Coronavirus Update 7-21

Limited Edition

July 21, 2020

Without reliable information, we rely on fear or luck.

Index

A. Numbers & Trends

B. New Scientific Findings & Research

1. More than 90% of coronavirus patients develop antibodies 
2. C19 intensive care mortality has fallen by a third 
3. Droplets from coughs and sneezes travel further and last longer in colder, humid climates
4. Foods containing cabbage could help fight coronavirus   (?!)

C. Improved & Potential Treatments

1. Inhaled Drug Reduces Odds of Hospitalized Patients Developing Severe Symptoms by 79%  (!!)
2. C19 could be crippled by an age-old blood thinner   (!)
3. CBD May Help Reduce the Cytokine Storm and Avert Lung Destruction 
4. Coronavirus vaccine from Oxford, AstraZeneca shows positive response in early trial 
5. Chinese C19 Vaccine Phase 2 Trial Results: Safe and Induces an Immune Response  

D. Concerns & Unknowns

1. 200,000 people in UK could die from disease unrelated to C19 because of delays in healthcare and economic effects of coronavirus lockdown 
2. What happens when the flu meets C19?   
3. C19 Spread Fastest by Older Children

E. Projections & Our (Possible) Future

1. The Link Between Face Masks, Infections and GDP 

F. Johns Hopkins COVID-19 Update (7/20)

G. Links to Other Stories 

Physicians provide first comprehensive review of C19’s effects beyond the lungs Researcher-clinicians have conducted an extensive review of the latest findings on COVID-19’s effect on organ systems outside the lungs. Their review, published in Nature Medicine, also summarized proposed mechanisms behind these wide-ranging systemic effects and provided clinical guidance for physicians. 

Lockdowns could have long-term effects on children’s health Sitting at home playing video games and eating crisps is not good for children.

Controversial ‘human challenge’ trials for C19 vaccines gain support Two key elements are taking shape: a large corps of volunteers willing to take part in a “human challenge” trial, and the well-understood lab-grown virus strains needed for the studies.  

How a Potential Treatment for the Coronavirus Turned Up in a Scientist’s Freezer In the race to develop antibody drugs for C19, a Dutch team found itself ahead of the pack. 

During Coronavirus Lockdowns, Some Doctors Wondered: Where Are the Preemies? This spring, as countries around the world told people to stay home to slow the spread of the coronavirus, doctors in neonatal intensive care units were noticing something strange: Premature births were falling, in some cases drastically.

People Who Got Anosmia Due to C19 Are Turning to ‘Smell Therapy’ A growing number of people who lost their smell during the COVID-19 pandemic and haven’t been able to get it back are now turning to “smell therapy.” 

Swedish firm claims its mouth spray can deactivate coronavirus by 98.3% in 20 minutes  ColdZyme sprayed onto the mouth and throat could lower the risk of infection, and decrease the viral load locally. The lowered viral load may decrease viral shedding and thus minimize the spread of coronavirus, says the company. [Note: Worth watching, but we recommend waiting for further research.]

U.S. will use pooling testing method that let Wuhan test 6.5 million people in 10 days  The FDA is allowing Quest Diagnostics to test individual samples for coronavirus using a method known as batch testing, which mixes specimens from multiple people and tests the combined sample for coronavirus instead of testing samples one by one.

Scientists Warn That More Bat Research Is Critical to Preventing Next Pandemic

Experts Call for Clear New C19 Pandemic Modeling Rules

A. Numbers & Trends

Note: Unless otherwise noted, (i) all cases/deaths are confirmed cases/deaths that have been reported, (ii) all numbers reported in this update are as of the end of the most recent reporting period, and (iii) all changes reflect changes since the preceding day.  Green highlights indicate a decrease or no change and yellow highlights indicate an increase. 

Sources: https://www.worldometers.info/coronavirus/ and https://covidtracking.com/

1. Cases & Tests (7/20)

Worldwide Cases:  

• Total Cases = 14,845,684 (+1.4%)
• New Cases = 205,348 (-17,321) (-7.8%)
• New Cases (7 day average) = 228,782 (+1,235) (+0.5%)

Observations:

• Number of new cases have declined for 4 consecutive days
• Number of new cases have declined 44,323 over last 4 days
• 7 day average of new cases was a record high on 7/20 

US Cases & Testing: 

• Total Cases = 3,961,429 (+1.6%)
• New Cases = 62,879 (-2,400)
• Percentage of New Global Cases = 30.6% 
• New Cases (7 day average) = 68,263 (-417) (-0.6%)
• Total Number of Tests = 49,161,907 (+820,171) 
• Percentage of positive tests (7 day average) = 8.5% 

Observations:

• Lowest number of new cases in 4 days
• 3 day average of new cases has declined 13.1% since 7/17
• 7 day average of new cases declined for the first time since 6/9

2. Deaths

Worldwide Deaths: 

• Total Deaths = 612,842 (0.7%)  
• New Deaths = 4,046 (-309) (-7.1%)
• New Deaths (7 day average) = 5,176 (+33) (+0.6%)

Observations:

• Number of new deaths have decreased 5 consecutive days
• Number of new deaths has declined 1,797 over last 5 days

US Deaths: 

• Total Deaths = 143,834 (+0.4%)
• New Deaths = 545 (+133) 
• Percentage of Global New Deaths = 13.5% 
• New Deaths (7 day average) = 802 (+11) (+1.4%)

Observations:

• 3 day average of new deaths has declined from 970 on 7/17 to 590 on 7/20, a decrease of 39.2%
• 7 day average of new deaths has generally been increasing since 7/5
• Highest 7 day average of new deaths since 6/11

3. Top 5 States in Cases, Deaths, Hospitalizations, and Positivity (7/20)

Source: Worldometer and The Covid Tracking Project

B. New Scientific Findings & Research  

1. More than 90% of coronavirus patients develop antibodies 

• The ‘vast majority’ of recovered coronavirus patients develop antibodies for several months, a new study suggests. 
• Researchers found that more than 90% of people previously infected with C19 developed an immune response that lasted at least 90 days.
• What’s more, most of the patients had levels that were not only attached to the virus but neutralized it so the pathogen could not enter and infect human cells. 
• In a new study from Mount Sinai, researchers found least 92% of recovered coronavirus patients had moderate to high levels of antibodies that attach to the spike protein the virus uses to infect cells
• For the study, published on the pre-print server medRxiv.org, the team analyzed more than 19,700 people screened at Mount Sinai Health System in New York. [Read the preprint study here]
• Researchers specifically looked for IgG antibodies, which are proteins that the body produces in the late stages of infection. IgG antibodies are believed to remain for months, and possibly years, after a person has recovered.
• Antibodies are defined at detectable at a titer, or level, of 1:80 or higher. Between 80 and 160 is low, 320 is moderate and 960 or above is high.
• Of the more than 19,000 positive samples, at least 92 percent have moderate to high levels of antibodies that attach to the spike protein the virus uses to enter human cells.
• Next, they determined if the antibodies are able to neutralize the virus by testing 120 samples. About 50 percent of the low level antibodies had neutralizing activity as did 90 percent in the moderate range and 100 percent did in the high range.  
• To see how long antibodies remained in the body, researchers tested 121 plasma donors who had a variety of levels three months after first experiencing symptoms. Those in the higher range had a slight drop but those with low and moderate levels saw increases. 
• ‘Our data suggests that more than 90%…make detectible neutralizing antibody responses and that these [levels] are stable for at least the near-term future,’ the authors wrote.
• The study does not provide ‘conclusive evidence’ that antibodies protect people from becoming reinfected.
• However, ‘researchers believe it’s very likely they will decrease the odds ratio of getting re-infected and may attenuate disease in the case of breakthrough infection,’ a Mount Sinai spokesperson told Fox News.

