a higher CD4+/CD8+ ratio, and that they had a higher Th1 response among the CD4+ cells. But you’d want to hear about the people who recovered smoothly as well as about the ones who ended up on respirators, wouldn’t you? The main thing I’ve been able to find on that is this paper, which also showed a shift towards CD4+ cells in pooled plasma from convalescent patients, and among those cells a very pronounced Th1-driven response (note: more on this one here, and in a separate blog post, coming shortly). So the Moderna data might well resemble the profile of recovered patients, which doesn’t sound so bad, although keep in mind that there might still be better ways to clear the virus than the response that we tend to get. We’re just going to have to see how things play out in Phase II/III, aren’t we? One also would like to see such profiles for the other vaccines in the race, and I assume that we will.

The comparisons are going to be pretty darn interesting. As you can see, Moderna’s candidate is absolutely going to need two injections (as did the Pfizer/BioNTech vaccine candidate), and the reaction to the second dose is pretty vigorous. Will that cause trouble in moving into a larger and more diverse patient cohort? The Moderna neutralizing antibody response seems broadly similar to the Pfizer study, but we don’t have any T-cell profiling from Pfizer yet, so it’s impossible to make any comparisons in that department. The Pfizer/BioNTech adverse event profiling looked a bit better – is that going to be a distinguishing characteristic as the various vaccines go on? Will there be (can there be?) a single-dose vaccine from someone, which would make life and logistics much easier? What will the differences be in the strength of  real-world protection against infection, and in its duration? I have no earthly idea, and neither does anyone else: that’s why everyone is charging into the later clinical trial phases.

https://blogs.sciencemag.org/pipeline/archives/2020/07/15/modernas-phase-i-data

Predictive analytics tools hospitals are using to forecast COVID-19 case surges

Hospitals nationwide have been utilizing predictive analytics tools to project the location and severity of future COVID-19 outbreaks.

Though COVID-19 forecasting tools vary on the data they use to make predictions, they all seek to help healthcare providers make informed decisions about care and how to best utilize their resources.

Boston-based Beth Israel Deaconess Medical Center appointed a research group within the Center for Healthcare Delivery Science to apply epidemiology, machine learning and causal inference to forecast where COVID-19 would surge next. The 670-bed academic medical center began to formulate its response in February, relying on national models to predict how the virus would spread. However, national models didn’t consider socioeconomic factors or local hospital and community decision-making. The research team created a hyper-local alert system, integrating a preliminary Susceptible, Infected and Recovered people model into the hospital’s incident command structure. The researchers also relied on machine learning to take real-time data from the EHR to examine disease characteristics like incubation time, infection period and transmissibility, which allowed them to predict peaks and declines five days before the national models.

Children’s Hospital of Philadelphia developed a tool to track COVID-19 cases in June that is the first of its kinds to utilize historic weather data. The tool uses temperature and humidity data from 389 U.S. counties experiencing some level of COVID-19 activity to predict the severity of future surges. COVID-19 transmission often seems to rise as temperatures do, which researchers say is likely attributed to people socializing more outside and the virus staying on surfaces longer during warmer months. The model also uses GPS data to track each county’s increase in visits to nonessential locations and takes into account demographic data, such as population density, poverty levels, number of people older than 65 and number of people with preexisting conditions.

Researchers at Cleveland Clinic developed a prediction model to forecast the likelihood of patients testing positive for COVID-19 and the potential disease outcomes in June. It makes projections based on age, race, gender, socioeconomic status, vaccination history and current medications. Cleveland Clinic researchers developed the tool, a nomogram, with data from about 12,000 patients enrolled in its COVID-19 registry. The tool is available freely online as a risk calculator, which can be found here.

In June, Chicago-based CommonSpirit Health created a COVID-19 forecasting tool using deidentified cellphone, public health and health system data. The health system took into consideration fixed data, including population and availability of healthcare providers, as well as variable data, including social-distancing relaxation and new cases. The collection of cellphone data used to show how much people travel outside their communities is HIPAA-compliant and can’t be associated with anyone. CommonSpirit can generate a predictive outlook for about 75 percent of its markets, including Texas, California, Arizona and the Pacific Northwest.