Source: Study: More than 90% of coronavirus patients DO develop antibodies 

2. C19 intensive care mortality has fallen by a third

• A systematic review and meta-analysis of published studies from 3 continents shows overall mortality of C19 patients in intensive care units (ICUs) has fallen from almost 60% at the end of March to 42% at the end of May — a relative decrease of one third since the start of the pandemic.
• The review (here), led by the University of Bristol and Royal United Hospitals Bath NHS Trust published today in Anaesthesia, a journal of the Association of Anaesthetists, also shows ICU mortality for the disease is similar across the three continents included: Europe, Asia and North America.
• “The important message is that as the pandemic has progressed and various factors combine, survival of patients admitted to ICU has significantly improved. There were no significant effects of geographical location, but reported ICU mortality fell over time. Optimistically, as the pandemic progresses, we may be coping better with C19,” said lead author Professor Tim Cook, Honorary Professor in Anaesthesia at the University of Bristol and Consultant in Anaesthesia and Intensive Care Medicine at Royal United Hospitals Bath NHS Foundation Trust.
• The researchers searched the MEDLINE, EMBASE, PubMed and Cochrane databases up to 31 May 2020 for studies reporting ICU mortality for adult patients admitted with C19. The primary outcome measure was death in ICU as a proportion of completed ICU admissions, either through discharge from the ICU or death. The definition therefore did not include patients still alive on ICU.
• A total of 24 observational studies including 10,150 patients were identified from centres across Asia, Europe, and North America. In patients with completed ICU admissions with C19 infection, combined ICU mortality across all the studies up to the end of May was 41.6%. This represents a fall of around a third from the 59.5% ICU mortality seen in the studies up to the end of March.
• Professor Cook said: “The in-ICU mortality from C19, at around 40%, remains almost twice that seen in ICU admissions with other viral pneumonias, at 22%.”
• There are several possible explanations for the findings regarding decreasing ICU mortality over time.
• Professor Cook said: “It may reflect the rapid learning that has taken place on a global scale due to the prompt publication of clinical reports early in the pandemic. It may also be that ICU admission criteria have changed over time, for example, with greater pressure on ICUs early in the pandemic surge.”
• The findings are also likely to reflect the fact that long ICU stays, for example, due slow weaning from a ventilator, take time to be reflected in the data. Critical illness associated with C19 can last for long periods, with approximately 20% of UK ICU admissions lasting more than 28 days, and 9% more than 42 days.
• The ICU mortality did not differ significantly across continents despite some evidence of variations in admission criteria, treatments delivered and the thresholds for their application. This is consistent with research findings up until the end of May suggesting that no specific therapy reduces ICU mortality. In the last few weeks dexamethasone has been found to have significant benefit and there is hope this will improve survival further.

Source: July: COVID-19 ICU mortality | News and features 

3. Droplets from coughs and sneezes travel further and last longer in colder, humid climates 

• Respiratory droplets from a cough or sneeze travel farther and last longer in humid, cold climates than in hot, dry ones, according to a study on droplet physics by an international team of engineers. The researchers incorporated this understanding of the impact of environmental factors on droplet spread into a new mathematical model that can be used to predict the early spread of respiratory viruses including C19, and the role of respiratory droplets in that spread.
• The team developed this new model to better understand the role that droplet clouds play in the spread of respiratory viruses. Their model is the first to be based on a fundamental approach taken to study chemical reactions called collision rate theory, which looks at the interaction and collision rates of a droplet cloud exhaled by an infected person with healthy people. Their work connects population-scale human interaction with their micro-scale droplet physics results on how far and fast droplets spread, and how long they last.
• Their results were published June 30 in the journal Physics of Fluids.
• “The basic fundamental form of a chemical reaction is two when molecules are colliding. How frequently they’re colliding will give you how fast the reaction progresses,” said Abhishek Saha, a professor of mechanical engineering at the University of California San Diego, and one of the authors of the paper. “It’s exactly the same here; how frequently healthy people are coming in contact with an infected droplet cloud can be a measure of how fast the disease can spread.”
• They found that, depending on weather conditions, some respiratory droplets travel between 8 feet and 13 feet away from their source before evaporating, without even accounting for wind. This means that without masks, six feet of social distance may not be enough to keep one person’s exhalated particles from reaching someone else.
• “Droplet physics are significantly dependent on weather,” said Saha. “If you’re in a colder, humid climate, droplets from a sneeze or cough are going to last longer and spread farther than if you’re in a hot dry climate, where they’ll get evaporated faster. We incorporated these parameters into our model of infection spread; they aren’t included in existing models as far as we can tell.”
• The researchers hope that their more detailed model for rate of infection spread and droplet spread will help inform public health policies at a more local level, and can be used in the future to better understand the role of environmental factors in virus spread.
• They found that at 95F and 40% relative humidity, a droplet can travel about 8 feet. However, at 41F and 80 percent humidity, a droplet can travel up to 12 feet. The team also found that droplets in the range of 14-48 microns possess higher risk as they take longer to evaporate and travel greater distances. Smaller droplets, on the other hand, evaporate within a fraction of a second, while droplets larger than 100 microns quickly settle to the ground due to weight.
• This is further evidence of the importance of wearing masks, which would trap particles in this critical range.
• The team of engineers from the UC San Diego Jacobs School of Engineering, University of Toronto and Indian Institute of Science are all experts in the aerodynamics and physics of droplets for applications including propulsion systems, combustion or thermal sprays. They turned their attention and expertise to droplets released when people sneeze, cough or talk when it became clear that C19 is spread through these respiratory droplets. They applied existing models for chemical reactions and physics principles to droplets of a salt water solution–saliva is high in sodium chloride–which they studied in an ultrasonic levitator to determine the size, spread, and lifespan of these particles in various environmental conditions.
• Many current pandemic models use fitting parameters to be able to apply the data to an entire population. The new model aims to change that.
• “Our model is completely based on “first principles” by connecting physical laws that are well understood, so there is next to no fitting involved,” said Swetaprovo Chaudhuri, professor at University of Toronto and a co-author. “Of course, we make idealized assumptions, and there are variabilities in some parameters, but as we improve each of the submodels with specific experiments and including the present best practices in epidemiology, maybe a first principles pandemic model with high predictive capability could be possible.”
• There are limitations to this new model, but the team is already working to increase the model’s versatility.
• “Our next step is to relax a few simplifications and to generalize the model by including different modes of transmission,” said Saptarshi Basu, professor at the Indian Institute of Science and a co-author. “A set of experiments are also underway to investigate the respiratory droplets that settle on commonly touched surfaces.”

Source: New model connects respiratory droplet physics with spread of Covid-19 

4. Foods containing cabbage could fight the coronavirus

• According to a new study from France, foods containing raw and fermented cabbage may be beneficial against the coronavirus by reducing the levels of a compound that helps the virus infect the body, the South China Morning Post reported Monday.
• The study found that cabbage — whether raw, pickled in sauerkraut or mixed into coleslaw — as well as cucumbers and Kimchi, the Korean delicacy made from pickled cabbage and other vegetables, could help people build up resistance to the virus.
• The European researchers said the abundant antioxidants in the vegetables could explain why countries where cabbage is a key part of the national diet, like Germany and South Korea, had lower fatality rates than hard-hit countries such as the US.
• Dr. Jean Bousquet, Professor of Pulmonary Medicine at Montpellier University in France, said diet may play a larger role in determining who contracts the virus and how well they fare fighting it off.
• “Little attention has been given to the spread and severity of the virus, and regional differences in diet, but diet changes may be of great benefit. Nutrition may play a role in the immune defense against C19 and may explain some of the differences seen in C19 across Europe. I have now changed my diet, and it includes raw cabbage three times a week, sauerkraut once a week, and pickled vegetables,” he said.
• “Understanding these differences, and protective factors, like diet, but many others too, is of paramount importance, and may eventually help to control these epidemics.”
• The study, published in the journal Clinical and Translational Allergy, looked at virus death rates and national dietary differences.
• It found Germany has significantly lower mortality, as did Austria, the Czech Republic, Poland, Slovakia, the Baltic States and Finland, where cabbage is popular.
• Bulgaria, Greece and Romania also had reduced death rates, whereas fatalities were much higher in Belgium, France, Italy, Spain and the UK, where less cabbage is consumed, The Sun reported.
• Bousquet, former chair of the World Health Organization’s Global Alliance against Chronic Respiratory Diseases, said the antioxidant-rich foods could be another arrow in the quiver of researchers seeking to stem the pandemic.
• “Fermented foods have potent antioxidant activity and can protect against severe C19,” he said.
• The study has not been peer-reviewed.

Source: Foods containing cabbage could help fight coronavirus 

C. Improved & Potential Treatments

1. Inhaled Drug Reduces Odds of Hospitalized Patients Developing Severe Symptoms by 79%

• A British pharmaceutical company on Monday announced that results from a clinical trial of a new coronavirus treatment could signal a “major breakthrough” in the battle against C19.
• Synairgen, a respiratory drug discovery and development company, said in a news release that the trial showed the odds of developing severe symptoms was cut by 79% for hospitalized patients who received its nebulizer treatment.
• Patients who received the drug, SNG001, were more than twice as likely to recover and have no limitation of activities “over the course of the treatment period compared to those receiving a placebo,” the company said.
• “We are all delighted with the trial results announced today, which showed that SNG001 greatly reduced the number of hospitalized C19 patients who progressed from ‘requiring oxygen’ to ‘requiring ventilation,’” Synairgen CEO Richard Marsden said in the release. “This assessment of SNG001 in C19 patients could signal a major breakthrough in the treatment of hospitalized C19 patients. Our efforts are now focused on working with the regulators and other key groups to progress this potential C19 treatment as rapidly as possible.”
• Professor Stephen Holgate, Medical Research Council Clinical Professor of Immunopharmacology at the University of Southampton and Co-Founder of Synairgen, said: “Recognising that SARS-CoV-2 is known to have evolved to evade the initial antiviral response of the lung, our inhaled treatment of giving high local concentrations of interferon beta, a naturally occurring antiviral protein, restores the lung’s ability to neutralise the virus, or any mutation of the virus or co-infection with another respiratory virus such as influenza or RSV, as could be encountered in the winter if there is a resurgence of C19.”

Source: British Pharmaceutical Says Coronavirus Drug Trial Shows Possible ‘Major Breakthrough’ 

2. C19 could be crippled by an age-old blood thinner

• Much of the effort to develop remedies and vaccines to fight C19 has centered around the spike protein that the coronavirus uses to invade healthy cells. Scientists at Rensselaer Polytechnic Institute believe they’ve found a way to block the spike protein’s ability to infect cells—and it involves a 78-year-old blood thinner.
• The drug is heparin, which is widely used to treat and prevent blood clots. The RPI team discovered that the coronavirus binds tightly to heparin, making the drug a potential “decoy” that could serve as a way to neutralize the virus before it can infect healthy cells. They reported the finding in the journal Antiviral Research. Read here: https://www.sciencedirect.com/science/article/pii/S0166354220302874
• The RPI researchers made the discovery by studying gene sequencing data for the coronavirus and recognizing certain characteristics of the spike protein they believed would make it likely to bind to heparin. They tested three variants of the drug, including a non-anticoagulant formulation, against the virus, using computational modeling to define how they bound to the pathogen.
• By binding to the coronavirus, the blood thinner traps the virus, “which can’t exist really sitting there, bound to the heparin. It’ll just degrade,” explained Jonathan Dordick, Ph.D., professor of chemical and biological engineering at RPI, in a video.
• Dordick’s team was already working on methods for trapping viruses when the C19 pandemic started spreading. The researchers developed a viral trap technology that uses pieces of DNA to mimic the latching sites on human cells, and they published research showing promising early data in dengue, influenza A and Zika.
• Some blood thinners are already being used by physicians treating C19. Demand for Bristol Myers Squibb’s Eliquis skyrocketed earlier this year following reports that the drug could prevent strokes in seriously ill patients.
• The RPI researchers are proposing that heparin be used as a stopgap measure against C19 until a vaccine is found. The drug could be delivered in an inhaled form to people who have been exposed to C19, they suggested.
• “This approach could be used as an early intervention to reduce the infection among people who have tested positive, but aren’t yet suffering symptoms,” said lead author Linhardt in a statement. “Ultimately, we want a vaccine, but there are many ways to combat a virus, and as we’ve seen with HIV, with the right combination of therapies, we can control the disease until a vaccine is found.”