Dallas-based Parkland Center for Clinical Innovation created a COVID-19 vulnerability calculator in June to measure communities’ vulnerability to COVID-19 by tracking and analyzing their comorbidity rates, population over age 65, social factors and ability to observe stay-at-home measures. The model determined social deprivations, such as inadequate access to food, medicine, employment and transportation, as the largest contributor to higher COVID-19 mortality rates among Black and Latinx communities. Local healthcare providers can use the vulnerability index as a tool to better tailor their COVID-19 response to the neighborhoods that need it most, deploy more testing and education in at-risk areas, and plan culturally sensitive initiatives to address infection disparities in Black and Latinx communities.

A team of researchers working at Ames-based Iowa State University, led by Lily Wang, PhD, developed a COVID-19 forecasting dashboard in June. The dashboard provides users with a seven-day rolling forecast and four-month predictions of COVID-19 infections and deaths, which can be viewed at both state and county levels. It analyzes data from Baltimore-based Johns Hopkins University, The New York Times, The Atlantic, the World Health Organization, the CDC and USAFacts. To produce county-specific predictions, it also uses data from state and county public health departments, censuses, local databases, mobility tracking and government news releases. Yuan Gu, a graduate student at Pittsburgh-based Carnegie Mellon University, is currently developing a mobile version of the dashboard.

https://www.beckershospitalreview.com/data-analytics/the-predictive-analytics-tools-hospitals-are-using-to-forecast-covid-19-case-surges.html

Medical Societies Advise on Vitamin D in Midst of COVID-19

Six medical societies from across the globe are emphasizing the importance of individuals obtaining the daily recommended dose of vitamin D, especially given the impact of the COVID-19 pandemic on outdoor time.

The statement, “Joint Guidance on Vitamin D in the Era of COVID-19,” is supported by the American Society for Bone and Mineral Research (ASBMR), the Endocrine Society, and the American Association of Clinical Endocrinologists (AACE), among others.

They felt the need to clarify the recommendations for clinicians. Central to the guidance is the recommendation to directly expose the skin to sunlight for 15-30 minutes per day, while taking care to avoid sunburn.

The statement notes that “Vitamin D is very safe when taken at reasonable dosages and is important for musculoskeletal health. Levels are likely to decline as individuals reduce outside activity (sun exposure) during the pandemic.”

It adds, “Most older and younger adults can safely take 400-1000 IU daily to keep vitamin D levels within the optimal range as recommended by [the US] Institute of Medicine guidelines.”

The statement adds that the scientific evidence clearly supports the benefits that vitamin D (in combination with calcium intake) plays in building a strong skeleton and preventing bone loss.

Other societies supporting the statement are the European Calcified Tissue Society (ECTS), the National Osteoporosis Foundation (NOF), and the International Osteoporosis Foundation (IOF).

What Role for Vitamin D in COVID-19?

Over recent months, the role of vitamin D in relation to prevention of COVID-19 has been the subject of intense debate. Now, these societies have joined forces and endorsed evidence-based guidance to clarify the issue around obtaining the daily recommended dosage of vitamin D.

During the pandemic, orders to stay at home meant individuals were likely to spend less time outdoors and have less opportunity to draw their vitamin D directly from sunlight, which is its main source, other than a limited number of foods or as a dietary supplement, the societies explain.

However, they acknowledge that the role of vitamin D in COVID-19 remains unclear.

“The current data do not provide any evidence that vitamin D supplementation will help prevent or treat COVID-19 infection; however, our guidance does not preclude further study of the potential effects of vitamin D on COVID-19,” says the joint statement.

Research to date suggests that vitamin D may play a role in enhancing the immune response, and given prior work demonstrating a role for the activated form of vitamin D [1,25(OH)2D] in immune responses, “further research into vitamin D supplementation in COVID-19 disease is warranted,” it adds.

“Trials to date have been observational and there have been no randomized controlled trials from which firm conclusions about causal relationships can be drawn. Observational studies suggest associations between low vitamin D concentrations and higher rates of COVID-19 infection.”

Medscape Medical News has previously reported on the existing observational data regarding vitamin D in COVID-19.

And a recent rapid evidence review by the UK National Institute for Health and Care Excellence (NICE), also reported by Medscape Medical News, failed to find any evidence that vitamin D supplementation reduces the risk, or severity, of COVID-19.

Joint Guidance on Vitamin D in the Era of COVID-19. Published July 9, 2020. Statement

https://www.medscape.com/viewarticle/933715