Source: How COVID-19 could be crippled by an age-old blood thinner

3. CBD May Help Reduce the Cytokine Storm and Avert Lung Destruction 

• Cannabidiol, or CBD, may help reduce the cytokine storm and excessive lung inflammation that is killing many patients with C19, researchers say.
• While more work, including clinical trials to determine optimal dosage and timing, is needed before CBD becomes part of the treatment for C19, researchers at the Dental College of Georgia and Medical College of Georgia have early evidence it could help patients showing signs of respiratory distress avoid extreme interventions like mechanical ventilation as well as death from acute respiratory distress syndrome.
• “ARDS is a major killer in severe cases of some respiratory viral infections, including the coronavirus, and we have an urgent need for better intervention and treatment strategies,” says Dr. Babak Baban, immunologist and interim associate dean for research at DCG and corresponding author of the study in the journal Cannabis and Cannabinoid Research.
• Our laboratory studies indicate pure CBD can help the lungs recover from the overwhelming inflammation, or cytokine storm, caused by the C19 virus, and restore healthier oxygen levels in the body, says co-author Dr. Jack Yu, physician-scientist and chief of pediatric plastic surgery at MCG.
• Their CBD findings were enabled by their additional finding of a safe and relatively inexpensive model to duplicate the lung damage caused by ARDS. Work on the virus itself is limited to a handful of labs in the nation that can safely manage the highly contagious virus, and their newly reported approach opens more doors for studying the coronavirus, C19 and similar virus-induced conditions, they say.
• Their model, which takes advantage of the large, unique genetic structure of the coronavirus, produced classic symptoms of ARDS like the overwhelming, destructive immune response, then CBD significantly downregulated classic indicators of the excess, like inflammation-promoting cytokines as it improved oxygen levels in the blood and enabled the lungs to recover from the structural damage.
• A major problem with the coronavirus is instead of just killing the virus, the over-the-top immune response can quickly disable the lungs, transforming them to a place where virus is replicated, rather than a place that makes oxygen available for our bodies and eliminates potentially harmful gases like carbon dioxide.
• Mechanical ventilators can take over these vital functions for a while, and enable critically ill people to use less energy to just breathe and have more energy to fight infection, while ideally the lungs recover from the assault. However evidence suggests 30-50% of patients who get to the point of mechanical ventilation, don’t survive.
• The cytokines in these now famous “storms” are a class of molecules like interferon and interleukin, secreted by immune cells and other cells like endothelial cells that line blood vessels, which impact cell communication and can both promote and deter inflammation. In the case of C19, there is excessive production of inflammation-promoting molecules like the interleukins IL-6 and IL-1β, as well as immune cells like neutrophils and monocytes, the researchers say.
• They looked at objective measures of lung function in mice like levels of proinflammatory cytokines, oxygen levels in the blood before and after treatment, as well as temperature, an indicator of inflammation. Oxygen levels went up, while temperatures and cytokine levels went down with CBD therapy. Days later, a more detailed analysis of the lungs, reinforced reduction of key indicators of destructive inflammation, which their model, like the virus, drove way up including reduced levels of IL-6 and infiltrating neutrophils.
• In fact, both clinical symptoms and physical lung changes resulting from ARDS were reversed with CBD treatment, they say.
• Their model was created with the help of a synthetic analog of double-stranded RNA called POLY (I:C). In humans, our double-stranded DNA contains our genetic information and our single-stranded RNA carries out the instruction of our DNA to make certain proteins. In the family of coronaviruses, the double-stranded RNA carries the genetic material needed to reproduce the viruses and hijacks the cell machinery of our body to do that, Baban says.
• “The natural instinct of the virus is to make more of itself,” Baban says. “It weaves with our DNA to make the cell produce food and everything it needs.” Viruses also tend to have a tissue or tissues they prefer — some can and do go anywhere — and for the coronavirus, the lungs are high on the list, he says.
• Our bodies aren’t used to this double-stranded RNA so, like the virus, POLY (I:C) gets the immediate and extreme attention of toll-like receptor 3, a family of receptors that help our body recognize invaders like a virus and activate our frontline, innate immune response.
• “The toll-like receptors 3 see this and just go nuts,” Yu says. The fact that the coronaviruses are literally big and have the largest known viral RNA genome make such a vigorous cytokine and immune response both plausible and probable, adds Baban.
• Mice received three, once-a-day doses of POLY (I:C) in the nasal passageway. CBD was given by a shot in the abdomen, the first dose two hours after the second POLY (I:C) treatment, then every other day for a total of three days in a process that sought to mimic mice getting treatment about the time a human would begin to experience trouble breathing and likely seek medical care. Given too early, CBD might actually interfere with a proper immune response against the virus, Yu says.
• CBD quickly improved the clinical symptoms, then later detailed studies of the lungs showed damage to their structure, like tissue overgrowth, scarring and swelling, also had totally or partially resolved. Their next steps include doing similar studies on other organs impacted by C19 including the gut, heart and brain, Baban says.
• At least one way CBD is thought to calm the immune response is because it looks similar to endocannabinoids, a natural cell signaling system in our bodies believed to be involved in a wide variety of functions from sleep to reproduction to inflammation and immune response. CB1 and CB2, the main receptors for this system, are found extensively throughout the body including the brain and respiratory system, where we breathe in manmade and natural irritants in the air — as well as viruses and bacteria — that might inflame. While understanding the workings of the natural endocannabinoid system is still very much a work in progress, it’s thought that one way CBD works to reduce seizures, for example, is indirectly through the large number of CB1 receptors in the brain, says Yu.
• CBD is available without a prescription, and is used to treat problems like seizures as well as Parkinson’s, Crohn’s and other conditions where pain and/or inflammation are a major factor. It’s derived from the hemp and cannabis plant, which are essentially the same although hemp has a much lower concentration of the “high” producing THC. Other investigators have shown the calming effect of CBD, for example, can block IL-6 in other models of inflammatory disease.

Source: CBD May Help Reduce the Cytokine Storm and Avert Lung Destruction in COVID-19

4. Coronavirus vaccine from Oxford and AstraZeneca shows positive response in early trial

• A potential coronavirus vaccine developed by Oxford University with pharmaceutical giant AstraZeneca has produced a promising immune response in a large, early-stage human trial, according to newly released data published Monday in the medical journal The Lancet.
• The researchers are calling their experimental vaccine ChAdOx1 nCoV-19 (AZD1222). It combines genetic material from the coronavirus with a modified adenovirus that is known to cause infections in chimpanzees. The phase one trial had more than 1,000 participants in people ages 18 to 55.
• The researchers said the vaccine produced antibodies and killer T-cells to combat the infection that lasted at least two months. Neutralizing antibodies, which scientists believe is important to gain protection against the virus, were detected in participants. The T-cell response did not increase with a second dose of the vaccine, they said, which is consistent with other vaccines of this kind.
• “The immune system has two ways of finding and attacking pathogens — antibody and T cell responses,” Oxford professor Andrew Pollard said in a release. “This vaccine is intended to induce both, so it can attack the virus when it’s circulating in the body, as well as attacking infected cells. We hope this means the immune system will remember the virus, so that our vaccine will protect people for an extended period.”
• The vaccine was found to be well-tolerated and there were no serious adverse events, according to the researchers. Fatigue and headache were the most commonly reported, they said. Other common side effects included pain at the injection site, muscle ache, chills and a fever.
• Adrian Hill, director of Oxford’s Jenner Institute, told CNBC on Monday the strong immune response means the vaccine is more likely to provide protection against the virus, though nothing is guaranteed. He said scientists hope to begin human trials in the United States in a few weeks.
• “We are using single-dose and two-dose of the vaccine,” he told “Worldwide Exchange.” “It looks like both give useful immune responses even though after two doses we see stronger immune responses.”
• AstraZeneca said in June it is working with industry partners to manufacture and distribute 2 billion doses of the vaccine with Oxford. 
• While Oxford’s data is promising, scientists warn that questions remain about how the human body responds once it’s been infected with the virus. The answers, they say, may have important implications for vaccine development, including how quickly it can be deployed to the public.
• “I would say there’s a lot of optimism,” said Dr. Jonathan Abraham, a professor at Harvard Medical School’s Department of Microbiology and Immunobiology. “But I think the optimism is making a lot of assumptions. The assumptions include that what we’re seeing now is a type of infection where if you get infected and you’re re-exposed shortly after that you won’t be infected again.”

Source: Coronavirus vaccine from Oxford, AstraZeneca shows positive response in early trial 

5. Chinese C19 Vaccine Phase 2 Trial Results: Safe and Induces an Immune Response  

• A phase 2 trial of an Ad5 vectored C19 vaccine candidate, conducted in China, has found that the vaccine is safe and induces an immune response, according to new research published in The Lancet.
• The randomized trial sought to evaluate the safety and immunogenicity of the vaccine candidate and follows a phase 1 trial published in May 2020. The results provide data from a wider group of participants than their phase 1 trial, including a small sub-group of participants aged over 55 years and older, and will inform phase 3 trials of the vaccine.
• However, the authors note that it is important to stress that no participants were exposed to coronavirus after vaccination, so it is not possible for this study to determine whether the vaccine candidate effectively protects against the coronavirus infection.
• Professor Feng-Cai Zhu, Jiangsu Provincial Center for Disease Control and Prevention, China, says: “The phase 2 trial adds further evidence on safety and immunogenicity in a large population than the phase 1 trial. This is an important step in evaluating this early-stage experimental vaccine and phase 3 trials are now underway.” 
• Currently, there are about 250 candidate vaccines against the coronavirus in development worldwide, including mRNA vaccines, replicating or non-replicating viral vectored vaccines, DNA vaccines, autologous dendritic cell-based vaccine and inactive virus vaccines. At least 17 of them are currently under evaluation in clinical trials.
• The vaccine in this trial uses a weakened human common cold virus (adenovirus, which infects human cells readily but is incapable of causing disease) to deliver genetic material that codes for the coronavirus spike protein to the cells. These cells then produce the spike protein, and travel to the lymph nodes where the immune system creates antibodies that will recognize that spike protein and fight off the coronavirus.
• 508 participants took part in the trial of the new vaccine. Of these, 253 received a high dose of the vaccine (at 1×1011 viral particles/1.0mL), 129 received a low dose (at 5×1010 viral particles/1.0mL) and 126 received placebo. Approximately two thirds of participants (309; 61%) were aged in 18-44 years, a quarter (134; 26%) were aged 45-54 years, and 13% (65) were 55 years or older.
• Participants were monitored for immediate adverse reactions for 30 minutes after injection and were followed for any injection-site or systemic adverse reactions within 14- and 28-days post-vaccination. Serious adverse events reported by participants during the whole study period were documented. Blood samples were taken from participants immediately before the vaccination and 14- and 28-days post-vaccination to measure antibody responses.
• The trial found that 95% (241/253) of participants in the high dose group and 91% (118/129) of the recipients in the low dose group showed either T cell or antibody immune responses at day 28 post-vaccination.
• The vaccine induced a neutralizing antibody response in 59% (148/253) and 47% (61/129) of participants, and binding antibody response in 96% (244/253) and 97% (125/129) of participants, in the high and low dose groups, respectively, by day 28. The participants in the placebo group showed no antibody increase from baseline.
• Both doses of the vaccine-induced significant neutralizing antibody responses to live coronavirus, with geometric mean titers of 19.5, and 18.3 in participants receiving the high and low dose, respectively. The binding antibody response peaked at 656.5 ELISA units and 571 ELISA units for the high and low dose of the vaccine, respectively.
• T cell responses were also found in 90% (227/253) and 88% (113/129) of participants receiving the vaccine at high and low dose, respectively. A median of 11 spot-forming cells and 10 spot-forming cells per 1 × 10? peripheral blood mononuclear cells in participants in the high dose and low dose groups, respectively, were observed at day 28.
• The proportions of participants who had any adverse reactions such as fever, fatigue and injection-site pain were significantly higher in vaccine recipients than those in placebo recipients (72% [183/253] in the high dose group, 74% [96/129] in the low dose group, 37% [46/126] in the placebo group). However, most adverse reactions were mild or moderate. Within 28 days, 24 (9%) participants in the high dose group had severe (grade 3) adverse reactions, which was significantly higher than in those receiving the low dose or placebo (one (1%) participant in the low dose group, and 2 people (2%) in the placebo group). The most common severe reaction was fever.
• The authors note that pre-existing immunity to the human adenovirus which was used as the vector (ie, the Ad5 vector) for this vaccine and increasing age could partially hamper the specific immune responses to vaccination, particularly for the antibody responses. Among the 508 participants, 266 (52%) participants showed a high pre-existing immunity to Ad5 vector, while 242 (48%) had low pre-existing immunity to Ad5 vector. Those with a higher pre-existing anti-Ad5 immunity showed an inferior immune response (the binding and neutralizing antibody levels were around two times larger in people with low pre-existing anti-Ad5 immunity, compared to those with high pre-existing immunity). Compared with the younger population, older participants generally had significantly lower immune responses and higher tolerability to the Ad5 vectored C19 vaccine.
• Professor Wei Chen, Beijing Institute of Biotechnology, China, says: “Since elderly individuals face a high risk of serious illness and even death associated with C19 infection, they are an important target population for a C19 vaccine. It is possible that an additional dose may be needed in order to induce a stronger immune response in the elderly population, but further research is underway to evaluate this.”
• The authors note that the trial was conducted in Wuhan, China, and the baseline immunity is representative of Chinese adults at that time, but other countries may have different rates of immunity which should be considered. Additionally, the trial only followed participants for 28 days and no data about the durability of the vaccine-induced immunity is available from this study. Importantly, no participants were exposed to the coronavirus after vaccination, so it is not possible for this study to determine the efficacy of the candidate vaccine or any immunological risk associated with antibody induced by vaccination when having a virus exposure.

Source: Chinese COVID-19 Vaccine Phase 2 Trial Results: Safe and Induces an Immune Response

D. Concerns & Unknowns

1. 200,000 people in UK could die from disease unrelated to C19 because of delays in healthcare and economic effects of coronavirus lockdown

• More than 200,000 people could die because of delays in healthcare and other economic and social effects all caused by lockdown, a [UK] government report has warned.
• The great majority of the deaths – 185,000 – are attributed to an extended wait for treatment in the longer term.
• But up to 25,000 deaths would have come in the first six months because of healthcare delays, according to experts at the Department of Health and Social Care, Office for National Statistics, Government Actuary’s Department and the Home Office.
• The number of NHS patients admitted for routine ops has dropped 82 per cent in a year and 1.5million have been forced to wait at least 18 weeks to start treatment, devastating statistics last week revealed.
• Shocking NHS England data that laid bare the strain C19 has put on hospitals showed only 54,550 patients were admitted for treatment in May — a fraction of the 295,000 recorded this time last year. 
• And 1.45million patients have had to wait at least 18 weeks to start hospital treatment for routine operations such as hip and knee replacements — the worst since 2007 and more than double last May. 
• Top surgeons warned the ‘time bomb’ — fueled by thousands of non-urgent operations being cancelled during the peak of the pandemic — had ‘detonated’, saying the crisis is ‘spiraling out of control’.  
• Analysts revealed the NHS faces a ‘long and difficult road ahead’ and that it faces an ‘enormous challenge’ in catching up with the backlog of patients whose treatments were postponed.
• The shocking NHS data also revealed: 
  • 26,000 people have been waiting more than a year for a routine operation — 26 times higher than this time last year and the most since September 2009;
  • Just 62.2% of people were treated within 18 weeks in May, well below the target of 95 per cent;
  • More than 500,000 patients in England have been waiting at least six weeks for a key diagnostic test – such as an MRI or gastroscopy;
  • Cancer waiting times hit an all-time high with fewer than half (47.9%) of diagnosed patients not starting life-saving treatments within two months.
• The figures equate to nearly one million years of life lost unnecessarily, in the worst-case scenario outlined in the report.
• With lockdown measures in place and hospital priorities shifted, patients have likely missed out on life-saving care for heart attacks and strokes and early diagnoses of diabetes and kidney disease.
• The University of Oxford discovered just last week that 5,000 fewer heart attack patients had attended hospital between March and May.
• The report – published in April but largely overlooked until now – has added credence to the view that patients with serious illnesses unrelated to coronavirus have been neglected during the pandemic.
• The report said: ‘Suspending “non-urgent” care is expected to have a short-term health impact in itself, since patients not receiving treatment will have reduced quality of life whilst not receiving these healthcare services. 
• ‘In the longer term their condition is likely to deteriorate without treatment and some could die earlier than otherwise. 

Source: 200,000 people could die because of delays in healthcare, report warns 

2. What happens when the flu meets C19?

• Optimists had hoped C19 might not withstand the blistering heat of a British summer. However those hopes have faded: the virus staged a recent resurgence in Iran amid actual blistering temperatures, and has had no trouble persisting in sultry Singapore.
• But what happens to C19, and us, when the rain and chill – and flu and sniffles – of autumn set in? Especially, how will the annual winter flu epidemic play out amid a C19 pandemic?
• One thing is a given. “We can expect waves of Covid in the fall,” says virologist Ab Osterhaus of the Research Centre for Emerging Infections and Zoonoses in Hanover. By then, he hopes, we might be better at treating severe cases, and more countries might be able to test, trace and quarantine all cases and their contacts, and contain the virus, better than they can now.
• The prospect of a flu pandemic hitting amid an existing C19 pandemic is chilling. Hospitals would be overwhelmed
• The biggest worry in the UK is that hospitals can struggle to cope with the winter flu season. This year they will have to cope with C19 as well, which shows no sign of going away by then, and could even surge if it turns out that cold temperatures, or the circulation of other autumn and winter viruses, boost its spread.
• The first problem will be figuring out which virus a patient has. Flu, C19 and other seasonal respiratory diseases are virtually indistinguishable on the basis of symptoms, warns Barbara Rath of the University of Nottingham: even the loss of taste and smell many people get with C19 is not unique. We need more and better diagnostic tests, she says, because the difference matters: medical staff need full protective gear to manage a Covid patient, but they can be vaccinated for flu.
• The real unknown is what C19 does around other viruses. Every autumn there is a predictable series of outbreaks of respiratory viruses. It starts with rhinovirus, the main cause of the common cold, which breaks out every September as young children go to school and swap mucus. As no parent needs to be told, children are to sniffles what mosquitoes are to malaria.
• The rhinovirus subsides as most children are exposed and their immune systems activate. Then another virus breaks out: respiratory syncytial virus, or RSV. Every year in October or November, this causes mild colds in people of all ages, but sometimes severe lung infections in the youngest and oldest of us. RSV is so common that virtually all two-year-olds have already had it, and it sends more babies to hospital with pneumonia than any other virus.
• Then RSV subsides, and the annual flu epidemic sets in, anywhere from early winter to spring, driven mainly by transmission among children, but taking its main toll among the elderly: some 8,000 on average die yearly of flu in the UK. This predictable parade of infections almost seems a spiteful campaign by viruses to keep people, especially families with young kids, sick for as long as possible.
• But it is just a product of a little-understood phenomenon called “viral interference”: while one of these viruses holds sway in a person, or the population, for some reason the others can’t get a toehold. In September 2009, the swine flu pandemic that went on to sweep the world should have invaded Europe from the Americas. But the annual rhinovirus epidemic actually kept it at bay. The highly contagious new flu took over only when rhinovirus subsided, bumping RSV down the queue: RSV moved in only after that first wave of flu subsided.
• The question now is where C19 is going to fit amid this viral jostling. Not every virus takes turns like this, says Ian MacKay of the University of Queensland. Sometimes you can be infected by two at once. So which kind is C19?
• We do know it can infect someone alongside flu: the first C19 case to die outside China was a 44-year-old man in the Philippines, who also had flu. We don’t know for sure that having flu at the same time makes Covid worse, but the fact that the Filipino victim was fairly young is worrying, says Florian Krammer of Mount Sinai School of Medicine in New York. “We assume the outcome of co-infection is not great.”
• Doctors at the Tongji Hospital in Wuhan report that in January and February this year, as C19 took hold in the city while flu was still circulating, many C19 patients had both viruses. Co-infection didn’t seem to change their chances of survival compared to people with Covid only, but they had more heart damage, and more and earlier runaway inflammation, the over-reaction of the immune system that kills many late-stage Covid patients.
• Elsewhere, however, we have had few chances to find out how often that happens. Last March, C19 hit Europe as flu season was winding down, while lockdown stopped Australians from spreading flu as well as Covid and snuffed out the incipient flu season. But with little lockdown expected this autumn in the northern hemisphere, seasonal viruses and Covid will collide head-on.
• If there is significant viral interference, optimists hope the child-driven autumn epidemics might keep C19 at bay, as they do each other. But those viruses are transmitted mostly by children, while it appears that Covid is mostly spread by adults: the viruses might just spread in parallel, in separate populations of children and adults. That might mean more sick people in total, with severe cases competing for a fast-dwindling supply of hospital beds.
• Or the fact that Covid seems to infect a different type of cell from the others might mean there is no interference, allowing co-infection with rhinovirus, RSV and flu, possibly making more people more seriously ill. “We need to hope for the best, but prepare for the worst,” says Osterhaus.
• And that basically means preparing for the flu, because it is the only one of these viruses for which we have a specific antiviral drug and a vaccine, despite years of intensive efforts to develop a vaccine for RSV. “That means, get your flu shot,” says Krammer.
• Because flu viruses constantly evolve, though, a flu shot is something you have to get every year. Every February virologists try to predict which viruses will circulate the following winter, and companies put vaccine viruses on to grow in chicken eggs, in a process (dating from the 1940s) that takes six months.
• Then those who want to avoid the flu get vaccinated in the autumn just before the virus hits. If the scientists guessed right, it is at best 70% effective – but that’s better than nothing.
• In the UK this is normally recommended for the pregnant, people over 65, schoolchildren and people at greater risk from flu because of underlying conditions such as diabetes, high blood pressure or lung disease – pretty much the same conditions that increase your risk from C19. “This year,” says Krammer, “it should be everybody,” as C19 could increase the risk for everyone.
• This is partly because people who normally don’t get a flu vaccination because they are not in those high-risk groups might end up severely ill after all, because they caught C19 at the same time – and of the two we can only prevent flu. Moreover, every year people who don’t officially need the flu vaccine end up in hospital anyway with some complication, typically pneumonia, that will further burden health services. Worse, they are then more likely to catch C19 as well, while in hospital.
• The nightmare scenario would be if this year’s flu was not the normal seasonal type.

Source: What happens when flu meets Covid-19? | Society 

3. C19 Spread Fastest by Older Children

• Older children are more likely to spread C19 within a household than younger children and adults, according to a new study of 5,706 coronavirus patients in South Korea.
• The researchers traced and tested nearly 60,000 people who had contact with the infected people and found that, on average, 11.8% of household contacts tested positive for C19, according to the early release of a study published on the U.S. Centers for Disease Control and Prevention website.
• For people who lived with patients between the ages of 10 and 19, 18.6% tested positive for the virus within about 10 days after the initial case was detected — the highest rate of transmission among the groups studied. Children younger than 10 spread the virus at the lowest rate, though researchers warned that could change when schools reopen.
• At the same time, virus rates have been rising again, even in places that thought they’d extinguished their outbreaks, and many teachers are wary of returning to the classroom. State data suggests the infection rates among children could also be far higher than the 2% reported by the CDC.
• The South Korean study suggests that older children may be particularly contagious, although the researchers point out that household contacts could have contracted the virus elsewhere. Still, given the high rates of infection within families, the study called for more research to understand how to limit the spread of the virus at home.
• Read the study:  https://wwwnc.cdc.gov/eid/article/26/10/20-1315_article

Source: Do Teens Spread Covid-19? Korean Study Asks the Question 

E. Projections & Our (Possible) Future 

1. The Link Between Face Masks, Infection and GDP

• New US coronavirus cases have risen sharply in recent weeks, leading investors to worry that renewed lockdowns will again depress economic activity. 
• But since the first infection wave in March and April, it has become clear that broad lockdowns are not the only way to lower virus transmission, and many governments have started to require the wearing of face masks in public settings. 
• Should the United States follow suit with a national mandate? This is inherently a political decision, but we can use our analytical tools to answer three questions that are relevant to it. 
  • First, how effective is a face mask mandate in increasing face mask usage? 
  • Second, does increased face mask usage lower virus transmission, and if so by how much? 
  • And third, how economically valuable is a face mask mandate in terms of reducing the need for broad lockdowns with their well-documented negative effects on GDP? 
• The sharp increase in confirmed coronavirus cases in the US Sun Belt has led investors to worry about renewed broad lockdowns with large negative effects on GDP. But there are also other ways to reduce infections, including stringent bans on large gatherings and greater use of face masks.
• In particular, we argue that a national face mask mandate could partially substitute for renewed lockdowns. We start by showing that a national mandate would likely increase face mask usage meaningfully, especially in states such as Florida and Texas where masks remain largely voluntary to date.
• We then investigate the link between face masks and coronavirus outcomes. Our analysis includes 1) a US regional panel in which we relate the growth rate of infections and fatalities to the introduction of state face mask mandates, 2) a large country-level cross section in which we relate cumulative infections and fatalities to the lag between the onset of spread and the introduction of a face mask mandate, and 3) a smaller country-level panel in which we relate the growth rate of infections and fatalities to lagged mask usage.
• We find that face masks are associated with significantly better coronavirus outcomes. Since this is true across all three of our models and the results are robust to the inclusion of a number of control variables, it seems to reflect a largely causal impact of masks rather than correlation with other factors (such as reduced mobility or avoidance of large gatherings). Our baseline estimate is that a national mandate could raise the percentage of people who wear masks by 15% and cut the daily growth rate of confirmed cases by 1.0% to 0.6%.
• Finally, we translate our results into GDP terms by asking how much our Effective Lockdown Index (ELI) would need to increase in order to cut infections by as much as a national mask mandate, and then converting the ELI impact into a GDP impact using the estimated cross-country relationship between the two. These calculations imply that a face mask mandate could potentially substitute for lockdowns that would otherwise subtract nearly 5% from GDP.

Source: Insights – Face Masks and GDP 

F. Johns Hopkins COVID-19 Update

July 20, 2020

1. Numbers & Trends

Overview

• The WHO COVID-19 Situation Report for July 19 reports 14.04 million cases (166,735 new) and 597,583 deaths (4,496 new). This is the lowest daily incidence reported since July 1; however, it includes zero new cases reported by the US. With the expected number of US cases, the global daily incidence would be closer to 230-240,000 cases. The WHO reported the global record high of 259,848 new cases on July 18. The pandemic has been ongoing for more than 6 months and continues to accelerate.

Central & South America

• Brazil reported 23,529 new cases, falling to #3 globally in terms of daily incidence. Two weeks ago (Week 28), Brazil’s weekly incidence was nearly identical to the previous week, and last week (Week 29), Brazil reported its first noticeable decrease in weekly incidence—down from 262,846 new cases to 235,010. The daily incidence still appears to be relatively consistent over the past 3 weeks; however, this could indicate that Brazil has passed its first peak. Colombia reported 6,578 new cases, and its epidemic continues to accelerate. Colombia is currently #5 globally with respect to daily incidence, and Mexico (5,311 new cases) is #6. Broadly, the Central and South American regions are still major C19 hotspots. Including Brazil, Colombia, and Mexico, the region represents 5 of the top 11 countries globally in terms of daily incidence, along with Peru (#8) and Argentina (#10). Additionally, 10 countries in the Americas, including the US and the Caribbean, are reporting more than 100 daily cases per million population.

India & Bangladesh

• India reported its highest daily incidence to date, with 40,425 new cases, exceeding 40,000 new cases for the first time. India surpassed Brazil to become #2 globally in terms of daily incidence. India’s daily incidence has more than doubled since the beginning of July and appears to be increasing exponentially. Bangladesh continues to report slowly decreasing daily incidence; however, it is also reporting decreased testing while its test positivity remains slightly above 20%. This could indicate that Bangladesh’s decreased incidence could be driven more by reduced testing than slowing transmission. Bangladesh is #9 globally in terms of daily incidence.

South Africa

• South Africa reported 13,449 new cases, and it remains among the top countries globally in terms of both per capita and total daily incidence.

Eastern Mediterranean Region

• Overall, the Eastern Mediterranean region remains a global C19 hotspot. In total, at least 20 countries globally are reporting more than 100 daily cases per million population, and 4 of those—Bahrain, Kuwait, Oman, and Qatar—are in the Eastern Mediterranean region. Additionally, nearby Armenia and Israel (WHO European region) are also reporting more than 100 daily cases per million population. Saudi Arabia is #11 globally in terms of total daily incidence.

Australia

• After its first peak, Australia appeared to gain control of its C19 epidemic; however, transmission has surged in recent weeks. At more than 300 new cases per day, Australia’s daily incidence is approaching the level reported during its first peak. In nearby New Zealand, daily totals have not exceeded 3 new cases since the country declared the disease eliminated in early June.

United States

• The US CDC reported 3.70 million total cases (67,574 new) and 139,659 deaths (877 new). In total, 25 states and New York City have reported more than 40,000 total cases, including California with more than 375,000 cases; Florida and Texas with more than 300,000; New York City with more than 200,000; and 7 additional states with more than 100,000. The US is currently averaging more than 750 deaths per day, and it could reach 150,000 cumulative deaths in the next 2 weeks.

• New York, including New York City, has reported the most C19 cases of any US state, with 406,807 total cases; however, California, Florida, and Texas continue on pace to surpass this total in the coming days. California is reporting an average daily incidence of 8,323 new cases per day; Florida is reporting 11,461 new cases per day; and Texas is reporting 9,886 new cases per day. New York is reporting fewer than 750 new cases per day, so we can expect California to surpass New York by the middle of this week, Florida by the end of this week, and Texas by the middle of next week.

• The Johns Hopkins CSSE dashboard reported 3.79 million US cases and 140,716 deaths as of 1:00 pm on July 20.

2. US C19 Relief Bill 

• Some portions of US C19 relief funding are expiring soon, and efforts are ongoing to evaluate the possibility of another round of stimulus funding. In particular, previous C19 funding bills provided for increased unemployment insurance—an extra US$600 per week—which will expire next week. Additionally, a federal moratorium on some evictions will also expire, which would put many individuals and families at risk of losing their homes, particularly those who remain unemployed. The expiration of state-level eviction moratoria are already resulting in substantial volumes of eviction proceedings in some states. Many individuals have used the extra unemployment funding to pay bills, including rent, and they may not be able to continue making their required payments without an extension or other federal funding support.

• With many Americans still unable to return to work—due to a variety of factors, including temporary or permanent closure of their business, remaining social distancing restrictions, children still home from school, or a lack of available jobs—federal lawmakers are discussing potential options for another stimulus package. There is some evidence that the expanded unemployment funding is allowing some individuals to make more money than if they were working, which could complicate decisions regarding when and how to return to work. Concerns about rising federal debt and potential misuse of federal funding are factoring into these plans.

• While the negotiations involve many complex issues and decisions, there are several primary proposals and areas of contention with respect to how future funding would be distributed. Democrats in the House of Representatives previously passed a US$3 trillion funding package that included a broad range of support for individuals, businesses, state and local governments, and hospitals; however, the bill never received a vote in the Senate. Senate Majority Leader Mitch McConnell has indicated that Senate Republicans are drafting their own legislation, potentially more limited in scope and funding, could be unveiled this week. One of Senator McConnell’s stated priorities is liability protection for businesses, including hospitals, to protect them against lawsuits following C19 infections among employees or patrons. Speaker of the House Nancy Pelosi emphasized the need for direct payments and extended unemployment insurance for individuals to ensure they have funds available for rent, food, and other necessities, but there are differing opinions regarding how best to accomplish it and who could be eligible. Additionally, US President Donald Trump has called for a payroll tax cut for businesses; however, there appears to be some opposition to this mechanism from both Republicans and Democrats. While a payroll tax cut could reduce financial burden on businesses, it could also reduce federal funding for programs such as Social Security.

3. Children & Schools 

• As the US school year rapidly approaches, federal, state, and local government officials are working to develop and implement plans to resume classes. Proposals range from full-time, in-person classes to online/remote classes only, including a myriad of hybrid options in between. Much of the uncertainty and debate revolves around the direct risk to children and the role they play in community transmission. It is generally understood that children are at lower risk for severe C19 disease and death than adults—although, certainly not zero risk—but it is much less clear how easily children transmit the infection to others, including adults or other high-risk individuals at home or in the community. 

• A recent study by researchers in South Korea, published in the US CDC’s Emerging Infectious Diseases journal, found that SARS-CoV-2 transmission was far more common in household settings compared to public settings. Based on analysis of more than 59,000 contacts of more than 5,700 C19 “index patients,” the researchers found that household contacts were more than 6 times more likely to become infected than non-household contacts. The study identified cases in 11.8% of household contacts, compared to only 1.9% of non-household contacts. Notably, households with an “index patient” aged 10-19 years were at even higher risk for transmission—cases identified in 18.6% of household contacts, compared to 11.8% in households with “index patients” of other ages. The lowest transmission risk among household contacts was for “index patients” aged 0-9 years. In these households, cases were identified in only 5.3% of household contacts; however, this was still greater than the overall risk for non-household contacts. This indicates that children who are infected at school could transmit the infection at home more easily than in other settings, particularly for older children, which would put other family members at increased risk. The study only evaluated symptomatic cases, so further evaluation is required to better characterize the role of asymptomatic or pre-symptomatic transmission by children.

• It appears that there may be significant risk of transmission by children as they return to in-person classes, and many schools are evaluating options for remote/online classes this fall. Other options include home schooling, which some parents are investigating after positive experiences with remote classes this spring after most schools closed. While these options may appear similar on the surface, remote classes and home schooling are very different. Home school options vary widely, including utilizing existing curricula or developing personalized course work, and the standards and requirements vary from state to state. While online classes and home school may be effective, they may not be viable options for everyone. These options may require computers, tablets, or smartphones and reliable high-speed internet service to fully participate, particularly for live-streamed classes or video sessions. Availability for both computers and internet services may not be feasible for lower-income families or those living in remote areas, and many parents may not be able to continue to work remotely or remain at home in order to supervise their children during the day.

4. Candidate Therapeutics  

• Synairgen, a biotechnology company based in the UK, announced preliminary findings from Phase 2 trials of a candidate treatment for hospitalized C19 patients. The therapeutic, dubbed SNG001 for now, is an aerosolized formulation of interferon beta, a protein commonly found in humans’ innate immune system and found to be protective against respiratory viruses. The study—a double-blind, placebo-controlled clinical trial—involved 100 hospitalized patients. Patients receiving the experimental therapeutic were more than twice as likely to recover and exhibited a 79% reduction in progression to severe disease. These results were reported by Synairgen via a press release and have not been peer-reviewed. The trial also includes 120 non-hospitalized C19 patients, but the data for that portion of the trial has not yet been published.

• Researchers published data from the UK RECOVERY clinical trial for dexamethasone in The New England Journal of Medicine.  Findings from the trial were previously summarized in a press release that described the drug’s effect in reducing mortality in severe C19 patients. The study involved 2,104 hospitalized patients in the treatment arm and 4,321 patients in the control arm (i.e., current standard of care). Overall, the study found that dexamethasone reduced mortality by 17%, adjusted for age. Notably, patients treated with the drug exhibited a statistically significant decrease in mortality among those receiving supplemental oxygen or mechanical ventilation but not for those receiving no respiratory support treatment. Dr. H. Clifford Lane and Dr. Anthony Fauci co-wrote a commentary in support of the RECOVERY trial results, emphasizing the importance of robust study designs, as opposed to relying on anecdotal evidence, in order to effectively evaluate candidate vaccines, therapeutics, and prophylactics.

5. Candidate Vaccines 

• Two studies were published in The Lancet, describing results of clinical trials for candidate vaccines from China and the UK. The candidate from Chinese pharmaceutical manufacturer CanSino is a single-dose vaccine that utilizes a recombinant adenovirus vector. The associated trial was a randomized, double-blind, placebo-controlled Phase 2 trial that involved 508 healthy human volunteers in Wuhan, China. Two dosages were tested, and both demonstrated high seroconversion after 4 weeks (96% and 97%, respectively) and significant neutralizing antibody response. Severe adverse reactions were reported in 9% of those receiving the higher dose and 1% of those receiving the lower dose, a statistically significant difference. Based on these results, the researchers intend to conduct a Phase 3 trial for the lower vaccine dose in the near future.

• The candidate from the UK utilizes a chimpanzee adenovirus vector, created through a collaboration between Oxford University and AstraZeneca. The randomized Phase 1/2 trial was single-blinded and utilized a meningococcal conjugate vaccine as a control. The researchers administered the candidate vaccine to 543 healthy adults—533 receiving a single dose and 10 receiving a prime-boost formulation. No serious adverse reactions were reported, and adverse events were reduced among individuals who also received paracetamol (also known as acetaminophen) prohpylactically. The results indicate that the vaccine induced both T-cell and anti-spike IgG immune responses, and the anti-spike IgG response increased following the boost vaccination among those who received it. Neutralizing antibody responses were detected in 91% of individuals after a single dose—and 100% of individuals following the booster dose, for those who received it. According to the researchers, “these results…support large-scale evaluation of this candidate vaccine in an ongoing phase 3 programme.”
• The UK government announced that it reached an agreement with multiple pharmaceutical companies to secure 90 million doses of candidate vaccines. This includes 30 million doses of an mRNA vaccine from BioNTech and Pfizer as well as 60 million doses of an inactivated whole-virus vaccine from Valneva (with an option to acquire an additional 40 million doses from Valneva). The UK government also secured 1 million doses of neutralizing antibodies from AstraZeneca for immunocompromised individuals who may not be able to receive a vaccination due to concerns about potential adverse events.

6. South Africa Shortens Isolation Period 

• South Africa announced that it is shortening its isolation period for C19 patients from 14 days to 10 days. The update is based on data that indicates that mild C19 cases are typically only infectious for 8-9 days after symptoms onset. The announcement states that the 10 days will apply from symptom onset for mild cases, but it will begin after severe patients are clinically stable (ie, no longer requiring supplemental oxygen or mechanical ventilation) in order to account for uncertainty regarding the infectious period in severe cases, consistent with the previous iteration of the guidance. Asymptomatic individuals who test positive can be removed from isolation 10 days after their positive test.
• This update largely aligns with current US CDC and WHO guidance, both of which recommend a minimum of 10 days after symptom onset. Both the US CDC and WHO also include a recommended minimum time after symptoms improve or resolve before being removed from isolation. The US CDC recommends that patients be afebrile for 24 hours and exhibit improving symptoms before being removed from isolation, and the WHO recommends a minimum of 10 days after symptom onset, plus an additional 3 days without fever or other symptoms (ie, a minimum of 13 total days) for symptomatic patients.